Existing methods for RNA diagnostics, such as reverse transcription PCR (RT-PCR), mainly rely on nucleic acid amplification (NAA) and RT processes, which are known to introduce substantial issues, ...including amplification bias, cross-contamination, and sample loss. To address these problems, we introduce a confinement effect-inspired Cas13a assay for single-molecule RNA diagnostics, eliminating the need for NAA and RT. This assay involves confining the RNA-triggered Cas13a catalysis system in cell-like-sized reactors to enhance local concentrations of target and reporter simultaneously, via droplet microfluidics. It achieves >10 000-fold enhancement in sensitivity when compared to the bulk Cas13a assay and enables absolute digital single-molecule RNA quantitation. We experimentally demonstrate its broad applicability for precisely counting microRNAs, 16S rRNAs, and SARS-CoV-2 RNA from synthetic sequences to clinical samples with excellent accuracy. Notably, this direct RNA diagnostic technology enables detecting a wide range of RNA molecules at the single-molecule level. Moreover, its simplicity, universality, and excellent quantification capability might render it to be a dominant rival to RT-qPCR.
Multiple studies have confirmed that speckle-type pox virus and zinc finger (POZ) protein (SPOP) functions as a substrate adaptor of cullin 3-based E3 ligase and has a crucial role in various ...cellular processes via specific targeting of proteins for ubiquitination and subsequent proteasomal degradation. Dysregulation of SPOP-mediated proteolysis might be involved in the development and progression of human prostate and kidney cancers. In prostate cancer, SPOP seems to function as a tumour suppressor by targeting several proteins, including androgen receptor (AR), steroid receptor coactivator 3 (SRC3) and BRD4, for degradation, whereas it might function as an oncoprotein in kidney cancer, for example, by targeting phosphatase and tensin homologue (PTEN) for proteasomal degradation. In addition, nuclear SPOP targets AR for degradation and has a role as a tumour suppressor in prostate cancer; however, in kidney cancer, SPOP largely accumulates in the cytoplasm and fails to promote degradation of AR located in the nucleus, resulting in activation of AR-driven pathways and cancer progression. Owing to the context-dependent function of SPOP in human malignancies, further assessment of the molecular mechanisms involving SPOP in prostate and kidney cancers is needed to improve our understanding of its role in the development of these cancer types. Treatments that target SPOP might become therapeutic strategies in these malignancies in the future.
We report a novel photoreversible color switching system based on the photocatalytic activity of TiO2 nanocrystals and the redox-driven color switching property of methylene blue (MB). This system ...rapidly changes from blue to colorless under UV irradiation and recovers its original blue color under visible light irradiation. We have identified four major competing reactions that contribute to the photoreversible switching, among which two are dominant: the decoloration process is mainly driven by the reduction of MB to leuco MB by photogenerated electrons from TiO2 nanocrystals under UV irradiation, and the recoloration process operates by the TiO2-induced self-catalyzed oxidation of LMB under visible irradiation. Compared with the conventional color switching systems based on photoisomerization of chromophores, our system has not only low toxicity but also significantly improved switching rate and cycling performance. It is envisioned that this photoreversible system may promise unique opportunities for many light-driven actuating or color switching applications.
The prognostic role of human epidermal growth factor receptor 2 (HER2) in ovarian cancer has been investigated in previous studies, but the results remain controversial. Here we present a ...meta-analysis to systematically review the association between HER2 expression and ovarian cancer prognosis.
Observational studies published until July 2017 were searched in Pubmed, Embase, and Cochrane library databases. Hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, publication bias and sensitivity analyses were implemented under a standard manner. Estimates of overall survival (OS), progress-free survival (PFS) and disease-free survival (DFS) were weighted and pooled using Der Simonian-Laird random-effect model.
Thirty-four studies that include 5180 ovarian cancer patients were collected for analysis. Expression of HER2 was negatively correlated with clinical prognosis of overall survival (HR = 1.57, 95% CI: 1.31 to 1.89, P < 0.001) and disease-free survival / progress-free survival (HR = 1.26, 95% CI = 1.06 to 1.49) in ovarian cancers. The association between HER2 expression and poor ovarian cancer prognosis in overall survival was also statistically significant in subgroups of unclassified ovarian cancer, Caucasian population and Asian population, while irrespective of detection method.
HER2 expression was related with poor prognosis in ovarian cancer patients and can be used as a predicting cancer prognostic biomarker in ovarian cancer patients.
Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition ...of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63-or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
A simple, low-dose, durable, and carbon nanotube-based floating solar still (CNTs-FSS) has been prepared for seawater desalination based on interfacial solar heating. The CNTs-FSS is composed of a ...surface layer of CNTs to absorb solar light, a thermal barrier layer of polyurethane sponge (PUS) to avoid the heat transfer into the underneath bulk water, and a water transport channel of air-laid paper to deliver sufficient water to the CNT layer. The water evaporation efficiency (k) of the CNTs-FSS can be optimized by tuning the thickness of the CNT layer and the PUS layer. The optimized CNT dose is only 4 g/m2, far less than that of other reported carbon-based photothermal materials. The k values of the CNTs-FSS are 0.88, 1.58, and 4.64 kg/m2·h under 1, 2, and 4 sun irradiance, respectively, which are correspondingly 2.8, 3.4, and 5.3 times higher than that of the control case of pure water. The excellent durability of the CNTs-FSS has been proven by monitoring the water evaporation efficiency during at least 20 cycles of use within 30 days. Finally, we have demonstrated that the organic and inorganic contaminants in condensed freshwater can be reduced well by the CNTs-FSS.
Mesoporous traps: The title clusters were fabricated through self‐assembly of nanocrystals in emulsion droplets and subsequent protective calcination. The specific affinity offered by the metal oxide ...and the size‐exclusion mechanism enabled by the mesoporous structure enable the use of these clusters for efficient enrichment of intact phosphorylated proteins from complex biological samples (see picture).
Objective
This study was performed to quantify hidden blood loss (HBL) and explore its influential factors in myomectomy.
Methods
Two hundred nine patients who underwent myomectomy by laparotomy or ...laparoscopy from 1 January 2017 to 31 December 2018 were analyzed. Each patient’s estimated blood volume and total blood loss (TBL) were calculated by the Nadler formula and Gross formula, respectively. The HBL was calculated by subtracting the visible blood loss (VBL) from the TBL. A multivariate linear stepwise analysis was applied to identify the influential factors of HBL in myomectomy.
Results
The mean perioperative VBL and estimated TBL during myomectomy were 137.81 ±104.43 and 492.24 ± 225.00 mL, respectively. The mean HBL was 354.39 ± 177.69 mL, which accounted for 71.52% ± 15.75% of the TBL and was two to three times higher than the VBL. The duration of surgery, number of removed leiomyomas, and location of removed leiomyomas were independent risk factors for HBL in myomectomy.
Conclusions
HBL accounted for a significant percentage of TBL in myomectomy. A full understanding of the HBL in perioperative blood management may improve patients’ postoperative rehabilitation.
Recently, solar-driven seawater desalination has received extensive attention since it can obtain considerable freshwater by accelerating water evaporation at the air–water interface through solar ...evaporators. However, the high air–water interface temperature can cause volatile organic compounds (VOCs) to enter condensed freshwater and result in water quality safety risk. In this work, an antioxidative solar evaporator, which was composed of MoS2 as the photothermal material, expandable polyethylene (EPE) foam as the insulation material, polytetrafluoroethylene (PTFE) plate as the corrosion resistant material, and fiberglass membrane (FB) as the seawater delivery material, was fabricated for the first time. The activated persulfate (PS) methods, including peroxymonosulfate (PMS) and peroxodisulfate (PDS), were applied to inhibit phenol from entering condensed freshwater during desalination. The distillation concentration ratio of phenol (RD) was reduced from 76.5% to 0% with the addition of sufficient PMS or PDS, which means that there was no phenol in condensed freshwater. It was found that the Cl− is the main factor in activating PMS, while for PDS, light, and heat are the dominant. Compared with PDS, PMS can make full utilization of the light, heat, Cl− at the evaporator’s surface, resulting in more effective inhibition of the phenol from entering condensed freshwater. Finally, though phenol was efficiently removed by the addition of PMS or PDS, the problem of the formation of the halogenated distillation by-products in condensed freshwater should be given more attention in the future.
Ultraviolet-activated permanganate (UV/PM) process is a novel advanced oxidation process (AOP), but its application potential remains to be evaluated. This work investigates the degradation of ...refractory organic pollutant by UV/PM in terms of efficiency, mechanism, and influencing factors. The target compound benzoic acid (BA), which is a micro-organic pollutant and is resistant to PM and UV treatment, can be efficiently degraded by UV/PM. The electron paramagnetic resonance spectra directly supported the formation of hydroxyl radical (HO•) and superoxide radical (O
) from UV photolysis of PM. Competitive kinetics experiments verified that O
acted as precursor of HO• and the good degradation performance of BA was due to the involvement of HO• and manganese(V). The rate constants of BA degradation showed a positive linear relationship with PM dosage in the range of 0.5-20 mg·L
, and the degradation process was significantly influenced by solution pH and natural organic matters but insensitive to chloride and bicarbonate at environmentally relevant concentrations. Compared to the typical UV-based AOP UV/hydrogen peroxide, UV/PM is a little inferior, indicating that optimization and enhancement is needed for this process before its possible practical application.
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