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1.
J Am Chem Soc ; 146(29): 19621-19628, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38739092

RESUMEN

For nearly 60 years, significant research efforts have been focused on developing strategies for the cycloaddition of bicyclobutanes (BCBs). However, higher-order cycloaddition and catalytic asymmetric cycloaddition of BCBs have been long-standing formidable challenges. Here, we report Pd-catalyzed ligand-controlled, tunable cycloadditions for the divergent synthesis of bridged bicyclic frameworks. The dppb ligand facilitates the formal (5+3) cycloaddition of BCBs and vinyl oxiranes, yielding valuable eight-membered ethers with bridged bicyclic scaffolds in 100% regioselectivity. The Cy-DPEphos ligand promotes selective hetero-[2σ+2σ] cycloadditions to access pharmacologically important 2-oxabicyclo[3.1.1]heptane (O-BCHeps). Furthermore, the corresponding catalytic asymmetric synthesis of O-BCHeps with 94-99% ee has been achieved using chiral (S)-DTBM-Segphos, representing the first catalytic asymmetric cross-dimerization of two strained rings. The obtained O-BCHeps are promising bioisosteres for ortho-substituted benzenes.

2.
Emerg Infect Dis ; 30(1): 29-38, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38146984

RESUMEN

Resurgence and spread of macrolide-resistant Bordetella pertussis (MRBP) threaten global public health. We collected 283 B. pertussis isolates during 2016-2022 in Shanghai, China, and conducted 23S rRNA gene A2047G mutation detection, multilocus variable-number tandem-repeat analysis, and virulence genotyping analysis. We performed whole-genome sequencing on representative strains. We detected pertussis primarily in infants (0-1 years of age) before 2020 and older children (>5-10 years of age) after 2020. The major genotypes were ptxP1/prn1/fhaB3/ptxA1/ptxC1/fim2-1/fim3-1 (48.7%) and ptxP3/prn2/fhaB1/ptxA1/ptxC2/fim2-1/fim3-1 (47.7%). MRBP increased remarkably from 2016 (36.4%) to 2022 (97.2%). All MRBPs before 2020 harbored ptxP1, and 51.4% belonged to multilocus variable-number tandem-repeat analysis type (MT) 195, whereas ptxP3-MRBP increased from 0% before 2020 to 66.7% after 2020, and all belonged to MT28. MT28 ptxP3-MRBP emerged only after 2020 and replaced the resident MT195 ptxP1-MRBP, revealing that 2020 was a watershed in the transformation of MRBP.


Asunto(s)
Bordetella pertussis , Tos Ferina , Niño , Lactante , Humanos , Adolescente , Preescolar , Bordetella pertussis/genética , Tos Ferina/epidemiología , China/epidemiología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Macrólidos/farmacología , Evolución Molecular
3.
Ann Clin Microbiol Antimicrob ; 22(1): 104, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37993871

RESUMEN

OBJECTIVE: To investigate the characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) in bone and joint infection (BJI) among children. METHODS: A total of 338 patients diagnosed with BJI from 2013 to 2022 in Children's Hospital of Fudan University were enrolled. Demographic information, microbiology culture results and laboratory findings, including white blood counts (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and erythrocyte sedimentation rate (ESR) were collected and analyzed. MRSA was confirmed by antimicrobial susceptibility testing. Other MRSA-caused infections were randomly selected for comparison. Twenty-three virulence and antimicrobial resistance (AMR) genes were screened for MRSA strains. Multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing were performed using PCR amplification and sequencing. RESULTS: Of the identified pathogens in BJI, MRSA accounted for 21.0% (47/224). Patients with BJI had high levels of initial CRP, white blood cell count (WBC) and IL-6. ST59 (43.9%) and t437 (37.6%) were the main MRSA subtypes isolated from the children. The major genotypes in BJI were ST59-t437 (29.8%) and ST22-t309 (14.9%), with high carriage of hemolysins including hla (94.4-100%), hlb (66.2-93.3%), and hld (100%). Notably, Panton-Valentine leukocidin (pvl) had a high prevalence (53.3%) in ST22-t309-MRSA. Other virulence genes including tst, seg and sei were more commonly detected in ST22-t309-MRSA (40.0-46.7%) than in ST59-t437-MRSA (4.2-9.9%). High-carriage AMR genes in MRSA included aph(3')/III (66.7-80%), ermB (57.5-73.3%) and ermC (66.7-78.9%). MRSA presented high-resistance to erythromycin (52.0-100%) and clindamycin (48.0-92.5%), different genotypes displayed variation in their susceptibilities to antibiotics. CONCLUSIONS: The major MRSA genotype in BJI was ST59-t437, followed by ST22-t309, with a higher prevalence of the pvl gene. Continuous surveillance of pvl-positive ST22-t309-MRSA in pediatric BJI infections is thus required.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Niño , Humanos , Tipificación de Secuencias Multilocus/métodos , Interleucina-6/genética , Infecciones Estafilocócicas/microbiología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
4.
Molecules ; 28(5)2023 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-36903420

RESUMEN

The development of an efficient and straightforward method for cyanation of alcohols is of great value. However, the cyanation of alcohols always requires toxic cyanide sources. Herein, an unprecedented synthetic application of an isonitrile as a safer cyanide source in B(C6F5)3-catalyzed direct cyanation of alcohols is reported. With this approach, a wide range of valuable α-aryl nitriles was synthesized in good to excellent yields (up to 98%). The reaction can be scaled up and the practicability of this approach is further manifested in the synthesis of an anti-inflammatory drug, naproxen. Moreover, experimental studies were performed to illustrate the reaction mechanism.

5.
Angew Chem Int Ed Engl ; 62(48): e202310066, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-37822277

RESUMEN

Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but are difficult to access. Here a silver-catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N-unprotected indoles and bicyclobutane precursors is described. The strain-release dearomative cycloaddition operates under mild conditions, tolerating a wide range of functional groups. It is capable of forming BCHs with up to four contiguous quaternary carbon centers, achieving yields of up to 99 %. In addition, a scale-up experiment and the synthetic transformations of the cycloadducts further highlighted the synthetic utility.

6.
Amino Acids ; 46(2): 449-57, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24414219

RESUMEN

A binary targeting vector that consists of peptide sequences of Arg-Gly-Asp (RGD) and Asn-Gly-Arg (NGR) motifs has been designed and synthesized using solid-phase peptide synthesis procedure. The vector is then coupled with Gd-DOTA to work as a targeting contrast agent (CA1) for magnetic resonance imaging of human lung adenocarcinoma cells A549. Its longitudinal relaxivity is measured to be 7.55 mM(-1) s(-1) in aqueous solution at a magnetic field of 11.7 T, which is higher than that of Magnevist (4.25 mM(-1) s(-1)) in the same conditions. The cell experiment shows, at the same concentration, uptake quantity of CA1 by A549 is much more than Magnevist and also superior over CA2 (a single targeting contrast agent contains only RGD). The uptake can be blocked by the targetable peptide containing RGD or NGR without coupling Gd. To summarize, CA1 has very good ability to target A549 and higher relaxivity than that of Magnevist. So CA1 is promising MRI contrast agent for high-resolution MR molecular imaging of human lung adenocarcinoma A549 cells.


Asunto(s)
Medios de Contraste/síntesis química , Complejos de Coordinación/síntesis química , Péptidos/síntesis química , Secuencia de Aminoácidos , Unión Competitiva , Línea Celular Tumoral , Medios de Contraste/metabolismo , Complejos de Coordinación/metabolismo , Gadolinio DTPA/química , Humanos , Imagen por Resonancia Magnética , Neoplasias/diagnóstico , Péptidos/metabolismo , Fantasmas de Imagen , Técnicas de Síntesis en Fase Sólida
7.
J Glob Antimicrob Resist ; 37: 199-207, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38641225

RESUMEN

OBJECTIVES: The blaNDM gene was prevalent among children and became the predominant cause of severe infection in infants and children. This study aimed to investigate the epidemiology and molecular characteristics of blaNDM in Enterobacteriaceae among children in China. METHODS: Carbapenem-resistant Enterobacteriaceae (CRE) were collected in the Children's Hospital of Fudan University from January 2016 to December 2022. Five carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48) were screened by PCR method. Multilocus sequence typing (MLST) was conducted for phylogenetic analyses. blaNDM-carrying plasmids were typed by PCR-based Incompatibility (Inc) typing method. Moreover, plasmid comparison was performed with 213 publicly available IncX3 plasmids. RESULTS: A total of 330 CRE strains were enrolled, 96.4% of which carried carbapenemase genes. blaNDM gene accounted for 64.8% (214 strains) and included four variants, including blaNDM-1 (59.8%), blaNDM-5 (39.3%), blaNDM-7 (0.5%), and blaNDM-9 (0.5%). There were no predominant MLST lineages of blaNDM carrying strains. IncX3 was the major plasmid carrying blaNDM-1 (68.0%) and blaNDM-5 (72.6%) and was dominant in blaNDM-Klebsiella penumoniae (79.8%), blaNDM-Escherichia coli (58.2%), and blaNDM-Enterobacter cloacae (61.0%), respectively. Most (79.0%) clinical IncX3 plasmids in the world carried blaNDM, and the prevalence of blaNDM in IncX3 plasmids was more common in China (95.8%) than other countries (58.1%, P <0.01). CONCLUSION: blaNDM is highly prevalent in CRE among children in China. The spread of blaNDM was mainly mediated by IncX3 plasmids. Surveillance and infection control on the spread of blaNDM among children are important.


Asunto(s)
Proteínas Bacterianas , Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Enterobacteriaceae , Tipificación de Secuencias Multilocus , Plásmidos , beta-Lactamasas , Humanos , China/epidemiología , Plásmidos/genética , beta-Lactamasas/genética , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/epidemiología , Niño , Lactante , Preescolar , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Proteínas Bacterianas/genética , Pruebas de Sensibilidad Microbiana , Femenino , Antibacterianos/farmacología , Filogenia , Enterobacteriaceae/genética , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/enzimología , Masculino
8.
Int J Antimicrob Agents ; 63(6): 107163, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38570018

RESUMEN

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses immense threats to the health of infected patients worldwide, especially children. This study reports the infection caused by CRKP in a paediatric intensive care unit (PICU) child and its drug-resistant mutation during the treatment. Twelve Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains were isolated from the child. Broth microdilution method, plasmid transformation assay, and whole genome sequencing (WGS) were performed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural features of CRKPs. The results showed that 12 strains were highly resistant to most available antimicrobial agents. Among them, K. pneumoniae FD11 and K. pneumoniae FD12 were resistant to ceftazidime-avibactam (CZA, MIC >64 mg/L) and restored the carbapenem susceptibility (Imipenem, MIC =0.25 mg/L; Meropenem, MIC =2 mg/L). The patient improved after treatment with CZA in combination with aztreonam. Plasmid transformation assay demonstrated that the blaKPC-33-positive transformant increased MICs of CZA by at least 33-fold and 8-fold compared with the recipient Escherichia coli DH5α and blaKPC-2-positive transformants. WGS analysis revealed that all strains belonged to the ST11-KL64 type and showed highly homologous (3-26 single nucleotide polymorphisms [SNPs]). A single base mutation (G532T) of blaKPC-2 resulted in a tyrosine to aspartic acid substitution at Ambler amino acid position 179 (D179Y), which conferred CZA resistance in K. pneumoniae. This is the first report of a drug-resistant mutation evolving into blaKPC-33 during the treatment of blaKPC-2-positive CRKP in paediatric-infected patients. It advises clinicians that routine sequential antimicrobial susceptibility testing and KPC genotyping are critical during CZA therapy in children infected with CRKP.


Asunto(s)
Antibacterianos , Compuestos de Azabiciclo , Proteínas Bacterianas , Ceftazidima , Combinación de Medicamentos , Infecciones por Klebsiella , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/enzimología , Klebsiella pneumoniae/aislamiento & purificación , Compuestos de Azabiciclo/farmacología , Ceftazidima/farmacología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , beta-Lactamasas/genética , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Secuenciación Completa del Genoma , Farmacorresistencia Bacteriana Múltiple/genética , Niño , Plásmidos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Masculino , Aztreonam/farmacología
9.
Artículo en Inglés | MEDLINE | ID: mdl-39209267

RESUMEN

OBJECTIVES: China has experienced a notable upsurge in pertussis cases post-COVID-19, alongside an age shift to older children, increased vaccine escape, and a notable rise in the prevalence of macrolide-resistant Bordetella pertussis. Here, we present a genomic epidemiological investigation of these events. METHODS: We performed a retrospective observational study using culture-positive B pertussis isolated in Shanghai, China, from 2016 to 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic profile, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains. RESULTS: From pre-COVID-19 (before December 2019) to post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to a higher proportion of infections in older children (infant: 16%, 132/844), with the share of vaccinated individuals surging from 31% (107/340) to 88% (664/756). The macrolide-resistant Bordetella pertussis prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3-lineage macrolide-resistant clone, MR-MT28, which is uniquely capable of causing substantial infections among older children and vaccinated individuals, was temporally strongly associated with the pertussis upsurge and epidemiological transition. Although MR-MT28 showed increased expression of genes encoding pertussis toxin, it was associated with significantly milder clinical symptoms and a lower hospitalization rate. MR-MT28 likely originated in China around 2016, after acquiring several key mutations, including a novel prn150 allele, and has been detected across multiple regions in China. In addition, 26% (50/195) of MR-MT28 has evolved into predicted Pertactin (PRN)-deficient strains, with an IS481 insertion being the predominant mechanism. DISCUSSION: We report that the post-COVID-19 upsurge of pertussis in China is associated with ptxP3-MR-MT28, and provide evidence that pathogen evolution is likely the primary factor driving + pertussis upsurge, age shift, and vaccine escape. MR-MT28 poses a high risk of global spread and warrants global surveillance.

10.
Chem Sci ; 14(36): 9696-9703, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37736637

RESUMEN

Ring-opening of bicyclo[1.1.0]butanes (BCBs) is emerging as a powerful strategy for 1,3-difunctionalized cyclobutane synthesis. However, reported radical strain-release reactions are typically plagued with diastereoselectivity issues. Herein, an atom-economic protocol for the highly chemo- and diastereoselective polar strain-release ring-opening of BCBs with hydroxyarenes catalyzed by a π-acid catalyst AgBF4 has been developed. The use of readily available starting materials, low catalyst loading, high selectivity (up to >98 : 2 d.r.), a broad substrate scope, ease of scale-up, and versatile functionalizations of the cyclobutane products make this approach very attractive for the synthesis of 1,1,3-trisubstituted cyclobutanes. Moreover, control experiments and theoretical calculations were performed to illustrate the reaction mechanism and selectivity.

11.
Chem Sci ; 14(45): 13060-13066, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-38023515

RESUMEN

Although ring-opening reactions of bicyclobutanes bearing electron-withdrawing groups, typically with ß-selectivity, have evolved as a powerful platform for synthesis of cyclobutanes, their application in the synthesis of cyclobutenes remains underdeveloped. Here, a novel visible light induced α-selective radical ring-opening reaction of 1,3-disubstituted acyl bicyclobutanes with alkyl radical precursors for the synthesis of functionalized cyclobutenes is described. In particular, primary, secondary, and tertiary alkyl halides are all suitable substrates for this photocatalytic transformation, providing ready access to cyclobutenes with a single all-carbon quaternary center, or with two contiguous centers under mild reaction conditions.

12.
Int J Infect Dis ; 128: 205-211, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36632892

RESUMEN

OBJECTIVES: To reveal the clinical and molecular characteristics of Bordetella pertussis (BP) prevalent in Shanghai, China. METHODS: A total of 9430 children with suspected pertussis from 2021 to 2022 were included, and nasopharyngeal swab samples were collected for polymerase chain reaction detection, culture, antimicrobial susceptibility testing, and 23S rRNA gene A2047G detection. BP strains were typed using multilocus variable-number tandem-repeat analysis and virulence genotyping. RESULTS: Of 9430 cases, 5.1% and 1.6% were confirmed by polymerase chain reaction and culture, respectively. Infants (aged <1 year) accounted for 24.7% and presented much more severe symptoms than noninfants. Pertussis was most frequently detected in infants aged 0-6 months (11.3∼14.0%) and children aged >6-10 years (10.8∼21.7%). Macrolide-resistant BP (MRBP) accounted for 89.3%, and all carried the A2047G mutation. There were six multilocus variable-number tandem-repeat analysis types (MTs), including MT28 (62.0%), MT195 (20%), MT27 (10.0%), MT104 (4.7%), MT55 (2.7%), and MT32 (0.7%). BP strains with pertussis toxin (ptx)P3/(pertactin) prn2/ptxC2/ptxA1/(fimbrial proteins) fim2-1/fim3-1, including MT27, MT28, and MT32, accounted for 72.7%, among which MT27 and MT32 were macrolide-sensitive BP, whereas most (94.6∼100%) of MT28 were MRBP. Strains harboring ptxP1/prn1/ptxC1/ptxA1/fim2-1/fim3-1, including MT55, MT104, and MT195, belonged to macrolide-sensitive BP. CONCLUSION: The emergence and spread of MT28 ptxP3-MRBP was first reported in China, highlighting the importance of continuous surveillance of ptxP3-MRBP to prevent its potential circulation.


Asunto(s)
Bordetella pertussis , Farmacorresistencia Bacteriana , Tos Ferina , Niño , Humanos , Lactante , Alelos , Antibacterianos , Bordetella pertussis/genética , China/epidemiología , Genotipo , Macrólidos , Tos Ferina/epidemiología
13.
Medicine (Baltimore) ; 100(2): e24261, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33466211

RESUMEN

BACKGROUND: Calcaneal fractures are a prevalent form of injury caused by high-energy trauma. This study aimed at investigating whether bone graft and non-bone graft are essential for the internal fixation of calcaneal fractures. A meta-analysis of relevant clinical studies evaluated radiographic parameters, functional outcomes, and complications that offer practical recommendations on the suitability of bone grafts for the management of Calcaneal fractures. METHODS AND ANALYSIS: This study performed a comprehensive search on PubMed, EMBASE, and Cochrane electronic to retrieve related clinical studies. The studies incorporated in our meta-analysis were identified after doing a preliminarily screening, reading of the full-text articles, and eliminating repeated studies. After quality assessment and data extraction, the standardized mean difference and risk ratio were selected as effect sizes. The data on Böhler angle, Gissane angle, calcaneal height, American Orthopaedic Foot and Ankle Society hindfoot scores, Maryland Foot Evaluation, and rate of wound infection were analyzed using Revman 5.3 software (Cochrane Collaboration). RESULTS AND CONCLUSIONS: This study did not reveal any significant differences (P < .05) in both Böhler and Gissane angles, calcaneal height, American Orthopaedic Foot and Ankle Society hindfoot scores, Maryland foot evaluation, and rate of wound infection between the 2 groups. Due to the lack of a large sample of comparative studies, the use of bone grafting for the management of calcaneal fractures requires additional substantiation.


Asunto(s)
Trasplante Óseo/métodos , Calcáneo/lesiones , Traumatismos de los Pies/cirugía , Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Calcáneo/diagnóstico por imagen , Calcáneo/cirugía , Estudios de Cohortes , Investigación sobre la Eficacia Comparativa , Femenino , Traumatismos de los Pies/diagnóstico por imagen , Fracturas Óseas/diagnóstico por imagen , Humanos , Masculino , Resultado del Tratamiento
14.
Food Chem Toxicol ; 151: 112111, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33716052

RESUMEN

Biologically active peptides released by proteins are important in regulating immunity. The purpose of this study was to isolate and purify an immunologically active peptide from Hericium erinaceus (H. erinaceus) and to explore its effect on cytokine secretion and differentiation of macrophages. An active peptide with an amino acid sequence, Lys-Ser-Pro-Leu-Tyr (KSPLY) was obtained from H. erinaceus protein by ultrafiltration combined with multistage chromatography separation and identification technology. Subsequently, it was confirmed that the synthetic peptide KSPLY had a good immunomodulatory activity at a concentration of 100 µmol/L and could promote the secretion of NO, IL-1ß, IL-6 and TNF-α by macrophages. The effects of KSPLY on M1 macrophages and M2 macrophages were also studied. Results showed that KSPLY inhibited the secretion of NO and IL-6 by M1 macrophages and promoted the tendency of M2 macrophages to transform to M1 macrophages. Therefore, it can be concluded that KSPLY is an effective immunomodulatory peptide that may be beneficial in cancer treatment and human health improvement.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Hericium/química , Macrófagos/efectos de los fármacos , Oligopéptidos/aislamiento & purificación , Proteínas de Plantas/química , Animales , Polaridad Celular/efectos de los fármacos , Concentración de Iones de Hidrógeno , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Ratones , Oligopéptidos/química , Oligopéptidos/farmacología , Hidrolisados de Proteína/química , Células RAW 264.7 , Factor de Crecimiento Transformador alfa/metabolismo
15.
ACS Appl Bio Mater ; 4(2): 1597-1604, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-35014508

RESUMEN

Molecular imaging based on magnetic resonance imaging (MRI) requires a contrast agent with high relaxivity and specificity. Much effort has been devoted to this goal over the past decades. In this work, we continue this endeavor by synthesizing an MRI contrast agent that can penetrate the cellular membrane and bind with specific proteins. It was characterized with one- and two-dimensional NMR spectroscopy, NMR micro-imaging, and mass spectroscopy. The target specificity has been further confirmed by both molecular dynamics simulation and micro-imaging on a living biological system. It is one of the largest of peptide-based bioactivated MRI contrast agents, and its relaxivity enhancement factor is among the highest of MRI contrast agents hitherto published. We envision interesting applications and extension of this smart MRI contrast agent with bio-specificity and high contrast for molecular imaging.


Asunto(s)
Medios de Contraste/química , Imagen por Resonancia Magnética/métodos , Imagen Molecular/métodos , Péptidos/metabolismo , Humanos
16.
Chem Commun (Camb) ; (48): 5200-2, 2007 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-18060141

RESUMEN

Chiral calix[4]arenes bearing long tertiary alkyl groups at the upper rim and S-1-phenylethylamine groups at the lower rim can form heat-set gels and egg-like vesicles enantioselectively with d-2,3-dibenzoyltartaric acid in cyclohexane, which is the first example of heat-set gels resulting from difference in interactions between two component gelators: in addition, the diameter of vesicles decreased with the increase in length of alkyl groups, which could be used to control the size of the vesicles.


Asunto(s)
Calixarenos/química , Calor , Fenoles/química , Ciclohexanos/química , Geles , Conformación Molecular , Tamaño de la Partícula , Estereoisomerismo , Tartratos/química
17.
Chem Commun (Camb) ; (32): 3398-400, 2007 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-18019510

RESUMEN

Chiral para-tert-butylcalix[4]arene bearing (S)-alpha-methylbenzylamine groups at lower rim only self-assembles with one of two enantiomers of 2,3-dibenzoyltartaric acid into coiled nanofibers and the coiled nanofibers only stack with the nanofibers having the same handedness to construct bigger ribbon-like fibers bearing porosity.


Asunto(s)
Calixarenos/química , Nanoestructuras/química , Nanotecnología , Fenetilaminas/química , Tartratos/química , Calixarenos/síntesis química , Estereoisomerismo
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 26(4): 670-3, 2006 Apr.
Artículo en Zh | MEDLINE | ID: mdl-16836136

RESUMEN

To look for new MRI (magnetic resonance imaging) contrast agents with higher relaxivity as well as liver-selecsivity, four novel ester-amino ligands were synthesized by bis-acylation of octadecanyl, hexadecanyl, tetradecanyl and dedecanyl L-lysine with diethylenetriaminepentaacetic acid mono-anhydride (DTPA-MA), respectively. The corresponding dimeric Gd(III) complexes were gained by the reaction of these ligands with GdCl3 x 6H2O. All ligands and complexes were characterized by FTIR, 1H NMR and elemental analysis. The longitudinal relaxation time (T1) was measured, and relevant longitudinal relaxivity (R1) of these neatral binuclear Gd(III) complexes is: 6.48, 6.02, 5.76 and 5.68 L x mmol(-1) x s(-1), respectively, and all are higher than that of Gd-DTPA (4.98 L x mmol(-1) x s(-1)) (300 MHz).


Asunto(s)
Medios de Contraste/química , Ésteres/química , Gadolinio DTPA/química , Lisina/química , Medios de Contraste/síntesis química , Dimerización , Gadolinio DTPA/síntesis química , Estructura Molecular , Espectroscopía Infrarroja por Transformada de Fourier
19.
Zhen Ci Yan Jiu ; 36(1): 57-61, 2011 Feb.
Artículo en Zh | MEDLINE | ID: mdl-21585061

RESUMEN

OBJECTIVE: To observe the clinical efficacy of pricking bleeding of 3 points of the thumb tip, and 3 points of the auricular helix for treatment of vocal cord submucosal bleeding (VCSB), so as to provide a better therapy for it. METHODS: Sixty VCSB patients were equally randomized into pricking bleeding group and ultrasonic atomizing inhalation (UAI) group. Pricking bleeding was applied to Shaoshang (LU 11, 0. 1 cun to the nail on the radial side), Zhongshang (the center of the thumb back, 0. 1 cun to the nail), Laoshang (0. 1 cun to the nail on the ulnar side), Lun 1, 3 and 5 (MA-H) of the helix, once daily for 7 days. Ultrasonic atomizing inhalation treatment was given to patients of the UAI group for 15 min every time, once daily for 7 days. The scores of symptoms and signs and their difference values were calculated before and after the treatment. The acoustical parameters maximum phonation time (MPT), frequency perturbation quotient (FPQ), amplitude perturbation quotient (APQ), ratio of harmonic to noise (H/N) were detected by using a USSA Computer Language Phonetic Spectrum Analysis System. RESULTS: Of the two 30 cases of VCSB patients in the pricking bleeding and UAI groups, 20 (66.67%) and 12(40.00%)were cured, 7 (23.33%) and 6 (20.00%) were improved remarkably, 3 (10.00%) and 8 (26.67%) improved, and 0 and 4 (13.33%) failed, with the cure plus markedly effective rates being 90% and 60%, respectively. The cure plus markedly effective rate of the pricking bleeding group was significantly superior to that of the UAI group (P<0. 01). The difference values between pre-treatment and post-treatment in hoarseness, laryngalgia, throat dryness, throat burning sensation, throat clearing, vocal bleeding, glottis dysraphism, and total score were significantly higher in the pricking bleeding group than those in the UAI group (P<0.05). In comparison with the pre-treatment, MPT and H/N values were increased obviously (P<0. 05), and FPQ and APQ decreased clearly in the two groups after the treatment (P<0.05), suggesting an improvement of the acoustical parameters after the treatment. But, no significant differences were found between the two groups (P>0. 05). CONCLUSION: Pricking bleeding therapy is effective in relieving submucosal bleeding of the vocal cord and can improve its clinical symptoms and signs.


Asunto(s)
Venodisección , Enfermedades de la Laringe/terapia , Pliegues Vocales/patología , Adolescente , Adulto , Femenino , Hemorragia , Humanos , Enfermedades de la Laringe/patología , Enfermedades de la Laringe/fisiopatología , Masculino , Persona de Mediana Edad , Fonación , Adulto Joven
20.
Se Pu ; 23(4): 411-4, 2005 Jul.
Artículo en Zh | MEDLINE | ID: mdl-16250455

RESUMEN

A procedure for the preparative isolation of 1-S-[(1Z)-3-hydroxy-1-[(sulfooxy) imino]-4-pentenyl]-1-thio-beta-D-glucopyanose, potassium salt (progoitrin) from Brassica oleracea is reported. The major steps in this procedure were: (1) extraction of glucosinolates with methanol from Brassica oleracea; (2) separation and purification of glucosinolates by chromatographic column on alumina support; and (3) a follow-up reversed-phase separation by octadecyl (C18) silica support yielding progoitrin as the main content of glucosinolate. The structure of progoitrin was identified on its physicochemical properties by ultraviolet absorption spectrometry, infrared absorption, 'H nuclear magnetic resonance spectroscopy, mass spectrometry and elemental analysis. Spectroscopic data of the sample isolated were in agreement with those reported in the literature. The purity of progoitrin obtained was determined to be 99% by high performance liquid chromatography. The simplicity of the separation and purification procedure for glucosinolates and the high purity of progoitrin isolated would make the method an important reference for future research on glucosinolates and a favorable technique for future development.


Asunto(s)
Brassica/química , Glucosinolatos/química , Glucosinolatos/aislamiento & purificación , Cromatografía , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Espectrometría de Masas
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