Distinct Processing of lncRNAs Contributes to Non-conserved Functions in Stem Cells.

Long noncoding RNAs (lncRNAs) evolve more rapidly than mRNAs. Whether conserved lncRNAs undergo conserved processing, localization, and function remains unexplored. We report differing subcellular localization of lncRNAs in human and mouse embryonic stem cells (ESCs). A significantly higher fraction of lncRNAs is localized in the cytoplasm of hESCs than in mESCs. This turns out to be important for hESC pluripotency. FAST is a positionally conserved lncRNA but is not conserved in its processing and localization. In hESCs, cytoplasm-localized hFAST binds to the WD40 domain of the E3 ubiquitin ligase ß-TrCP and blocks its interaction with phosphorylated ß-catenin to prevent degradation, leading to activated WNT signaling, required for pluripotency. In contrast, mFast is nuclear retained in mESCs, and its processing is suppressed by the splicing factor PPIE, which is highly expressed in mESCs but not hESCs. These findings reveal that lncRNA processing and localization are previously under-appreciated contributors to the rapid evolution of function.

Nucleolar URB1 ensures 3' ETS rRNA removal to prevent exosome surveillance.

The nucleolus is the most prominent membraneless condensate in the nucleus. It comprises hundreds of proteins with distinct roles in the rapid transcription of ribosomal RNA (rRNA) and efficient processing within units comprising a fibrillar centre and a dense fibrillar component and ribosome assembly in a granular component1. The precise localization of most nucleolar proteins and whether their specific localization contributes to the radial flux of pre-rRNA processing have remained unknown owing to insufficient resolution in imaging studies2-5. Therefore, how these nucleolar proteins are functionally coordinated with stepwise pre-rRNA processing requires further investigation. Here we screened 200 candidate nucleolar proteins using high-resolution live-cell microscopy and identified 12 proteins that are enriched towards the periphery of the dense fibrillar component (PDFC). Among these proteins, unhealthy ribosome biogenesis 1 (URB1) is a static, nucleolar protein that ensures 3' end pre-rRNA anchoring and folding for U8 small nucleolar RNA recognition and the subsequent removal of the 3' external transcribed spacer (ETS) at the dense fibrillar component-PDFC boundary. URB1 depletion leads to a disrupted PDFC, uncontrolled pre-rRNA movement, altered pre-rRNA conformation and retention of the 3' ETS. These aberrant 3' ETS-attached pre-rRNA intermediates activate exosome-dependent nucleolar surveillance, resulting in decreased 28S rRNA production, head malformations in zebrafish and delayed embryonic development in mice. This study provides insight into functional sub-nucleolar organization and identifies a physiologically essential step in rRNA maturation that requires the static protein URB1 in the phase-separated nucleolus.

UHRF2 commissions the completion of DNA demethylation through allosteric activation by 5hmC and K33-linked ubiquitination of XRCC1.

The transition of oxidized 5-methylcytosine (5mC) intermediates into the base excision repair (BER) pipeline to complete DNA demethylation remains enigmatic. We report here that UHRF2, the only paralog of UHRF1 in mammals that fails to rescue Uhrf1-/- phenotype, is physically and functionally associated with BER complex. We show that UHRF2 is allosterically activated by 5-hydroxymethylcytosine (5hmC) and acts as a ubiquitin E3 ligase to catalyze K33-linked polyubiquitination of XRCC1. This nonproteolytic action stimulates XRCC1's interaction with the ubiquitin binding domain-bearing RAD23B, leading to the incorporation of TDG into BER complex. Integrative epigenomic analysis in mouse embryonic stem cells reveals that Uhrf2-fostered TDG-RAD23B-BER complex is functionally linked to the completion of DNA demethylation at active promoters and that Uhrf2 ablation impedes DNA demethylation on latent enhancers that undergo poised-to-active transition during neuronal commitment. Together, these observations highlight an essentiality of 5hmC-switched UHRF2 E3 ligase activity in commissioning the accomplishment of active DNA demethylation.

Nascent Pre-rRNA Sorting via Phase Separation Drives the Assembly of Dense Fibrillar Components in the Human Nucleolus.

Fibrillar centers (FCs) and dense fibrillar components (DFCs) are essential morphologically distinct sub-regions of mammalian cell nucleoli for rDNA transcription and pre-rRNA processing. Here, we report that a human nucleolus consists of several dozen FC/DFC units, each containing 2-3 transcriptionally active rDNAs at the FC/DFC border. Pre-rRNA processing factors, such as fibrillarin (FBL), form 18-24 clusters that further assemble into the DFC surrounding the FC. Mechanistically, the 5' end of nascent 47S pre-rRNA binds co-transcriptionally to the RNA-binding domain of FBL. FBL diffuses to the DFC, where local self-association via its glycine- and arginine-rich (GAR) domain forms phase-separated clusters to immobilize FBL-interacting pre-rRNA, thus promoting directional traffic of nascent pre-rRNA while facilitating pre-rRNA processing and DFC formation. These results unveil FC/DFC ultrastructures in nucleoli and suggest a conceptual framework for considering nascent RNA sorting using multivalent interactions of their binding proteins.

SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46-mediated HDAC1 degradation.

Identification of the driving force behind malignant transformation holds the promise to combat the relapse and therapeutic resistance of cancer. We report here that the single nucleotide polymorphism (SNP) rs4971059, one of 65 new breast cancer risk loci identified in a recent genome-wide association study (GWAS), functions as an active enhancer of TRIM46 expression. Recreating the G-to-A polymorphic switch caused by the SNP via CRISPR/Cas9-mediated homologous recombination leads to an overt upregulation of TRIM46. We find that TRIM46 is a ubiquitin ligase that targets histone deacetylase HDAC1 for ubiquitination and degradation and that the TRIM46-HDAC1 axis regulates a panel of genes, including ones critically involved in DNA replication and repair. Consequently, TRIM46 promotes breast cancer cell proliferation and chemoresistance in vitro and accelerates tumor growth in vivo. Moreover, TRIM46 is frequently overexpressed in breast carcinomas, and its expression is correlated with lower HDAC1 expression, higher histological grades, and worse prognosis of the patients. Together, our study links SNP rs4971059 to replication and to breast carcinogenesis and chemoresistance and support the pursuit of TRIM46 as a potential target for breast cancer intervention.

BRD4-directed super-enhancer organization of transcription repression programs links to chemotherapeutic efficacy in breast cancer.

BRD4 is well known for its role in super-enhancer organization and transcription activation of several prominent oncogenes including c-MYC and BCL2 As such, BRD4 inhibitors are being pursued as promising therapeutics for cancer treatment. However, drug resistance also occurs for BRD4-targeted therapies. Here, we report that BRD4 unexpectedly interacts with the LSD1/NuRD complex and colocalizes with this repressive complex on super-enhancers. Integrative genomic and epigenomic analyses indicate that the BRD4/LSD1/NuRD complex restricts the hyperactivation of a cluster of genes that are functionally linked to drug resistance. Intriguingly, treatment of breast cancer cells with a small-molecule inhibitor of BRD4, JQ1, results in no immediate activation of the drug-resistant genes, but long-time treatment or destabilization of LSD1 by PELI1 decommissions the BRD4/LSD1/NuRD complex, leading to resistance to JQ1 as well as to a broad spectrum of therapeutic compounds. Consistently, PELI1 is up-regulated in breast carcinomas, its level is negatively correlated with that of LSD1, and the expression level of the BRD4/LSD1/NuRD complex-restricted genes is strongly correlated with a worse overall survival of breast cancer patients. Together, our study uncovers a functional duality of BRD4 in super-enhancer organization of transcription activation and repression linking to oncogenesis and chemoresistance, respectively, supporting the pursuit of a combined targeting of BRD4 and PELI1 in effective treatment of breast cancer.

Zinc-finger protein CXXC5 promotes breast carcinogenesis by regulating the TSC1/mTOR signaling pathway.

CXXC5, a member of the CXXC family of zinc-finger proteins, is associated with numerous pathological processes. However, the pathophysiological function of CXXC5 has not been clearly established. Herein, we found that CXXC5 interacts with the CRL4B and NuRD complexes. Screening of transcriptional targets downstream of the CXXC5-CRL4B-NuRD complex by next-generation sequencing (chromatin immunoprecipitation sequencing) revealed that the complex regulates the transcriptional repression process of a cohort of genes, including TSC1 (tuberous sclerosis complex subunit 1), which play important roles in cell growth and mammalian target of rapamycin signaling pathway regulation, and whose abnormal regulation results in the activation of programmed cell death-ligand protein 1 (PD-L1). Intriguingly, CXXC5 expression increased after stimulation with vitamin B2 but decreased after vitamin D treatment. We also found that the CXXC5-CRL4B-NuRD complex promotes the proliferation of tumor cells in vitro and accelerates the growth of breast cancer in vivo. The expression of CXXC5, CUL4B, and MTA1 increased during the occurrence and development of breast cancer, and correspondingly, TSC1 expression decreased. Meanwhile, a high expression of CXXC5 was positively correlated with the histological grade of high malignancy and poor survival of patients. In conclusion, our study revealed that CXXC5-mediated TSC1 suppression activates the mammalian target of rapamycin pathway, reduces autophagic cell death, induces PD-L1-mediated immune suppression, and results in tumor development, shedding light on the mechanism of the pathophysiological function of CXXC5.

Pseudotetrahedral Organotin-Capped Chalcogenidometalate Supermolecules with Optical Limiting Performance.

The rational design of crystalline clusters with adjustable compositions and dimensions is highly sought after but quite challenging as it is important to understand their structural evolution processes and to systematically establish structure-property relationships. Herein, a family of organotin-based sulfidometalate supertetrahedral clusters has been prepared via mixed metal and organotin strategies at low temperatures (60-120 °C). By engineering the metal composition, we can effectively control the size of the clusters, which ranges from 8 to 35, accompanied by variable configurations: P1-[(RSn)4M4S13], T3-[(RSn)4In4M2S16] (R = nbutyl-Bu and phenyl-Ph; M = Cd, Zn, and Mn), T4-[(BuSn)4In13Cu3S31], truncated P2, viz. TP2-[(BuSn)6In10Cu6S31], and even T5-[(BuSn)4In22Zn6Cu3S52], all of which are the largest organometallic supertetrahedral clusters known to date. Of note, the arylstannane approach plays a critical role in regulating the peripheral ligands and further enriching geometric structures of the supertetrahedral clusters. This is demonstrated by the formation of tin-oxysulfide clusters, such as T3-[(RSn)4Sn6O4S16] (R = Bu, Ph, and benzyl = Be) and its variants, truncated T3, viz., TT3-[(BuSn)6Sn3O4S13] and augmented T3, viz., T3-[(Bu3SnS)4Sn6O4S16]. Especially, two extraordinary truncated clusters break the tetrahedral symmetry observed in typical supertetrahedral clusters, further substantiating the advantages offered by the arylstannane approach in expanding cluster chemistry. These organometallic supertetrahedral clusters are highly soluble and stable in common solvents. Additionally, they have tunable third-order nonlinear optical behaviors by controlling the size, heterometallic combination, organic modification, and intercluster interaction.

Screening for functional circular RNAs using the CRISPR-Cas13 system.

Circular RNAs (circRNAs) produced from back-spliced exons are widely expressed, but individual circRNA functions remain poorly understood owing to the lack of adequate methods for distinguishing circRNAs from cognate messenger RNAs with overlapping exons. Here, we report that CRISPR-RfxCas13d can effectively discriminate circRNAs from mRNAs by using guide RNAs targeting sequences spanning back-splicing junction (BSJ) sites featured in RNA circles. Using a lentiviral library that targets sequences across BSJ sites of highly expressed human circRNAs, we show that a group of circRNAs are important for cell growth mostly in a cell-type-specific manner and that a common oncogenic circRNA, circFAM120A, promotes cell proliferation by preventing the mRNA for family with sequence similarity 120A (FAM120A) from binding the translation inhibitor IGF2BP2. Further application of RfxCas13d-BSJ-gRNA screening has uncovered circMan1a2, which has regulatory potential in mouse embryo preimplantation development. Together, these results establish CRISPR-RfxCas13d as a useful tool for the discovery and functional study of circRNAs at both individual and large-scale levels.

Meta-analysis and systematic review of the relationship between sex and the risk or incidence of poststroke aphasia and its types.

OBJECTIVE: To analyse and discuss the association of gender differences with the risk and incidence of poststroke aphasia (PSA) and its types, and to provide evidence-based guidance for the prevention and treatment of poststroke aphasia in clinical practice. DATA SOURCES: Embase, PubMed, Cochrane Library and Web of Science were searched from January 1, 2002, to December 1, 2023. STUDY SELECTION: Including the total number of strokes, aphasia, the number of different sexes or the number of PSA corresponding to different sex. DATA EXTRACTION: Studies with missing data, aphasia caused by nonstroke and noncompliance with the requirements of literature types were excluded. DATA SYNTHESIS: 36 papers were included, from 19 countries. The analysis of 168,259 patients with stroke and 31,058 patients with PSA showed that the risk of PSA was 1.23 times higher in female than in male (OR = 1.23, 95% CI = 1.19-1.29, P < 0.001), with a prevalence of PSA of 31% in men and 36% in women, and an overall prevalence of 34% (P < 0.001). Analysis of the risk of the different types of aphasia in 1,048 patients with PSA showed a high risk in females for global, broca and Wenicke aphasia, and a high risk in males for anomic, conductive and transcortical aphasia, which was not statistically significant by meta-analysis. The incidence of global aphasia (males vs. females, 29% vs. 32%) and broca aphasia (17% vs 19%) were higher in females, and anomic aphasia (19% vs 14%) was higher in males, which was statistically significant (P < 0.05). CONCLUSIONS: There are gender differences in the incidence and types of PSA. The risk of PSA in female is higher than that in male.

SCFJFK is functionally linked to obesity and metabolic syndrome.

Dysregulation of lipid metabolism could lead to the development of metabolic disorders. We report here that the F-box protein JFK promotes excessive lipid accumulation in adipose tissue and contributes to the development of metabolic syndrome. JFK transgenic mice develop spontaneous obesity, accompanied by dyslipidemia, hyperglycemia, and insulin resistance, phenotypes that are further exacerbated under high-fat diets. In contrast, Jfk knockout mice are lean and resistant to diet-induced metabolic malfunctions. Liver-specific reconstitution of JFK expression in Jfk knockout mice leads to hepatic lipid accumulation resembling human hepatic steatosis and nonalcoholic fatty liver disease. We show that JFK interacts with and destabilizes ING5 through assembly of the SCF complex. Integrative transcriptomic and genomic analysis reveals that the SCFJFK -ING5 axis interferes with AMPK activity and fatty acid ß-oxidation, leading to the suppression of hepatic lipid catabolism. Significantly, JFK is upregulated and AMPKα1 is down-regulated in liver tissues from NAFLD patients. These results reveal that SCFJFK is a bona fide E3 ligase for ING5 and link the SCFJFK -ING5 axis to the development of obesity and metabolic syndrome.

Bimodal regulation of the PRC2 complex by USP7 underlies tumorigenesis.

Although overexpression of EZH2, a catalytic subunit of the polycomb repressive complex 2 (PRC2), is an eminent feature of various cancers, the regulation of its abundance and function remains insufficiently understood. We report here that the PRC2 complex is physically associated with ubiquitin-specific protease USP7 in cancer cells where USP7 acts to deubiquitinate and stabilize EZH2. Interestingly, we found that USP7-catalyzed H2BK120ub1 deubiquitination is a prerequisite for chromatin loading of PRC2 thus H3K27 trimethylation, and this process is not affected by H2AK119 ubiquitination catalyzed by PRC1. Genome-wide analysis of the transcriptional targets of the USP7/PRC2 complex identified a cohort of genes including FOXO1 that are involved in cell growth and proliferation. We demonstrated that the USP7/PRC2 complex drives cancer cell proliferation and tumorigenesis in vitro and in vivo. We showed that the expression of both USP7 and EZH2 elevates during tumor progression, corresponding to a diminished FOXO1 expression, and the level of the expression of USP7 and EZH2 strongly correlates with histological grades and prognosis of tumor patients. These results reveal a dual role for USP7 in the regulation of the abundance and function of EZH2, supporting the pursuit of USP7 as a therapeutic target for cancer intervention.

Engineered Cas12a-Plus nuclease enables gene editing with enhanced activity and specificity.

BACKGROUND: The CRISPR-Cas12a (formerly Cpf1) system is a versatile gene-editing tool with properties distinct from the broadly used Cas9 system. Features such as recognition of T-rich protospacer-adjacent motif (PAM) and generation of sticky breaks, as well as amenability for multiplex editing in a single crRNA and lower off-target nuclease activity, broaden the targeting scope of available tools and enable more accurate genome editing. However, the widespread use of the nuclease for gene editing, especially in clinical applications, is hindered by insufficient activity and specificity despite previous efforts to improve the system. Currently reported Cas12a variants achieve high activity with a compromise of specificity. Here, we used structure-guided protein engineering to improve both editing efficiency and targeting accuracy of Acidaminococcus sp. Cas12a (AsCas12a) and Lachnospiraceae bacterium Cas12a (LbCas12a). RESULTS: We created new AsCas12a variant termed "AsCas12a-Plus" with increased activity (1.5~2.0-fold improvement) and specificity (reducing off-targets from 29 to 23 and specificity index increased from 92% to 94% with 33 sgRNAs), and this property was retained in multiplex editing and transcriptional activation. When used to disrupt the oncogenic BRAFV600E mutant, AsCas12a-Plus showed less off-target activity while maintaining comparable editing efficiency and BRAFV600E cancer cell killing. By introducing the corresponding substitutions into LbCas12a, we also generated LbCas12a-Plus (activity improved ~1.1-fold and off-targets decreased from 20 to 12 while specificity index increased from 78% to 89% with 15 sgRNAs), suggesting this strategy may be generally applicable across Cas12a orthologs. We compared Cas12a-Plus, other variants described in this study, and the reported enCas12a-HF, enCas12a, and Cas12a-ultra, and found that Cas12a-Plus outperformed other variants with a good balance for enhanced activity and improved specificity. CONCLUSIONS: Our discoveries provide alternative AsCas12a and LbCas12a variants with high specificity and activity, which expand the gene-editing toolbox and can be more suitable for clinical applications.

Two Polarity-Sensitive Fluorescent Probes Based on Curcumin Analogs for Visualizing Polarity Changes in Lipid Droplets.

As a class of highly dynamic organelles, lipid droplets (LDs) are involved in numerous physiological functions, and the changes in polarity of LDs are closely related to a variety of diseases. In this work, we developed two polarity-sensitive fluorescent probes (CC-CH and CC-Cl) based on curcumin analogs. CC-CH and CC-Cl with a donor-acceptor-donor (D-A-D) structure exhibited the property of intramolecular charge transfer (ICT); thus, their fluorescence emissions were significantly attenuated with increasing ambient polarity. Cell experiments indicated that CC-CH and CC-Cl showed excellent photostability, a low cytotoxicity, and a superior targeting ability regarding LDs. After treatment with oleic acid (OA) and methyl-ß-cyclodextrin (M-ß-CD), the polarity changes of LDs in living cells could be visualized by using CC-CH and CC-Cl. In addition, CC-CH and CC-Cl could monitor polarity changes of LDs in different pathological processes, including inflammatory responses, nutrient deprivation, and H2O2-induced oxidative stress. Therefore, CC-CH and CC-Cl are promising potential fluorescent probes for tracking intracellular LD polarity changes.

The In Vivo Pharmacokinetics of Block Copolymers Containing Polyethylene Glycol Used in Nanocarrier Drug Delivery Systems.

Polyethylene glycol (PEG) is one of the most commonly used synthetic macromolecular polymers for modifying small molecule drugs, peptides, proteins, or nanodrug delivery systems to improve their water solubility, biocompatibility, and stability. Block copolymers containing PEG have been widely used in nanodrug delivery systems such as solid lipid nanoparticles, polymeric nanoparticles, polymeric micelles, and liposomes. To date, although numerous PEGylated nanodrug delivery systems have been developed, only a few have been approved for clinical application. Poor safety and effectivity are important reasons for the high failure rate of nanodrug delivery system clinical trials. These factors are not only related to the loaded drugs and released drugs but are also related to the nanocarriers. Therefore, investigating the in vivo spatiotemporal fate of block copolymers containing PEG used in nanodrug delivery systems is necessary and important for evaluating their safety, efficacy, and toxicity. In this article, we will review the information that has been reported about the absorption, distribution, metabolism, and excretion of block copolymers containing PEG. We believe this review is helpful to understand the biologic fate of block copolymers containing PEG.This review describes pharmacokinetic study of block copolymers containing polyethylene glycol. The main focus of this paper is the in vivo fate of these polyethylene glycol-related copolymers after their release from nanocarriers. This review is helpful for understanding of the in vivo fate of block copolymers containing polyethylene glycol used in nanocarrier drug delivery systems.

Clinical features and ultrasound findings of a rare musculoskeletal system disease-neuromuscular choristoma.

BACKGROUND: Neuromuscular choristomas (NMCs), are extremely rare developmental lesions that, have been previously established associated with recurrent fibromatosis after surgery, leading to several operations or even amputation. However, reports on the ultrasound imaging features and clinical conditions of NMCs are rare. The purpose of this study is to describe the ultrasound features and clinical analysis of NMCs to provide suggestions to identify the optimal management strategy. METHODS: From September 2020 to September 2021, 7 patients with a confirmed diagnosis of NMC who underwent ultrasound examination in our department were enrolled in our study. Physical examinations were performed to detect motor deficits, sensory deficits, neuropathic pain, limb undergrowth, muscular atrophy, cavus foot and bone dysplasia. Ultrasound imaging was performed and investigated both in affected nerves and neuromuscular choristomas associated desmoid-type fibromatosis (NMC-DTF). All patients had a definite history and regular follow-up. The clinical course, physical examinations, ultrasound features and pathologic results of NMC patients were analyzed. RESULTS: Seven patients with an average age of 7.0 ± 7.2 years (range: 2-22 years) were enrolled in our study. The affected nerves included the sciatic nerve (6 cases) and the brachial plexus (1 case). Six patients (85.7%) presented with limb undergrowth, 6 (85.7%) with muscular atrophy, and 5 (71.4%) with cavus foot deformity. Based on ultrasound findings, all the visibly affected nerve segments presented with hypoechoic and fusiform enlargement with intraneural skeletal muscle elements. Five patients (71.4%) had NMC-DTFs at the site of the affected nerve. All NMC-DTFs were shown as hypoechoic solid lesions adjacent to the nerve and were well circumscribed. In the subset of the surgery group, all 5 patients presented with progression to NMC-DTFs at the site of the NMCs. No fibromatosis was detected in the other two nonsurgical patients. CONCLUSIONS: Understanding the typical ultrasound features and clinically associated conditions would support the early diagnosis of this rare disease. When a potential diagnosis is determined, an invasive procedure such as biopsy or resection might not be a good choice given the frequent occurrence of complications such as aggressive recurrence.

Microstructure and Ablation Behavior of Low-Pressure Plasma Sprayed ZrB2 Coatings Down to 100 Pa.

The effect of chamber pressure on the microstructure and ablation behavior of ZrB2 coatings deposited by low-pressure plasma spraying was investigated. The results showed that as the spray chamber pressure further was reduced to less than 50 kPa, the porosity of the coating deposited at the same distance decreased with the chamber pressure, and the coating prepared under 100 Pa presented the lowest porosity of about 0.89%. The ablation performance test subjected to high-temperature plasma jet revealed that the linear ablation rate of ZrB2 coating increased with the porosity of the coating. As a result, among the ZrB2 coatings deposited at chamber pressures of 100 Pa, 5 kPa, 10 kPa and 50 kPa, the dense coating deposited at 100 Pa showed the lowest ablation rate of 0.33 µm/s. The dense ZrB2 coating with a thickness of about 100 µm was able to withstand 300 s ablation by a plasma flame with a net power of 25 kW resulting in an ablating coating surface temperature of about 2000 °C. The ablation mechanism of the coating was also examined.

Plasma-Sprayed High-Performance (Bi2O3)0.75(Y2O3)0.25 Electrolyte for Intermediate-Temperature Solid Oxide Fuel Cells (IT-SOFCs).

Rare earth element-doped bismuth oxides with the fluorite structure (δ-Bi2O3) exhibit high oxygen ion conductivity at low temperature, which is promising electrolyte materials for intermediate-temperature solid oxide fuel cells (IT-SOFCs). However, traditional co-sintering process is not applicable to the manufacturing of IT-SOFCs using low melting point Bi2O3-based electrolyte, while further high-temperature processing is not required for deposition Bi2O3-based electrolytes. In this study, plasma spraying was used to examine the possibility to deposit high-performance Bi2O3-based electrolytes without the following high-temperature process. (Bi2O3)0.75 (Y2O3)0.25 (YSB) spray powders were prepared by the sinter-crushing method. The YSB electrolytes were fabricated by plasma spraying at different deposition temperatures. The effects of deposition temperature on the coating microstructure, crystalline stability, and ion conductivity were investigated. Results showed that the as-sprayed YSB electrolytes present a dense microstructure with well-bonded lamellar interfaces. The pure δ-phase YSB electrolyte was deposited with 37.5-75 µm powders at a deposition temperature of 350 °C. The deposited YSB electrolyte presented the excellent ionic conductivity of 0.19 S cm-1 at 700 °C in comparison with 0.21 S cm-1 for sintered bulk.

Effect of Powder Particle Size and Spray Parameters on the Ni/Al Reaction During Plasma Spraying of Ni-Al Composite Powders.

It was known for long that Ni-Al composite powders can be used to deposit self-bonding coating as a bond coat for common ceramic coatings due to the exothermic reaction between Ni and Al. However, it was found that with commercial Ni-Al composite powders with a large particle size, it is difficult to ignite the self-propagating reaction between Ni and Al to form Ni-Al intermetallics by plasma spraying. In this study, Ni-Al composite powder particles of different sizes were used to prepare Ni-Al intermetallics-based coatings by plasma spraying. The dependencies of the exothermic reaction between Ni and Al and the coating microstructure on powder particle size and spray parameters were investigated. The phase composition, microstructure, porosity and oxide content of the coatings were characterized by x-ray diffraction, scanning electron microscope and image analyzing. The results show that particle size of Ni-Al composite powders is the dominant factor controlling the exothermic reaction for the formation of Ni-Al intermetallics during plasma spraying. When the powders larger than about 50 µm are used, the reaction forming aluminide cannot complete even by heating of plasma flame generated at high plasma arc power. However, when smaller powders less than 50 µm are used, the exothermic reaction can completely occur rapidly in plasma spraying, contributing to heating of Ni-Al droplets to the highest temperature for development of the self-bonding effect. The positive relationship between molten droplet temperature and tensile adhesive strength of the resultant coatings is recognized to confirm the contribution of high droplet temperature to the adhesive or cohesive strength.

Association Between TP53 Mutation and Prognosis in Wilms Tumor: A Meta-Analysis.

BackgroundTP53 mutation has been suggested to have prognostic value for patients with Wilms tumor (WT), but the results are still controversial. Methods: Relevant studies published until August 1, 2019 were identified by searching PubMed, EMBASE and Cochrane Library. A random-effect model was performed to assess pooled data. Begg's and Egger's test were used to evaluate the potential publication bias. Sensitivity analysis was used to evaluate the stability of results. Results: A total of seven eligible articles were included. There was no significant difference in the risk of death among patients with WT with different TP53 mutation status (odds ratio [OR] = 3.09, 95% confidence interval[CI]: 0.81-11.84). Combined hazard ratio (HR) suggested that TP53 mutation had an unfavorable impact on overall survival (OS) (HR = 4.17, 95% CI: 1.97-6.36) and disease-free survival (DFS) (HR = 2.23, 95% CI: 1.29-3.17) in WT. Conclusions: This meta-analysis demonstrates that TP53 mutations are associated with poorer prognosis in WT.