Bladder cancer remains a significant health challenge due to its high recurrence and progression rates. This study aims to evaluate the role of POLR3G in the development and progression of bladder ...cancer and the potential of POLR3G to serve as a novel therapeutic target. We constructed a bladder cancer model in Wistar rats by administering N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), which successfully induced a transition from normal mucosa to hyperplasia and ultimately to urothelial carcinoma. We observed a progressive upregulation of POLR3G expression during the bladder cancer development and progression. To investigate the functional role of POLR3G, we performed functional experiments in bladder cancer cell lines. The results demonstrated that knocking down POLR3G significantly inhibited cell proliferation, migration, and invasion. We further conducted RNA sequencing on POLR3G-knockdown bladder cancer cells, and Metascape was employed to perform the functional enrichment analysis of the differentially expressed genes (DEGs). Enrichment analysis revealed the enrichment of DEGs in the RNA polymerase and apoptotic cleavage of cellular proteins pathways, as well as their involvement in the Wnt and MAPK signaling pathways. The downregulation of Wnt pathway-related proteins such as Wnt5a/b, DVL2, LRP-6, and phosphorylated LRP-6 upon POLR3G knockdown was further confirmed by Western blotting, indicating that POLR3G might influence bladder cancer behavior through the Wnt signaling pathway. Our findings suggest that POLR3G plays a crucial role in bladder cancer progression and could serve as a potential therapeutic target. Future studies should focus on the detailed mechanisms by which POLR3G regulates these signaling pathways and its potential as a biomarker for early detection and prognosis of bladder cancer.
The MinION nanopore sequencing device (Oxford Nanopore Technologies, Oxford, UK) is the smallest commercially available sequencer and can be used outside of conventional laboratories. The use of the ...MinION for forensic applications, however, is hindered by the high error rate of nanopore sequencing. One approach to solving this problem is to identify forensic genetic markers that can consistently be typed correctly based on nanopore sequencing. In this pilot study, we explored the use of nanopore sequencing for single nucleotide polymorphism (SNP) and short tandem repeat (STR) profiling using Verogen’s (San Diego, CA, USA) ForenSeq DNA Signature Prep Kit. Thirty single-contributor samples and DNA standard material 2800 M were genotyped using the Illumina (San Diego, CA, USA) MiSeq FGx and MinION (with R9.4.1 flow cells) devices. With an optimized cutoff for allelic imbalance, all 94 identity-informative SNP loci could be genotyped reliably using the MinION device, with an overall accuracy of 99.958% (1 error among 2926 genotypes). STR typing was notably error prone, and its accuracy was locus dependent. We developed a custom-made bioinformatics workflow, and finally selected 13 autosomal STRs, 14 Y-STRs, and 4 X-STRs showing high consistency between nanopore and Illumina sequencing among the tested samples. These SNP and STR loci could be candidates for panel design for forensic analysis based on nanopore sequencing.
Extracellular vesicles (EVs) are small membranous particles that contribute to intercellular communications. Separating EVs from tissue is still a technical challenge. Here, we present a rigorous ...method for extracting EVs from intestinal tissue in a mouse intestinal ischemia/reperfusion (I/R) model, and for analyzing their miRNA content. The isolated EVs show a typical cup shape with a size peak of 120–130 nm in diameter, confirmed by TEM and NTA. They also express EV markers such as CD9, CD63, CD81, Tsg101 and Alix. Real-time qPCR confirmed that these pellets contain miRNAs related to I/R injury. Our study presents a practical way to isolate EVs from intestinal tissue which is suitable for downstream applications such as miRNA analysis, and provides a novel method for investigating the mechanism of intestinal I/R injury.
We present a practical way to isolate EVs from intestinal tissue; the method consists of enzymatic digestion, differential centrifugation and density gradient centrifugation. This method is suitable for downstream studies such as miRNA analysis.
A localized Pc4‐5 ultralow‐frequency (ULF) wave event associated with a plasmaspheric plume was observed by THEMIS‐E on the dawnside near L = 6, which was identified as a second harmonic poloidal ...wave. The plume was identified as a sudden density enhancement during an outbound pass. The charged particle populations in the plume have a variety of periodic modulation characteristics at different energies. First, there is an antiphase relationship between magnetic field Br and particle flux across a wide energy range both for ions and electrons (~50 keV to 1 MeV). Second, there is a 180° phase shift in the modulated ion flux within an energy range of ~2–6 keV, with negative slope dispersions of ion pitch angle distributions at ~2–6 keV and ~50–75 keV, which are characteristic of drift‐bounce resonances. Third, the lower‐energy (<32 eV) ion flux is modulated at double the wave frequency, which are the result of E × B effect. Considering the generation mechanism of this poloidal mode wave within the plume, we find that it is likely generated by drift‐bounce resonance from an unstable population of ions, due to an inward radial phase space density gradient. We suggest that the localization of waves to the plume is because the high plasma density reduces the local poloidal mode eigenfrequency, enabling a match to the drift‐bounce frequencies of these ions, and resonant energy transfer from these particles to the eigenfunction at this location. This generates the Pc4‐5 second harmonic poloidal waves at a much lower L region than would otherwise be expected.
Key Points
The high‐m poloidal waves in the dawnside plume were observed by THEMIS‐E
The inward radial gradient of ~57 keV and higher plasma density enable the second harmonic poloidal wave to occur in the dawnside plume
Three types of particle flux modulations are observed simultaneously along with the wave in different energy bands
On Monday, May 12, 2008, a devastating mega-earthquake of magnitude 8.0 struck the Wenchuan area, northwestern Sichuan Province, China. The focal mechanism of the earthquake was successive massive ...rock fracturing 15 km in depth at Yingxiu. Seismic analysis confirms that the major shock occurred on the Beichuan–Yingxiu Fault and that aftershocks rapidly extended in a straight northeast–southeast direction along the Longmenshan Fault zone. Fatalities approaching a total of 15,000 occurred, with a significant number resulting from four types of seismically triggered geohazards—rock avalanches and landslides, landslide-dammed lakes (“earthquake lakes”), and debris flows. China Geological Survey has identified 4,970 potentially risky sites, 1,701 landslides, 1,844 rock avalanches, 515 debris flows, and 1,093 unstable slopes. Rock avalanches and landslides caused many fatalities directly and disrupted the transportation system, extensively disrupting rescue efforts and thereby causing additional fatalities. Landslide-dammed lakes not only flooded human habitats in upstream areas but also posed threats to potentially inundated downstream areas with large populations. Debris flows become the most remarkable geohazards featured by increasing number, high frequency, and low triggering rainfall. Earthquake-triggered geohazards sequentially induced and transformed to additional hazards. For example, debris flows occurred on rock avalanches and landslides, followed by landslide-dammed lakes, and then by additional debris flows and breakouts of the landslide-dammed lakes and downstream flooding. Earthquake-induced geohazards occurred mainly along the fault zone and decreased sharply with distance from the fault. It can be anticipated that post-earthquake geohazards, particularly for debris flows, will continue for 5–10 years and even for as long as 20 years. An integrated strategy of continuing emergency response and economic reconstruction is required. The lesson from Wenchuan Earthquake is that the resulted geohazards may appear in large number in active fault regions. A plan for geohazard prevention in the earthquake-active mountainous areas is needed in advance.
Development of anion exchange membranes (AEMs) with high hydroxide conductivity, good dimensional and alkaline stabilities is still a challenge for the practical application of AEM fuel cells. In ...this study, we report a new strategy to prepare high-performance AEMs with crosslinked ionic regions. A series of phenolphthalein-containing poly(arylene ether sulfone)s crosslinked AEMs was synthesized by grafting ion groups selectively and densely on the phenolphthalein units to form ion clusters that are further crosslinked to generate the hydrophilic ionic regions. The crosslinking reaction not only improved the dimensional stability of the AEMs, but also increased the aggregation of the ion clusters leading to the formation of hydrophilic/hydrophobic phase-separated morphology and ion-conducting channels. As a result, enhancements in both ion conductivity and dimensional stability can be achieved. The crosslinked AEMs showed high hydroxide conductivities in the range of 52.2–143.4 mS cm−1 from 30 to 80 °C and a superb ratio of relative conductivity to relative swelling at 80 °C. Furthermore, the crosslinked AEMs also exhibited good mechanical properties, thermal and alkaline stabilities and desirable single cell performance. This work presents a promising strategy for the synthesis of high-performance AEMs for fuel cells.
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•Crosslinked AEMs was prepared via crosslinking of ion cluster regions.•Effect of crosslinking on AEMs' morphology and properties was studied.•The AEMs showed high ionic conductivity in the range 52.2–143.4 mS cm−1.•The AEMs showed superb ratio of relative conductivity to relative swelling.•The single cell achieved a peak power density of 83.6 mW cm−2 at 80 °C.
Delivery of the CRISPR/Cas9 ribonucleoprotein (RNP) complex has provided an alternative strategy for the regulation of CRISPR functions, offering a transient and DNA-free means for genomic editing. ...Chemical methods of delivering the RNPs via nanocomplexes have the potential to address these delivery problems for efficiency, safety, and packaging capacity. Here, we developed a biomimetic mineralization-mediated strategy for efficient DNA-free genome editing by using CRISPR/Cas9 RNPs. We found that the RNPs have the ability to form the biomimetic mineralized RNP nanoparticles (Bm-RNP NPs) quickly in situ and can be effectively delivered into the fungal protoplast cells. Biomimetic mineralization can maintain the natural function of Cas9 protein and protect the sgRNA activity. At the same time, the encapsulated RNPs can be effectively released into the cytoplasm, and the Sytalone dehydratase (SDH) gene can be edited in a targeted manner. Except for phenotypic defects, molecular detections indicated that the delivery of Bm-RNP NPs achieved 20% genomic editing for Magnaporthe oryzae compared to RNPs alone. Moreover, the Bm-RNP NP-mediated editing of the SDH gene significantly affects the appressorium-mediated penetration and invasive growth in M. oryzae. Our system has the advantages of being cheap, fast, and effective, without the traditional transformation process, suggesting the potential application of this DNA-free gene-editing strategy in different organisms.
Supersaturation of calcium salts of low solubility is important for biomineralisation. The dynamics of solutions supersaturated in calcium citrate prepared by dissolving calcium lactate and sodium ...citrate in water, serving as a mineralisation model, were characterised electrochemically and by small-angle X-ray scattering. The process was divided into: (i) citrate assisted dissolution of calcium lactate with an enthalpy of activation of 115 kJ mol−1; (ii) a metastable homogeneous supersaturation phase, where calcium ion activity continues to increase despite constant calcium concentration; (iii) calcium ion activity decreasing with an enthalpy of activation of 30 kJ mol−1 together with 3-dimensional crystallisation with an enthalpy of activation of 177 kJ mol−1. The differences in activation enthalpies lead to a higher degree of supersaturation at higher temperatures but longer lasting supersaturation at low temperature as was seen for critical supersaturation of up to a factor of 20 resulting in non-linear temperature effects for calcium mobility.
Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early biomarker for prediction of acute kidney injury (AKI). However, the utility of NGAL to predict the occurrence of AKI ...in septic patients remains controversial. We performed a systematic review and meta-analysis to evaluate the evidence on diagnosis of sepsis AKI and the prediction of other clinical outcomes.
The MEDLINE, EMBASE, Cochrane Library, Wanfang, and CNKI databases were systematically searched up to August 19, 2015. Quality assessment was applied by using the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tool. The diagnostic performance of NGAL for the prediction of AKI in sepsis was evaluated using pooled estimates of sensitivity, specificity, likelihood ratio, and diagnostic odds ratio (DOR), as well as summary receiver operating characteristic curves (SROC).
Fifteen studies with a total of 1,478 patients were included in the meta-analysis. For plasma NGAL, the pooled sensitivity and specificity with corresponding 95% confidence intervals (CI) were 0.83 (95% CI: 0.77 - 0.88) and 0.57 (95% CI: 0.54 - 0.61), respectively. The pooled positive likelihood ratio (PLR) was 3.10 (95% CI: 1.57 - 6.11) and the pooled negative likelihood ratio (NLR) was 0.24 (95% CI: 0.13 - 0.43). The pooled DOR was 14.72 (95% CI: 6.55 - 33.10) using a random effects model. The area under the curve (AUC) for SROC to summarize diagnostic accuracy was 0.86. For urine NGAL, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC values were 0.80 (95% CI: 0.77 - 0.83), 0.80 (95% CI: 0.77 - 0.83), 4.42 (95% CI: 2.84 - 6.89), 0.21 (95% CI: 0.13 - 0.35), 24.20 (95% CI: 9.92 - 59.05) and 0.90, respectively. Significant heterogeneity was explored as a potential source. There was no notable publication bias observed across the eligible studies. NGAL for prediction of renal replacement therapy (RRT) and mortality associated with AKI in septic patients were also evaluated.
To a certain extent, NGAL is not only an effective predictive factor for AKI in the process of sepsis, but also shows potential predictive value for RRT and mortality. However, future trials are needed to clarify this controversial issue.
Abstract
Ferroelectricity, existing in either solid crystals or liquid crystals, gained widespread attention from science and industry for over a century. However, ferroelectricity has never been ...observed in both solid and liquid crystal phases of a material simultaneously. Inorganic ferroelectrics that dominate the market do not have liquid crystal phases because of their completely rigid structure caused by intrinsic chemical bonds. We report a ferroelectric homochiral cholesterol derivative,
β
-sitosteryl 4-iodocinnamate, where both solid and liquid crystal phases can exhibit the behavior of polarization switching as determined by polarization–voltage hysteresis loops and piezoresponse force microscopy measurements. The unique long molecular chain, sterol structure, and homochirality of
β
-sitosteryl 4-iodocinnamate molecules enable the formation of polar crystal structures with point group 2 in solid crystal phases, and promote the layered and helical structure in the liquid crystal phase with vertical polarization. Our findings demonstrate a compound that can show the biferroelectricity in both solid and liquid crystal phases, which would inspire further exploration of the interplay between solid and liquid crystal ferroelectric phases.
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