Lead-free double perovskite Cs2NaInCl6 nanocrystals doped with Sb3+ and Tb3+ for copper ions detection in lubricating oil.

Detecting heavy metal copper ions in lubricating oil holds immense significance for assessing mechanical wear and predicting mechanical failure. While perovskite nanocrystals offer high sensitivity in detecting copper ions, traditional lead halide perovskites suffer from lead toxicity defects. Lead-free perovskites, like Cs2NaInCl6, avoid the issue of lead toxicity but display lower luminescence intensity due to the presence of forbidden optical transitions. To address these issues, this study synthesized Cs2NaInCl6 nanocrystals (NCs) co-doped with Sb3+ and Tb3+ ions for copper ions detection in lubricating oil. The introduction of Sb3+ effectively reduced the band gap of the Cs2NaInCl6 host, creating an energy transfer pathway for Tb3+ emission via self-trapped excitations (STEs). Moreover, the doping of Tb3+ ions resulted in the suppression of STEs emission due to electron transfer from STEs to Tb3+. The emission of Tb3+ increased initially and then decreased with the increasing Tb3+ concentration, peaking at 40 %. Finally, Cs2NaInCl6: 2.5 %Sb3+, 40 %Tb3+ NCs were employed as probes for copper ions detection, exhibiting superior sensitivity and selectivity compared to similar probes. The presence of copper ions introduced competition between copper and Tb3+ for electrons from STEs, consequently leading to the quenching of multiple emission intensities associated with STEs and Tb3+. This method shows promising potential in predicting mechanical failure.

Cancer Risk and Mutational Patterns Following Organ Transplantation.

The rapid development of medical technology and widespread application of immunosuppressive drugs have improved the success rate of organ transplantation significantly. However, the use of immunosuppressive agents increases the frequency of malignancy greatly. With the prospect of "precision medicine" for tumors and development of next-generation sequencing technology, more attention has been paid to the application of high-throughput sequencing technology in clinical oncology research, which is mainly applied to the early diagnosis of tumors and analysis of tumor-related genes. All generations of cancers carry somatic mutations, meanwhile, significant differences were observed in mutational signatures across tumors. Systematic sequencing of cancer genomes from patients after organ transplantation can reveal DNA damage and repair processes in exposed cancer cells and their precursors. In this review, we summarize the application of high-throughput sequencing and organoids in the field of organ transplantation, the mutational patterns of cancer genomes, and propose a new research strategy for understanding the mechanism of cancer following organ transplantation.

Folic acid supplementation during pregnancy modulates hepatic methyl metabolism and genes expression profile of neonatal lambs of different litter sizes.

Maternal folic acid (FA) plays an important role in the fetus development, but it is unknown the response of hepatic metabolism in the offspring from different litter sizes to maternal FA supplementation. In the present study, this was done by feeding the ewes with 0, 16 and 32 mg/(kg·DM) FA supplemented diet during pregnancy and analysing the hepatic one-carbon metabolism-related indices and gene expression in the neonatal lambs of different litter sizes (twins, TW; triplets, TR). Regardless of litter sizes, the concentrations of folate, methionine, S-adenosylmethionine and DNA methyltransferase increased significantly, but homocysteine and S-adenosylhomocysteine decreased in the liver of newborn lambs from ewes whose diet was supplemented with FA. In TW, maternal FA status has little effect on hepatic genes expression profile of newborn lambs, and no significant enriched pathway was found. However, DEG involved in cell proliferation such as CCNA2, CCNB2, CCNE2, CDK1 and BUB1 were significantly enriched when the ewes were supplemented with FA in TR groups. In addition, nucleotide synthesis-related genes such as POLD1, POLD2, MCM4 and MCM5 were enriched markedly in DNA replication and pyrimidine metabolism pathways in triplets when a higher FA ingestion [32 mg/(kg·DM)] was implemented in ewes. This finding demonstrated that the hepatic methyl metabolism in TW and TR newborn lambs was regulated by maternal FA status. The hepatic cell proliferation and nucleotide metabolism related genes in TR were more susceptible to maternal dietary FA supplementation during pregnancy.

Vitamin E can promote spermatogenesis by regulating the expression of proteins associated with the plasma membranes and protamine biosynthesis.

Vitamin E is generally believed to promote the production of ovine sperm mainly through its antioxidant effect. Our previous studies have shown that some non-antioxidant genes may also be key in mediating this process. The objective of this study was to identify key candidate proteins that were differentially expressed in response to a treatment with Vitamin E. Prepubertal ovine testicular cells were isolated and divided into two groups. They were either treated with 800 µM Vitamin E (based on our previous results) or used as a non-treated control. After 24 h, all the cells were harvested for proteomic analysis. We found 115 differentially expressed proteins, 4 of which were up-regulated and 111 were down-regulated. A GO term enrichment analysis identified 127 Biological Process, 63 Cell Component and 26 Molecular Function terms that were enriched. Within those terms, 13, 11 and 26 terms were significantly enriched, respectively. Terms related to membrane and enzyme activity including the inner acrosomal membrane, signal peptidase complex, cysteine-type endopeptidase activity, etc., were also markedly enriched, while none of the KEGG pathways were enriched. We found that many of the differentially expressed proteins, such as CD46 (membrane cofactor protein), FLNA (Filamin A), DYSF (Dysferlin), IFT20 (Intraflagellar transport 20), SPCS1 (Signal peptidase complex subunit 1) and SPCS3 (Signal peptidase complex subunit 3) were related to the acrosomal and plasma membranes. A parallel reaction monitoring (PRM) analysis verified that Vitamin E improved spermatogenesis by regulating the expression of FLNA, SPCS3, YBX3 and RARS, proteins that are associated with the plasma membranes and protamine biosynthesis of the spermatozoa.

Triplet Male Lambs Are More Susceptible than Twins to Dietary Soybean Oil-Induced Fatty Liver.

BACKGROUND: Litter size affects fetal development but its relation to diet-induced fatty liver later in life is unknown. OBJECTIVES: This aim of this study was to test the hypothesis that litter size influences postweaning fatty liver development in response to soybean oil-supplemented diet. METHODS: Weanling twin (TW) or triplet (TP) male lambs (n = 16) were fed a control diet or 2% soybean oil-supplemented diet (SO) for 90 d. Liver tissue morphology, biochemical parameters, and lipid metabolic enzymes were determined. Hepatic gene expression was analyzed by RNA sequencing (n = 3), followed by enrichment analysis according to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes involved in lipid metabolism were further verified by quantitative reverse transcriptase-polymerase chain reaction (n = 4). All data were analyzed by a 2-factor ANOVA, apart from differentially expressed genes, which were identified by the Benjamini-Hochberg approach (q value ≤0.05). RESULTS: SO increased liver triglyceride (by 55%) and nonesterified fatty acid (by 54%) concentrations in TPs (P ≤ 0.05) but not in TWs (P > 0.05). SO also induced a 2.3- and 2.1-fold increase in the liver steatosis score of TPs and TWs, respectively (P ≤ 0.05). Moreover, SO reduced the activity of lipolytic enzymes including hepatic lipase and total lipase in TPs by 47% and 25%, respectively (P ≤ 0.05). In contrast, activities of lipogenic enzymes, including malic enzyme and acetyl coenzyme A carboxylase, were significantly higher in TPs (P ≤ 0.05). Moreover, TPs had higher expression of lipogenic genes, such as FASN (by 45%) and APOB (by 72%), and lower expression of lipolytic genes, such as PRKAA2 (by 28%) and CPT1A (by 43%), compared with TWs (P ≤ 0.05). CONCLUSIONS: TPs have a gene expression profile that is more susceptible to SO-induced fatty liver than that of TWs, which indicates that insufficient maternal nutrient supply at fetal and neonatal stages may increase the risk of nonalcoholic fatty liver disease.

Mesoporous silica coating NaYF4:Yb,Er@NaYF4 upconversion nanoparticles loaded with ruthenium(II) complex nanoparticles: Fluorometric sensing and cellular imaging of temperature by upconversion and of oxygen by downconversion.

Accurate detection of temperature and oxygen concentration at the cellular level is important in tumor diagnosis. Multifunctional nanocomposites are described that consist of upconversion luminescent nanoparticles capped with mesoporous silica and loaded with an oxygen-sensitive luminescent ruthenium complex. The nanocomposites of type NaYF4:Yb,Er@NaYF4@mSiO2-Ru have two modes of operation: Its red downconversion luminescence (at excitation/emission peaks of 455/606 nm) is quenched by oxygen (O2), and this is used to sense and image O2. The green upconversion luminescence (typically acquired at excitation/emission wavelengths of 980/525 and 544 nm), in turn, is used to measure temperature. The nanocomposites were then applied to dual mode in-vitro imaging of temperature and O2 in hepatocellular carcinoma cells (HepG-2). Graphical abstract A new multifunctional nanocomposite of mesoporous silica coating NaYF4:Yb,Er@NaYF4 upconversion nanopaticless loaded with ruthenium (II) complex has been designed with both green upconversion and red downconversion luminescence for temperature detection, oxygen sensing and dual mode cell imaging.

p53 activates transcription by directing structural shifts in Mediator.

It is not well understood how the human Mediator complex, transcription factor IIH and RNA polymerase II (Pol II) work together with activators to initiate transcription. Activator binding alters Mediator structure, yet the functional consequences of such structural shifts remain unknown. The p53 C terminus and its activation domain interact with different Mediator subunits, and we find that each interaction differentially affects Mediator structure; strikingly, distinct p53-Mediator structures differentially affect Pol II activity. Only the p53 activation domain induces the formation of a large pocket domain at the Mediator-Pol II interaction site, and this correlates with activation of stalled Pol II to a productively elongating state. Moreover, we define a Mediator requirement for TFIIH-dependent Pol II C-terminal domain phosphorylation and identify substantial differences in Pol II C-terminal domain processing that correspond to distinct p53-Mediator structural states. Our results define a fundamental mechanism by which p53 activates transcription and suggest that Mediator structural shifts trigger activation of stalled Pol II complexes.

Ubiquitination of p27Kip1 requires physical interaction with cyclin E and probable phosphate recognition by SKP2.

p27Kip1 is an essential cell cycle inhibitor of Cyclin-dependent kinases. Ubiquitin-mediated proteolysis of p27Kip1 is an important mechanism for activation of Cyclin E-Cdk2 and facilitates G1/S transition. Ubiquitination of p27 is primarily catalyzed by a multisubunit E3 ubiquitin ligase, SCF(Skp2), and requires an adapter protein Cks1. In addition, phosphorylation of p27 at Thr187 by Cyclin E and Cdk2 is also essential for triggering substrate ubiquitination. Here we investigate the molecular mechanism of p27 ubiquitination. We show that Cyclin E-Cdk2 is essential for targeting the p27 substrate to SCF(Skp2). Direct physical contact between Cyclin E but not Cdk2 and p27 is required for p27 recruitment to SCF(Skp2). In a search for positively charged amino acid residues that may be involved in recognition of the Thr187 phosphate group, we found that Arg306 of Skp2 is required for association and ubiquitination of phosphorylated p27 but dispensable for ubiquitination of unphosphorylated p21. Thus, our data unravel the molecular organization of the ubiquitination complex that catalyzes p27 ubiquitination and provide unique insights into the specificity of substrate recognition by SCF(Skp2).