Synthesis and Preclinical Evaluation of Novel 68Ga-DOTA-RBB as Potential PET Radiotracer for Imaging CDK4/6 in Tumors.

Many malignant tumors, including breast cancer, exhibit amplification and overexpression of cyclin-dependent kinase 4 and 6 (CDK4/6). Ribociclib, approved and used in clinical treatment, acts as a highly selective CDK4/6 inhibitor for ER+/HER2- breast cancer. By modifying ribociclib with the chelator DOTA, we designed and synthesized a novel CDK4/6-positive PET imaging agent, which was radiolabeled by 68Ga for radioactive tagging. The radiotracer demonstrates high radiochemical purity, excellent stability in vitro and in vivo, and favorable pharmacokinetic characteristics. Cell uptake experiments using MCF-7 cells indicate that an excess of ribociclib (RBB) can inhibit cellular uptake of 68Ga-DOTA-RBB. Imaging and biodistribution experiments in MCF-7 tumor-bearing nude mice show significant radioactive accumulation in the tumor. However, preadministration of excess ribociclib results in a substantial reduction in radioactive accumulation within the tumor. On the basis of our explorations, 68Ga-DOTA-RBB, as a targeted imaging agent for CDK4/6-positive tumors, holds significant potential application values.

Examining the linkage between economic policy uncertainty, coal price, and carbon pricing in China: Evidence from pilot carbon markets.

Economic policies affect companies' production decisions. And the energy consumption volume is an intuitive reflection of the enterprise's production decisions. In China, coal is the main source of carbon emissions and the most important energy source. Therefore, the coal market and the uncertainty of economic policies are both directly tied to the carbon market. This study explores both the direct impact of economic policy uncertainty and coal price on carbon prices as well as the indirect impact of economic policy uncertainty on carbon prices through coal prices by utilizing the DCC-GARCH model and the NARDL model. The findings indicate that the dynamic correlations between coal prices and the CEPU are always negative and that those between the price of carbon and the CEPU vary by area. Meanwhile, the dynamic correlations between coal and carbon prices are only positive in Shenzhen and Beijing. Both coal prices and economic policy uncertainty produce asymmetrical impacts on carbon prices. Some policy implications are provided for developing the carbon markets in light of the results drawn from the study.

The impact of COVID-19 on the stock market crash risk in China.

This study investigates the impact of the COVID-19 pandemic on the stock market crash risk in China. For this purpose, we first estimated the conditional skewness of the return distribution from a GARCH with skewness (GARCH-S) model as the proxy for the equity market crash risk of the Shanghai Stock Exchange. We then constructed a fear index for COVID-19 using data from the Baidu Index. Based on the findings, conditional skewness reacts negatively to daily growth in total confirmed cases, indicating that the pandemic increases stock market crash risk. Moreover, the fear sentiment exacerbates such risk, especially with regard to the impact of COVID-19. In other words, when the fear sentiment is high, the stock market crash risk is more strongly affected by the pandemic. Our evidence is robust for the number of daily deaths and global cases.

tert-Butyl Nitrite as a Twofold Hydrogen Abstractor for Dehydrogenative Coupling of Aldehydes with N-Hydroxyimides.

A synthetically practical transition metal/catalyst/halogen-free dehydrogenative coupling of aldehydes with N-hydroxyimides promoted solely by tert-butyl nitrite under mild conditions was developed. tert-Butyl nitrite generates two radicals (tBuO and NO) and thus works as a twofold hydrogen abstractor. A diverse array of N-hydroxyimide esters were prepared from either aliphatic or aromatic aldehydes. Benzoyl-substituted aldehydes such as 2-oxo-2-phenylacetaldehyde are also suitable.

Is the cross-correlation of EU carbon market price with policy uncertainty really being? A multiscale multifractal perspective.

This paper aims to examine the cross-correlation relationship between EU carbon market price and the economic policy uncertainty. The United Kingdom and the United State of America are chosen as the representative countries. We first conduct the linear analysis to explore the correlation of EU carbon market futures return with the economic policy uncertainty of the two countries. Our findings show that there is no linear correlation between EU carbon market return and economic policy uncertainty. Then, we apply the multifractal detrended cross-correlation analysis to examine the cross-correlation between the return of EU carbon market futures and economic policy uncertainty. The empirical results indicate that the cross-correlations really exist, and the cross-correlation behavior structure over different carbon trading phases are not the same. Moreover, the empirical results show that the anti-persistence between the EU carbon futures return and economic policy uncertainty changes from the UK and the USA are both relatively strong. The findings provide deeper insights and management implications for the carbon market from a new perspective.

Penfluridol triggers mitochondrial-mediated apoptosis and suppresses glycolysis in colorectal cancer cells through down-regulating hexokinase-2.

Penfluridol, a commonly used antipsychotic agent in a clinical setting, exhibits potential anticancer properties against various human malignancies. Here, we investigated the effect of penfluridol on the biological behavior of colorectal cancer (CRC) cells. Cell viability and clonogenic potential were detected by the cell counting kit-8 and colony formation assay. The cell apoptosis and cell cycle distribution were quantified through flow cytometry. Caspase-3 activity, glucose consumption, lactate production, and intracellular ATP levels were evaluated using the corresponding commercial detection kits. The protein levels of related genes were detected through western blotting. Mitochondrial membrane potential was detected using JC-1 staining. A CRC xenograft tumor model was used to validate the antitumor activity of penfluridol in vivo. Penfluridol reduced cell survival and promoted apoptotic cell death effectively through the mitochondria-mediated intrinsic pathway in a dose-dependent manner. Furthermore, the process of glycolysis in HCT-116 and HT-29 cells was inhibited upon penfluridol treatment, as evidenced by the decrease in glucose consumption, lactate production, and intracellular ATP levels. Further mechanistic studies revealed that penfluridol influenced cell apoptosis and glycolysis in CRC cells by downregulating hexokinase-2 (HK-2). The proapoptotic effect and glycolytic inhibition-induced by penfluridol were effectively reversed by HK-2 overexpression. Consistent with in vitro results, penfluridol could also suppress tumor growth and trigger apoptosis in vivo. Penfluridol triggers mitochondrial-mediated apoptosis and induces glycolysis inhibition via modulating HK-2 in CRC and provides a theoretical basis to support penfluridol as a repurposed drug for CRC patients.

Preventing crash in stock market: The role of economic policy uncertainty during COVID-19.

This paper investigates the impact of economic policy uncertainty (EPU) on the crash risk of US stock market during the COVID-19 pandemic. To this end, we use the GARCH-S (GARCH with skewness) model to estimate daily skewness as a proxy for the stock market crash risk. The empirical results show the significantly negative correlation between EPU and stock market crash risk, indicating the aggravation of EPU increase the crash risk. Moreover, the negative correlation gets stronger after the global COVID-19 outbreak, which shows the crash risk of the US stock market will be more affected by EPU during the epidemic.

Cleavage of C(aryl)-CH3 Bonds in the Absence of Directing Groups under Transition Metal Free Conditions.

Organic chemists now can construct carbon-carbon σ-bonds selectively and sequentially, whereas methods for the selective cleavage of carbon-carbon σ-bonds, especially for unreactive hydrocarbons, remain limited. Activation by ring strain, directing groups, or in the presence of a carbonyl or a cyano group is usually required. In this work, by using a sequential strategy site-selective cleavage and borylation of C(aryl)-CH3 bonds has been developed under directing group free and transition metal free conditions. Methyl groups of various arenes are selectively cleaved and replaced by boryl groups. Mechanistic analysis suggests that it proceeds by a sequential intermolecular oxidation and coupling of a transient aryl radical, generated by radical decarboxylation, involving a pyridine-stabilized persistent boryl radical.

Organocatalyzed Aerobic Oxidation of Aldehydes to Acids.

The first example organocatalyzed aerobic oxidation of aldehydes to carboxylic acids in both organic solvent and water under mild conditions is developed. As low as 5 mol % N-hydroxyphthalimide was used as the organocatalyst, and molecular O2 was used as the sole oxidant. No transition metals or hazardous oxidants or cocatalysts were involved. A wide range of carboxylic acids bearing diverse functional groups were obtained from aldehydes, even from alcohols, in high yields.

Study of genetic diversity of killer cell immunoglobulin-like receptor loci in the Tujia ethnic minority.

The aim of this study was to analyze the genetic profiles of 14 killer cell immunoglobulin-like receptor (KIR) genes and 2 pseudogenes of 124 individuals from Tujia ethnic minority residing in Enshi Tujia and Miao autonomous prefecture of Hubei province of China and investigate the genetic relationships between the Tujia ethnic minority and other reported groups for the first time. Sequence specific primer amplification (PCR-SSP) methods were used to genotype the 14 KIR genes and 2 pseudogenes. The observed carrier frequencies (OF) and the gene frequencies (GF) of the KIR genes were measured. Neighbor-joining (N-J) tree and the principal component analysis (PCA) plot were constructed. All individuals were typed positive for the three framework loci KIR3DL3, 2DL4 and 3DL2, as well as for pseudogene KIR3DP1. The gene frequencies of the other KIR genes ranged from 9% in KIR2DS2 to 98% in KIR2DP1 and KIR3DL1. The present study of the KIR genes may be a powerful tool for enriching the Chinese ethnical gene information resources of the KIR gene pool, as well as for the anthropological research.