Chemical compositions, antioxidants, and anti-aging activities of Cortex Moutan (CM), from different collection periods and different producing areas, were measured and compared in order to obtain ...excellent CM extracts. The bioactivities of CM extracts were examined by an in vitro antioxidant method and a UVB irradiated human dermal fibroblast (HDF) model. Phytochemical properties were obtained from ultra-fast liquid chromatography quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF-MS) prior to the multivariate statistical analysis. As for the results, the extracts of Heze CM (HZCM) and Luoyang CM (LYCM) collected in June had better in vitro antioxidant activities, significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA), compared to other CM extracts. HZCM and LYCM extracts could upregulate the relative expression of SOD and GSH-Px mRNA. The extract of HZCM collected in June could significantly repress the production of matrix metalloproteinase 1 (MMP-1) and improve the production of procollagen type I (PCOL)-I in UVB irradiated HDF. In total, 50 compounds, including 17 monoterpenoids, 19 flavonoids, 13 phenols, and 1 amino acid were identified or tentatively identified in the CM extracts. Gallic acid,
-hydroxybenzoic acid, oxypaeoniflorin, paeoniflorin, 1,2,3,4,6-
-pentagalloyl glucose, and paeonol were predominant compounds in the CM extracts. Taken together, CM collected from April to September had better antioxidant and anti-aging effects for external usage.
When processing silicon wafers for photovoltaic power generation, approximately 35 % of high-purity silicon is lost as a diamond wire saw silicon powder (DWSSP) waste cake with a high moisture ...content. The high moisture content of DWSSP results in the oxidation of high-purity silicon, which hinders the recovery and utilization of silicon resources. Disappointingly, a method for the removal of moisture from the DWSSP waste cake, which is crucial for silicon recovery, has not yet been revealed. In the present study, a novel investigation was conducted to determine the moisture classification of a DWSSP waste cake and to reveal the moisture removal behavior. The results indicate that the moisture content in the DWSSP waste cake can be divided into two distinct categories: surface adsorbed water and capillary water. Moreover, the kinetics analysis and simulation demonstrated that the elimination of moisture predominantly takes place during the constant-rate period and the falling-rate period. Increasing the drying temperature and reducing the equivalent diameter of the DWSSP waste cake will contribute to improving the efficiency of moisture removal. The application of the findings of this study can help to reduce the harmful environmental impacts of DWSSP and achieve the efficient recovery of silicon resources.
A 63-year-old man with an 8-year history of proteinuria was diagnosed with nephrotic syndrome, and a renal biopsy was performed. Light and electron microscopic analyses showed classic features of ...idiopathic membranous nephropathy (IMN). However, immunofluorescence tests revealed solitary polyclonal granular IgA deposition along the glomerular capillary walls, rather than IgG, which is often dominant in IMN. The combined use of corticosteroids and calcineurin inhibitor was noticeably effective in reducing proteinuria and improving edema in the current case. Two additional rare cases of IMN with solitary IgA deposition were reviewed, and long-term surveillance is still warranted to characterize its clinicopathological features and outcome.
Cables/hangers are important load-bearing components of suspension, cable-stayed, and through-arch bridges. Their reliability throughout their service life directly affects the safety of these ...bridges. In this study, to provide a reference for the design, maintenance, and inspection of bridge cables/hangers, their damage and failure mechanisms were theoretically analyzed using finite element analysis and corrosion-fatigue simulation tests of steel wires, based on the characteristics of the cable/hanger damage. The finite element analysis showed that a rotation of 0.00113 rad in the lower anchorage area results in a bending stress of 18.8 MPa, indicating that the effect of the bending stress on the steel wires in this area cannot be neglected, as it is a factor contributing to the failure of long cables/hangers. We further used a salt spray chamber to simulate an acid-rain environment. The results showed the following: (1) corrosion-fatigue damage of the cables/hangers occurs under the combined action of a corrosive environment and an alternating stress. This leads to an intensified corrosion damage, reduced ductility, increased brittleness, and eventually, brittle fracturing of the cables/hangers. (2) In the same corrosive environment, the highest degree of specimen corrosion occurred during alternating stress, followed by static stress, and no stress. (3) After corrosion-fatigue damage occurred for a specimen, its breaking stress was about 60% in comparison to the uncorroded specimen. The percentage elongation at the break also decreased; this was about 40% in comparison to the uncorroded specimen, indicating brittle fracturing. (4) The steel wires of the cables/hangers with corrosion-fatigue damage are more prone to brittle fracture if they are exposed to complex spatial stresses.
Several studies have reported that tacrolimus (TAC) significantly reduced proteinuria in lupus nephritis (LN) patients and mouse models. However, the mechanism for this effect remains undetermined. ...This study explored the mechanism of how TAC protects podocytes from injury to identify new targets for protecting renal function.
MRL/lpr mice were given TAC at a dosage of 0.1 mg/kg per day by intragastric administration for 8 weeks. Urine and blood samples were collected. Kidney sections (2 μm) were stained with hematoxylin-eosin (HE), periodic acid-Schiff base (PAS) and Masson's trichrome stain. Mouse podocyte cells (MPC5) were treated with TAC and/or TGF-β1 for 48 h. The mRNA levels and protein expression of synaptopodin and Wilms' tumor 1 (WT1) were determined by real-time PCR, Western blotting and/or immunofluorescence, respectively. Flow cytometry was used to detect cell apoptosis with annexin V. Podocyte foot processes were observed under transmission electron microscopy. IgG and C3 deposition were assessed with immunofluorescence assays and confocal microscopy.
Synaptopodin expression significantly decreased in MRL/lpr disease control mice, accompanied by increases in 24-h proteinuria, blood urea nitrogen, and serum creatinine. TAC, however, reduced proteinuria, improved renal function, attenuated renal pathology, restored synaptopodin expression and preserved podocyte numbers. In MPC5 cells, TGF-β1 enhanced F-actin damage in podocytes and TAC stabilized it. TAC also decreased TGF-β1-induced podocyte apoptosis in vitro and inhibited foot process fusion in MRL/lpr mice. In addition, our results also showed TAC inhibited glomerular deposition of IgG and C3.
This study demonstrated that TAC reduced proteinuria and preserved renal function in LN through protecting podocytes from injury partly by stabilizing podocyte actin cytoskeleton and inhibiting podocyte apoptosis.
Clear cell renal cell carcinoma (ccRCC) is a tumor that frequently shows the hematogenous pathway and tends to be resistant to radiotherapy and chemotherapy. However, the exact mechanism of ccRCC ...metastasis remains unknown.
Differentially expressed genes (DEGs) of three gene expression profiles (GSE85258, GSE105288 and GSE22541) downloaded from the Gene Expression Omnibus (GEO) database were analyzed by GEO2R analysis, and co-expressed DEGs among the datasets were identified using a Venn drawing tool. The co-expressed DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and hub genes were determined based on the protein-protein interaction network established by STRING. After survival analysis performed on UALCAN website, possible key genes were selected and verified in ccRCC cell lines and ccRCC tissues (
= 44). Statistical analysis was conducted using GraphPad Prism (Version 8.1.1).
A total of 104 co-expressed DEGs were identified in the three datasets. Pathway analysis revealed that these genes were enriched in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption and focal adhesion. Survival analysis on 17 hub genes revealed that four key genes with a significant impact on survival: procollagen C-endopeptidase enhancer (
), prolyl 4-hydroxylase subunit beta (
), collagen type VI alpha 2 (
) and collagen type VI alpha 3 (
). Patients with higher expression of these key genes had worse survival than those with lower expression.
experiments revealed that the mRNA expression levels of
,
and
were three times higher and that of
mRNA was 16 times higher in the metastatic ccRCC cell line Caki-1 than the corresponding primary cell line Caki-2. Immunohistochemistry revealed higher expression of the proteins encoded by these four genes in metastatic ccRCC compared with tumors from the corresponding primary sites, with statistical significance.
PCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.
No study has validated, compared and adapted scoring systems for prognosis prediction based on donor kidney core biopsy (CB), with less glomeruli than wedge biopsy.
A total of 185 donor kidney CB ...specimens were reviewed using seven scoring systems. The association between the total score, item scores, score-based grading, and allograft prognosis was investigated. In specimens with less than ten glomeruli (88/185, 47.6%), scoring systems were modified by adjusting weights of the item scores.
The Maryland aggregate pathology index (MAPI) score-based grading and periglomerular fibrosis (PGF) associated with delayed graft function (DGF) (Grade: OR = 1.59,
< 0.001; PGF: OR = 1.06,
= 0.006). Total score, score-based grading and chronic lesion score in scoring systems associated with one-year and 3-year eGFR after transplantation. Total-score-based models had similar predictive capacities for eGFR in all scoring systems, except MAPI and Ugarte. Score of glomerulosclerosis (GS), interstitial fibrosis (IF), tubular atrophy (TA), and arteriolar hyalinosis (AH) had good eGFR predictive capacities. In specimens with less than ten glomeruli, modified scoring systems had better eGFR predictive capacities than original scoring systems.
Scoring systems could predict allograft prognosis in paraffin-embedded CB with ten more glomeruli. A simple and pragmatic scoring system should include GS, IF, TA and AH, with weights assigned based on predictive capacity for prognosis. Replacing GS scores with tubulointerstitial scores could significantly improve the predictive capacity of eGFR. The conclusion should be further validated in frozen section.
Background
We developed a pragmatic dichotomous grading criterion to stratify the acute tubular injury (ATI) of deceased-donor kidneys. We intended to verify the predictive value of this criterion ...for the prognosis of deceased-donor kidney transplantation.
Methods
The allografts with ATI were classified into severe and mild groups. Severe ATI was defined as the presence of extreme and diffuse flattening of the tubular epithelial cells, or denudement of the tubular basement membrane. The clinical delayed graft function (DGF) risk index was calculated based on a regression model for posttransplant DGF using 17 clinical parameters related to donor–recipient characteristics.
Results
A total of 140 recipients were enrolled: 18 severe and 122 mild ATI. Compared with the mild ATI group, the severe ATI group had more donors after cardiac death, higher median donor terminal serum creatinine level (dScr), and longer median cold ischemia time. Severe ATI had a higher DGF rate (55.6% vs 14.6%, p < 0.001), longer DGF recovery time (49.6 vs 26.3 days, p < 0.001), and a lower estimated glomerular filtration rate (eGFR) at 1 month (23.5 vs 54.0 ml/min/1.73 m
2
, p < 0.001), 3 months (40.4 vs 59.0, p = 0.001), and 6 months after transplant (46.8 vs 60.3, p = 0.033). However, there was no significant difference in eGFR at 1 year or beyond, graft, and patient survival. The predictive value of combined dScr with ATI severity for DGF rate and DGF recovery time was superior to that of dScr alone. The predictive value of the combined DGF risk index with ATI severity for DGF was also better than that of the DGF risk index alone; however, the association of the DGF risk index with DGF recovery time was not identified. Chronic lesions including glomerulosclerosis, interstitial fibrosis, arterial intimal fibrosis, and arteriolar hyalinosis were associated with declined posttransplant 1-year eGFR.
Conclusion
Based on our pragmatic dichotomous grading criterion for ATI in a preimplantation biopsy, donor kidneys with severe ATI increased DGF risk, prolonged DGF recovery, and decreased short-term graft function but demonstrated favorable long-term graft function. Our grading method can offer additive valuable information for assessing donor kidneys with acute kidney injury and may act as an effective supplementary index of the Banff criteria.
Anastomosis of renal artery and renal vein in mouse models of kidney transplantation is technically challenging. Conventional technique using suture may result in vascular thrombosis. We developed a ...simple cuff method to anastomose both renal artery and vein.
Briefly, the left renal artery was occluded at the junction with abdominal aorta using a small vessel clip, transected at the renal hilum, irrigated with heparinized saline, and passed through the lumen of a seamless tubing made of polyimide. The loose end of the artery was everted over the cuff and secured using an 8-0 silk suture. The cuffed artery was inserted into the donor renal artery and secured with an 8-0 suture. Anastomosis of the renal vein was performed similarly. Isograft transplantation was conducted using BALB/c mice as donor and recipient mice (n = 20). The total operative time was 77 ± 3 min, and the cold ischemic time of the graft kidney was minimized to 20 min. One animal was excluded due to anatomic variant vessels and another one died at three day after surgery without thrombosis.
Serum creatinine increased insignificantly after transplantation and remained stable over 12 weeks posttransplant. Five recipient mice were sacrificed for histologic examination at 12 weeks after transplantation. No vascular thrombosis was observed at the site of anastomosis. The isografts showed no evidence of acute and chronic lesions such as extinctive ischemic sclerosis and interstitial fibrosis.
In summary, cuff anastomosis can be used to eliminate thrombosis formation in the mouse model of kidney transplantation.
Objective
To investigate the efficacy and safety of bone marrow-derived mesenchymal stem cells (BM-MSCs) on chronic active antibody-mediated rejection (cABMR) in the kidney allograft.
Methods
Kidney ...recipients with biopsy-proven cABMR were treated with allogeneic third-party BM-MSCs in this open-label, single-arm, single-center, two-dosing-regimen phase I/II clinical trial. In Regimen 1 (n=8), BM-MSCs were administered intravenously at a dose of 1.0×10
6
cells/kg monthly for four consecutive months, while in Regimen 2 (n=15), the BM-MSCs dose was 1.0×10
6
cells/kg weekly during four consecutive weeks. The primary endpoints were the absolute change of estimated glomerular filtration rate (eGFR) from baseline (delta eGFR) and the incidence of adverse events associated with BM-MSCs administration 24 months after the treatment. Contemporaneous cABMR patients who did not receive BM-MSCs were retrospectively analyzed as the control group (n =30).
Results
Twenty-three recipients with cABMR received BM-MSCs. The median delta eGFR of the total BM-MSCs treated patients was -4.3 ml/min per 1.73m
2
(interquartile range, IQR -11.2 to 1.2) 2 years after BM-MSCs treatment (P=0.0233). The median delta maximum donor-specific antibody (maxDSA) was -4310 (IQR -9187 to 1129) at 2 years (P=0.0040). The median delta eGFR of the control group was -12.7 ml/min per 1.73 m
2
(IQR -22.2 to -3.5) 2 years after the diagnosis, which was greater than that of the BM-MSCs treated group (P=0.0342). The incidence of hepatic enzyme elevation, BK polyomaviruses (BKV) infection, cytomegalovirus (CMV) infection was 17.4%, 17.4%, 8.7%, respectively. There was no fever, anaphylaxis, phlebitis or venous thrombosis, cardiovascular complications, or malignancy after BM-MSCs administration. Flow cytometry analysis showed a significant decreasing trend of CD27
-
IgD
-
double negative B cells subsets and trend towards the increase of CD3
+
CD4
+
PD-1
+
/lymphocyte population after MSCs therapy. Multiplex analysis found TNF-α, CXCL10, CCL4, CCL11 and RANTES decreased after MSCs treatment.
Conclusion
Kidney allograft recipients with cABMR are tolerable to BM-MSCs. Immunosuppressive drugs combined with intravenous BM-MSCs can delay the deterioration of allograft function, probably by decreasing DSA level and reducing DSA-induced injury. The underlying mechanism may involve immunomodulatory effect of MSCs on peripheral B and T cells subsets.