Watkinsmccoy0043
This work will broaden the potential applications of the ammonium-ion battery for sustainable energy storage.CRISPR Cas9-based screening is a powerful approach for identifying and characterizing novel drug targets. Here, we elucidate the synthetic lethal mechanism of deubiquitinating enzyme USP1 in cancers with underlying DNA damage vulnerabilities, specifically BRCA1/2 mutant tumors and a subset of BRCA1/2 wild-type (WT) tumors. In sensitive cells, pharmacological inhibition of USP1 leads to decreased DNA synthesis concomitant with S-phase-specific DNA damage. Genome-wide CRISPR-Cas9 screens identify RAD18 and UBE2K, which promote PCNA mono- and polyubiquitination respectively, as mediators of USP1 dependency. The accumulation of mono- and polyubiquitinated PCNA following USP1 inhibition is associated with reduced PCNA protein levels. Ectopic expression of WT or ubiquitin-dead K164R PCNA reverses USP1 inhibitor sensitivity. Our results demonstrate, for the first time, that USP1 dependency hinges on the aberrant processing of mono- and polyubiquitinated PCNA. Moreover, this mechanism of USP1 dependency extends beyond BRCA1/2 mutant tumors to selected BRCA1/2 WT cancer cell lines enriched in ovarian and lung lineages. We further show PARP and USP1 inhibition are strongly synergistic in BRCA1/2 mutant tumors. We postulate USP1 dependency unveils a previously uncharacterized vulnerability linked to post-translational modifications of PCNA. Taken together, USP1 inhibition may represent a novel therapeutic strategy for BRCA1/2 mutant tumors and a subset of BRCA1/2 WT tumors.Sulfated cyclodextrins have recently emerged as potential candidates for producing host-induced guest aggregation with properties better than p-sulfonatocalixarenes that have previously shown numerous applications involving the phenomena of host-induced guest aggregation. In the class of sulfated cyclodextrins (SCD), sulfated β-cyclodextrin (β-SCD) remains the most extensively investigated host molecule. Although it is assumed that the host-induced guest aggregation is predominantly an outcome of interaction of the guest molecule with the charges on the exterior of SCD cavity, it has not been deciphered whether the variation in the cavity size will make a difference in the efficiency of host-induced guest-aggregation process. In this investigation, we present a systematic study of host-induced guest aggregation of a cationic molecular rotor dye, Thioflavin T (ThT) with three different sulfated cyclodextrin molecules, α-SCD, β-SCD and γ-SCD, which differ in their cavity size, using steady-state emission, ground-state absorption and time-resolved emission measurements. The obtained photophysical properties of ThT, upon interaction with different SCD molecules, indicate that the binding strength of ThT with different SCD molecules correlate with the cavity size of the host molecule, giving rise to the strongest complexation of ThT with the largest host molecule (γ-SCD). The binding affinity of ThT towards different host molecules has been supported by molecular docking calculations. The results obtained are further supported with the temperature and ionic strength dependent studies performed on the host-guest complex. Our results indicate that for host-induced guest aggregation, involving oppositely charged molecules, the size of the cavity also plays a crucial role beside the charge density on the exterior of host cavity.Heme is an indispensable cofactor for almost all aerobic life, including the human host and many bacterial pathogens. During infection, heme and hemoproteins are the largest source of bioavailable iron, and pathogens have evolved various heme acquisition pathways to satisfy their need for iron and heme. Many of these pathways are regulated transcriptionally by intracellular iron levels, however, host heme availability and intracellular heme levels have also been found to regulate heme uptake in some species. Knowledge of these pathways has helped to uncover not only how these bacteria incorporate host heme into their metabolism but also provided insight into the importance of host heme as a nutrient source during infection. Within this review is covered multiple aspects of the role of heme at the host pathogen interface, including the various routes of heme biosynthesis, how heme is sequestered by the host, and how heme is scavenged by bacterial pathogens. Also discussed is how heme and hemoproteins alter the behavior of the host immune system and bacterial pathogens. Finally, some unanswered questions about the regulation of heme uptake and how host heme is integrated into bacterial metabolism are highlighted.A series of luminescent Pb2+ complexes, [Pb(L1)2]n (1), [Pb(L2)2]n (2), [Pb(L3)(NO3)(H2O)2]n (3), [Pb(L3)(Br)(H2O)]n (4), [Pb(L3)(Cl)(H2O)]n (5), and [Pb(L4)(H2O)2] (6) have been synthesized by treatment of polydentate tetrazolato ligands with various hydrated Pb2+ salts (HL1 = 2-(1H-tetrazol-5-yl)pyridine, HL2 = 3-(1H-tetrazol-5-yl)isoquinoline, HL3 = 6-(1H-tetrazol-5-yl)-2,2'-bipyridine, and H2L4 = 6,6'-bis(1H-tetrazol-5-yl)-2,2'-bipyridine). These complexes have been characterized by IR, TGA, and elemental analysis. Their crystal structures have been determined by X-ray crystallography, and the phase purity of bulk samples were further confirmed by PXRD. Their luminescence properties have been investigated in detail, and their emission origin may involve ligand-centered π-π* transition, metal-centered s-p transition and charge-transfer character. It is interesting to note that 5 exhibits obviously enhanced red-shifted emission, whose photoluminescence quantum yield (PLQY = 16.5%) is much higher than the other compounds (≤2%). Most importantly, the emission property of 5 was strongly affected by temperature. When the temperature rises from 295 to 493 K, the emission maximum gradually shifts to high energy due to the loss of the aqua ligand. In contrast, when the temperature is lowered from 295 to 13 K, two emission bands were observed. The low-energy emission band exhibits a slight blue shift, while a new high-energy emission band appears at around 520 nm, which is assigned to ligand-centered phosphorescence. After removal of the coordinated aqua ligand, the emission of 5-H2O is very sensitive to the vapors of volatile primary amines and acids, although they have different response mechanisms. This result indicates that 5-H2O may be a potential multifunctional sensor for temperature, volatile amines, and acids. To decipher the emission origin, DFT calculations have also been carried out based on the structure units of these compounds.
Research of diced cartilage for rhinoplasty mainly explored the efficacy of wrapped materials, with rare studies on the sizes of diced cartilage.
To evaluate the viability and stability of various sized free diced cartilage.
The remaining costal cartilage was harvested during rhinoplasties and implanted into subcutaneous pockets on the backs of nude mice shaved cartilage (group A, n = 8), diced cartilage with a diameter of < 0.5 mm (group B, n = 8), 0.5-1.0 mm (group C, n = 8), and 1.0-1.5 mm (group D, n = 8). After 12 weeks, weight and volume retention rates, histopathological examinations, and biomechanical properties were evaluated.
Cartilage grafts in groups A and B showed an obvious loss of contour and severe dispersion. The weight and volume of cartilage graft in group A were significantly decreased (all p < 0.05). Although there was no significant difference, group D (122.8 ± 15.4%) achieved the highest weight retention rate compared with groups B and C (114.6 ± 7.1% and 114.3 ± 10.1%, respectively). Group A showed the most apparent chondrocyte nucleus loss with the least peripheral proliferation, and group D showed the best regeneration potential (all p < 0.05). Group C achieved less chondrocyte nucleus loss than group B (p < 0.05). The compressive elastic modulus increased with the diameter of diced cartilage (all p < 0.05).
Diced cartilage with a diameter of 1.0-1.5 mm may have the highest viability and stability, followed by those of 0.5-1.0 mm and < 0.5 mm.
Diced cartilage with a diameter of 1.0-1.5 mm may have the highest viability and stability, followed by those of 0.5-1.0 mm and less then 0.5 mm.Aqueous zinc ion batteries are a promising alternative secondary battery technology due to their excellent safety and environmental friendliness. T-DM1 Vanadium-based compounds as a highly promising class of cathode materials still suffer from structural collapse and slow kinetics. Studies have shown that metal ion pre-introduction is an effective method to solve these problems and enhance battery performance. Here, the introduction of Al3+ , Cr3+ , Cu2+ and Fe3+ is found to effectively reduce the migration energy barrier of Zn2+ with the density functional theory calculations, while Al3+ exhibits the best induction effects. Subsequently, Al0.34 V5 O12 ·2.4H2 O (AlVOH) nanoribbons are synthesized by hydrothermal introduction of Al3+ , demonstratin excellent electrochemical properties (407.8 mAh g-1 at 0.2 A g-1 and 176.3 mAh g-1 after 2000 cycles at 20 A g-1 ). By further compounding with redox graphene (rGO), AlVOH/rGO exhibits high capacitance and specific capacity (460.4 mAh g-1 at 0.2 A g-1 and 180.6 mAh g-1 after 2000 cycles at 20 A g-1 ). In addition, it is found that the introduction of metal ions adjusts the structural water content of the material. Especially, the introduction of Al3+ can increase the interlayer structural water content and make the electrochemical properties of the material more stable.
Previous genome-wide association studies (GWASs) of bone mineral density (BMD) were mainly conducted in Europeans.
To explore genetic variants that affect BMD and sex differences in a Chinese population.
A total of 5428 middle-aged and elderly Chinese were included. Dual-energy X-ray absorptiometry was used to measure BMD at the lumbar spine, and total and specific sites of the hip. A mixed linear model was used to analyze the associations between BMD and autosomal genetic variants, adjusting for age, age squared, sex, and menopausal women (model 1); model 2 was further adjusted for height and weight. A GWAS of osteoporosis in the Biobank Japan (BBJ) project was used for replication. GWAMA software was used to detect the statistical significance of sex differences of estimated effects. Gene annotation and pathway enrichment analysis were performed.
Women lost BMD at earlier ages and faster than men. The 2 models identified a total of 12 loci that were associated with BMD at any site. Single nucleotide polymorphisms rs72354346, rs2024219, rs1463093, rs10037512, and rs5880932 were successfully replicated in the BBJ. Variations of rs79262027 G>A (VKORC1L1) and rs4795209 A>G (DDX52) were associated with BMD only in men, and rs1239055408 G>GA (KCNJ2) was associated with BMD only in women. Gene enrichment analysis showed that BMD in a Chinese elderly population was mainly related to ossification, bone resorption, sex hormones, and kidney physiology.
The present GWAS identified 12 loci that were significantly associated with BMD at any site in a Chinese population, and 3 of them showed sex differences in their effects.
The present GWAS identified 12 loci that were significantly associated with BMD at any site in a Chinese population, and 3 of them showed sex differences in their effects.
