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Use of ctDNA can effectively guide panitumumab rechallenge in metastatic colorectal cancer.Multicellular dynamics, including neoadjuvant treatment-associated changes, were uncovered in PDAC.Supported Au catalysts are highly selective and size-sensitive in catalytic hydrogenation of alkynes under mild conditions. Using thermal-programmed desorption and density functional theory calculations, we study the hydrogenation reactions of C2 hydrocarbons with atomic H and clarify the site-specific selective hydrogenation of C2H2 on Au(997) at low temperatures. On atomic H(a) covered Au(997), hydrogenation of C2H2 goes with 100% selectivity to C2H4 at steps, yet no hydrogenation occurs at terraces; adsorbed C2H4 on neither steps nor terraces reacts with H(a). DFT calculations suggest that the increased adsorption free energies and appropriate reaction barriers of C2 species at steps lead to the step-site specific semihydrogenation of C2H2. These results elucidate the elementary surface reactions between C2 hydrocarbons and atomic H on Au surfaces at the molecular level and significantly deepen the fundamental understanding of the unique selectivity of Au catalysts.

Adult granulosa cell tumors (AGCTs) are rare ovarian malignant neoplasms; their etiopathogenetic mechanisms remain largely unelucidated. Lately, defects in mismatch repair (MMR) have been implicated in the pathogenesis of AGCTs. Demonstration of MMR deficiency in these tumors can help identify patients potentially eligible for immune checkpoint inhibition therapy. The present study was done to explore the role of MMR deficiency in the etiopathogenesis of AGCTs.

This was a retrospective study conducted on histopathologically confirmed AGCT cases. MMR protein expression was evaluated by immunohistochemistry (IHC) on tissue microarrays using an antibody panel of MSH2, MSH6, MLH1, and PMS2.

Of a total of 40 ovarian AGCTs evaluated for MMR deficiency, none demonstrated loss of expression of any of the 4 MMR proteins.

The results of our preliminary study show that there is no association between MMR deficiency with AGCT. Nevertheless, larger multicenter studies are needed to confirm or refute this observation.

The results of our preliminary study show that there is no association between MMR deficiency with AGCT. Nevertheless, larger multicenter studies are needed to confirm or refute this observation.A growing number of environmental contaminants have been proved to have reproductive toxicity to males and females. However, the unclear toxicological mechanism of reproductive toxicants limits the development of virtual screening methods. By consolidating androgen (AR)-/estrogen receptors (ERs)-mediated adverse outcome pathways (AOPs) with more than 8000 chemical substances, we uncovered relationships between chemical features, a series of pathway-related effects, and reproductive apical outcomes─changes in sex organ weights. An AOP-based computational model named RepTox was developed and evaluated to predict and characterize chemicals' reproductive toxicity for males and females. Results showed that RepTox has three outstanding advantages. (I) Compared with the traditional models (37 and 81% accuracy, respectively), AOP significantly improved the predictive robustness of RepTox (96.3% accuracy). (II) Compared with the application domain (AD) of models based on small in vivo datasets, AOP expanded the ADs of RepTox by 1.65-fold for male and 3.77-fold for female, respectively. (III) RepTox implied that hydrophobicity, cyclopentanol substructure, and several topological indices (e.g., hydrogen-bond acceptors) were important, unbiased features associated with reproductive toxicants. Finally, RepTox was applied to the inventory of existing chemical substances of China and identified 2100 and 7281 potential toxicants to the male and female reproductive systems, respectively.In recent years, lignin has drawn increasing attention for different applications due to its intrinsic antibacterial and antioxidant properties, coupled with biodegradability and biocompatibility. However, chemical modification or combination with metals is usually required to increase its antimicrobial functionality and produce biobased added-value materials for applications wherein bacterial growth should be avoided, such as biomedical and food industries. In this work, a sonoenzymatic approach for the simultaneous functionalization and nanotransformation of lignin to prepare metal-free antibacterial phenolated lignin nanoparticles (PheLigNPs) is developed. The grafting of tannic acid, a natural phenolic compound, onto lignin was achieved by an environmentally friendly approach using laccase oxidation upon the application of high-intensity ultrasound to rearrange lignin into NPs. PheLigNPs presented higher antibacterial activity than nonfunctionalized LigNPs and phenolated lignin in the bulk form, indicating the contribution of both the phenolic content and the nanosize to the antibacterial activity. Studies on the antibacterial mode of action showed that bacteria in contact with the functionalized NPs presented decreased metabolic activity and high levels of reactive oxygen species (ROS). Moreover, PheLigNPs demonstrated affinity to the bacterial surface and the ability to cause membrane destabilization. Antimicrobial resistance studies showed that the NPs did not induce resistance in pathogenic bacteria, unlike traditional antibiotics.An organoid-based, 3D imaging-transcriptomic platform was developed to investigate immunotherapy modes of action.Constructing a heterostructure is an efficient strategy to enhance the catalytic activity toward the oxygen evolution reaction (OER). Herein, Ce-modified Ni(OH)2 nanoparticles are anchored on Ni-MOF nanosheets by the electrodeposition strategy, forming a self-supporting electrode of Ce-m-Ni(OH)2@Ni-MOF. The Raman spectrum proves that both Ce(OH)3 and Ce doping exist in Ce-modified Ni(OH)2 nanoparticles. The heterostructure possesses an open nanosheet structure, with a good interaction between Ni-MOF and Ce-m-Ni(OH)2, which enables efficient mass/charge transfer and the synergetic effect between Ni and Ce, leading to a high-performance electrocatalyst. Specifically, Ce-m-Ni(OH)2@Ni-MOF achieves current densities of 50 and 100 mA cm-2 at low overpotentials of 219 and 272 mV, respectively, and retains high activity for at least 30 h.Molecular structures, packings, and intermolecular interactions significantly affect the photophysical properties of organic luminogens. In this work, the photoluminescence (PL) and mechanoluminescence (ML) of two pairs of isomers, 1/2 and 3/4, were systematically explored. The fluorescence of crystals 1c and 4c is much brighter than that of their isomers 2c and 3c, respectively. Only 1c is ML-active among all four molecules. Single-crystal structural analysis revealed that isomerization of a substituent group affected their molecular packing and intermolecular interactions. Stronger intermolecular interaction and intact three-dimensional hydrogen-bonded networks were formed only in crystal 1c, which were essential for preventing slippage of molecular layers and generating ML; the other molecules were either lacking π-π interactions or C-H···π interactions. Theoretical calculation suggested that the energy barrier between the Franck-Condon (FC) structure and minimum energy crossing point (MECP) structure of 2/3 was much lower than that of 1/4. Nonradiative decay channels of molecules 2 and 3 were thus more easily activated, which led to their lower quantum yield.Reliable patterning of organic semiconductors (OSCs) with high uniformity is essential to all-photolithography organic electronics. However, the majority of cross-linked OSCs experience performance fluctuations after photolithography because of the inherent vulnerability of low-ordered regions. Herein, we develop an anti-solution penetration photolithography process to achieve the reliable patterning of the OSC layer for all-photolithography integrated organic electronics. Using a thick and highly cross-linked semiconductor film and a low-solubility developer, an erosion-free semiconductor channel is obtained with a high mobility of up to 1.254 cm2 V-1 s-1 and a uniform threshold voltage close to zero. Compared with existing all-photolithography organic circuits, the unit logic gate area consumption is lower by 1-3 orders of magnitude at 0.0069 mm2, while the transistor density is higher by 1-2 orders of magnitude at 6780 Tr cm-2. The miniaturized organic inverters maintain uncompromised voltage gains, and the 15-stage organic ring oscillators feature higher oscillation frequencies, making them promising for applications in wide-ranging integrated organic circuits.Sodium ion batteries (SIBs), as an alternative and promising energy storage system, have attracted considerable attention due to the abundant reserves and low cost of sodium. buy SP-2577 However, it remains a great challenge to achieve high capacity and rate capability required for practical applications. Herein, hollow octahedral Co3Se4 particles encapsulated in reduced graphene oxide (Co3Se4@rGO) were designed and synthesized and exhibited excellent electrochemical performances as anodes of SIBs, especially rate capability. Sodiation/desodiation processes and involved mechanisms were investigated by using in situ TEM and in situ XRD. During sodiation, a crystalline Na2Se layer with numerous amorphous fine Co nanoparticles dispersed on it was observed to appear on the surface of the original Co3Se4@rGO particles, and the movable Co-Na2Se composites further migrated to the rGO network with high electron/ion dual conductivity, resulting in ultrafast sodium storage kinetics and remarkable rate performance of the Co3Se4@rGO anode evidenced by delivering a discharge capacity of 229.3 mAh g-1 at a large current density of 50 A g-1. Our findings reveal the fundamental mechanism behind the enhanced performance of the Co3Se4@rGO anode and offer valuable insights into the rational design of electrode materials for high-performance SIBs.This study aimed to analyze the immunohistochemical expression of H3K9ac and H4K12ac in oral leukoplakia (OL) and its association with cell proliferation marker Ki-67 and clinicopathologic data. Paraffin-embedded, formalin-fixed tissue samples from 50 OLs and 15 fragments of the normal oral mucosa (NOM) were submitted to immunohistochemical assay using the streptavidin-biotin-peroxidase method. Quantitative analysis of the antigen-antibody reaction was performed by obtaining integrated optical density (IOD) and the percentage of positive nuclei (PPN) with ImageJ software. OL samples presented higher PPN ( P =0.02) and lower IOD values ( P =0.007) for H4K12ac in comparison to NOM. The area under the receiver operating characteristic curve for PPN and IOD values of H4K12ac immunostaining were 0.70 ( P =0.02) and 0.73 ( P =0.007), respectively. No differences were found between OL and NOM for H3K9ac. Cell proliferation marker Ki-67 had a positive correlation with PPN ( P less then 0.0001) and IOD ( P =0.0007) for H3K9ac expression and with IOD values ( P =0.002) for H4K12ac expression. The present findings suggest that alterations in the acetylation pattern of H4K12 occur in the early stages of oral carcinogenesis and that both H3K9ac and H4K12ac might have a role in the regulation of epithelial cell proliferation of OL.

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