In chronic kidney disease (CKD), endothelin-1 (ET-1) always increases and there are changes in cardiac ultrasonography. In the present study, we aimed at investigating the role of serum ET-1 in ...predicting cardiac complications in patients with CKD.
The level of serum ET-1 was measured by enzyme-linked immunosorbent assay (ELISA) and cardiac ultrasonography was performed in enrolled patients. Indexes of heart failure, such as left ventricular mass index, interventricular septum thickness and left ventricular end diastolic diameter, were measured in patients with CKD.
In the present study, we found that the level of serum ET-1 was significantly correlated with left ventricular mass index, interventricular septum thickness and left ventricular end diastolic diameter (p < .001) in non-dialysis patients with CKD.
The results of the present study indicated that the level of serum ET-1 is closely related to the cardiac complications of CKD and is a useful predictor of cardiac complication.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Although the prognostic value of lymphovascular invasion (LVI) for upper tract urinary carcinoma (UTUC) has been reported, there is a lack of consensus regarding the prognostic factor of LVI in UTUC ...after radical nephroureterectomy (RNU). The aim of the present study was to evaluate the contemporary role of LVI using systematic review and meta-analysis.
Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we performed a systematic search of Web of Science, PubMed, and EMBASE for all reports published up to July 2019. Cumulative analyses of hazard ratios (HRs)/odds ratios (ORs) and their corresponding 95% confidence intervals were conducted to assess the association between LVI and oncological outcomes and clinicopathological features.
Our meta-analysis included 31 eligible studies containing 14,653 patients with UTUC (81-1,363 per study). Our results indicated a significant correlation of LVI with worse cancer-specific survival (HR = 1.59,
< 0.001), overall survival (HR = 1.55,
< 0.001), recurrence-free survival (HR = 1.46,
< 0.001), cancer-specific mortality (HR = 1.25,
= 0.047), and recurrence (HR = 1.23,
= 0.026). LVI was also correlated with advanced tumor stage (III/IV vs. I/II: OR = 7.63,
< 0.001), higher tumor grade (3 vs. 1/2: OR = 5.61,
< 0.001), lymph node metastasis (yes vs. no: OR = 4.95,
< 0.001), carcinoma
(yes vs. no: OR = 1.92,
< 0.001), and positive surgical margin (yes vs. no: OR = 4.38,
< 0.001), but not related to gender (male vs. female: OR = 0.98,
= 0.825), and multifocality (multifocal vs. unifocal: OR = 1.09,
= 0.555). The funnel plot test indicated no significant publication bias.
This study demonstrated that LVI was associated with aggressive clinicopathological features. LVI may serve as a poor prognostic factor for patients with UTUC after RNU.
Renal ischemia/reperfusion (I/R), a major cause of acute kidney injury (AKI), is a serious clinical event in patients during post-renal transplantation. I/R is associated with renal dysfunction and ...tubular apoptosis, and calcium (Ca
2+
) overload has been reported to be a crucial factor on tubular apoptosis in I/R injury (IRI). The canonical transient receptor potential channel 6 (TRPC6), a type of non-selective Ca
2+
channel, is involved in many renal diseases. Our earlier study identified that TRPC6-mediated Ca
2+
influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in primary tubular epithelial cells (TECs). This study explored the potential beneficial impact of TRPC6 knockout (TRPC6
−/−
) and the relevant cellular mechanisms against I/R-induced AKI in mice. Measuring changes of renal function, apoptotic index, and autophagy in mouse kidneys that suffered 24 h reperfusion after 40 min ischemia and working
in vitro
with TECs that suffered 24 h reoxygenation after 24 h hypoxia, we found that 1) IRI tissues had increased TRPC6 expression and TRPC6 knockout significantly ameliorated renal damage induced by IRI; 2) TRPC6 knockout enhanced the level of autophagy and alleviated the depolarization of mitochondrial membrane potential (ψm, MMP) and apoptotic changes upon IRI; and 3) IRI tissues had increased p-AKT and p-ERK1/2 expressions, while TRPC6 knockout could markedly reduce the phosphorylation of AKT and ERK1/2. These discoveries suggest that, by reducing Ca
2+
overload, the underlying protective mechanism of TRPC6
−/−
may be involved in down-regulation of PI3K/AKT and ERK signaling, which is likely to provide a new avenue for future AKI therapies.
As a novel type of genetic marker, the microhaplotype has shown promising potential in forensic research. In the present study, we analyzed maternal plasma cell-free DNA (cfDNA) samples from twin ...pregnancies to validate microhaplotype-based noninvasive prenatal testing (NIPT) for paternity, zygosity, and fetal fraction (FF). Paternity was determined with the combined use of the relMix package, zygosity was evaluated by examining the presence of informative loci with two fetal genome complements, and FF was assessed through fetal allele ratios. Paternity was determined in 19 twin cases, among which 13 cases were considered dizygotic (DZ) twins based on the presence of 3~10 informative loci and the remaining 6 cases were considered monozygotic (MZ) twins because no informative locus was observed. With the fetal genomic genotypes as a reference, the accuracy of paternity and zygosity determination were confirmed by standard short tandem repeat (STR) analysis. Moreover, the lower FF, higher FF, and combined FF in each DZ plasma sample were closely related to the estimated value. This present preliminary study proposes that microhaplotype-based NIPT is applicable for paternity, zygosity, and FF determination in twin pregnancies, which are expected to be advantageous for both forensic and clinical settings.
Background:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may persist in patients with coronavirus disease 2019 (COVID-19) despite receiving standard care.
Methods:
In this pilot ...study of hospitalized adult patients (≥18 years of age), with radiologically confirmed pneumonia who were SARS-CoV-2 positive for more than 28 days despite standard care, were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate.
Results:
12 patients were enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide
vs.
16.7% for grp 1 patients (2/12) (
p
= 0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1–12, IQR 1–12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 (
p =
0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 vs. 8.3% (1/12) for grp 1 (
p =
0.001). The 30 days discharge rate was 100% (15/15) for the grp 2 vs. 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported.
Conclusion:
Leflunomide may improve the SARS-CoV-2 clearance rate and discharge rate in patients with refractory COVID-19. The tolerability of the 14–28 days course of treatment with leflunomide is acceptable. These preliminary observations need to be verified by a large sample size and randomized controlled trial.
Objectives
Dental implants are major treatment options for restoring teeth loss. Biological processes at the implant‐tissue interface are critical for implant osseointegration. Superior mechanical ...properties of the implant constitute a major challenge for traditional histological techniques. It is imperative to develop new technique to investigate the implant‐tissue interface.
Materials and methods
Our laboratory developed the polyethylene glycol (PEG)‐associated solvent system (PEGASOS) tissue clearing method. By immersing samples into various chemical substances, bones and teeth could be turned to transparent with intact internal structures and endogenous fluorescence being preserved. We combined the PEGASOS tissue clearing method with transgenic mouse line and other labelling technique to investigate the angiogenesis and osteogenesis processes occurring at the implant‐bone interface.
Results
Clearing treatment turned tissue highly transparent and implant could be directly visualized without sectioning. Implant, soft/hard tissues and fluorescent labels were simultaneously imaged in decalcified or non‐decalcified mouse mandible samples without disturbing their interfaces. Multi‐channel 3‐dimensional image stacks at high resolution were acquired and quantified. The processes of angiogenesis and osteogenesis surrounding titanium or stainless steel implants were investigated.
Conclusions
Both titanium and stainless steel implants support angiogenesis at comparable levels. Successful osseointegration and calcium precipitation occurred only surrounding titanium, but not stainless steel implants. PEGASOS tissue clearing method provides a novel approach for investigating the interface between implants and hard tissue.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The authors note that there is an extra incorrect citation for Fig. S5 appeared on page 2770. It has also come to our attention that Figs. 5 and 6 appeared incorrectly. The correct figures and their ...legend appear below. These errors don’t affect the conclusions of the article.
Figure 5
(a) Typical SEM image (scale bar: 1 μm), inset shows the close magnification of two overlapping branched NWs (NS-NWs), scale bar is 100 nm. (b) TEM observation of prepared samples (scale bar: 1 μm) and (c) a single NS-NW (scale bar: 100 nm), where the inset of panel (c) is the corresponding selected area electron diffraction (SAED) pattern. (d) EDS point scanning data from the three regions of the NS-NW. Scale bar: 100 nm. Al signals generated from the Al substrate. (e) Cu and (f) O elemental distribution across the axis of the heterostructures.
Figure 6
Typical galvanostatic charge–discharge curves of (a) Cu/Cu
2
O/CuO NS-NW and (b) Cu/Cu
2
O/CuO NW cells at a current density of 100 mA·g
−1
in the range 0.005–3 V vs. Li. (c) Cyclic voltammograms of the Cu/Cu
2
O/CuO NS-NW cell cycled between 0.02–3 V vs. Li at a scan rate of 2 mV·s
−1
. (d) Cycling performances of Cu/Cu
2
O/CuO NS-NW (black) and Cu/Cu
2
O/CuO NW cells (red). Inset: corresponding TEM images of triplex components NS-NW (black framed) and NW (red framed). (e) Representative charge and discharge voltage profiles of Cu/Cu
2
O/CuO NS-NW cell at various current densities. (f) Capacity retention of Cu/Cu
2
O/CuO NS-NW (black) and Cu/Cu
2
O/CuO NW (red) cells at different current rates.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Diatoms detected in human organs have been considered as supportive evidence for the diagnosis of drowning. During drowning, the vast majority of diatoms are retained in lung tissues, and only few ...are transported to distant organs via the bloodstream. In this article, we quantitatively analysed diatom contents in the lung tissues, liver tissues, kidney tissues and the drowning mediums of 165 drowning death cases. The results showed that the diatom content in lung tissues was positively correlated with that in the water samples. However, there was no linear correlation between the diatom content in the liver tissues and that in the water samples. Our study also showed no linear correlation between the diatom content in the kidney tissues and in the water samples. The diatom contents in the liver tissues and kidney tissues were positively correlated, while no linear correlations of diatom contents were found between the liver tissues and lung tissues, and the kidney tissues and lung tissues. These correlations of diatom content in the organs and drowning mediums provide valuable information to interpret and analyse the quantitative results of diatom tests.
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BFBNIB, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: Abnormal DNA methylation of is one of the important mechanisms leading to tumor pathogenesis. The purpose of this study was to explore differentially methylated genes that may drive the ...development of renal clear cell carcinoma through a comprehensive analysis of the TCGA database. Materials and methods: Methylation data and RNA-seq data for clear cell renal cell carcinoma were downloaded from The Cancer Genome Atlas (TCGA). Differentially methylated genes and the differential genes associated with survival were then screened by MethylMix R package and univariate Cox proportional-hazards model, respectively. Their common genes were then intersected and obtained for further analysis. Correlation of gene expression and methylation levels, gene set enrichment analysis (GSEA) enrichments, survival curve, and ROC curve plotting for DNA methylation-driven genes were finally performed. The methylation alterations of the three genes were validated via two GEO datasets (GSE70303 and GSE113501), and the genes expression level was verified through two GEO datasets (GSE6344 and GSE53757). Results: Three novel DNA methylation-driven genes LAT, HOXD3 and NFE2L3 were identified in clear cell renal cell carcinoma. Expression analysis further revealed that hypomethylation levels of LAT and NFE2L3 showed higher gene expression levels, while HOXD3 exhibited opposite methylation-expression pattern. The CpG sites of LAT (cg16462073), HOXD3 (cg24000528) and NFE2L3 (cg16882373) that may affect respective gene expressions were also identified. For the survival analysis, we found that hypomethylation and over-expression of LAT and NFE2L3 were correlated with poor survival, while hypermethylation and low-expression HOXD3 was correlated with poor survival of clear cell renal cell carcinoma patients. In addition, GSEA KEGG analysis and biological processes of these genes were also enriched for functional analysis. Kaplan-Meier survival and ROC analyses of these genes showed an average risk score of 0.9140593, AUC = 0.692, which suggested a good clinical application value. Finally, the opposite methylation-expression pattern of these three genes were verified in GEO datasets. Conclusions: In this study, we successfully exhibited the potential DNA methylation-driven genes LAT, HOXD3, and NFE2L3 involved in clear cell renal cell carcinoma. Moreover, gene functions and prognostic risk models were also elucidated, which facilitated the expansion of the current study on the role of methylation in the pathology process of clear cell renal cell carcinoma.
Wheat (Triticum aestivum L.) is one of the major grain crops, and heat stress adversely affects wheat production in many regions of the world. Previously, we found a heat-responsive gene named Lipid ...Transfer Protein 3 (TaLTP3) in wheat. TaLTP3 was deduced to be regulated by cold, ABA, MeJA, Auxin and oxidative stress according to cis-acting motifs in its promoter sequences. In this study, we show that TaLTP3 is responsive to prolonged water deficit, salt or ABA treatment in wheat seedlings. Also, TaLTP3 accumulation was observed after the plant suffered from heat stress both at the seedling and the grain-filling stages. TaLTP3 protein was localized in the cell membrane and cytoplasm of tobacco epidermal cells. Overexpression of TaLTP3 in yeast imparted tolerance to heat stress compared to cells expressing the vector alone. Most importantly, transgenic Arabidopsis plants engineered to overexpress TaLTP3 showed higher thermotolerance than control plants at the seedling stage. Further investigation indicated that transgenic lines decreased H2O2 accumulation and membrane injury under heat stress. Taken together, our results demonstrate that TaLTP3 confers heat stress tolerance possibly through reactive oxygen species (ROS) scavenging.
•TaLTP3 could respond to drought, salt and heat stress.•Overexpression of TaLTP3 conferred thermotolerance to yeast and Arabidopsis.•TaLTP3 overexpressed Arabidopsis accumulates less ROS after heat stress.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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