Herein,we report tunable asymmetric addition and telomerization of butadiene by synergistic chiral primary amine/achiral palladium catalysis.A selection of different achiral phosphine ligand in concert with the chiral...Herein,we report tunable asymmetric addition and telomerization of butadiene by synergistic chiral primary amine/achiral palladium catalysis.A selection of different achiral phosphine ligand in concert with the chiral primary amine-trifluoromethanesulfonic acid(TfOH)conjugates enables both chemo-and enantioselective control of the coupling with butadiene.Bidentate[(oxydi-2,1-phenylene)-bis-(diphenylphosphine)](DPEPhos)ligand led to 1,4-addition adduct whereas monodentate(p-Tol)3P ligand gave the telomerization product.A range ofα-branchedβ-ketoesters and aldehydes could be applied to afford allylation or telomerization products bearing allcarbon quaternary centers at high efficiency and good chemo-,regio-,and stereoselectivities.展开更多
This article is based on a recent bibliometric analysis of research progress on liver aging.The liver is notable for its extraordinary ability to rejuvenate,thereby safeguarding and maintaining the organism’s integri...This article is based on a recent bibliometric analysis of research progress on liver aging.The liver is notable for its extraordinary ability to rejuvenate,thereby safeguarding and maintaining the organism’s integrity.With advancing age,there is a noteworthy reduction in both the liver’s size and blood circulation.Furthermore,the wide range of physiological alterations driven on by aging may foster the development of illnesses.Previous studies indicate that liver aging is linked to impaired lipid metabolism and abnormal gene expression associated with chronic inflammation.Factors such as mitochondrial dysfunction and telomere shortening accumulate,which may result in increased hepatic steatosis,which impacts liver regeneration,metabolism,and other functions.Knowing the structural and functional changes could help elderly adults delay liver aging.Increasing public awareness of anti-aging interventions is essential.Besides the use of dietary supplements,alterations in lifestyle,including changes in dietary habits and physical exercise routines,are the most efficacious means to decelerate the aging process of the liver.This article highlights recent advances in the mechanism research of liver aging and summarizes the promising intervention options to delay liver aging for preventing related diseases.展开更多
By introducing hydroxyl group into PPh3 ligand,a promoter-free palladium catalytic system based on(p-HOC6H4)PPh2 ligand was developed for the telomerization of 1,3-butadiene with CO_(2).High activity and selectivity t...By introducing hydroxyl group into PPh3 ligand,a promoter-free palladium catalytic system based on(p-HOC6H4)PPh2 ligand was developed for the telomerization of 1,3-butadiene with CO_(2).High activity and selectivity towards CO_(2)-incorporated divinylδ-lactone monomer were achieved(TON/TOF:up to 4540/568 h–1;selectivity ofδ-lactone and its isomers:up to 97%).The key role of phenolic hydroxyl group of the ligand in attaining high activity was validated.The good performance of large-scale reaction in batch reactor demonstrated the potential utility of this simple catalytic system in valorizing CO_(2) with bulk chemical feedstock.展开更多
Amborella trichopoda(Amborellaceae;hereafter simply Amborella)(Fig.1A)is a shrub endemic to New Caledonia in the Southwest Pacific that represents the sole sister species of all other extant angiosperms(Qiu et al.,199...Amborella trichopoda(Amborellaceae;hereafter simply Amborella)(Fig.1A)is a shrub endemic to New Caledonia in the Southwest Pacific that represents the sole sister species of all other extant angiosperms(Qiu et al.,1999;One Thousand Plant Transcriptomes Initiative,2019).Due to its unique phylogenetic status,it holds tremendous interest for botanists.The nuclear and mitochondrial genomes of Amborella were first published in 2013,providing valuable resources for studies on genome and gene family evolution,phylogenomics,and flower development,despite the fact that the assembly is heavily fragmented(Amborella Genome Project,2013;Rice et al.,2013).In 2024,a haplotype-resolved Amborella genome assembly was published,showing significant improvement in quality and completeness(Carey et al.,2024).展开更多
Telomeres have been a subject of genetic research since the 1930s. They play a crucial role in cancer biology, as they influence both cellular senescence and genomic stability. In cancer cells, dysfunctional telomeres...Telomeres have been a subject of genetic research since the 1930s. They play a crucial role in cancer biology, as they influence both cellular senescence and genomic stability. In cancer cells, dysfunctional telomeres can lead to chromosomal fusions and, through deregulation of telomerase, allow replication of mutated chromosomes that might otherwise lead to apoptosis. Research is now focused on improving telomere-based cancer cell detection and developing potential therapies that inhibit telomerase activity in cancerous cells. Telomere research is crucial in understanding the molecular mechanisms influencing tumor growth and invasiveness because of the central role played by telomeres in various cancer types. Several telomerase inhibitors and immunotherapy treatments are in pre-clinical or clinical development. Research on the role of telomeres in oncogenesis has made significant strides, but obstacles remain, including a lack of high-resolution structural understanding, inadequate preclinical models, and concern over potential side effects. Even so, the current path of telomere research holds promise.展开更多
Background:Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes.The effect on markers of health and disease,such as offspring telomere length...Background:Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes.The effect on markers of health and disease,such as offspring telomere length(TL)and mitochondrial DNA content(mtDNAc)is unknown.Objectives:We assessed the efficacy of maternal multiple micronutrient(MMN)-fortified balanced-energy protein(BEP)and iron-folic acid(IFA)supplementation on newborn TL as a secondary outcome and mtDNAc as a non-declared outcome.Design:We conducted a randomized controlled trial in rural Burkina Faso,among pregnant females(15-40 years old)enrolled at<21 weeks of gestation.Mothers received either MMN-fortified BEP and IFA(intervention)or IFA only(control)throughout pregnancy.Whole arterial blood samples were collected from the umbilical cord of 104 control and 90 intervention group infants,respectively.Average relative TL and mtDNAc were measured using quantitative polymerase chain reaction.Linear regression models were fitted to assess TL and mtDNAc differences across trial arms.Results:We found that a combined daily MMN-fortified BEP supplement and IFA tablet did not affect newborn TL[β=-0.010(95%CI:-0.057,0.036);P=0.662]or mtDNAc[β=0.065(95%CI:-0.203,0.073);P=0.354],as compared to an IFA tablet alone.These findings were confirmed(P>0.05)by adjusting the regression models for potential prognostic factors of study outcomes at enrollment.Exploratory analyses indicated higher,but non-significantly different mtDNAc among children born either small-for-gestational age,low birthweight,or preterm.Conclusion:Newborns from mothers who received daily nutritional supplements across gestation did not have different relative TL or mtDNAc.展开更多
Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,a...Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,and effective treatments are still lacking.Renal tubular epithelial cells(RTECs)maintain kidney function,and their dysfunction has emerged as a critical contributor to renal fibrosis.Cellular quality control comprises several components,including telomere homeostasis,ubiquitin-proteasome system(UPS),autophagy,mitochondrial homeostasis(mitophagy and mitochondrial metabolism),endoplasmic reticulum(ER,unfolded protein response),and lysosomes.Failures in the cellular quality control of RTECs,including DNA,protein,and organelle damage,exert profibrotic functions by leading to senescence,defective autophagy,ER stress,mitochondrial and lysosomal dysfunction,apoptosis,fibroblast activation,and immune cell recruitment.In this review,we summarize recent advances in understanding the role of quality control components and intercellular crosstalk networks in RTECs,within the context of renal fibrosis.展开更多
The integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation was analyzed by Multiplex Ligation-Dependent Probe Amplification (MLPA)....The integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation was analyzed by Multiplex Ligation-Dependent Probe Amplification (MLPA). The TK6 cell line has the native p53 tumor-suppressor gene, whereas WTK1 cells contain a p53 mutation. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. The impact of irradiation on these two cell lines was investigated using probes that target specific regions on chromosomes associated with subtelomeric regions. Results indicate that WTK1 and TK6 are impacted differently after irradiation, and that each cell line presents its own unique MLPA profile. The most notable differences are the appearance of a number of probes in the post-irradiated MLPA profile that are not present in the controls, and two unique probe signals only seen in WTK1 cells. These results build on our previous studies that indicate how different human cell lines can be affected by radiation in significantly different ways depending on the presence or absence of wild type p53.展开更多
Purpose: Telomere length (TL) is an indicator of age;however, hormonal influences complicate individual aging. It remains unclear whether TL shortening is a direct factor in both individual and cellular aging. Therefo...Purpose: Telomere length (TL) is an indicator of age;however, hormonal influences complicate individual aging. It remains unclear whether TL shortening is a direct factor in both individual and cellular aging. Therefore, we examined the direct relationship between TL and cellular senescence at the cellular level. Methods: Telomerase activity, TL, and gene expression were measured in cultured human lung-, fetal-, and skin-derived fibroblasts, human skin keratinocytes, and telomerase reverse transcriptase (TERT) gene-immortalized cells using detection kits, Cawthon’s method, and reverse transcription-quantitative polymerase chain reaction, respectively. Novel substances that elongate telomeres were screened to confirm cell rejuvenation effects. Results: Long-term cell culture of TIG-1-20 normal human fibroblasts resulted in TL shortening, decreased division rate, and senescence progression, whereas in OUMS-36T-2 cells, TL elongation via TERT gene transfer increased the division rate, reduced endoplasmic reticulum stress, and upregulated genes associated with young individuals, indicating that cellular rejuvenation occurs via TL elongation. In addition, a honey child powder (HCP) extract was found through screening, and the HCP extract strongly suppressed the menin gene, resulting in increased telomerase activity and extended cell lifespan. Upon addition of the HCP extract to skin fibroblasts, gene expression of moisturizing components, including collagen, hyaluronic acid, and elastin, increased, and exhibited a rejuvenating effect with an increase in elastin amount. Conclusions: TL elongation or shortening is involved in cell proliferation rate and cellular aging, and TL elongation rejuvenates cells. In addition, HCP extract has a rejuvenating effect on cells and is expected to be a rejuvenating compound.展开更多
The importance of telomeres as special structures at the ends of chromosomes is gradually gaining prominence. They are composed of short, multi-repeated non-transcribed sequences (TTAGGG) and binding proteins, and the...The importance of telomeres as special structures at the ends of chromosomes is gradually gaining prominence. They are composed of short, multi-repeated non-transcribed sequences (TTAGGG) and binding proteins, and their main role is to protect chromosome ends from degradation. Recent studies have shown that the length of telomeres may affect the outcome of COVID-19 infection, and the severity of COVID-19 is associated with shortened or dysfunctional telomeres, which may be an important factor contributing to the deterioration of the patient’s condition. In conjunction with this, COVID-19 patients with longer telomeres tended to have better outcomes compared to those with shorter telomeres. This suggests that telomere length can be used as a potential marker to predict the progress of COVID-19 patients’ recovery, highlighting the potential role of telomeres in the immune system. The involvement of telomeres in the recovery and virological processes of COVID-19 patients demonstrates that telomeres contribute to the maintenance of chromosome stability and promote the normal restoration of cellular functions during the recovery process, thereby improving patient outcomes. This review examines the complex relationship between telomere length and COVID-19 disease. Telomere abnormalities may exacerbate lung injury and fibrosis in COVID-19 patients, while COVID-19 infection accelerates telomere shortening, leading to premature cellular senescence. The aim of this review is to gain a deeper understanding of how telomere length affects disease severity and how COVID-19 in turn affects telomere structure and function. In addition, the impact of COVID-19 on the aging process is explored to provide scientific rationale and insights for the development of targeted therapeutic interventions in the future.展开更多
Objective: To study the telomerase activity in human renal cell carcinoma and to evaluate the correlation with the clinicobiologic features of the neogrowth.Methods: The telomerase activity was studied by means of a m...Objective: To study the telomerase activity in human renal cell carcinoma and to evaluate the correlation with the clinicobiologic features of the neogrowth.Methods: The telomerase activity was studied by means of a modified telomeric repeat amplification protocol (TRAP) in 32 renal cell carcinoma tissues, 32 normal renal tissues and 32 paracancer tissues and its correlation with the clinicopathologic features of the tumor was evaluated.Results: Telomerase activity was strongly positive in 17, positive in 12 and negative in 3 cases of renal cell carcinoma tissues, the total positive rate being 91%. Telomerase activity was weakly positive (6%) in only 2 out of 32 samples of normal renal cortex tissues and positive in 6 paracancer tissues (19%), the difference was conspicuous (P<0.01).Conclusion: The positive rate of telomerase activity was significantly higher in renal cell carcinoma tissues and might serve as a prognostic marker for estimating the biologic characteristics of renal cell carcinoma.展开更多
A study has been conducted on the synthesis and characterization of a kind of novel polyrotaxanes comprisingα- cyclodextrins (α-CDs) threaded on triblock eopolymers with poly(ethylene glycol) (PEG) as a central axle...A study has been conducted on the synthesis and characterization of a kind of novel polyrotaxanes comprisingα- cyclodextrins (α-CDs) threaded on triblock eopolymers with poly(ethylene glycol) (PEG) as a central axle and flanked by two low molecular weight polystyrenes as outer stoppers.Styrene was allowed to telomerize with polypseudorotaxanes as chain transfer agents made from the self-assembly of a distal thiol-capped PEG with a varying amount ofα-CDs in the presence of a redox initiation system at 40~C i...展开更多
Aryloxy--terminated polydimethylsiloxanes (AOS) were synthesized by the telomerization of hexamethylcyclotrisiloxane(D3) with phenols. The structures of AOS were characterized by UV, IR, 2HNMR and elemental analysis, ...Aryloxy--terminated polydimethylsiloxanes (AOS) were synthesized by the telomerization of hexamethylcyclotrisiloxane(D3) with phenols. The structures of AOS were characterized by UV, IR, 2HNMR and elemental analysis, The effects of the reaction conditions and the mole ratios of the reactants on foe molecular weight of the polymer were discussed. A OS's structural influence on bactericidal action, flocculation and hydrolysis was studied.展开更多
INTRODUCTION Human tissue homeostasis is precisely regulated bycellular division,differentiation and death.Normalhuman somatic cells progressively lose telomererestriction fragment(TRF)length with eachsuccessive cell ...INTRODUCTION Human tissue homeostasis is precisely regulated bycellular division,differentiation and death.Normalhuman somatic cells progressively lose telomererestriction fragment(TRF)length with eachsuccessive cell division,eventually leading tocellular quiescence,chromosomal end-degradationand apoptosis.On the contrary,stabilization oftelomere lengths by expressing telomerase,an RNA-dependent DNA polymerase,may be involved incellular immortality and carcinogenesis.展开更多
INTRODUCTIONLiver fibrosis or cirrhosis is a common progressively pathological lesion of chronic liver diseases in response to various liver-damaging factors. The main mechanisms of fibrotic or cirrhotic initiation an...INTRODUCTIONLiver fibrosis or cirrhosis is a common progressively pathological lesion of chronic liver diseases in response to various liver-damaging factors. The main mechanisms of fibrotic or cirrhotic initiation and progression at the level of cellular and molecular events have been elucidated in the past two decades[1,2].展开更多
The pathogenesis of liver cirrhosis is not completely elucidated.Although in the majority of patients,the risk factors may be identified in B and C viral hepatitis,alcohol intake,drugs or fatty liver disease,there is ...The pathogenesis of liver cirrhosis is not completely elucidated.Although in the majority of patients,the risk factors may be identified in B and C viral hepatitis,alcohol intake,drugs or fatty liver disease,there is a small percentage of patients with no apparent risk factors.In addition,the evolution of chronic liver disease is highly heterogeneous from one patient to another.Among patient with identical risk factors,some rapidly progress to cirrhosis and hepatocellular carcinoma(HCC)whereas others have a benign course.Therefore,a genetic predisposition may contribute to the development of cirrhosis and HCC.Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years.In addition to the results from epidemiological studies,polymorphisms studies and data on twins,the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed.Here we review the literature on telomerase mutations,telomere shortening and liver disease including hepatocellular carcinoma.展开更多
AIM: To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas. METHODS: Telomeric restriction fragment (TRF) length o...AIM: To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas. METHODS: Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-betaRII and BAX genes were analyzed by PCR-based methods. RESULTS: Sixty-eight cases of sporadic gastric carcinoma were studied for MSI using five microsatellite markers. MSI in at least one locus was detected in 17 (25%) of 68 tumors analyzed. Frameshift mutations of hMSH6, TGF-betaRII and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (】 or = 2 loci, n = 8), but none was found in those showing low MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and low MSI, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters. No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P【0.01). This tendency was also observed in APC and MCC genes, although there was no statistical significance. CONCLUSION: The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either low MSI or MSS, multiple deletions may represent the LOH pathway. Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer.展开更多
The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutat...The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an “inflammatory cancer”, arising from a context of inflammation, and characterized by inflammation-related mechanisms that favor tumor cell survival, proliferation, and invasion. Molecular mechanisms that link inflammation and neoplasia have been widely investigated, and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species. The latter, in turn, probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation, and ultimately leading to cancer. The relationship amongst chronic liver injury, free radical production, and development of HCC is explored in the present review, particularly in the light of the complex network that involves oxidative DNA damage, cytokine synthesis, telomere dysfunction, and microRNA regulation.展开更多
The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. F...The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS 1 complex （MRN） that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome （NBS）, a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance oftelomere stability.展开更多
Nasopharyngeal carcinoma （NPC） is a common cancer in Southern China and Southeast Asia. The disease is a poorly differentiated carcinoma without effective cure, and the mechanism underlying its development remains l...Nasopharyngeal carcinoma （NPC） is a common cancer in Southern China and Southeast Asia. The disease is a poorly differentiated carcinoma without effective cure, and the mechanism underlying its development remains largely unknown. Of several factors identified in NPC aetiology in recent years, Epstein-Barr virus （EBV） infection has emerged to be most important. In almost all NPC cells, EBV uses several intracellular mechanisms to cause oncogenic evolution of the infected cells. One such mechanism by which EBV infection induces cellular immortalization is believed to be through the activation of telomerase, an enzyme that is normally repressed but becomes activated during cancer development. Studies show that greater than 85% of primary NPC display high telomerase activity by mechanisms involving EBV infection, consistent with the notion that EBV is commonly involved in inducing cell immortalization. More recently, different EBV proteins have been shown to activate or inhibit the human telomerase reverse transcriptase gene, by modulating intracellular signalling pathways. These findings suggest a new model with a number of challenges towards our understanding, molecular targeting and therapeutic intervention in NPC.展开更多
基金the Natural Science Foundation of China(nos.21672217,21861132003,and 22031006)Tsinghua University Initiative Scientific Research Program for financial support.
文摘Herein,we report tunable asymmetric addition and telomerization of butadiene by synergistic chiral primary amine/achiral palladium catalysis.A selection of different achiral phosphine ligand in concert with the chiral primary amine-trifluoromethanesulfonic acid(TfOH)conjugates enables both chemo-and enantioselective control of the coupling with butadiene.Bidentate[(oxydi-2,1-phenylene)-bis-(diphenylphosphine)](DPEPhos)ligand led to 1,4-addition adduct whereas monodentate(p-Tol)3P ligand gave the telomerization product.A range ofα-branchedβ-ketoesters and aldehydes could be applied to afford allylation or telomerization products bearing allcarbon quaternary centers at high efficiency and good chemo-,regio-,and stereoselectivities.
基金Supported by the National Natural Science Foundation of China,No.82104525Open Foundation of Key Laboratory of Tropical Plant Resource Chemistry of Hainan Province,No.rdzw2024s01.
文摘This article is based on a recent bibliometric analysis of research progress on liver aging.The liver is notable for its extraordinary ability to rejuvenate,thereby safeguarding and maintaining the organism’s integrity.With advancing age,there is a noteworthy reduction in both the liver’s size and blood circulation.Furthermore,the wide range of physiological alterations driven on by aging may foster the development of illnesses.Previous studies indicate that liver aging is linked to impaired lipid metabolism and abnormal gene expression associated with chronic inflammation.Factors such as mitochondrial dysfunction and telomere shortening accumulate,which may result in increased hepatic steatosis,which impacts liver regeneration,metabolism,and other functions.Knowing the structural and functional changes could help elderly adults delay liver aging.Increasing public awareness of anti-aging interventions is essential.Besides the use of dietary supplements,alterations in lifestyle,including changes in dietary habits and physical exercise routines,are the most efficacious means to decelerate the aging process of the liver.This article highlights recent advances in the mechanism research of liver aging and summarizes the promising intervention options to delay liver aging for preventing related diseases.
基金supported by the National Key R&D Program of China(No.2020YFA0710201)the Science and Technology Commission of Shanghai Municipality(20ZR1471400)+1 种基金the Shanghai Rising Star Program(21QA1402800)the Fundamental Research Funds for the Central Universities.
文摘By introducing hydroxyl group into PPh3 ligand,a promoter-free palladium catalytic system based on(p-HOC6H4)PPh2 ligand was developed for the telomerization of 1,3-butadiene with CO_(2).High activity and selectivity towards CO_(2)-incorporated divinylδ-lactone monomer were achieved(TON/TOF:up to 4540/568 h–1;selectivity ofδ-lactone and its isomers:up to 97%).The key role of phenolic hydroxyl group of the ligand in attaining high activity was validated.The good performance of large-scale reaction in batch reactor demonstrated the potential utility of this simple catalytic system in valorizing CO_(2) with bulk chemical feedstock.
基金supported by the National Natural Science Foundation of China(32270217,31970205,31770211)Metasequoia funding of Nanjing Forestry University to YY。
文摘Amborella trichopoda(Amborellaceae;hereafter simply Amborella)(Fig.1A)is a shrub endemic to New Caledonia in the Southwest Pacific that represents the sole sister species of all other extant angiosperms(Qiu et al.,1999;One Thousand Plant Transcriptomes Initiative,2019).Due to its unique phylogenetic status,it holds tremendous interest for botanists.The nuclear and mitochondrial genomes of Amborella were first published in 2013,providing valuable resources for studies on genome and gene family evolution,phylogenomics,and flower development,despite the fact that the assembly is heavily fragmented(Amborella Genome Project,2013;Rice et al.,2013).In 2024,a haplotype-resolved Amborella genome assembly was published,showing significant improvement in quality and completeness(Carey et al.,2024).
文摘Telomeres have been a subject of genetic research since the 1930s. They play a crucial role in cancer biology, as they influence both cellular senescence and genomic stability. In cancer cells, dysfunctional telomeres can lead to chromosomal fusions and, through deregulation of telomerase, allow replication of mutated chromosomes that might otherwise lead to apoptosis. Research is now focused on improving telomere-based cancer cell detection and developing potential therapies that inhibit telomerase activity in cancerous cells. Telomere research is crucial in understanding the molecular mechanisms influencing tumor growth and invasiveness because of the central role played by telomeres in various cancer types. Several telomerase inhibitors and immunotherapy treatments are in pre-clinical or clinical development. Research on the role of telomeres in oncogenesis has made significant strides, but obstacles remain, including a lack of high-resolution structural understanding, inadequate preclinical models, and concern over potential side effects. Even so, the current path of telomere research holds promise.
基金supported by the Bill&Melinda Gates Foundation(OPP1175213)supported by the Research Foundation Flanders(12X9620N and 12X9623N)the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation program(946192,HUMYCO)。
文摘Background:Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes.The effect on markers of health and disease,such as offspring telomere length(TL)and mitochondrial DNA content(mtDNAc)is unknown.Objectives:We assessed the efficacy of maternal multiple micronutrient(MMN)-fortified balanced-energy protein(BEP)and iron-folic acid(IFA)supplementation on newborn TL as a secondary outcome and mtDNAc as a non-declared outcome.Design:We conducted a randomized controlled trial in rural Burkina Faso,among pregnant females(15-40 years old)enrolled at<21 weeks of gestation.Mothers received either MMN-fortified BEP and IFA(intervention)or IFA only(control)throughout pregnancy.Whole arterial blood samples were collected from the umbilical cord of 104 control and 90 intervention group infants,respectively.Average relative TL and mtDNAc were measured using quantitative polymerase chain reaction.Linear regression models were fitted to assess TL and mtDNAc differences across trial arms.Results:We found that a combined daily MMN-fortified BEP supplement and IFA tablet did not affect newborn TL[β=-0.010(95%CI:-0.057,0.036);P=0.662]or mtDNAc[β=0.065(95%CI:-0.203,0.073);P=0.354],as compared to an IFA tablet alone.These findings were confirmed(P>0.05)by adjusting the regression models for potential prognostic factors of study outcomes at enrollment.Exploratory analyses indicated higher,but non-significantly different mtDNAc among children born either small-for-gestational age,low birthweight,or preterm.Conclusion:Newborns from mothers who received daily nutritional supplements across gestation did not have different relative TL or mtDNAc.
基金financially supported by the National Natural Science Foundation of China(Grant No.:82204625)the Natural Science Foundation of Zhejiang Province(Grant Nos.:LQ23H280013 and LZ22H280001)+1 种基金the Chinese Medicine Research Program of Zhejiang Province(Program Nos.:2021ZZ009,2023ZR009,and 2021ZQ023)the Youth Natural Science Program of Zhejiang Chinese Medical University(Program No.:2021RCZXZK14).
文摘Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,and effective treatments are still lacking.Renal tubular epithelial cells(RTECs)maintain kidney function,and their dysfunction has emerged as a critical contributor to renal fibrosis.Cellular quality control comprises several components,including telomere homeostasis,ubiquitin-proteasome system(UPS),autophagy,mitochondrial homeostasis(mitophagy and mitochondrial metabolism),endoplasmic reticulum(ER,unfolded protein response),and lysosomes.Failures in the cellular quality control of RTECs,including DNA,protein,and organelle damage,exert profibrotic functions by leading to senescence,defective autophagy,ER stress,mitochondrial and lysosomal dysfunction,apoptosis,fibroblast activation,and immune cell recruitment.In this review,we summarize recent advances in understanding the role of quality control components and intercellular crosstalk networks in RTECs,within the context of renal fibrosis.
文摘The integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation was analyzed by Multiplex Ligation-Dependent Probe Amplification (MLPA). The TK6 cell line has the native p53 tumor-suppressor gene, whereas WTK1 cells contain a p53 mutation. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. The impact of irradiation on these two cell lines was investigated using probes that target specific regions on chromosomes associated with subtelomeric regions. Results indicate that WTK1 and TK6 are impacted differently after irradiation, and that each cell line presents its own unique MLPA profile. The most notable differences are the appearance of a number of probes in the post-irradiated MLPA profile that are not present in the controls, and two unique probe signals only seen in WTK1 cells. These results build on our previous studies that indicate how different human cell lines can be affected by radiation in significantly different ways depending on the presence or absence of wild type p53.
文摘Purpose: Telomere length (TL) is an indicator of age;however, hormonal influences complicate individual aging. It remains unclear whether TL shortening is a direct factor in both individual and cellular aging. Therefore, we examined the direct relationship between TL and cellular senescence at the cellular level. Methods: Telomerase activity, TL, and gene expression were measured in cultured human lung-, fetal-, and skin-derived fibroblasts, human skin keratinocytes, and telomerase reverse transcriptase (TERT) gene-immortalized cells using detection kits, Cawthon’s method, and reverse transcription-quantitative polymerase chain reaction, respectively. Novel substances that elongate telomeres were screened to confirm cell rejuvenation effects. Results: Long-term cell culture of TIG-1-20 normal human fibroblasts resulted in TL shortening, decreased division rate, and senescence progression, whereas in OUMS-36T-2 cells, TL elongation via TERT gene transfer increased the division rate, reduced endoplasmic reticulum stress, and upregulated genes associated with young individuals, indicating that cellular rejuvenation occurs via TL elongation. In addition, a honey child powder (HCP) extract was found through screening, and the HCP extract strongly suppressed the menin gene, resulting in increased telomerase activity and extended cell lifespan. Upon addition of the HCP extract to skin fibroblasts, gene expression of moisturizing components, including collagen, hyaluronic acid, and elastin, increased, and exhibited a rejuvenating effect with an increase in elastin amount. Conclusions: TL elongation or shortening is involved in cell proliferation rate and cellular aging, and TL elongation rejuvenates cells. In addition, HCP extract has a rejuvenating effect on cells and is expected to be a rejuvenating compound.
文摘The importance of telomeres as special structures at the ends of chromosomes is gradually gaining prominence. They are composed of short, multi-repeated non-transcribed sequences (TTAGGG) and binding proteins, and their main role is to protect chromosome ends from degradation. Recent studies have shown that the length of telomeres may affect the outcome of COVID-19 infection, and the severity of COVID-19 is associated with shortened or dysfunctional telomeres, which may be an important factor contributing to the deterioration of the patient’s condition. In conjunction with this, COVID-19 patients with longer telomeres tended to have better outcomes compared to those with shorter telomeres. This suggests that telomere length can be used as a potential marker to predict the progress of COVID-19 patients’ recovery, highlighting the potential role of telomeres in the immune system. The involvement of telomeres in the recovery and virological processes of COVID-19 patients demonstrates that telomeres contribute to the maintenance of chromosome stability and promote the normal restoration of cellular functions during the recovery process, thereby improving patient outcomes. This review examines the complex relationship between telomere length and COVID-19 disease. Telomere abnormalities may exacerbate lung injury and fibrosis in COVID-19 patients, while COVID-19 infection accelerates telomere shortening, leading to premature cellular senescence. The aim of this review is to gain a deeper understanding of how telomere length affects disease severity and how COVID-19 in turn affects telomere structure and function. In addition, the impact of COVID-19 on the aging process is explored to provide scientific rationale and insights for the development of targeted therapeutic interventions in the future.
文摘Objective: To study the telomerase activity in human renal cell carcinoma and to evaluate the correlation with the clinicobiologic features of the neogrowth.Methods: The telomerase activity was studied by means of a modified telomeric repeat amplification protocol (TRAP) in 32 renal cell carcinoma tissues, 32 normal renal tissues and 32 paracancer tissues and its correlation with the clinicopathologic features of the tumor was evaluated.Results: Telomerase activity was strongly positive in 17, positive in 12 and negative in 3 cases of renal cell carcinoma tissues, the total positive rate being 91%. Telomerase activity was weakly positive (6%) in only 2 out of 32 samples of normal renal cortex tissues and positive in 6 paracancer tissues (19%), the difference was conspicuous (P<0.01).Conclusion: The positive rate of telomerase activity was significantly higher in renal cell carcinoma tissues and might serve as a prognostic marker for estimating the biologic characteristics of renal cell carcinoma.
基金supported by the National Natural Science Foundation of China (Nos.20374008 and 20674006).
文摘A study has been conducted on the synthesis and characterization of a kind of novel polyrotaxanes comprisingα- cyclodextrins (α-CDs) threaded on triblock eopolymers with poly(ethylene glycol) (PEG) as a central axle and flanked by two low molecular weight polystyrenes as outer stoppers.Styrene was allowed to telomerize with polypseudorotaxanes as chain transfer agents made from the self-assembly of a distal thiol-capped PEG with a varying amount ofα-CDs in the presence of a redox initiation system at 40~C i...
文摘Aryloxy--terminated polydimethylsiloxanes (AOS) were synthesized by the telomerization of hexamethylcyclotrisiloxane(D3) with phenols. The structures of AOS were characterized by UV, IR, 2HNMR and elemental analysis, The effects of the reaction conditions and the mole ratios of the reactants on foe molecular weight of the polymer were discussed. A OS's structural influence on bactericidal action, flocculation and hydrolysis was studied.
基金the Natural Science Foundation of Gansu Province,China,No.ZS981-A23-086-Y
文摘INTRODUCTION Human tissue homeostasis is precisely regulated bycellular division,differentiation and death.Normalhuman somatic cells progressively lose telomererestriction fragment(TRF)length with eachsuccessive cell division,eventually leading tocellular quiescence,chromosomal end-degradationand apoptosis.On the contrary,stabilization oftelomere lengths by expressing telomerase,an RNA-dependent DNA polymerase,may be involved incellular immortality and carcinogenesis.
文摘INTRODUCTIONLiver fibrosis or cirrhosis is a common progressively pathological lesion of chronic liver diseases in response to various liver-damaging factors. The main mechanisms of fibrotic or cirrhotic initiation and progression at the level of cellular and molecular events have been elucidated in the past two decades[1,2].
文摘The pathogenesis of liver cirrhosis is not completely elucidated.Although in the majority of patients,the risk factors may be identified in B and C viral hepatitis,alcohol intake,drugs or fatty liver disease,there is a small percentage of patients with no apparent risk factors.In addition,the evolution of chronic liver disease is highly heterogeneous from one patient to another.Among patient with identical risk factors,some rapidly progress to cirrhosis and hepatocellular carcinoma(HCC)whereas others have a benign course.Therefore,a genetic predisposition may contribute to the development of cirrhosis and HCC.Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years.In addition to the results from epidemiological studies,polymorphisms studies and data on twins,the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed.Here we review the literature on telomerase mutations,telomere shortening and liver disease including hepatocellular carcinoma.
基金National Natural Science Foundation of China,No.30070043"10.5"Scientific Research Foundation of PLA,No.01Z075
文摘AIM: To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas. METHODS: Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-betaRII and BAX genes were analyzed by PCR-based methods. RESULTS: Sixty-eight cases of sporadic gastric carcinoma were studied for MSI using five microsatellite markers. MSI in at least one locus was detected in 17 (25%) of 68 tumors analyzed. Frameshift mutations of hMSH6, TGF-betaRII and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (】 or = 2 loci, n = 8), but none was found in those showing low MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and low MSI, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters. No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P【0.01). This tendency was also observed in APC and MCC genes, although there was no statistical significance. CONCLUSION: The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either low MSI or MSS, multiple deletions may represent the LOH pathway. Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer.
文摘The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an “inflammatory cancer”, arising from a context of inflammation, and characterized by inflammation-related mechanisms that favor tumor cell survival, proliferation, and invasion. Molecular mechanisms that link inflammation and neoplasia have been widely investigated, and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species. The latter, in turn, probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation, and ultimately leading to cancer. The relationship amongst chronic liver injury, free radical production, and development of HCC is explored in the present review, particularly in the light of the complex network that involves oxidative DNA damage, cytokine synthesis, telomere dysfunction, and microRNA regulation.
文摘The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS 1 complex （MRN） that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome （NBS）, a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance oftelomere stability.
文摘Nasopharyngeal carcinoma （NPC） is a common cancer in Southern China and Southeast Asia. The disease is a poorly differentiated carcinoma without effective cure, and the mechanism underlying its development remains largely unknown. Of several factors identified in NPC aetiology in recent years, Epstein-Barr virus （EBV） infection has emerged to be most important. In almost all NPC cells, EBV uses several intracellular mechanisms to cause oncogenic evolution of the infected cells. One such mechanism by which EBV infection induces cellular immortalization is believed to be through the activation of telomerase, an enzyme that is normally repressed but becomes activated during cancer development. Studies show that greater than 85% of primary NPC display high telomerase activity by mechanisms involving EBV infection, consistent with the notion that EBV is commonly involved in inducing cell immortalization. More recently, different EBV proteins have been shown to activate or inhibit the human telomerase reverse transcriptase gene, by modulating intracellular signalling pathways. These findings suggest a new model with a number of challenges towards our understanding, molecular targeting and therapeutic intervention in NPC.
