A bibliometric analysis of insomnia in adolescent.

Background: The negative effects of insomnia on adolescents' development, academic performance, and quality of life place a burden on families, schools, and society. As one of the most important research directions for insomnia, adolescent insomnia has significant research value, social value, and practical significance. Unfortunately, there is no bibliometric analysis in this field of study. This study aims to analyze published articles using bibliometrics, summarize the current research progress and hot topics in this field systematically and exhaustively, and predict the future direction and trend of research. Methods: For this study, the Web of Science Core Collection (WoSCC) database was searched between 2002 and 2022 for publications related to adolescent insomnia. The R-bibliometrix, VOSViewer, and CiteSpace software were utilized for bibliometric analysis. Results: This investigation included 2468 publications from 3102 institutions in 87 countries, led by China and the United States. This field of research has entered a period of rapid development since 2017. The journal with the most publications on adolescent insomnia is Sleep, which is also the most co-cited journal. American Journal of Psychology has the highest impact factor among the top 10 journals. These papers were written by 10605 authors; notably, Liu Xianchen emerged as the author with the highest frequency of publications, while Mary A. Carskadon was the most frequently co-cited author. Mental health and comorbid diseases were the main research directions in this field. "Depression," "anxiety," "mental health," "COVID-19," "stress," "quality of life," "heart rate variability," and "attention-deficit hyperactivity disorder" were hot spots and trends in this field at the current moment. Conclusion: The research on adolescent insomnia has social value, research value, and research potential; its development is accelerating, and an increasing number of researchers are focusing on it. This study summarized and analyzed the development process, hot spots, and trends of adolescent insomnia research using bibliometric analysis, which identified the current hot topics in this field and predicted the development trend for the future.

Discovery of Selective and Potent Macrocyclic CDK9 Inhibitors for the Treatment of Osimertinib-Resistant Non-Small-Cell Lung Cancer.

Effectiveness of epidermal growth factor receptor (EGFR) inhibitors, including Osimertinib, for treating non-small-cell lung cancer (NSCLC) is limited due to the continuous emergence of drug resistance. Hence, it is urgent to develop new therapeutic approaches. CDK9, a key regulator of RNA transcription, has emerged as a promising target for the development of antitumor drugs due to its crucial role in modulating the levels of antiapoptotic protein Mcl-1. Herein, we present the synthesis, optimization, and evaluation of selective CDK9 inhibitors with a macrocyclic scaffold that effectively suppresses the growth of NSCLC cells. Notably, compound Z11, a potent CDK9 inhibitor (IC50 = 3.20 nM) with good kinase selectivity, significantly inhibits cell proliferation and colony formation and induces apoptosis in Osimertinib-resistant H1975 cells. Furthermore, Z11 demonstrates a significant suppression of tumor growth in six patient-derived organoids, including three organoids resistant to Osimertinib. Overall, Z11 served as a promising macrocycle-based CDK9 inhibitor for treating Osimertinib-resistant NSCLC.

Discovery of novel flavonoid-based CDK9 degraders for prostate cancer treatment via a PROTAC strategy.

CDK9 plays a vital role in regulating RNA transcription and significantly impacts the expression of short-lived proteins such as Mcl-1 and c-Myc. Thus, targeting CDK9 holds great promise for the development of antitumor drugs. Natural flavonoid derivatives have recently gained considerable attention in the field of antitumor drug research due to their broad bioactivity and low toxicity. In this study, the PROTAC strategy was used to perform structural modifications of the flavonoid derivative LWT-111 to design a series of flavonoid-based CDK9 degraders. Notably, compound CP-07 emerged as a potent CDK9 degrader, effectively suppressing the proliferation and colony formation of 22RV1 cells by downregulating Mcl-1 and c-Myc. Moreover, CP-07 exhibited significant tumor growth inhibition with a TGI of 75.1% when administered at a dose of 20 mg/kg in the 22RV1 xenograft tumor model. These findings demonstrated the potential of CP-07 as a powerful flavonoid-based CDK9 degrader for prostate cancer therapy.

Small-molecule degraders of cyclin-dependent kinase protein: a review.

Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics involving the induction of protein degradation. Cyclin-dependent kinase (CDK) protein, which is involved in cycles and transcription cycles, participates in regulation of the cell cycle, transcription and splicing. Proteolysis-targeting chimeras targeting CDKs show several advantages over traditional CDK small-molecule inhibitors in potency, selectivity and drug resistance. In addition, the discovery of molecule glues promotes the development of CDK degraders. Herein, the authors describe the existing CDK degraders and focus on the discussion of the structural characteristics and design of these degraders.

Mechanisms underlying mercury detoxification in soil-plant systems after selenium application: a review.

Feasible countermeasures to mitigate mercury (Hg) accumulation and its deleterious effects on crops are urgently needed worldwide. Selenium (Se) fertilizer application is a cost-effective strategy to reduce Hg concentrations, promote agro-environmental sustainability and food safety, and decrease the public health risk posed by Hg-contaminated soils and its accumulation in food crops. This holistic review focuses on the processes and detoxification mechanisms of Hg in whole soil-plant systems after Se application. The reduction of Hg bioavailability in soil, the formation of inert HgSe or/and HgSe-containing proteinaceous complexes in the rhizosphere and/or roots, and the reduction of plant root uptake and translocation of Hg in plant after Se application are systemically discussed. In addition, the positive responses in plant physiological and biochemical processes to Se application under Hg stress are presented to show the possible mechanisms for protecting the plant. However, application of high levels Se showed synergistic toxic effect with Hg and inhibited plant growth. The effectiveness of Se application methods, rates, and species on Hg detoxification is compared. This review provides a good approach for plant production in Hg-contaminated areas to meet food security demands and reduce the public health risk.

Effects of selenium combined with zinc amendment on zinc fractions and bioavailability in calcareous soil.

Selenium (Se) and zinc (Zn) are two important trace elements for human being and animals. The interaction between Se and Zn on the bioavailability of Zn in soil is still unclear. Therefore, pot experiments exposed to different dosages of zinc sulfate (ZnSO4) (0, 20, and 50 mg/kg soil) and sodium selenite (Na2SeO3) (0, 0.5, 1.0, and 2.5 mg/kg soil) were conducted to investigate the effects of selenite application on Zn bioavailability in calcareous soil and its related mechanisms. The total Zn content of different tissues (roots and shoots) of pak choi (Brassica chinensis L.) and the changes in Zn fraction distribution in soil before planting and after harvest were determined, and the mobility factor (MF) and distribution index (DI) of Zn in soils were calculated. In addition, the Pearson correlation and path analysis were conducted to clarify the relationships between Zn fractions in soil and the Zn uptake of pak choi. Results showed that Se amendment elevated soil Zn bioavailability at appropriate levels of Se and Zn. When 1.0 and 2.5 mg/kg of Se and 20 mg/kg of Zn were applied in soil, the proportion of exchangeable Zn (Ex-Zn) and Zn weakly bound to organic matter (Wbo-Zn) to the total content of Zn was significantly increased by 28.14%-82.52% compared with that of the corresponding single Zn treatment. Therefore, the Zn concentration in the shoots of pak choi was significantly increased by 27.2%-31.1%. High Zn (50 mg/kg) and Se co-amended treatments showed no significantly beneficial effect on the bioavailability of Zn. In addition, the potential available Zn content in soil (weakly bound to organic matter and carbonate bound Zn) and MF and DI values were all positively correlated with the Zn concentrations in pak choi, indicating that these indexes can be used to predict the bioavailability of Zn in soil. This study can provide a good reference for Se and Zn biofortification of plants in calcareous soil.

Effect of phosphate and silicate on selenite uptake and phloem-mediated transport in tomato (Solanum lycopersicum L.).

The ambiguous mechanism that selenite seems to be absorbed by roots via phosphorus (P) and silicon (Si) transporters signifies P and Si may affect selenite uptake. However, the role of P and Si in phloem-mediated selenium (Se) transport within plant tissue is unknown. Therefore, in this work, tomato (Solanum lycopersicum L.) seedlings were exposed to selenite under different hydroponic conditions firstly. And then, split-root experiments were conducted. Results showed that Se uptake decreased as external pH increased. At pH 8, more selenite in the form of SeO32- was assimilated under P-deficient conditions than under P-normal conditions. Silicate inhibited Se uptake only at pH 3 (27.5% H2SeO3 +72.5% HSeO3-). The results of split-root experiments showed that Se concentrations in seedlings increased under heterogeneously high P or Si. Selenium transport from shoots to roots immersed in solution without selenite was also enhanced. This study illustrated that the affinity of tomato roots to assimilate selenite species followed the order of H2SeO3 >HSeO3- >SeO32-. H2SeO3 was absorbed into roots via Si transporters, whereas HSeO3- and a portion of SeO32- were absorbed via low- and high-affinity P transporters, respectively. In addition, heterogeneously high P or Si concentrations in environmental media could enhance phloem-mediated Se redistribution.

Leaching behaviors and chemical fraction distribution of exogenous selenium in three agricultural soils through simulated rainfall.

To clarify the leaching risk of selenium (Se) in agricultural soils, a laboratory column experiment was conducted to study the characteristics of leaching and chemical fractions of Se in three different soils treated with different levels of exogenous selenate under simulated local rainfall. Results demonstrated that the Se concentration in leachates of all tested soils decreased rapidly at the beginning of leaching and slowly decreased thereafter. After leaching, Se concentrations in leachates of all tested soils at 1, 3, and 6 mg/kg exogenous Se concentrations were 0.06-0.24, 0.25-0.84, and 0.60-1.65 mg/L, respectively, which exceeded the standard limit of the Chinese Environmental Quality Standards for Groundwater (<0.01 mg/L) (GB/T 14848-2017). The cumulative leached Se amount accounted for 51.27-86.22% of the total Se. Those results indicated the high risk of Se leaching in the tested soils. The Elovich model could better describe Se leaching processes in krasnozem, while the leaching processes of Se in black soil and loess soil accorded with the power function model. Se mainly existed in soluble fraction (61.33-81.05%) before leaching and residual fraction (48.91-68.04%) after leaching. The soluble and exchangeable Se fractions were the main contributors of Se in leachates. In addition, the parameters of the Uts and IR values could well describe the distribution of Se fractions in soil during leaching. In general, more attention should be placed on the assessment of Se leaching in soil.