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1.
Bioconjug Chem ; 35(8): 1166-1171, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39046902

ABSTRACT

Programmed DNA structures and assemblies are readily accessible, but site-specific functionalization is critical to realize applications in various fields such as nanoelectronics, nanomaterials and biomedicine. Besides pre- and post-DNA synthesis conjugation strategies, on-solid support reactions offer advantages in certain circumstances. We describe on-solid support internucleotide coupling reactions, often considered undesirable, and a workaround strategy to overcome them. Palladium coupling reactions enabled on-solid support intra- and interstrand coupling between single-stranded DNAs (ss-DNAs). Dilution with a capping agent suppressed interstrand coupling, maximizing intrastrand coupling. Alternatively, interstrand coupling actually proved advantageous to provide dimeric organic/DNA conjugates that could be conveniently separated from higher oligomers, and was more favorable with longer terphenyl coupling partners.


Subject(s)
Palladium , Palladium/chemistry , DNA/chemistry , DNA, Single-Stranded/chemistry
2.
Mol Phylogenet Evol ; 190: 107962, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37926394

ABSTRACT

Polygonatum is the largest genus of tribe Polygonateae (Asparagaceae) and is widely distributed in the temperate Northern Hemisphere, especially well diversified in southwestern China to northeastern Asia. Phylogenetic relationships of many species are still controversial. Hence it is necessary to clarify their phylogenetic relationships and infer possible reticulate relationships for the genus. In this study, genome-wide data of 43 species from Polygonatum and its closely related taxa were obtained by Hyb-Seq sequencing. The phylogenetic trees constructed from genome-wide nuclear and chloroplast sequences strongly supported the monophyly of Polygonatum with division into three major clades. A high level of incongruence was detected between nuclear and chloroplast trees as well as among gene trees within the genus, but all occurred within each major clade. However, introgression tests and reticulate evolution analyses revealed low level of gene flow and weak introgression events in the genus, suggesting hybridization and introgression were not dominant during the evolutionary diversification of Polygonatum in the Northern Hemisphere. This study provides important insights into reconstructing evolutionary relationships and speciation pattern of taxa from the north temperate flora.


Subject(s)
Asparagaceae , Polygonatum , Phylogeny , China
3.
Environ Toxicol ; 39(6): 3537-3547, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38469959

ABSTRACT

The antioxidant properties of crocin are attracting interest, yet the underlying mechanisms by which crocin mitigates oxidative stress-induced intestinal damage have not been determined. This study aimed to elucidate the effects of crocin on oxidative stress, apoptosis, and intestinal epithelial injury in intestinal epithelial cells (IPEC-J2). Using an H2O2-induced oxidative stress model in IPEC-J2 cells, crocin was added to assess its effects. Cell viability and apoptosis were evaluated using methyl thiazolyl tetrazolium assays and flow cytometry. Additionally, oxidative stress markers, such as superoxide dismutase (SOD), catalase (CAT), reactive oxygen species (ROS), and malondialdehyde (MDA), were quantified. We investigated, in which cell oxidation and apoptosis were measured at the gene and protein levels and employed transcriptome analysis to probe the mechanism of action and validate relevant pathways. The results showed that crocin ameliorates H2O2-induced oxidative stress by reducing ROS and MDA levels and by countering the reductions in CAT, total antioxidant capacity, and SOD. Crocin also attenuates the upregulation of key targets in the Nrf2 pathway. Furthermore, it effectively mitigated IPEC-J2 cell apoptosis caused by oxidative stress, as evidenced by changes in cell cycle factor expression, apoptosis rate, mitochondrial membrane potential, and apoptosis pathway activity. In addition, crocin preserves the integrity of the intestinal barrier by protecting tight junction proteins against oxidative stress. Transcriptome sequencing analysis suggested that the mitochondrial pathway may be a crucial mechanism through which crocin exerts its protective effects. In summary, crocin decreases oxidative stress molecule formation, inhibits Nrf2 pathway activity, prevents apoptosis-induced damage, enhances oxidative stress resistance in IPEC-J2 cells, and maintains redox balance in the pig intestine.


Subject(s)
Antioxidants , Apoptosis , Carotenoids , Hydrogen Peroxide , Oxidative Stress , Reactive Oxygen Species , Carotenoids/pharmacology , Oxidative Stress/drug effects , Apoptosis/drug effects , Animals , Cell Line , Hydrogen Peroxide/toxicity , Antioxidants/pharmacology , Reactive Oxygen Species/metabolism , Swine , Cell Survival/drug effects , Epithelial Cells/drug effects , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Malondialdehyde/metabolism , Membrane Potential, Mitochondrial/drug effects
4.
J Am Chem Soc ; 145(32): 17945-17953, 2023 08 16.
Article in English | MEDLINE | ID: mdl-37530628

ABSTRACT

Metal-mediated DNA (mmDNA) presents a pathway toward engineering bioinorganic and electronic behavior into DNA devices. Many chemical and biophysical forces drive the programmable chelation of metals between pyrimidine base pairs. Here, we developed a crystallographic method using the three-dimensional (3D) DNA tensegrity triangle motif to capture single- and multi-metal binding modes across granular changes to environmental pH using anomalous scattering. Leveraging this programmable crystal, we determined 28 biomolecular structures to capture mmDNA reactions. We found that silver(I) binds with increasing occupancy in T-T and U-U pairs at elevated pH levels, and we exploited this to capture silver(I) and mercury(II) within the same base pair and to isolate the titration points for homo- and heterometal base pair modes. We additionally determined the structure of a C-C pair with both silver(I) and mercury(II). Finally, we extend our paradigm to capture cadmium(II) in T-T pairs together with mercury(II) at high pH. The precision self-assembly of heterobimetallic DNA chemistry at the sub-nanometer scale will enable atomistic design frameworks for more elaborate mmDNA-based nanodevices and nanotechnologies.


Subject(s)
Mercury , Silver , Base Pairing , Silver/chemistry , DNA/chemistry , Mercury/chemistry
5.
Sensors (Basel) ; 23(10)2023 May 22.
Article in English | MEDLINE | ID: mdl-37430882

ABSTRACT

With the promotion of Industry 4.0, which emphasizes interconnected and intelligent devices, several factories have introduced numerous terminal Internet of Things (IoT) devices to collect relevant data or monitor the health status of equipment. The collected data are transmitted back to the backend server through network transmission by the terminal IoT devices. However, as devices communicate with each other over a network, the entire transmission environment faces significant security issues. When an attacker connects to a factory network, they can easily steal the transmitted data and tamper with them or send false data to the backend server, causing abnormal data in the entire environment. This study focuses on investigating how to ensure that data transmission in a factory environment originates from legitimate devices and that related confidential data are encrypted and packaged. This paper proposes an authentication mechanism between terminal IoT devices and backend servers based on elliptic curve cryptography and trusted tokens with packet encryption using the TLS protocol. Before communication between terminal IoT devices and backend servers can occur, the authentication mechanism proposed in this paper must first be implemented to confirm the identity of the devices and, thus, the problem of attackers imitating terminal IoT devices transmitting false data is resolved. The packets communicated between devices are also encrypted, preventing attackers from knowing their content even if they steal the packets. The authentication mechanism proposed in this paper ensures the source and correctness of the data. In terms of security analysis, the proposed mechanism in this paper effectively withstands replay attacks, eavesdropping attacks, man-in-the-middle attacks, and simulated attacks. Additionally, the mechanism supports mutual authentication and forward secrecy. In the experimental results, the proposed mechanism demonstrates approximately 73% improvement in efficiency through the lightweight characteristics of elliptic curve cryptography. Moreover, in the analysis of time complexity, the proposed mechanism exhibits significant effectiveness.

6.
Neoplasma ; 68(5): 975-982, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34263649

ABSTRACT

Overexpression of discoidin domain receptor 1 (DDR1) is known to enhance the malignancy of breast cancer considerably. This study reports the identification of a potent DDR1 inhibitor, nilotinib, for the treatment of breast cancer. MTT assay was used to evaluate the inhibitory activity of nilotinib and meantime we used flow cytometry to evaluate the pro-apoptotic activity of nilotinib in MCF-7 and MDA-MB-231 cells. Expression of DDR1 was manipulated in MDA-MB-231 and MCF-7 cell lines with low-level DDR1 expression by transfecting with plasmids containing shRNA. The effect of DDR1 or treatment with nilotinib on cell migration was assayed. The expression of p-DDR1, DDR1, p-ERK1/2, ERK1/2 and E-cadherin, Vimentin, Snail1, and caspase 3 were detected by western blot and immunofluorescent staining. Nilotinib in MCF-7 (IC50=0.403 µM) and MDA-MB-231 (IC50=0.819 µM) also indicated induced apoptotic cell death. After co-culturing with nilotinib (500 nM), apoptosis rate is 29.60±2.19% and 18.75±2.30%, respectively. Moreover, nilotinib effectually blocked the cellular migration of MCF-7 cells. Interestingly, the knock-down DDR1 could significantly block the migration of breast cancer, while the sensitivity of MCF-7 and MDA-MB-231 cells to nilotinib was reduced. Targeting DDR1 therapeutically could potentially affect survival and influence metabolism in breast cancer, and nilotinib could be used as a candidate for the treatment of breast cancer.


Subject(s)
Breast Neoplasms , Discoidin Domain Receptor 1 , Apoptosis , Breast Neoplasms/drug therapy , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Humans , Pyrimidines/pharmacology
7.
Sensors (Basel) ; 21(8)2021 Apr 11.
Article in English | MEDLINE | ID: mdl-33920332

ABSTRACT

The vigorous development of the Industrial Internet of Things brings the advanced connection function of the new generation of industrial automation and control systems. The Supervisory Control and Data Acquisition (SCADA) network is converted into an open and highly interconnected network, where the equipment connections between industrial electronic devices are integrated with a SCADA system through a Modbus protocol. As SCADA and Modbus are easily used for control and monitoring, the interconnection and operational efficiency between systems are highly improved; however, such connectivity inevitably exposes the system to the open network environment. There are many network security threats and vulnerabilities in a SCADA network system. Especially in the era of the Industrial Internet of Things, any security vulnerability of an industrial system may cause serious property losses. Therefore, this paper proposes an encryption and verification mechanism based on the trusted token authentication service and Transport Layer Security (TLS) protocol to prevent attackers from physical attacks. Experimentally, this paper deployed and verified the system in an actual field of energy management system. According to the experimental results, the security defense architecture proposed in this paper can effectively improve security and is compatible with the actual field system.

8.
J Org Chem ; 84(1): 181-190, 2019 Jan 04.
Article in English | MEDLINE | ID: mdl-30556392

ABSTRACT

A base-promoted amination of aromatic halides has been developed using a limited amount of dimethylformamide (DMF) or amine as an amino source. Various aryl halides, including F, Cl, Br, and I, have been successfully aminated in good to excellent yields. Although the amination of aromatic halides with amines or DMF is usually considered as an aromatic nucleophilic substitution (SNAr) process, and the reactivity of an aromatic halide is F > Cl > Br > I, the reactivity of aromatic halides in this system was found to be I > Br ≈ F > Cl. This protocol also showed a good regioselectivity for multihalogenated aromatics. This protocol is valuable for industrial application due to the simplicity of operation, the unrestricted availability of amino sources and aromatic halides, transition metal-free conditions, no requirement for solvent, and scalability.

9.
PLoS Genet ; 12(5): e1006061, 2016 05.
Article in English | MEDLINE | ID: mdl-27195782

ABSTRACT

Associative olfactory memory in Drosophila has two components called labile anesthesia-sensitive memory and consolidated anesthesia-resistant memory (ARM). Mushroom body (MB) is a brain region critical for the olfactory memory and comprised of 2000 neurons that can be classified into αß, α'ß', and γ neurons. Previously we demonstrated that two parallel pathways mediated ARM consolidation: the serotonergic dorsal paired medial (DPM)-αß neurons and the octopaminergic anterior paired lateral (APL)-α'ß' neurons. This finding prompted us to ask how this composite ARM is retrieved. Here, we showed that blocking the output of αß neurons and that of α'ß' neurons each impaired ARM retrieval, and blocking both simultaneously had an additive effect. Knockdown of radish and octß2R in αß and α'ß' neurons, respectively, impaired ARM. A combinatorial assay of radish mutant background rsh1 and neurotransmission blockade confirmed that ARM retrieved from α'ß' neuron output is independent of radish. We identified MBON-ß2ß'2a and MBON-ß'2mp as the MB output neurons downstream of αß and α'ß' neurons, respectively, whose glutamatergic transmissions also additively contribute to ARM retrieval. Finally, we showed that α'ß' neurons could be functionally subdivided into α'ß'm neurons required for ARM retrieval, and α'ß'ap neurons required for ARM consolidation. Our work demonstrated that two parallel neural pathways mediating ARM consolidation in Drosophila MB additively contribute to ARM expression during retrieval.


Subject(s)
Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Olfactory Cortex/metabolism , Phosphoproteins/genetics , Receptors, G-Protein-Coupled/genetics , Smell/genetics , Anesthesia/adverse effects , Animals , Animals, Genetically Modified , Drosophila melanogaster/metabolism , Gene Knockdown Techniques , Memory/drug effects , Mushroom Bodies/drug effects , Mushroom Bodies/metabolism , Neurons/drug effects , Neurons/metabolism , Smell/physiology , Synaptic Transmission/drug effects , Synaptic Transmission/genetics
10.
J Cell Mol Med ; 22(1): 646-654, 2018 01.
Article in English | MEDLINE | ID: mdl-29047214

ABSTRACT

The study aimed to investigate the role of Tanshinone IIA (Tan IIA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in its regulation of TRPM7. Wistar male rats were randomly divided into the normal saline (NS), LPS, knockout (KO) + LPS, low-dose Tan IIA (Tan-L), middle-dose Tan IIA (Tan-M), high-dose Tan IIA (Tan-H) and KO + high-dose Tan IIA (KO + Tan-H) groups. The level of tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, TRPM7 protein expression, current density-voltage curve and Ca2+ concentration were detected through ELISA, Western blotting, electrophysiological experiment and a calcium-imaging technique, respectively. The rats in the KO + LPS, Tan-L, Tan-M, Tan-H and KO + Tan-H groups all displayed lower levels of TNF-α, IL-1ß and IL-6 than the LPS group. Rats in the KO + Tan-H group exhibited lower levels of NF-α, IL-1ß and IL-6 than rats in the Tan-H group. Elevated levels of TRPM7 protein expression in the LPS and Tan groups were detected in comparison with the NS group. However, TRPM7 protein expression in Tan-M and Tan-H groups was notably lower than in that of the LPS group. In comparison with the NS group, the LPS and Tan groups had a greater PIMs cell density and a higher concentration of Ca2+ . Contrary results were observed in the KO + LPS, Tan-H and KO + Tan-H groups. Tan IIA decreases calcium influx in PIMs and inhibits pro-inflammatory factors which provide an alleviatory effect in regards to LPS-induced ALI by suppressing TRPM7 expression.


Subject(s)
Abietanes/therapeutic use , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Down-Regulation , Inflammation Mediators/metabolism , TRPM Cation Channels/metabolism , Abietanes/pharmacology , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Animals , Calcium/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Lipopolysaccharides , Lung/drug effects , Lung/pathology , Macrophages/drug effects , Macrophages/metabolism , Male , Organ Size , Oxygen/metabolism , Partial Pressure , Rats, Wistar , Serous Membrane/pathology , Tumor Necrosis Factor-alpha/metabolism
11.
J Cell Biochem ; 119(1): 701-711, 2018 01.
Article in English | MEDLINE | ID: mdl-28636082

ABSTRACT

This study aimed to investigate the protective effects of salvianolic acid B (SA-B) on acute lung injury (ALI) through decreasing the expressions of channel kinase's TRPM6 and TRPM7. Wistar Septic rat models were established by lipopolysaccharide (LPS), which were separated into the control, lipopolysaccharide (LPS), SA-B, SA-B + si-TRPM6, SA-B + si-TRPM7, si-TRPM6, and si-TRPM7 groups. Arterial blood gas, protein content, total white blood cell (WBC) count and the percentage of polymorphonuclear neutrophils (PMN%) were measured. Levels of TNF-α and IL-6 levels in bronchoalveolar lavage fluid (BALF) were monitored. Lung coefficient, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity were conducted by MPO and SOD kit. The mRNA expressions of TRPM6 and TRPM7 were detected by qRT-PCR. Compared with the control group, the PaO2 and PaO2 /FiO2 values exhibited decreases in other group, while the PaCO2 value, protein content, total WBC, PMN%, TNF-α, IL-6 levels and lung coefficient values all increased. MPO activity in lung tissue increased, while SOD activity decreased. TRPM6 and TRPM7 expressions increased significantly. Compared with the LPS group, the SA-B, SA-B + si-TRPM6, SA-B + si-TRPM7, si-TRPM6, and si-TRPM7 groups had increased PaO2 and the PaO2 /FiO2 , while decreased PaCO2, protein content, total WBC, PMN%, TNF-α, IL-6 levels, and lung coefficient. MPO activity in lung tissue decreased while SOD activity increased. Decreased mRNA expressions of TRPM6 and TRPM7 in the SA-B, SA-B + si-TRPM6, and SA-B + si-TRPM6 groups were observed. Through decreasing the expressions of the channel kinase TRPM6 and TRPM7, SA-B protects against ALI in septic rats.


Subject(s)
Acute Lung Injury/prevention & control , Benzofurans/administration & dosage , Down-Regulation , Protein Serine-Threonine Kinases/genetics , Sepsis/drug therapy , Sepsis/genetics , TRPM Cation Channels/genetics , Acute Lung Injury/etiology , Animals , Benzofurans/pharmacology , Bronchoalveolar Lavage Fluid/immunology , Disease Models, Animal , Gene Expression Regulation/drug effects , Interleukin-6/metabolism , Lipopolysaccharides/adverse effects , Male , Protein Serine-Threonine Kinases/metabolism , Rats , Rats, Wistar , Sepsis/chemically induced , Sepsis/metabolism , TRPM Cation Channels/metabolism , Tumor Necrosis Factor-alpha/metabolism
12.
Neurobiol Learn Mem ; 150: 13-19, 2018 04.
Article in English | MEDLINE | ID: mdl-29477608

ABSTRACT

Glucose catabolism, also known as glycolysis, is important for energy generation and involves a sequence of enzymatic reactions that convert a glucose molecule into two pyruvate molecules. The glycolysis process generates adenosine triphosphate as a byproduct. In this study, we investigated whether glycolysis plays a role in maintaining neuronal functions in the Drosophila mushroom bodies (MBs), which are generally accepted to be an olfactory learning and memory center. Our data showed that individual knockdown of glycolytic enzymes in the MBs, including hexokinase (HexA), phosphofructokinase (Pfk), or pyruvate kinase (PyK), disrupts olfactory memory. Whole-mount brain immunostaining indicated that pyruvate kinase is strongly expressed in the MB αß, α'ß', and γ neuron subsets. We conclude that HexA, Pfk, and PyK are required in each MB neuron subset for olfactory memory formation. Our data therefore indicates that glucose catabolism in the MBs is important for olfactory memory formation in Drosophila.


Subject(s)
Glycolysis/physiology , Memory/physiology , Mushroom Bodies/metabolism , Olfactory Perception/physiology , Animals , Animals, Genetically Modified , Drosophila , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Hexokinase/genetics , Hexokinase/metabolism , Neurons/physiology , Phosphofructokinase-1/genetics , Phosphofructokinase-1/metabolism , Pyruvate Kinase/genetics , Pyruvate Kinase/metabolism , Smell/physiology
13.
Chemistry ; 24(41): 10324-10328, 2018 Jul 20.
Article in English | MEDLINE | ID: mdl-29897649

ABSTRACT

Pd-catalyzed Hiyama vinylation reaction of non-activated aryl chlorides and bromides under mild conditions was developed. The use of efficient vinyl donors and electron-rich sterically hindered phosphine ligands was critical for the success of the reaction. The products of this transformation can be used for Am/Cm separation, an important challenge in nuclear fuel reprocessing. The substituent effect on Am/Cm separating selectivity was also achieved, which could contribute to the development of new chromatographic materials for the separation of Am and Cm.

14.
Breast Cancer Res Treat ; 163(2): 241-254, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28299476

ABSTRACT

BACKGROUND: "Precision medicine" is a concept that by utilizing modern molecular diagnostics, an effective therapy is accurately applied for each cancer patient to improve their survival rates. The treatment of triple-negative breast cancer (TNBC) remains a challenging issue. The aim of this study was to compare the molecular subtypes of triple-negative breast cancer (TNBC) between Taiwanese and Non-Asian women. METHODS: GEO Datasets for non-Asian (12 groups, n = 1450) and Taiwanese (3 groups, n = 465) breast cancer, including 617 TNBC, were acquired, normalized and cluster analyzed. Then, using TNBC cell lines of different subtypes, namely, MDA-MB-468 (basal-like1, BL1), MDA-MB-231 (mesenchymal stem like, MSL), BT-549 (mesenchymal, M), MDA-MB-453 (luminal androgen receptor, LAR), and DU4475 (immunomodulatory, IM), real-time PCR in triplicate for 47 genes signatures were performed to validate the specificity of these subtypes. RESULTS: The results showed that the percentage of TNBC subtypes in non-Asian women, namely, BL1, BL2, IM, M, MSL, and LAR was 13.56, 8.91, 16.80, 20.45, 8.30, and 11.13%, respectively. When data from Taiwanese were normalized and clustered, five TNBC subtypes, namely, BL (8.94%), IM (13.82%), M (22.76%), MSL (30.89%), and LAR (23.58%), were classified. Real-time PCR validated the specificity of these subtypes. Besides, the presence of interaction between IM- and MSL-subtypes suggests the involvement of tumor microenvironment in TNBC subtype classification. CONCLUSION: Our data suggested that there exist different presentations between non-Asian and Taiwanese TNBC subtypes, which provides important information when selection of therapeutic targets or designs for clinical trials for TNBC patients.


Subject(s)
Triple Negative Breast Neoplasms/genetics , Cell Line, Tumor , Cluster Analysis , Female , Humans , Signal Transduction , Taiwan , Triple Negative Breast Neoplasms/ethnology , Triple Negative Breast Neoplasms/metabolism
15.
Inorg Chem ; 56(19): 11917-11928, 2017 Oct 02.
Article in English | MEDLINE | ID: mdl-28933540

ABSTRACT

A hexadentate macrocyclic N-heterocyclic carbene (NHC) ligand precursor (H4L)(PF6)4 containing four benzimidazolium and two secondary amine groups, has been synthesized and characterized. Coordination chemistry of this new macrocyclic diamine-tetracarbene ligand has been studied by the synthesis of its Ag(I), Au(I), Ni(II), and Pd(II) complexes. Reactions of (H4L)(PF6)4 with different equiv of Ag2O result in Ag(I) complexes [Ag(H2L)](PF6)3 (1) and [Ag2(H2L)](PF6)4 (2). A mononuclear Au(I) complex [Au(H2L)](PF6)3 (3) and a trinuclear Au(I) complex [Au3(H2L)(Cl)2](PF6) (4) are obtained by transmetalation of 1 and 2 with AuCl(SMe2), respectively. Reactions of (H4L)(PF6)4 with Ni(OAc)2 and Pd(OAc)2 in the presence of NaOAc yield [Ni(L)](PF6)2 (5) and [Pd(L)](PF6)2 (6), respectively, containing one Ni(II) and Pd(II) ion with distorted square-planar geometry. Using more NaOAc results in the formation of unusual dinuclear complexes [Ni2(L-2H)](PF6)2 (7) and [Pd2(L-2H)](PF6)2 (8) (L-2H = deprotonated ligand after removing two H+ ions from two secondary amine groups in L), respectively, featuring a rare M2N2 core formed by two bridging amides. 7 is also formed by the reaction of 5 with 1.0 equiv of Ni(OAc)2·4H2O in the presence of NaOAc. Transmetalation of 2 with 2.0 equiv of Ni(PPh3)2Cl2 gives [Ni2(L)(µ-O)](PF6)2 (9), the first example of a dinuclear Ni(II) complex with a singly bridging oxo group. 9 is converted to 7 in good yield through the treatment with NaOAc.

16.
Genes Dev ; 23(10): 1183-94, 2009 May 15.
Article in English | MEDLINE | ID: mdl-19451219

ABSTRACT

CISD2, the causative gene for Wolfram syndrome 2 (WFS2), is a previously uncharacterized novel gene. Significantly, the CISD2 gene is located on human chromosome 4q, where a genetic component for longevity maps. Here we show for the first time that CISD2 is involved in mammalian life-span control. Cisd2 deficiency in mice causes mitochondrial breakdown and dysfunction accompanied by autophagic cell death, and these events precede the two earliest manifestations of nerve and muscle degeneration; together, they lead to a panel of phenotypic features suggestive of premature aging. Our study also reveals that Cisd2 is primarily localized in the mitochondria and that mitochondrial degeneration appears to have a direct phenotypic consequence that triggers the accelerated aging process in Cisd2 knockout mice; furthermore, mitochondrial degeneration exacerbates with age, and the autophagy increases in parallel to the development of the premature aging phenotype. Additionally, our Cisd2 knockout mouse work provides strong evidence supporting an earlier clinical hypothesis that WFS is in part a mitochondria-mediated disorder; specifically, we propose that mutation of CISD2 causes the mitochondria-mediated disorder WFS2 in humans. Thus, this mutant mouse provides an animal model for mechanistic investigation of Cisd2 protein function and help with a pathophysiological understanding of WFS2.


Subject(s)
Aging, Premature/physiopathology , Aging/genetics , Aging/metabolism , Carrier Proteins/metabolism , Mitochondria/metabolism , Nerve Tissue Proteins/deficiency , Nerve Tissue Proteins/metabolism , Aging, Premature/genetics , Animals , Autophagy , Autophagy-Related Proteins , Disease Models, Animal , Female , Glucose Intolerance/genetics , Glucose Intolerance/physiopathology , Humans , Longevity/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Muscles/pathology , Neurons/pathology , Optic Nerve Diseases/genetics , Optic Nerve Diseases/physiopathology , Wolfram Syndrome/physiopathology
17.
Org Biomol Chem ; 13(9): 2541-5, 2015 Mar 07.
Article in English | MEDLINE | ID: mdl-25598077

ABSTRACT

A novel "one-pot" reaction was developed for the synthesis of aryl or heteroaryl-substituted amidoxime compounds containing various functional groups. Fluorescence titration experiments coupled with theoretical analysis revealed that the steric hindrance and electronic effects of substituents influence the binding ability of the amidoxime compounds to uranyl ions.

18.
Diabetologia ; 57(2): 424-34, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24317792

ABSTRACT

AIMS/HYPOTHESIS: Chronic inflammatory processes have been increasingly shown to be involved in the pathogenesis of diabetes and diabetic nephropathy. Recently, we demonstrated that a lectin-like domain of thrombomodulin (THBD), which is known as THBD domain 1 (THBDD1) and which acts independently of protein C activation, neutralised an inflammatory response in a mouse model of sepsis. Here, therapeutic effects of gene therapy with adeno-associated virus (AAV)-carried THBDD1 (AAV-THBDD1) were tested in a mouse model of type 2 diabetic nephropathy. METHODS: To assess the therapeutic potential of THBDD1 and the mechanisms involved, we delivered AAV-THBDD1 (10(11) genome copies) into db/db mice and tested the effects of recombinant THBDD1 on conditionally immortalised podocytes. RESULTS: A single dose of AAV-THBDD1 improved albuminuria, renal interstitial inflammation and glomerular sclerosis, as well as renal function in db/db mice. These effects were closely associated with: (1) inhibited activation of the nuclear factor κB (NF-κB) pathway and the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome; (2) promotion of nuclear factor (erythroid-derived 2)-like 2 (NRF2) nuclear translocation; and (3) suppression of mitochondria-derived apoptosis in the kidney of treated mice. CONCLUSIONS/INTERPRETATION: AAV-THBDD1 gene therapy resulted in improvements in a model of diabetic nephropathy by suppressing the NF-κB-NLRP3 inflammasome-mediated inflammatory process, enhancing the NRF2 antioxidant pathway and inhibiting apoptosis in the kidney.


Subject(s)
Antioxidants/pharmacology , Carrier Proteins/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/pathology , Diabetic Nephropathies/metabolism , Genetic Therapy , Inflammasomes/metabolism , NF-kappa B/metabolism , Thrombomodulin/metabolism , Animals , Apoptosis/drug effects , Carrier Proteins/antagonists & inhibitors , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/immunology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/immunology , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/immunology , Genetic Therapy/methods , Inflammation/drug therapy , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein
19.
Chemistry ; 20(47): 15334-8, 2014 Nov 17.
Article in English | MEDLINE | ID: mdl-25308802

ABSTRACT

A copper-catalyzed reductive cross-coupling reaction of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides was developed. It provides a practical method for efficient and cost-effective construction of aryl-alkyl and alkyl-alkyl CC bonds with stereocontrol from readily available substrates. When used in an intramolecular fashion, the reaction enables convenient access to various substituted carbo- or heterocycles, such as 2,3-dihydrobenzofuran and benzochromene derivatives.

20.
ScientificWorldJournal ; 2014: 101529, 2014.
Article in English | MEDLINE | ID: mdl-24955382

ABSTRACT

Finding ways to distribute workloads to each processor core and efficiently reduce power consumption is of vital importance, especially for real-time systems. In this paper, a novel scheduling algorithm is proposed for real-time multicore systems to balance the computation loads and save power. The developed algorithm simultaneously considers multiple criteria, a novel factor, and task deadline, and is called power and deadline-aware multicore scheduling (PDAMS). Experiment results show that the proposed algorithm can greatly reduce energy consumption by up to 54.2% and the deadline times missed, as compared to the other scheduling algorithms outlined in this paper.


Subject(s)
Algorithms , Computer Systems
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