Design, Synthesis and Characterization of Palladium-Functionalized Covalent Organic Framework and Its Application as Heterogeneous Catalysis for C-H Arylation of Azoles.

A novel triazine-based covalent organic framework (TFPT-Bz COF) has been constructed by the condensation of 2,4,6-tris(5-formyl-2-pyridinoxy)-1,3,5-triazine (TFPT) and benzidine (BZ) with deep eutectic solvent (DES) as the reaction medium. After the introduction of Pd ions through strong coordination to TFPT-Bz COF matrix, the constructed TFPT-Bz COF/Pd composite exhibited excellent catalytic activity for C-H arylation of azoles with aryl halides in 2-methyltetrahydrofuran. The protocol allows the arylation of a variety of substituted azoles with diverse aryl halides in high to excellent yield. Moreover, the TFPT-Bz COF/Pd catalyst can be recycled several times without significantly reducing its activity.

Visible-Light-Mediated Oxidative Amidation of Aldehydes by Using Magnetic CdS Quantum Dots as a Photocatalyst.

A magnetic CdS quantum dot (Fe3 O4 /polydopamine (PDA)/CdS) was synthesized through a facile and convenient method from inexpensive starting materials. Characterization of the prepared catalyst was performed by means of FTIR spectroscopy, XRD, SEM, TEM, energy-dispersive X-ray spectroscopy, and vibrating-sample magnetometer techniques. Fe3 O4 /PDA/CdS was found to be a highly active photocatalyst for the amidation of aromatic aldehydes by using air as a clean oxidant under mild conditions. The photocatalyst can be recovered by magnetic separation and successfully reused for five cycles without considerable loss of its catalytic activity.

Physical and neuropsychological development of children with Citrin deficiency. / Citrinç¼ºé™·ç— æ‚£å„¿ä½“æ ¼å’Œç¥žç»å¿ƒç†å‘è‚²çŠ¶å†µ.

OBJECTIVES: To study the physical and neuropsychological development of children with Citrin deficiency (CD). METHODS: A total of 93 children, aged 1.9-59.8 months, who were diagnosed with CD by SLC25A13 gene analysis in the First Affiliated Hospital of Jinan University from August 2010 to August 2015, were enrolled as subjects. A retrospective analysis was performed for their birth condition and physical growth and neuropsychological development indices. Among these children, 7 underwent physical measurement and neuropsychological development assessment within 1 year old and after 1 year old, and therefore, a total of 100 cases were included for analysis. RESULTS: For the 93 children with CD, the incidence rate of failure to thrive was 25% (23 children) and the proportion of small for gestational age was 47% (44 children). For the 100 cases of CD, the incidence rates of growth retardation, underweight, emaciation, overweight, and microcephalus were 23% (23 cases), 14% (14 cases), 4% (4 cases), 8% (8 cases), and 9% (9 cases), respectively. The incidence rate of neuropsychological developmental delay was 25% (25 cases), and the incidence rates of development delay in the five domains of adaptability, gross motor, fine motor, language, and social ability were 7% (7 cases), 15% (15 cases), 7% (7 cases), 9% (9 cases), and 7% (7 cases), respectively. CONCLUSIONS: Physical and neuropsychological developmental delay can be observed in children with CD, and physical and neuropsychological development should be regularly assessed.

Photocontrolled Reversible Luminescent Lanthanide Molecular Switch Based on a Diarylethene-Europium Dyad.

A new europium complex coordinated between a Eu(III) ion and an unsymmetrical diarylperfluorocyclopentene yields a light-controlled diarylethene-europium dyad, DAE@TpyEu(tta)3, whose photophysical properties can be reversibly switched by optical stimuli. When DAE@TpyEu(tta)3 is exposed to 365 nm UV light, an efficient intramolecular photochromic fluorescence resonance energy transfer (pc-FRET) occurs between the emission of the Eu(3+) donor (D) and the absorption of the diarylethene acceptor (A) in closed-form DAE@TpyEu(tta)3 accompanied by luminescence quenching. However, the pc-FRET process could be effectively inhibited by visible light (λ > 600 nm) irradiation, and the lanthanide emission of DAE@TpyEu(tta)3 is rapidly recovered. Furthermore, this luminescent lanthanide molecular switch could serve as a highly reliable and sensitive "turn on" fluorescent marker in living cells irradiated by red light without any optical interference.

[Clinical features and DGUOK mutations of an infant with mitochondrial DNA depletion syndrome].

The aim of this study was to investigate the clinical features and DGUOK gene mutations of an infant with mitochondrial DNA depletion syndrome (MDS). The patient (more than 7 months old) manifested as hepatosplenomegaly, abnormal liver function, nystagmus and psychomotor retardation. Genetic DNA was extracted from peripheral blood samples of the patient and her parents. Targeted Exome Sequencing was performed to explore the genetic causes. Sanger sequencing was carried out to confirm the detected mutations. The sequencing results showed that the patient was a compound heterozygote for c.679G>A and c.817delT in the DGUOK gene. The former was a reportedly pathogenic missense mutation of maternal origin, while the latter, a frameshift mutation from the father, has not been described yet. The findings in this study expand the mutation spectrum of DGUOK gene, and provide molecular evidence for the etiologic diagnosis of the patient as well as for the genetic counseling and prenatal diagnosis in the family.

Screening for five prevalent mutations of SLC25A13 gene in Guangdong, China: a molecular epidemiologic survey of citrin deficiency.

Citrin is the liver-type aspartate/glutamate carrier isoform 2 (AGC2) encoded by SLC25A13 gene, playing important roles in the urea cycle and the malate-aspartate shuttle. Citrin deficiency (CD) has proven a disease entity with high prevalence in south China, including Guangdong with the largest population, but CD epidemiology in this province has not been well characterized. This study aims to screen for five prevalent SLC25A13 mutations, c.851_854del (p.R284fs286X), c.1638_1660dup (p.A554fs570X), c.615+5G>A (p.A206fs212X), IVS16ins3kb (p.A584fs585X) and c.1399C>T (p.R467X), to calculate the mutation carrier rate in Guangdong. A total of 2,428 used blood samples for health examination were collected as the research subjects, including 1,558 from 5 cities in the Pearl River Delta area and the remaining 870 from 4 peripheral cities, and the 5 mutations screened using High Resolution Melting Assay and HybProbe assay. A total of 52 carriers were detected, including 2 carriers of a novel c.1420G>A (p.V474M) mutation that impairs citrin function, as judged by the functional analysis in the yeast system. The carrier rate was higher in Pearl River Delta area than that in the peripheral cities (26/1,558 vs. 26/870, with χ(2) = 4.639 and P < 0.05). The carrier rate was around 1/47 (52/2,428), theoretically with the CD morbidity of 1/8,800 and the number of CD patients over 11,800 in Guangdong population. This study has provided primary epidemiologic data for the evaluation of CD effect in Guangdong province. Moreover, the newly identified c.1420G>A mutation that impairs AGC2 function has enriched the mutation spectrum of human SLC25A13 gene.

Silencing LINC00987 ameliorates adriamycin resistance of acute myeloid leukemia via miR-4458/HMGA2 axis.

BACKGROUND: Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML. METHODS: In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML. RESULTS: We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells. CONCLUSIONS: Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.

[Cloning and sequence analysis of SLC25A13 transcripts in human amniocytes].

OBJECTIVE: This research intends to amplify the entire coding region sequences of SLC25A13 mRNA which encodes citrin, and to investigate sequence features of the transcripts for this gene in cultured human amniocytes. This study will provide laboratory evidence for prenatal diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) at mRNA level. METHODS: One amniocyte sample was collected from a pregnant woman who underwent prenatal diagnosis of citrin deficiency and whose fetus has proven a carrier of 851del4 mutation by genomic DNA analysis. Another amniocyte sample, as a control, was from a fetus without family history of citrin deficiency. Total RNA was extracted from cultured amniocytes, cDNA was synthesized, and then nested-PCR was performed to amplify the entire coding region sequences of SLC25A13. The PCR products were cloned and analyzed by sequencing. RESULTS: The entire coding region of SLC25A13 gene was successful amplified from two cultured human amniocytes. The splice variant of SLC25A13, SLCA (normal mRNA), was identified in the two samples. SLCB (CAG insertion between exon 9-10) was identified in the control. SLCC (exon 5-11 skipping), but not transcriptional product from the allele with 851del4 mutation, was identified in the 851del4 mutation carrier. CONCLUSIONS: This study demonstrated that the entire coding region of SLC25A13 cDNA can be successfully amplified from two cultured human amniocytes, and revealed exon 5-11 skipping as a novel SLC25A13 transcript. Normal mRNA predominated in the transcripts in normal control and 851del4 mutation carrier, suggesting that the two fetuses were not at risk for NICCD. These SLC25A13 transcription features provided laboratory evidence for prenatal diagnosis of NICCD.

Alagille syndrome associated with total anomalous pulmonary venous connection and severe xanthomas: A case report.

BACKGROUND: Alagille syndrome (ALGS) is an autosomal dominant genetic disorder caused by mutations in the JAG1 or NOTCH2 gene. It is characterized by decreased intrahepatic bile ducts associated with a variety of abnormalities in many other organ systems, such as the cardiovascular, skeletal, and urinary systems. CASE SUMMARY: We report a rare case of ALGS. A 1-month-old male infant presented with sustained jaundice and had a rare congenital heart disease: Total anomalous pulmonary venous connection (TAPVC). Sustained jaundice, particularly with cardiac murmur, caught our attention. Laboratory tests revealed elevated levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, and total bile acids, indicating serious intrahepatic cholestasis. Imaging confirmed the presence of butterfly vertebra at the seventh thoracic vertebra. This suggested ALGS, which was confirmed by genetic testing with a c.3197dupC mutation in the JAG1 gene. Ursodiol was administered immediately after confirmation of the diagnosis, and cardiac surgery was performed when the patient was 1.5 month old. He recovered well after treatment and was discharged at the age of 3 mo. At the age of two years, the patient returned to our clinic because multiple cutaneous nodules with xanthomas appeared, and their size and number increased over time. CONCLUSION: We report a unique case of ALGS associated with TAPVC and severe xanthomas. This study has enriched the clinical manifestations of ALGS and emphasized the association between JAG1 gene and TAPVC.

Histone H3K4me3 modification is a transgenerational epigenetic signal for lipid metabolism in Caenorhabditis elegans.

As a major risk factor to human health, obesity presents a massive burden to people and society. Interestingly, the obese status of parents can cause progeny's lipid accumulation through epigenetic inheritance in multiple species. To date, many questions remain as to how lipid accumulation leads to signals that are transmitted across generations. In this study, we establish a nematode model of C. elegans raised on a high-fat diet (HFD) that leads to measurable lipid accumulation, which can transmit the lipid accumulation signal to their multigenerational progeny. Using this model, we find that transcription factors DAF-16/FOXO and SBP-1/SREBP, nuclear receptors NHR-49 and NHR-80, and delta-9 desaturases (fat-5, fat-6, and fat-7) are required for transgenerational lipid accumulation. Additionally, histone H3K4 trimethylation (H3K4me3) marks lipid metabolism genes and increases their transcription response to multigenerational obesogenic effects. In summary, this study establishes an interaction between a network of lipid metabolic genes and chromatin modifications, which work together to achieve transgenerational epigenetic inheritance of obesogenic effects.

Catalyst-free Synthesis of Aminomethylphenol Derivatives in Cyclopentyl Methyl Ether via Petasis Borono-Mannich Reaction.

OBJECTIVE: Aminomethylphenol molecules have wider applications in pharmaceuticals, agrochemicals, plant protection and promising functional materials. The development of an efficient and practical method to prepare this class of compound is highly desirable from both environmental and economical points of view. MATERIALS AND METHODS: In order to establish an effective synthetic method for preparing aminomethylphenol derivatives, the Petasis borono-Mannich reaction of salicylaldehyde, phenylboronic acid and 1,2,3,4- tetrahydroisoquinoline was selected as a model reaction. A variety of reaction conditions are investigated, including solvent and temperature. The generality and limitation of the established method were also evaluated. RESULTS AND DISCUSSION: It was found that model reaction can be carried out in cyclopentyl methyl ether at 80 oC under catalyst-free conditions. This protocol, with broad substrate applicability, the reaction of various arylboronic acid, secondary amine and salicylaldehyde proceeded smoothly under optimal reaction conditions to afford various aminomethylphenol derivatives in high yields. A practical, scalable, and high-yielding synthesis of aminomethylphenol derivatives was successfully accomplished. CONCLUSION: A catalyst-free practical method for the synthesis of minomethylphenol derivatives based on Petasis borono-Mannich (PBM) reaction of various arylboronic acid, secondary amine and salicylaldehyde in cyclopentyl methyl ether has been developed. The salient features of this protocol are avoidance of any additive/catalyst and toxic organic solvents, use of cyclopentyl methyl ether as the reaction medium, clean reaction profiles, easy operation, and high to excellent yield.

A terbium(III) lanthanide-organic framework as a selective and sensitive iodide/bromide sensor in aqueous medium.

A potent luminescent sensor for the detection of iodide ions was developed based on a terbium(iii)-based lanthanide-organic framework [Tb(cpia)(H2O)2]n·nH2O (1), which was prepared under hydrothermal conditions using the 5-(4-carboxyphenoxy)isophthalic acid (H3cpia) bridging ligand. Compound 1 exhibits superior luminescence quenching behavior towards I- with high sensitivity and selectivity among various anions and shows real-time response. Moreover, the mechanism of the selective luminescence quenching response for I- can be mainly explained by the absorption competition between 1 and I-. According to this quenching mechanism, we find that compound 1 can also detect Br- by adjusting the excitation wavelength. Significantly, this work could serve as a general guidance for the design and synthesis of pollutant sensors.

Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency: In vivo and in vitro studies of the aberrant transcription arising from two novel splice-site variants in SLC25A13.

Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD) is an autosomal recessive disease resulting from biallelic SLC25A13 mutations, and its diagnosis relies on genetic analysis. This study aimed to characterize the pathogenicity of 2 novel splice-site variants of SLC25A13 gene. Two patients (C0476 and C0556) suspected to have NICCD, their family members and 9 healthy volunteers were recruited as the research subjects. The SLC25A13 genotypes NG_012247.2(NM_014251.3): c.[852_855del]; [69+5G > A] in patient C0476 and c.[1453-1G > A]; [1751-5_1751-4ins (2684)] in patient C0556 were identified by means of polymerase chain reaction, long and accurate polymerase chain reaction, as well as Sanger sequencing. The 2 splice-site variants were absent in control databases and predicted to be pathogenic by computational analysis. The alternative splice variants in monocyte-derived macrophages from patient C0476 demonstrated exon 2 skipping [r.16_69del; p.(Val6_Lys23del)] in vivo, while minigene analysis revealed both exon 2-skipping and retained products from c.69+5G > A in vitro. In the patient C0556, an aberrant transcript [r.1453del; p.(Gly485Valfs*22)] resulting from c.1453-1G > A was detected on minigene splicing study. Thus, c.69+5G > A and c.1453-1G > A were both proved to be pathogenic. The 2 novel splice-site variants expanded the SLC25A13 mutation spectrum and provided reliable molecular markers for the definite diagnosis and genetic counseling of NICCD in the affected families.

Molecular epidemiologic study of citrin deficiency by screening for four reported pathogenic SLC25A13 variants in the Shaanxi and Guangdong provinces, China.

BACKGROUND: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China. METHODS: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG_012247.2 (NM_014251.3): c.852_855del, c.1638_1660dup, c.615+5G>A, and c.1751-5_1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests. RESULTS: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ2=8.570, P=0.003) in general, with higher c.852_855del (54/6,818 vs. 13/5,492, χ2=17.328, P=0.000) but lower c.1751-5_1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638_1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly. CONCLUSIONS: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China.

Synthesis of 2,3-dihydroquinazolin-4(1H)-ones by three-component coupling of isatoic anhydride, amines, and aldehydes catalyzed by magnetic Fe(3)O(4) nanoparticles in water.

A simple and efficient protocol for one-pot three-component coupling of isatoic anhydride, amines, and aldehydes in water using magnetically recoverable Fe(3)O(4) nanoparticles is reported. This methodology results in the synthesis of a variety of 2,3-dihydroquinazolin-4(1H)-ones in high yields. The catalyst can be recovered and recycled without a significant loss in the catalytic activity.

Visible-Light-Initiated One-Pot, Three-Component Synthesis of 2-Amino-4H-pyran-3,5-dicarbonitrile Derivatives.

A novel approach for the visible-light-initiated synthesis of 2-amino-4H-pyran-3,5-dicarbonitrile derivatives via a one-pot, three-component reaction of aldehydes or isatins, malononitrile, and α-cyano ketones has been developed. The reaction was carried out at room temperature in ethanol/water to give the corresponding products with a wide range of functional groups in high yields. This process did not require any additives or chromatographic separation and could be applied for gram-scale synthesis.

Bioinformatic and functional analysis of promoter region of human SLC25A13 gene.

The human SLC25A13 gene encodes the liver type aspartate/glutamate carrier isoform 2 (AGC2, commonly named as citrin), which plays a key role in the main NADH-shuttle of human hepatocyte. Biallelic SLC25A13 mutations result in Citrin deficiency (CD). In order to identify the important regulatory region of SLC25A13 gene and elucidate the way how potential promoter mutations affect the citrin expression, we performed promoter deletion analysis and established the reporter constructs of luciferase gene-carrying SLC25A13 promoter containing several mutations located in putative transcription factor-binding sites. The luciferase activities of all promoter constructs were measured using a Dual-Luciferase Reporter Assay System. Bioinformatic analysis showed that the promoter of SLC25A13 gene lacks TATA box and obviously typical initiator element, but contains a CCAAT box and two GC box. Promoter deletion analysis confirmed the region from -221 to -1 upstream ATG was essential for SLC25A13 to maintain the promoter activity. We utilized dual-luciferase reporter system as function analytical model to tentatively assess the effect of artificially constructed promoter mutations on citrin expression, and our analysis revealed that mutated putative CCAAT box and GC box could significantly affect the citrin expression. Our study confirmed the important SLC25A13 promoter regions that influenced citrin expression in HL7702 cells, and constructed a function analytical model. This work may be useful to further identify the pathogenic mutations leading to CD in the promoter region.

Ultrasound-assisted synthesis of pyrroles catalyzed by zirconium chloride under solvent-free conditions.

A straightforward synthesis of substituted pyrroles using zirconium chloride-catalyzed modified Paal-Knorr method has been accomplished under ultrasound irradiation. Compared to known methods, this new method provides as easy access to various substituted pyrroles in good to excellent yields with short reaction times.

(Z)-3-[1-(4-Methoxy-anilino)ethyl-idene]-4,5-dihydro-furan-2(3H)-one.

In the title compound, C(13)H(15)NO(3), the dihydro-furan-one ring is planar to within 0.012 (4) Šand it forms a dihedral angle of 42.8 (2)° with the benzene ring. The amino-ethyl-idene group is coplanar with the dihydro-furan-one ring. The meth-oxy group is slightly twisted away from the benzene ring. An intra-molecular N-H⋯O hydrogen bond, generating an S(6) ring, is observed. In the crystal structure, the mol-ecules exist as C-H⋯O hydrogen-bonded dimers.

(Z)-3-Anilino-1,3-diphenylprop-2-en-1-one.

In the title compound, C(21)H(17)NO, the phenyl ring directly linked to the carbonyl group is oriented at an angle of 7.3 (2)° with respect to the aniline ring, and at an angle of 55.6 (2)° with respect to the other phenyl ring. There is an intra-molecular hydrogen bond involving the NH group and the carbonyl O atom. The crystal structure is stabilized by weak C-H⋯π inter-actions, which link the mol-ecules into a herringbone arrangement.