ABSTRACTA new polyurethane with unsaturated pendent chains is described and chemically derivatized. By employing the palladium‐catalyzed 1,3‐butadiene telomerization reaction with solketal followed by a deprotection step of the ketal group using sulfonic acid resins, a diol derived from glycerol was prepared in pure form. The resulting diol was used as a comonomer and polymerized with either toluene diisocyanate (TDI) or hexamethylene diisocyanate (HMDI) under controlled conditions in DMF, yielding polyurethanes (PUs) with molecular weights ranging from 6500 to 34,000 g/mol. The study shows that the PUs' characteristics are significantly influenced by the NCO/OH ratio, catalyst loading, and reaction medium. Thermal analyses indicate that TDI‐based PUs exhibit higher glass transition temperatures compared to HMDI‐based PUs. Furthermore, hydroformylation reactions were performed to convert the double bonds of the PU side chains introduced thanks to the telomerization reaction into pending aldehyde groups. The newly synthesized PUs were characterized using 1H NMR and FT‐IR spectroscopy, confirming the successful formation and functionalization of the polymers.

This study speculates that gestational diabetes mellitus (GDM) may reduce fetal telomere length (TL),which may be related to modification of methylation in the promoter region of the telomerase (TE) gene promoter region. In this study, umbilical cord blood samples from patients with and without GDM (N = 100 each) were analyzed by prospective case-control. The TL, TE expression levels, and methylation levels of TERT and TERC gene promoter regions in two groups were measured. The significance of the methylation level of each CpG locus employed logistic regression analysis of R software, and the analysis of covariance (ANCOVA) was used to control the influence of confounding factors. Correlation analysis was performed by the Spearman. The TL and TE expression levels of the offspring of GDM patients were decreased despite adjusting for PBMI, PWG, and TG. A total of two CpG islands were screened in the promoter region of the TERT gene and three fragments (TERT_2, TERT_3, and TERT_4) containing a total of 70 CpG sites were designed. Additionally, four CpG sites of the TERT gene in the GDM group (TERT_2_40, TERT_2_47, TERT_3_46, and TERT_3_212) showed increased methylation levels compared with the control group (all P < 0.05). In the promoter region of the TERC gene, one CpG island containing 19 CpG loci was screened and designed, and the methylation levels of the two CpG sites were significantly different in TERC_1_67 (0.65 ± 0.21 versus 0.57 ± 0.30; P = 0.040) and TERC_1_120 (0.68 ± 0.23 versus 0.59 ± 0.27; P = 0.014). The methylation levels of TERC gene fragments of GDM patients were significantly higher than those of the control group (0.69 ± 0.06 versus 0.65 ± 0.08, P = 0.001). This study revealed that GDM may induce decreased TE expression by increasing the methylation levels of TE genes promoter region, thereby reducing the TL.

The mechanism by which PdII precursors are reduced to catalytically active low-valent Pd species has been a subject of interest for developing better catalysts. This process is well understood for catalytic systems employing a combination of palladium(ii) acetate [Pd(OAc)2] and tertiary phosphines. However, the mechanism of reduction of palladium(ii) acetylacetonate [Pd(acac)2] in the presence of phosphines has not been thoroughly investigated. This is especially important in the context of the Pd-catalyzed butadiene telomerization process, which uses a combination of Pd(acac)2 and tertiary phosphines in methanol to produce the commercially valuable precursor 1-methoxyoctadiene (MOD-1). In this work, we elucidate the steps for generating the active Pd0 species for this reaction using a combination of Pd(acac)2 and triphenylphosphine (PPh3). The investigations presented in this study provide the following key insights: (a) unification of the steps involved in the generation of the active precatalyst [PdII(acac)(PPh3)2]+; (b) elucidation of the mechanism of reduction of the precatalyst to Pd0 without MOD-1, which parallels the chemistry of the Pd(OAc)2/PPh3 system; and (c) the generation of PdII-octadienyl species from the reaction between the precatalyst and MOD-1, the product of the telomerization reaction. A reversible C-O bond cleavage process was identified that leads to the formation of the PdII π-octadienyl species as the active catalyst in the commercial telomerization process. These studies provide important insights into the reduction of Pd(acac)2 into active Pd0 species or PdII π-allyl species, which have wide implications for both cross-coupling catalysis as well as the telomerization reaction.

Gestational diabetes mellitus (GDM) is a common complication during pregnancy and increases the risk of metabolic diseases in offspring. We hypothesize that the poor intrauterine environment in pregnant women with GDM may lead to chromosomal DNA damage and telomere damage in umbilical cord blood cells, providing evidence of an association between intrauterine programming and increased long-term metabolic disease risk in offspring. We measured telomere length (TL), serum telomerase (TE) activity, and oxidative stress markers in umbilical cord blood mononuclear cells (CBMCs) from pregnant women with GDM (N=200) and healthy controls (Ctrls) (N=200) and analysed the associations of TL with demographic characteristics, biochemical indicators, and blood glucose levels. The length of telomeres in umbilical CBMCs in the GDM group was significantly shorter than that in the Ctrl group (P<0.001), and the shortening of telomeres in male infants in the GDM group was more significant than that in the Ctrl group (P<0.001) after adjustment for Pre-pregnancy body mass index (PBMI), Pregnancy weight gain (PGW), and Triglyceride (TG) as confounding factors. In addition, the TE expression level in the GDM group was lower after adjustment. There was no statistically significant difference in oxidative stress hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA) and superoxide dismutase (SOD) between the two groups. TL was positively correlated with TE activity, and both were negatively correlated with blood glucose levels. There was no correlation between TL and Gestational age (GA), PBMI, PGW, or TG levels. The poor intrauterine environment in pregnant women with GDM increases telomere attrition and reduces TE activity, which may be potential genetic risk factors for an increased risk of metabolic diseases in offspring later in life due to intrauterine reprogramming.

Endogenous enzyme-activated AND-gate DNA nanomachines for intracellular miRNA detection and cell-selective imaging

Diverted Telomerization Reaction with Aryl Boronic Derivatives: Expeditious Synthesis of Aryl-Substituted 1,6- and 1,7-dienes

Endowing current artificial chemical reactions (ACRs) with high specificity and intricate activation capabilities is crucial for expanding their applications in accurate bioimaging within living cells. However, most of the reported ACR-based evaluations relied on either single biomarker stimuli or dual activators without obvious biological relevance, still limiting their accuracy and fidelity. Herein, taking the metal-ion-dependent DNAzyme cleavage reaction as a model ACR, two regulators, glutathione (GSH) and telomerase (TE) activated DNAzyme cleavage reactions, were exploited for precise discrimination of cancerous cells from normal cells. DNA probe was self-assembled into the ZIF-90 nanoparticle framework to construct coordination-driven nanoprobes. This approach enhances the stability and specificity of tumor imaging by utilizing biomarkers associated with rapid tumor proliferation and those commonly overexpressed in tumors. In conclusion, the research not only paves the way for new perspectives in cell biology and pathology studies but also lays a solid foundation for the advancement of biomedical imaging and disease diagnostic technologies.

Cell fate instability is a crucial characteristic of aging and appears to contribute to various age-related pathologies. Exploring the connection between bioactive substances and cell fate stability may offer valuable insights into longevity. Therefore, the objective of this study was to investigate the potential beneficial effects of ginseng oligopeptides (GOPs) isolated from Panax ginseng C. A. Meyer at the cellular level. Disruption of homeostasis of human umbilical vein endothelial cells (HUVECs) and PC-12 was achieved by culturing them in the growth medium supplemented with 200 µM of H2O2, and 25, 50, and 100 µg/mL GOPs for 4 h. Then, they were cultured in a H2O2-free growth medium containing different concentration of GOPs. We found that GOP administration retards the oxidative stress-induced cell instability in HUVECs by increasing cell viability, inhibiting the cell cycle arrest, enhancing telomerase (TE) activity, suppressing oxidative stress and an inflammatory attack, and protecting mitochondrial function. Furthermore, we hypothesized that GOPs may promote mitochondrial biosynthesis by upregulating PGC-1α expression. Similarly, GOPs positively regulated cell stability in PC-12; notably, the protective effect of GOPs on PC-12 mainly occurred through the inhibition of autophagic cell death of neuronal cells, while the protective effect on mitochondria was weak. In conclusion, it is evident that GOPs demonstrate potential beneficial effects in maintaining cell fate stability, thereby potentially contributing to an enhanced health span and overall well-being.

In situ monitoring of the actions of correlated enzymes in living cells is crucial for expanding our understanding of disease progression and evaluating drug efficacy. However, due to the diverse functions of different enzymes, currently available methods for comprehensive analysis of these events are limited. Here, we present an in situ track-generated DNA walker for AND-gate logic imaging of telomerase (TE) and flap endonuclease 1 (FEN1) activities in live cells. TE is in charge of generating the tracks for the walking strands by extending the TE primer on a gold nanoparticle, while FEN1 is responsible for recognizing the overlapping structure formed by the walking strands and the tracks and then cleaving the fluorescent reporter to produce signals. By utilizing the DNA walker, we successfully determined the expression levels and activities of TE and FEN1 in various cancer cell lines, offering promising prospects for screening inhibitors and investigating the biomolecular mechanisms of diseases.

Telomerization of butadiene with ethanol mediated by palladium N-heterocyclic carbene catalysts

A target-triggered fluorescence-SERS dual-signal nano-system for real-time imaging of intracellular telomerase activity

Associations between exposure to ambient air pollution and changes in blood telomeres in young people: A repeated-measure study

The fragrance compound indomuscone is used here as ascaffold toprepare two different sterically hindered phosphines, one aromaticand another alkylic, in good yields, after four synthetic steps. Thenew phosphines show enhanced electronic and steric properties whencompared to benchmark commercial phosphine ligands, which is reflectedin the catalytic results obtained for representative palladium-catalyzedreactions such as the telomerization reaction, the Buchwald–Hartwigand Suzuki cross-coupling reactions of chloroaromatic rings, and thesemi-hydrogenation reaction of an alkyne. In particular, the indomuscone-basedaromatic phosphine ligand leads to the highest selectivity for thetail-to-head telomerization product between isoprene and methanol,while the indomuscone-based alkylic phosphine ligand shows extraordinarysimilarities with the Buchwald-type SPhos phosphine ligand.

The research's main aim is to synthesize saturated alcohols containing four or more carbon atoms in the chain from ethylene and ethanol, which are products of natural gas processing. During of investigation, isobutyl and isohexyl alcohols were synthesized, and the optimal conditions for the process were determined. The dependence of the product yield on various factors has been studied.

Abstract DNA nanomachines have been engineered into diverse personalized devices for diagnostic imaging of biomarkers; however, the regeneration of DNA nanomachines in living cells remains challenging. Here, we report an ingenious DNA nanomachine that can implement telomerase (TE)‐activated regeneration in living cells. Upon apurinic/apyrimidinic endonuclease 1 (APE1)‐responsive initiation of the nanomachine, the walker of the nanomachine moves along tracks regenerated by TE, generating multiply amplified signals through which APE1 can be imaged in situ. Additionally, augmentation of the signal due to the regeneration of the nanomachines could reveal differential expression of TE in different cell lines. To the best of our knowledge, this is the first proof‐of‐concept demonstration of the use of biomarkers to assist in the regeneration of nanomachines in living cells. This study offers a new paradigm for the development of more applicable and efficient DNA nanomachines.

DNA nanomachines have been engineered into diverse personalized devices for diagnostic imaging of biomarkers; however, the regeneration of DNA nanomachines in living cells remains challenging. Here, we report an ingenious DNA nanomachine that can implement telomerase (TE)-activated regeneration in living cells. Upon apurinic/apyrimidinic endonuclease 1 (APE1)-responsive initiation of the nanomachine, the walker of the nanomachine moves along tracks regenerated by TE, generating multiply amplified signals through which APE1 can be imaged in situ. Additionally, augmentation of the signal due to the regeneration of the nanomachines could reveal differential expression of TE in different cell lines. To the best of our knowledge, this is the first proof-of-concept demonstration of the use of biomarkers to assist in the regeneration of nanomachines in living cells. This study offers a new paradigm for the development of more applicable and efficient DNA nanomachines.

The physicochemical properties and multiple bioactive effects of ginseng oligopeptides (GOPs), plant-derived small molecule bioactive peptides, suggest a positive influence on health span and longevity. Given this, cellular senescence is the initiating factor and key mechanism of aging in the organism, and thus the current study sought to explore the effects of GOPs on H2O2-induced cellular senescence and its potential mechanisms. Senescence was induced in mouse embryonic fibroblasts NIH/3T3 by 4 h of exposure to 200 µM H2O2 and confirmed using CCK-8 assay and Western blot analyses of p16INK4A and p21Waf1/Cip1 after 24 h of growth medium administration with or without GOPs supplementation (25, 50, and 100 µg/mL). We found that GOPs delayed oxidative stress-induced NIH/3T3 senescence by inhibiting the G1 phase arrest, increasing DNA synthesis in the S phase, decreasing the relative protein expression of p16INK4A and p21Waf1/Cip1, promoting cell viability, protecting DNA, and enhancing telomerase (TE) activity. Further investigation revealed that the increase in antioxidative capacity and anti-inflammation capacity might form the basis for the retarding of the senescence effects of GOPs. Furthermore, GOPs supplementation significantly improved mitochondrial function and mitochondrial biogenesis via the NAD+/SIRT1/PGC-1𝛼 pathway. These findings indicate that GOPs may have a positive effect on health span and lifespan extension via combating cellular senescence, oxidative stress, and inflammation, as well as modulating longevity regulating pathway NAD+/SIRT1/PGC-1𝛼.

Age-related deterioration in the reproductive capacity of women is directly related to the poor developmental potential of ovarian follicles. Although telomerase plays a key role in female fertility, TERT-targeting therapeutic strategies for age-related female infertility have yet to be investigated. This study elucidated the effect of Telomerase activation on mice ovaries and more specifically on Klb (β-Klotho) gene expression, which is linked to ageing, female hormonal regulation, and cyclicity. The homology-based 3D model of hTERT was used to predict its binding mode of Cycloastragenol (CAG) using molecular docking and molecular dynamics simulations. Based on docking score, simulation behavior, and interaction with hTERT residues it was observed that CAG could bind with the hTERT model. CAG treatment to primary cultured mouse granulosa cells and activation of telomerase was examined via telomerase activity assay (Mouse TE (telomerase) ELISA Kit) and telomere length by quantitative fluorescence in situ hybridization. CAG mediated telomerase also significantly improved β-Klotho protein level in the aged granulosa cells. To demonstrate that β-Klotho is telomerase dependent, the TERT was knocked down via siRNA in granulosa cells and protein level of β-Klotho was examined. Furthermore, CAG-mediated telomerase activation significantly enhanced the level of Klb and recovered ovarian follicles in the D-galactose (D-gal)-induced ovarian ageing mouse model. Moreover, Doxorubicin-induced ovarian damage, which changes ovarian hormones, and inhibit follicular growth was successfully neutralized by CAG activated telomerase and its recovery of β-Klotho level. In conclusion, TERT dependent β-Klotho regulation in ovarian tissues is one of the mechanisms, which can overcome female infertility.

Telomerase-initiated three-dimensional DNAzyme motor for monitoring of telomerase activity in living cells

Telomerase (TE), a ribonucleoprotein reverse transcriptase, is enzymatically activated in most tumor cells and is responsible for promoting tumor progression and malignancy by enabling replicative immortality of cancer cells. TE has become an important hallmark for cancer diagnosis and a potential therapy target. Therefore, accurate in situ detection of TE activity, especially the simultaneous imaging of TE activity and its correlated biomolecules, is essential to medical diagnostics and therapeutics. DNA-based nanoprobes, with their effective cell penetration capability and programmability, are the most advantageous for detection of intracellular TE activity. This concept article introduces the recent strategies for in situ sensing and imaging of TE activity, with a focus on simultaneous detection of TE and related biomolecules, and provides challenges and perspectives for the development of new strategies for such correlated imaging.