Five cadmium naphthalene-diphosphonates,formulated as[Cd_(1.5)(1,4-ndpaH_(2))2(4,4'-bpyH)(4,4'-bpy)0.5(H_(2)O)_(2)]2(1),[Cd(1,4-ndpaH_(2))(1,4-bib)0.5(H_(2)O)](2),[Cd(1,4-ndpaH3)2(1,2-dpe)(H_(2)O)]·(1,2-d...Five cadmium naphthalene-diphosphonates,formulated as[Cd_(1.5)(1,4-ndpaH_(2))2(4,4'-bpyH)(4,4'-bpy)0.5(H_(2)O)_(2)]2(1),[Cd(1,4-ndpaH_(2))(1,4-bib)0.5(H_(2)O)](2),[Cd(1,4-ndpaH3)2(1,2-dpe)(H_(2)O)]·(1,2-dpe)·7H_(2)O(3),(1,2-bixH)[Cd3(1,4-ndpaH)(1,4-ndpaH_(2))2(H_(2)O)_(2)](4),and[Cd(1,4-ndpaH_(2))(H_(2)O)]·H_(2)O(5),have been synthesized from the selfassembly reactions of 1,4-naphthalenediphosphonic acid(1,4-ndpaH4)with Cd(NO3)2·4H_(2)O by introducing auxiliary ligands with variation of rigidity,such as 4,4'-bipyridine(4,4'-bpy),1,4-bis(1-imidazolyl)benzene(1,4-bib),1,2-di(4-pyridyl)ethylene(1,2-dpe),1,3-di(4-pyridyl)propane(1,3-dpp),and bis(imidazol-1-ylmethyl)benzene(1,2-bix),respectively.Structure resolution by single-crystal X-ray diffraction reveals that compound 1 possesses a layered framework,in which the{Cd3(PO2)2}trimers made up of corner-sharing two{CdO4N2}and one{CdO6}octahedra are connected by phosphonate groups,forming a ribbon,which are cross-linked by 4,4'-bipy ligands,forming a 2D layer.Compound 2 shows a 3D open-framework structure,where chains of corner-sharing{CdO4N}trigonal bipyramids and{PO3C}tetrahedra are cross-linked by 1,4-bib and/or phosphonate groups.A 1D ladder-like chain structure is found in compound 3,where the ladder-like chains made up of corner-sharing{CdO5N}octahedra and{PO3C}tetra hedra are connected by 1,4-ndpaH_(2)^(2-).Both compounds 4 and 5 obtained by the introduction of flexible ligands during the synthesis show a 2D layered structure,which is formed by ligand crosslinking double metal chains.Interestingly,In 4,flexible 1,2-bix was singly protonated,as vip molecules,filled between layer and layer,while flexible ligand 1,3-dpp is absent in 5.Photophysical measurements indicate that compounds 1-5 show ligand-centered emissions.展开更多
Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capa...Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capacity compared to olaparib.It is not affected by adenosine triphosphate(ATP)-binding cassette transporters.展开更多
GTs(Glycosyltransferases)are important in plant growth and abiotic stresses.However,its role in maize heat response is far from clear.Here,we describe the constitutively expressed UDP-glycosyltransferase ZmUGT92A1,whi...GTs(Glycosyltransferases)are important in plant growth and abiotic stresses.However,its role in maize heat response is far from clear.Here,we describe the constitutively expressed UDP-glycosyltransferase ZmUGT92A1,which has a highly conserved PSPG box and is localized in chloroplasts,is induced under heat stress.Functional disruption of ZmUGT92A1 leads to heat sensitivity and reactive oxygen species accumulation in maize.Metabolomics analysis revealed that ZmUGT92A1 affected multiple metabolic pathways and altered the metabolic homeostasis of flavonoids under heat stress.In vitro assay showed ZmUGT92A1 exhibits glycosyltransferase activity on flavonoids and hormones.Additionally,we identified a rapidly heat-induced transcription factor,ZmHSF08,which can directly bind and repress the promoter region of ZmUGT92A1.The ZmHSF08 overexpression line exhibits heat sensitivity and reactive oxygen species accumulation.These findings reveal that the ZmHSF08-ZmUGT92A1 module plays a role in heat tolerance in maize and provide candidate strategies for the development of heat-tolerant varieties.展开更多
BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage re...BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.METHODS We investigated the relationship between UGT1A1 expression and liver injury through clinical research.Additionally,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.展开更多
The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronos...The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronosyltransferase 1A1 during liver injury could mitigate damage by reducing endoplasmic reticulum stress,oxidative stress,and dysregulated lipid metabolism,impeding hepatocyte apoptosis and necroptosis.展开更多
Objective: To study the effects of sodium magnesiusm fructose diphosphate(FDPM) on brain damage of rats after ischemia-reperfusion. Methods: Rats were subjected to cerebral ischemia-reperfusion induced by inserting a ...Objective: To study the effects of sodium magnesiusm fructose diphosphate(FDPM) on brain damage of rats after ischemia-reperfusion. Methods: Rats were subjected to cerebral ischemia-reperfusion induced by inserting a nylon thread into internal carotid artery to block the origin of middle cerebral artery and removing the thread later. FDPM (400 mg·kg -1), fructose-1,6-diphosphate (FDP, 400 mg·kg -1)and magnesium sulfate (MgSO 4, 30 mg·kg -1) were administrated 10 min after the onset of ischemia. Neurological scale, brain infarct area, Malondialdehyde(MDA) content and histopathological changes of brain tissue were studied. Results: FDPM decreased neurological scale, diminished brain infarct area, reduced MDA content and relieved histopathological change of rat brain tissue subjected to ischemia-reperfusion. These effects were more powerful than that of FDP or MgSO 4. Conclusions: It is suggested that FDPM markedly prevented rats against brain damage after cerebral ischemia-reperfusion, and its effect was better than that of FDP or MgSO 4.展开更多
The effect of tetrandrine (Tet) on the infarction area and volume of rat brain induced by middle cerebral artery occlusion (MCAO) was investigated. The treatment with Tet 7.5, 12.0 or 15.0 mg·kg 1 , or with...The effect of tetrandrine (Tet) on the infarction area and volume of rat brain induced by middle cerebral artery occlusion (MCAO) was investigated. The treatment with Tet 7.5, 12.0 or 15.0 mg·kg 1 , or with fructose 1,6 diphosphate (FDP) 200 and 350 mg·kg 1 ip immediately after MCAO, respectively, significantly reduced the infarction area and volume in a dose dependent manner. MK801 and FDP also displayed a protective effect on brain ischemia. A combination of Tet and FDP administered immediately after MCAO, produced a more potent protective effect than those treated with Tet or FDP alone. When Tet or FDP was administered 1 h and 2 h after MCAO, respectively, they could still significantly reduce the infarction area and volume of brain tissue. But, there was no significant protective effect when these two compounds were given 3 h after MCAO.展开更多
A distinctive feature of phosphates is their special and significant ability to form inorganic polymeric compounds---condensed phosphates, which are destined to play a considerable role in our ＂high-tech＂ society in...A distinctive feature of phosphates is their special and significant ability to form inorganic polymeric compounds---condensed phosphates, which are destined to play a considerable role in our ＂high-tech＂ society in the future. Numerous olygophosphates, polyphosphates, double condensed phosphates and cyclophosphates with diverse formula, such as double tetra-, octa- and dodecaphosphates were obtained and described by us last years. The offered data are the outcomes of our scientific researches： of synthesis, analysis, and estimation of results in correlation with new achievements in inorganic polymer＇s chemistry. Many double condensed compounds, containing monovalent metals are obtained by us during systematic investigation of polycomponent systems, containing mono- and trivalent metals at temperature range 100-600 ~C. Synthesised condensed phosphates, in fact--inorganic polymers were examined in detail by chemical and thermogravimetric analysis, most compounds were examined by paper chromatography and the structures are determined by X-ray structural techniques/diffraction analysis. During our fundamental researches numerous new （about 70） unknown until now condensed phosphates have been obtained. Dependency of composition VS temperature and molar ratio, reliance of structure from duration of synthesis and radius of the ions are revealed.展开更多
In recent years, biosynthesis of triterpenoid saponins in medicinal plants has been widely studied because of their active ingredients with diverse pharmacological activities. Various oxidosqualene cyclases, cytochrom...In recent years, biosynthesis of triterpenoid saponins in medicinal plants has been widely studied because of their active ingredients with diverse pharmacological activities. Various oxidosqualene cyclases, cytochrome P450 monooxygenases, uridine diphosphate glucuronosyltransferases, and transcription factors related to triterpenoid saponins biosynthesis have been explored and identified. In the biosynthesis of triterpenoid saponins, the progress of gene mining by omics-based sequencing, gene screening, gene function verification, catalyzing mechanism of key enzymes and gene regulation are summarized and discussed. By the progress of the biosynthesis pathway of triterpenoid saponins, the large-scale production of some triterpenoid saponins and aglycones has been achieved through plant tissue culture, transgenic plants and engineered yeast cells. However, the complex biosynthetic pathway and structural diversity limit the biosynthesis of triterpenoid saponins in different system. Special focus can further be placed on the systematic botany information of medicinal plants obtained from omics large dataset, and triterpenoid saponins produced by synthetic biology strategies, gene mutations and gene editing technology.展开更多
OBJECTIVE: To evaluate the anti-platelet aggregation effects of extracts from 31 Traditional Chinese Medicines(TCM) with the property of activating blood and resolving stasis in terms of TCM theory.METHODS: The 31 TCM...OBJECTIVE: To evaluate the anti-platelet aggregation effects of extracts from 31 Traditional Chinese Medicines(TCM) with the property of activating blood and resolving stasis in terms of TCM theory.METHODS: The 31 TCMs extracts were prepared using water, 90% ethanol and ethyl acetate., and the effects on anti-platelet aggregation were tested on a platelet aggregation analyzer in vitro with adenosine 5'-diphosphate, bovine thrombin and arachi-donic acid(AA) as aggregation inducers, respectively. Aspirin was the positive control.RESULTS: Lots of the tested TCMs had inhibitory effects with concentration-dependent manner on platelet aggregations induced by various agonists.Especially, some of the TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae) showed good anti-platelet aggregation effect similar or higher than that in positive control group.CONCLUSION: The study provided scientific references that several TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae),possess the property of anti-platelet aggregation.展开更多
AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with ris...AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with risk of colon cancer.METHODS： NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms （SNPs） in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS： No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk （P 〉 0.05）,and we did not observe that these variants modify the protective effect of NSAIDs （P 〉 0.05）. We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION： Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.展开更多
BACKGROUND Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However...BACKGROUND Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate(GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels.AIM To survey the literature to capture the involvement of genes regulating core Nlinked fucosylation in hepatocellular carcinoma METHODS The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma(LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal.RESULTS A total of 27 citations involving one or more of the core fucosylation-related genes(FPGT, FUK, FUT8, GMDS, SLC35 C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the371 patients with liver cancer in the LIHC dataset to identify the frequency of m RNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to moresamples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the de novo synthesis pathway, GMDS(27 samples) and TSTA3(78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples.CONCLUSION Amplification of genes involved in the de novo pathway for generation of GDPfucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.展开更多
This study attempts to discuss the correlation between UGT1A1＊28 as uridine diphosphate glucuronosyltransferase gene promoter and coding region Gly71 Arg gene polymorphism with neonatal hyperbilirubinemia of neonates...This study attempts to discuss the correlation between UGT1A1＊28 as uridine diphosphate glucuronosyltransferase gene promoter and coding region Gly71 Arg gene polymorphism with neonatal hyperbilirubinemia of neonates in Wuhan. A total of 168 neonates were divided into the hyperbilirubinemia group（case group, n=108） and healthy neonates group（control group, n=60）. Their DNA was obtained through blood extraction. The gene exon mutation of UGT1A1 was detected by Sanger sequencing, which revealed the relationship between UGT1A1＊28 and Gly71 Arg polymorphism with neonatal hyperbilirubinemia of neonates. The results showed that：（1） The frequency of UGT1A1＊28 allele mutation in the case group and the control group was 9.3% and 10% respectively, with the difference being not significant between the two groups（P〉0.05）.（2） The frequency of Gly71 Arg allele mutation in the case group and the control group was 35.1% and 21.7% respectively, with the difference being significant between the two groups（P〈0.01）.（3） The serum bilirubin level of Gly71 Arg mutant homozygous and heterozygous subgroups（n=66） in the case group was 302.7±31.4 μmol/L, which was significantly higher than 267.3±28.5 μmol/L of the wild subgroup（n=42）（P〈0.01）. It was suggested that the occurrence of neonatal hyperbilirubinemia of neonates in Wuhan was not associated with UGT1A1＊28 gene polymorphism, but closely with the Gly71 Arg gene polymorphism. Meanwhile, the Arg allele mutation was related to the degree of jaundice.展开更多
Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across dif...Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.展开更多
BACKGROUND Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin,resulting in sequelaes such as hearing loss,motor and intellectual development diso...BACKGROUND Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin,resulting in sequelaes such as hearing loss,motor and intellectual development disorders,and even death.The pathogenic factors of neonatal hyperbilirubinemia are complex.Different cases of hyperbilirubinemia may have a single or mixed etiology.AIM To explore the etiological characteristics of severe hyperbilirubinemia in term newborns of eastern Guangdong of China.METHODS Term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed.The etiology was determined according to the laboratory results and clinical manifestations.RESULTS Among 1602 term newborns with hyperbilirubinemia in eastern Guangdong of China,32.20%(580/1602)was severe hyperbilirubinemia.Among the causes of severe hyperbilirubinemia,neonatal hemolysis accounted for 15.17%,breast milk jaundice accounted for 12.09%,infection accounted for 10.17%,glucose-6-phosphate dehydrogenase(G6PD)deficiency accounted for 9.14%,and the coexistence of multiple etiologies accounted for 6.55%,unknown etiology accounted for 41.72%.ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy.94 severe hyperbilirubinemia newborns were tested for uridine diphosphate glucuronosyl transferase 1A1(UGT1A1)*6 variant(rs4148323,c.211G>A,p.Arg71Gly),9 cases were 211 G to A homozygous variant,37 cases were 211 G to A heterozygous variant,and 48 cases were wild genotypes.CONCLUSION The main cause for severe hyperbilirubinemia and bilirubin encephalopathy in eastern Guangdong of China were the hemolytic disease of the newborns,G6PD deficiency and infection.UGT1A1 gene variant was also a high-risk factor for neonatal hyperbilirubinemia.Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.展开更多
Mobilization of intracellular Ca2+ stores is involved inmany diverse cell functions, including: cell proliferation;differentiation; fertilization; muscle contraction; secre-tion of neurotransmitters, hormones and enzy...Mobilization of intracellular Ca2+ stores is involved inmany diverse cell functions, including: cell proliferation;differentiation; fertilization; muscle contraction; secre-tion of neurotransmitters, hormones and enzymes;and lymphocyte activation and proliferation. Cyclic ad-enosine diphosphate ribose(cADPR) is an endogenousCa2+ mobilizing nucleotide present in many cell typesand species, from plants to animals. cADPR is formedby ADP-ribosyl cyclases from nicotinamide adenine di-nucleotide. The main ADP-ribosyl cyclase in mammalsis CD38, a multi-functional enzyme and a type Ⅱ mem-brane protein. It has been shown that many extracel-lular stimuli can induce cADPR production that leadsto calcium release or influx, establishing cADPR as asecond messenger. cADPR has been linked to a widevariety of cellular processes, but the molecular mecha-nisms regarding cADPR signaling remain elusive. Theaim of this review is to summarize the CD38/cADPR/Ca2+ signaling pathway, focusing on the recent advanc-es involving the mechanism and physiological functionsof cADPR-mediated Ca2+ mobilization.展开更多
AIM:To investigate the involvement of decaprenyl diphosphate synthase subunit 2(PDSS2) in development and progression of human hepatocellular carcinoma(HCC).METHODS:PDSS2 protein expression was examined in well-and po...AIM:To investigate the involvement of decaprenyl diphosphate synthase subunit 2(PDSS2) in development and progression of human hepatocellular carcinoma(HCC).METHODS:PDSS2 protein expression was examined in well-and poorly differentiated HCC tumor samples.The levels of PDSS2 expression were compared with clinical features and prognosis of HCC patients.The effects of PDSS2 on cell proliferation,cell cycle,apoptosis,cell migration,and invasion in HCC Hep G2 cells were also investigated.RESULTS:PDSS2 was downregulated in poorly differentiated cancer samples compared with welldifferentiated tumor samples,and the expression level was markedly lower in HCC tissues than in histologically normal tissue adjacent to the cancer.Reduced protein expression was negatively associated with the status of HCC progression.In addition,overexpression of PDSS2dramatically suppressed cell proliferation and colony formation,and induced apoptosis in Hep G2 cells by inducing G1-phase cell-cycle arrest.The migration and invasion capabilities of Hep G2 cells were significantly decreased following PDSS2 overexpression.CONCLUSION:Decreased PDSS2 expression is an unfavorable prognostic factor for HCC,and PDSS2 has potent anticancer activity in HCC tissues and Hep G2cells.展开更多
文摘Five cadmium naphthalene-diphosphonates,formulated as[Cd_(1.5)(1,4-ndpaH_(2))2(4,4'-bpyH)(4,4'-bpy)0.5(H_(2)O)_(2)]2(1),[Cd(1,4-ndpaH_(2))(1,4-bib)0.5(H_(2)O)](2),[Cd(1,4-ndpaH3)2(1,2-dpe)(H_(2)O)]·(1,2-dpe)·7H_(2)O(3),(1,2-bixH)[Cd3(1,4-ndpaH)(1,4-ndpaH_(2))2(H_(2)O)_(2)](4),and[Cd(1,4-ndpaH_(2))(H_(2)O)]·H_(2)O(5),have been synthesized from the selfassembly reactions of 1,4-naphthalenediphosphonic acid(1,4-ndpaH4)with Cd(NO3)2·4H_(2)O by introducing auxiliary ligands with variation of rigidity,such as 4,4'-bipyridine(4,4'-bpy),1,4-bis(1-imidazolyl)benzene(1,4-bib),1,2-di(4-pyridyl)ethylene(1,2-dpe),1,3-di(4-pyridyl)propane(1,3-dpp),and bis(imidazol-1-ylmethyl)benzene(1,2-bix),respectively.Structure resolution by single-crystal X-ray diffraction reveals that compound 1 possesses a layered framework,in which the{Cd3(PO2)2}trimers made up of corner-sharing two{CdO4N2}and one{CdO6}octahedra are connected by phosphonate groups,forming a ribbon,which are cross-linked by 4,4'-bipy ligands,forming a 2D layer.Compound 2 shows a 3D open-framework structure,where chains of corner-sharing{CdO4N}trigonal bipyramids and{PO3C}tetrahedra are cross-linked by 1,4-bib and/or phosphonate groups.A 1D ladder-like chain structure is found in compound 3,where the ladder-like chains made up of corner-sharing{CdO5N}octahedra and{PO3C}tetra hedra are connected by 1,4-ndpaH_(2)^(2-).Both compounds 4 and 5 obtained by the introduction of flexible ligands during the synthesis show a 2D layered structure,which is formed by ligand crosslinking double metal chains.Interestingly,In 4,flexible 1,2-bix was singly protonated,as vip molecules,filled between layer and layer,while flexible ligand 1,3-dpp is absent in 5.Photophysical measurements indicate that compounds 1-5 show ligand-centered emissions.
基金supported in part by funding from BeiGene,Ltd.,USA(Grant No.:KPR081)with additional support from the Alessandra Bono Foundation,Italy.
文摘Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capacity compared to olaparib.It is not affected by adenosine triphosphate(ATP)-binding cassette transporters.
基金supported by the National Key Research and Development Program of China (2021YFF1000301)the National Natural Science Foundation of China (31771805)。
文摘GTs(Glycosyltransferases)are important in plant growth and abiotic stresses.However,its role in maize heat response is far from clear.Here,we describe the constitutively expressed UDP-glycosyltransferase ZmUGT92A1,which has a highly conserved PSPG box and is localized in chloroplasts,is induced under heat stress.Functional disruption of ZmUGT92A1 leads to heat sensitivity and reactive oxygen species accumulation in maize.Metabolomics analysis revealed that ZmUGT92A1 affected multiple metabolic pathways and altered the metabolic homeostasis of flavonoids under heat stress.In vitro assay showed ZmUGT92A1 exhibits glycosyltransferase activity on flavonoids and hormones.Additionally,we identified a rapidly heat-induced transcription factor,ZmHSF08,which can directly bind and repress the promoter region of ZmUGT92A1.The ZmHSF08 overexpression line exhibits heat sensitivity and reactive oxygen species accumulation.These findings reveal that the ZmHSF08-ZmUGT92A1 module plays a role in heat tolerance in maize and provide candidate strategies for the development of heat-tolerant varieties.
基金the Science and Technology Research Foundations of Guizhou Province,No.QKHJC-ZK(2022)YB642Zunyi Science and Technology Plan Project,No.ZSKHHZ(2022)344,No.ZSKHHZ(2022)360,and No.ZYK160+2 种基金Hubei Province Central Leading Local Science and Technology Development Special Project,No.2022BCE030Changzhou Science and Technology Projects,No.CE20225054Bijie City Science and Planning Bureau,No.BKH(2022)8.
文摘BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.METHODS We investigated the relationship between UGT1A1 expression and liver injury through clinical research.Additionally,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.
文摘The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronosyltransferase 1A1 during liver injury could mitigate damage by reducing endoplasmic reticulum stress,oxidative stress,and dysregulated lipid metabolism,impeding hepatocyte apoptosis and necroptosis.
文摘Objective: To study the effects of sodium magnesiusm fructose diphosphate(FDPM) on brain damage of rats after ischemia-reperfusion. Methods: Rats were subjected to cerebral ischemia-reperfusion induced by inserting a nylon thread into internal carotid artery to block the origin of middle cerebral artery and removing the thread later. FDPM (400 mg·kg -1), fructose-1,6-diphosphate (FDP, 400 mg·kg -1)and magnesium sulfate (MgSO 4, 30 mg·kg -1) were administrated 10 min after the onset of ischemia. Neurological scale, brain infarct area, Malondialdehyde(MDA) content and histopathological changes of brain tissue were studied. Results: FDPM decreased neurological scale, diminished brain infarct area, reduced MDA content and relieved histopathological change of rat brain tissue subjected to ischemia-reperfusion. These effects were more powerful than that of FDP or MgSO 4. Conclusions: It is suggested that FDPM markedly prevented rats against brain damage after cerebral ischemia-reperfusion, and its effect was better than that of FDP or MgSO 4.
文摘The effect of tetrandrine (Tet) on the infarction area and volume of rat brain induced by middle cerebral artery occlusion (MCAO) was investigated. The treatment with Tet 7.5, 12.0 or 15.0 mg·kg 1 , or with fructose 1,6 diphosphate (FDP) 200 and 350 mg·kg 1 ip immediately after MCAO, respectively, significantly reduced the infarction area and volume in a dose dependent manner. MK801 and FDP also displayed a protective effect on brain ischemia. A combination of Tet and FDP administered immediately after MCAO, produced a more potent protective effect than those treated with Tet or FDP alone. When Tet or FDP was administered 1 h and 2 h after MCAO, respectively, they could still significantly reduce the infarction area and volume of brain tissue. But, there was no significant protective effect when these two compounds were given 3 h after MCAO.
文摘A distinctive feature of phosphates is their special and significant ability to form inorganic polymeric compounds---condensed phosphates, which are destined to play a considerable role in our ＂high-tech＂ society in the future. Numerous olygophosphates, polyphosphates, double condensed phosphates and cyclophosphates with diverse formula, such as double tetra-, octa- and dodecaphosphates were obtained and described by us last years. The offered data are the outcomes of our scientific researches： of synthesis, analysis, and estimation of results in correlation with new achievements in inorganic polymer＇s chemistry. Many double condensed compounds, containing monovalent metals are obtained by us during systematic investigation of polycomponent systems, containing mono- and trivalent metals at temperature range 100-600 ~C. Synthesised condensed phosphates, in fact--inorganic polymers were examined in detail by chemical and thermogravimetric analysis, most compounds were examined by paper chromatography and the structures are determined by X-ray structural techniques/diffraction analysis. During our fundamental researches numerous new （about 70） unknown until now condensed phosphates have been obtained. Dependency of composition VS temperature and molar ratio, reliance of structure from duration of synthesis and radius of the ions are revealed.
基金the Central Significant Increase or Decrease Program of China(No.2060302-1604-05)NSFC(No.81703639)。
文摘In recent years, biosynthesis of triterpenoid saponins in medicinal plants has been widely studied because of their active ingredients with diverse pharmacological activities. Various oxidosqualene cyclases, cytochrome P450 monooxygenases, uridine diphosphate glucuronosyltransferases, and transcription factors related to triterpenoid saponins biosynthesis have been explored and identified. In the biosynthesis of triterpenoid saponins, the progress of gene mining by omics-based sequencing, gene screening, gene function verification, catalyzing mechanism of key enzymes and gene regulation are summarized and discussed. By the progress of the biosynthesis pathway of triterpenoid saponins, the large-scale production of some triterpenoid saponins and aglycones has been achieved through plant tissue culture, transgenic plants and engineered yeast cells. However, the complex biosynthetic pathway and structural diversity limit the biosynthesis of triterpenoid saponins in different system. Special focus can further be placed on the systematic botany information of medicinal plants obtained from omics large dataset, and triterpenoid saponins produced by synthetic biology strategies, gene mutations and gene editing technology.
基金the National Natural Science Foundation of China(Magnetic Nanoparticles-based Cell Affinity Capillary Electrochromatography and Its Applications,No.21275169Screening of Bioactive Compounds From Typical Huoxue Huayu Medicine by Platelet Based Capillary Electrochromatography,No.81202886)+1 种基金the Fundamental Research Funds for the Central Universities(Study on the Quality Control Method for the Animal Glue Medicine,No.CQDXWL-2012-028)the Chongqing Postdoctoral Funds(No.RC20120027)
文摘OBJECTIVE: To evaluate the anti-platelet aggregation effects of extracts from 31 Traditional Chinese Medicines(TCM) with the property of activating blood and resolving stasis in terms of TCM theory.METHODS: The 31 TCMs extracts were prepared using water, 90% ethanol and ethyl acetate., and the effects on anti-platelet aggregation were tested on a platelet aggregation analyzer in vitro with adenosine 5'-diphosphate, bovine thrombin and arachi-donic acid(AA) as aggregation inducers, respectively. Aspirin was the positive control.RESULTS: Lots of the tested TCMs had inhibitory effects with concentration-dependent manner on platelet aggregations induced by various agonists.Especially, some of the TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae) showed good anti-platelet aggregation effect similar or higher than that in positive control group.CONCLUSION: The study provided scientific references that several TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae),possess the property of anti-platelet aggregation.
基金Supported by A Damon Runyon Cancer Research Foundation Clinical Investigator Award,CI-8An R25 training grant from the National Cancer Institute,R25T CA094186+1 种基金The Case Center for Transdisciplinary Research on Energetics and Cancer,1U54 CA-116867-01A National Cancer Institute K22 Award,1K22 CA120545-01
文摘AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with risk of colon cancer.METHODS： NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms （SNPs） in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS： No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk （P 〉 0.05）,and we did not observe that these variants modify the protective effect of NSAIDs （P 〉 0.05）. We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION： Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.
文摘BACKGROUND Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate(GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels.AIM To survey the literature to capture the involvement of genes regulating core Nlinked fucosylation in hepatocellular carcinoma METHODS The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma(LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal.RESULTS A total of 27 citations involving one or more of the core fucosylation-related genes(FPGT, FUK, FUT8, GMDS, SLC35 C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the371 patients with liver cancer in the LIHC dataset to identify the frequency of m RNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to moresamples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the de novo synthesis pathway, GMDS(27 samples) and TSTA3(78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples.CONCLUSION Amplification of genes involved in the de novo pathway for generation of GDPfucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.
基金supported by the National Natural Science Foundation of China(No.81370099)
文摘This study attempts to discuss the correlation between UGT1A1＊28 as uridine diphosphate glucuronosyltransferase gene promoter and coding region Gly71 Arg gene polymorphism with neonatal hyperbilirubinemia of neonates in Wuhan. A total of 168 neonates were divided into the hyperbilirubinemia group（case group, n=108） and healthy neonates group（control group, n=60）. Their DNA was obtained through blood extraction. The gene exon mutation of UGT1A1 was detected by Sanger sequencing, which revealed the relationship between UGT1A1＊28 and Gly71 Arg polymorphism with neonatal hyperbilirubinemia of neonates. The results showed that：（1） The frequency of UGT1A1＊28 allele mutation in the case group and the control group was 9.3% and 10% respectively, with the difference being not significant between the two groups（P〉0.05）.（2） The frequency of Gly71 Arg allele mutation in the case group and the control group was 35.1% and 21.7% respectively, with the difference being significant between the two groups（P〈0.01）.（3） The serum bilirubin level of Gly71 Arg mutant homozygous and heterozygous subgroups（n=66） in the case group was 302.7±31.4 μmol/L, which was significantly higher than 267.3±28.5 μmol/L of the wild subgroup（n=42）（P〈0.01）. It was suggested that the occurrence of neonatal hyperbilirubinemia of neonates in Wuhan was not associated with UGT1A1＊28 gene polymorphism, but closely with the Gly71 Arg gene polymorphism. Meanwhile, the Arg allele mutation was related to the degree of jaundice.
基金supported by Georgia Research Alliance and the National Natural Science Foundation of China(Grant Nos.81320108025,61402194,61572227)the Science-Technology Development Project from Jilin Province(Nos.20160101259JC,20160204022GX,20170520063JH)
文摘Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.
基金Supported by the Natural Science Foundation of Guangdong Province,No.2016A030307035Special Research Plan 2019 of Chaozhou,No.2020xg01High-Level Development Plan of People’s Hospital of Yangjiang,No.G2020007.
文摘BACKGROUND Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin,resulting in sequelaes such as hearing loss,motor and intellectual development disorders,and even death.The pathogenic factors of neonatal hyperbilirubinemia are complex.Different cases of hyperbilirubinemia may have a single or mixed etiology.AIM To explore the etiological characteristics of severe hyperbilirubinemia in term newborns of eastern Guangdong of China.METHODS Term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed.The etiology was determined according to the laboratory results and clinical manifestations.RESULTS Among 1602 term newborns with hyperbilirubinemia in eastern Guangdong of China,32.20%(580/1602)was severe hyperbilirubinemia.Among the causes of severe hyperbilirubinemia,neonatal hemolysis accounted for 15.17%,breast milk jaundice accounted for 12.09%,infection accounted for 10.17%,glucose-6-phosphate dehydrogenase(G6PD)deficiency accounted for 9.14%,and the coexistence of multiple etiologies accounted for 6.55%,unknown etiology accounted for 41.72%.ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy.94 severe hyperbilirubinemia newborns were tested for uridine diphosphate glucuronosyl transferase 1A1(UGT1A1)*6 variant(rs4148323,c.211G>A,p.Arg71Gly),9 cases were 211 G to A homozygous variant,37 cases were 211 G to A heterozygous variant,and 48 cases were wild genotypes.CONCLUSION The main cause for severe hyperbilirubinemia and bilirubin encephalopathy in eastern Guangdong of China were the hemolytic disease of the newborns,G6PD deficiency and infection.UGT1A1 gene variant was also a high-risk factor for neonatal hyperbilirubinemia.Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.
基金Supported by Research Grant Council grants,No.782709M,No.785911M,No.769912M and No.785213M
文摘Mobilization of intracellular Ca2+ stores is involved inmany diverse cell functions, including: cell proliferation;differentiation; fertilization; muscle contraction; secre-tion of neurotransmitters, hormones and enzymes;and lymphocyte activation and proliferation. Cyclic ad-enosine diphosphate ribose(cADPR) is an endogenousCa2+ mobilizing nucleotide present in many cell typesand species, from plants to animals. cADPR is formedby ADP-ribosyl cyclases from nicotinamide adenine di-nucleotide. The main ADP-ribosyl cyclase in mammalsis CD38, a multi-functional enzyme and a type Ⅱ mem-brane protein. It has been shown that many extracel-lular stimuli can induce cADPR production that leadsto calcium release or influx, establishing cADPR as asecond messenger. cADPR has been linked to a widevariety of cellular processes, but the molecular mecha-nisms regarding cADPR signaling remain elusive. Theaim of this review is to summarize the CD38/cADPR/Ca2+ signaling pathway, focusing on the recent advanc-es involving the mechanism and physiological functionsof cADPR-mediated Ca2+ mobilization.
基金Supported by Funding from the Fundamental Research Funds for the First Clinical College of Jinan University,No.2014110the National Natural Science Foundation of China,No.81401973+1 种基金the Fundamental Research Funds for the Central Universities of China,No.21614304the Medical Scientific Research Foundation of Guangdong Province of China,No.B2014222
文摘AIM:To investigate the involvement of decaprenyl diphosphate synthase subunit 2(PDSS2) in development and progression of human hepatocellular carcinoma(HCC).METHODS:PDSS2 protein expression was examined in well-and poorly differentiated HCC tumor samples.The levels of PDSS2 expression were compared with clinical features and prognosis of HCC patients.The effects of PDSS2 on cell proliferation,cell cycle,apoptosis,cell migration,and invasion in HCC Hep G2 cells were also investigated.RESULTS:PDSS2 was downregulated in poorly differentiated cancer samples compared with welldifferentiated tumor samples,and the expression level was markedly lower in HCC tissues than in histologically normal tissue adjacent to the cancer.Reduced protein expression was negatively associated with the status of HCC progression.In addition,overexpression of PDSS2dramatically suppressed cell proliferation and colony formation,and induced apoptosis in Hep G2 cells by inducing G1-phase cell-cycle arrest.The migration and invasion capabilities of Hep G2 cells were significantly decreased following PDSS2 overexpression.CONCLUSION:Decreased PDSS2 expression is an unfavorable prognostic factor for HCC,and PDSS2 has potent anticancer activity in HCC tissues and Hep G2cells.
