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1.
BMC Pediatr ; 24(1): 341, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755560

RESUMO

BACKGROUND: The Premonitory Urge for Tics Scale (PUTS) is a common self-report measure of premonitory urges for patients with tic disorders. This study aims to evaluate the Chinese version of the PUTS (PUTS-C) and to explore its association with psychiatric symptoms in Chinese children diagnosed with tic disorders. METHODS: The psychometric evaluation involved 204 outpatients with tic disorders, aged 7-16 years, who were divided into two age groups: (7-10 years, n = 103; 11-16 years, n = 95). RESULTS: The PUTS-C demonstrated good internal consistency (McDonald'sω = 0.84) and two-week test-retest reliability (0.76). We observed a statistically significant correlation between the total PUTS-C score and various Yale Global Tic Severity Scale (YGTSS) subscales and total tic severity scores. The PUTS-C score also showed significant correlations with the Children Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Screening Child Anxiety-Related Emotional Disorders (SCARED), and Children's Depression Inventory (CDI). Notably, premonitory urges independently predicted tic severity, beyond the influence of comorbid symptoms. A two-factor structure of the PUTS-C was identified in the total sample through factor analysis. CONCLUSIONS: The PUTS-C possesses acceptable validity and good reliability. It appears that premonitory urges in Chinese patients with tic disorders are associated with obsessive-compulsive symptoms, anxiety, and depression, but can independently predict tic severity. Specific PUTS-C factors possibly related to motor and vocal tics. Future research should continue to investigate age-related differences and the association with tics and other sensory symptoms.


Assuntos
Psicometria , Transtornos de Tique , Humanos , Criança , Transtornos de Tique/diagnóstico , Transtornos de Tique/psicologia , Masculino , Adolescente , Feminino , Reprodutibilidade dos Testes , China , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Autorrelato
2.
Plant Dis ; 2023 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37005506

RESUMO

Mango (Mangifera indica L.), belongs to the family Anacardiacea, and is one of the most popular tropical fruits in the world. Stem-end rot is a major postharvest disease of mango fruit, causing severe losses during storage in China (Chen et al., 2015). In July 2021, the mango fruits harvested from Baise Municipal National Agricultural Science and Technology Park (23.683568 N, 106.986325 E) of Guangxi province in China developed stem-end rot during storage. The disease incidence reached ca. 8.3%. The initial symptoms appeared as light brown lesions surrounding the peduncle, which quickly expanded becoming large dark-brown lesions. Small pieces of epidermis (5 mm × 5 mm) from 8 typical diseased friuts were cut from the edges of lesions surface-sterilized with 2% sodium hypochlorite and rinsed with sterile distilled water. The tissue was plated on potato dextrose agar (PDA) and incubated at 28 ℃ in the dark for 3 days. Fifteen, similarcolonies were isolated from the symptomatic tissue. The representative isolates DF-1, DF-2 and DF-3 were selected for morphological characterization, molecular identification, and pathogenicity testing. The colonies were circular with fluffy aerial mycelium, initially white turning to smoke-gray from the center in upper side and greenish black in reverse side, covering the 90 mm diameter Petri dish after 4 days of incubation on PDA at 28 ℃ in dark. Pycnidia were produced on the surface of the colony after 30 days. Conidia were fusiform, aseptate, hyaline, thin-walled with granular contents, apex sub-obtuse, base subtruncate to bluntly rounded, 14.0-20.3 (16.8±1.6) µm × 3.1-7.2 (5.1±0.9) µm (n=50). The sexual stage was absent. Based on morphology, isolates were preliminarily identified as Botryosphaeria speices. To accurately identify the pathogen, genomic DNA was extracted from the mycelium of the three isolates DF-1, DF-2 and DF-3. The internal transcribed spacer of rDNA region (ITS), elongation factor 1-alpha (EF-1α) and beta-tubulin gene (TUB) genes were amplified using primers ITS1/ITS4, EF1-728F/EF1-986R and Bt2a/Bt2b, respectively (Slippers et al., 2004). The nucleotide sequences were all deposited in GenBank (ITS: OP729176-OP729178 EF-1α: OP758194-OP758196 and TUB: OP758197-OP758199). Based on the BLASTn analysis, the ITS, EF1-α and TUB sequences of three isolates were 100%, 99% and 99% similar to the Botryosphaeria fabicerciana MFLUCC 10-0098 sequences (ITS: JX646789, EF-1α: JX646854 and TUB: JX646839). Multi-locus phylogenetic analyses (ITS, EF-1α and TUB) showed that the isolate DF-1, DF-2 and DF-3 were clustered within Botryosphaeria fabicerciana clade based on the maximum likelihood , Bayesian inference, and maximum parsimony methods. The pathogenicity test was performed by placing discs mycelium around the peduncle of mature mango fruits by pin-prick method. Each treatment carried out with 12 fruits. The inoculated fruits were placed in plastic boxes at 28 ℃ with three replicates. Three days after inoculation, typical symptoms of stem-end rot were observed. The control fruits were inoculated with sterile PDA discs, and remained symptomless. The same fungus was re-isolated from the symptomatic tissue to complete Koch's postulate. Botryosphaeria fabicerciana (basionym: Fusicoccum fabicercianum) was first reported as pathogen causing senescent twig of Eucalyptus spp. in China (Chen et al., 2011; Phillips et al., 2013). To our knowledge, this is the first report of Botryosphaeria fabicerciana causing stem-end rot of Mangifera indica in China.

3.
Plant Dis ; 2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37807094

RESUMO

Dalbergia odorifera (Family: Fabaceae) is a national second-grade protected tree in China with high medicinal and economic value (Zhao et al., 2020). In July, 2022, a leaves spot disease on D. odorifera with typical anthracnose symptoms was observed in plantations in Haikou (110.319153°E, 19.072900°N), Dongfang (108.630297°E, 19.103838°N) and Qiongzhong (109.704460°E, 19.088440°N), Hainan Province, China. Disease incidence was 7.5% (n = 50 plants). Early symptoms of infected leaves were small and round dark brown spots, which developed into larger irregular necrotic lesions and leaves withered. Leaf tissues (5×5 mm) at the disease-health junction of spots from 19 leaves were sterilized with 2.5% sodium hypochlorite for 1 min, and rinsed with sterile distilled water three times. These sterilized tissues were placed on potato dextrose agar (PDA) and incubated at 28 ℃ for 5 d. 7 strains of fungi with similar morphology were isolated, and 3 single-hyphal isolates (HHL01, HHL02 and HHL03) from each location were selected for further study. Colonies on PDA were fluffy orange-yellow mycelium. Conidia were aseptate, cylindrical, smooth-walled, straight, hyaline with both ends bluntly rounded, 11.82 to 15.77 × 3.87 to 6.71 µm (n = 100; average = 13.75 × 5.52 µm). Appressoria formed on slides, measured 5.54 to 10.64 × 4.19 to 7.41 µm (n = 30; average = 8.06 × 5.97 µm) were brown to black, elliptical to irregular. For molecular biological identification, the genomic DNA of three isolates was extracted by fungal genomic DNA extraction kit (Tiangen Biotech (Beijing) Co., Ltd.). The partial sequences of internal transcribed spacer region (ITS; ITS1/ITS4), glyceraldehyde-3-phosphate dehydrogenase (GAPDH; GDF1/GDR1), actin (ACT; ACT512F/ACT783R), ß-tubulin (TUB2; TI/Bt2b) and calmodulin (CAL; CL1C/CL2C) were amplified and sequenced by Sangon Biotech (Shanghai) Co., Ltd (Carbone and Kohn, 1999; Weir et al., 2012). The sequences were deposited as GenBank Accession Nos. OR018110-OR018112 (ITS); OR050529-OR050537 (GAPDH, ACT and CAL) and OR192168-OR192170 (TUB). BLASTn results showed these sequences were more than 99% identity with the strain of C. karstii CORCK1 (GenBank Accession Nos. HM585406, HM585387, HM581991, HM585424 and HM582010, respectively). Multi-locus phylogenetic tree of Colletotrichum spp. showed that those three isolates were sister to C. karstii based on the maximum likelihood and bayesian inference methods. To verify pathogenicity, 2 mL spore suspension (1 × 106conidia/ml) of the isolates was sprayed on each leaves of 1-year-old D. odorifera plants, and sterile distilled water was similarly sprayed on other leaves as a negative control. The plants were incubated in a greenhouse under 90% ± 5% RH at 28 °C. Light brown small round necrotic patches developed 3 days after inoculation, while the control was asymptomatic. Photographs were taken on the fifth day after inoculation. The fungi were re-isolated from the diseased leaves and identified by morphological characterization and molecular identification, fulfilling Koch's postulates. C. karstii has been reported causing leaf rot of Carissa grandiflora in Spain (Garcia-Lopez et al., 2021), and anthracnose caused by C.tropicale was reported on D. odorifera (Yi et al., 2023). To our knowledge, this is the first report of Dalbergia odorifera leaf spot disease caused by Colletotrichum karstii. This finding provides an important basis for further research on the control of the disease.

4.
Plant Dis ; 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38127631

RESUMO

Papaya (Carica papaya L.) belonging to the family Caricaceae is well known for its economic and nutritional value. Anthraconse caused by Colletotrichum spp. is a main postharvest disease of papaya fruit during storage (Cia et al., 2007). In July 2022, papaya fruits with anthracnose symptoms were collected in Changjiang County (108.996180E, 19.246560N), Hainan Province, China. The disease incidence of fruit rot reached 6.3%. Initial symptoms appeared as the watery lesions with tiny black spots, turning to dark brown, sunken necrotic lesions. The diseased tissues were cut into 18 pieces (5×5 mm) from 6 papaya fruits, disinfected with 2% sodium hypochlorite for 60 s, and rinsed three times with sterilized water. The pieces were air-dried and then placed on potato dextrose agar (PDA) at 28 ℃ for five days. Twelve isolates with similar morphology were obtained from 18 tissue pieces. Three isolates (FMG01, FMG02 and FMG03) were selected for morphological identification, molecular identification, and pathogenicity tests. Colonies were initially white, then gradually became dark grey on PDA. The ascospores were hyaline, fusoid, rounded at both ends, 37.43-84.32 (55.79±7.61) µm × 4.30-6.55 (5.36±0.60) µm (n=50). The conidia were hyaline, unicellular, long cylindrical, bluntly rounded at both ends, 11.59-25.54 (18.62±2.33) µm × 5.12-8.44 (7.19±0.62) µm (n=100). Appressoria were gray to dark brown, irregular, pyriform, or ovoid, 10.14-21.40 (13.81±2.25) µm × 6.05-11.85 (9.16±1.29) µm (n=50). Morphological features are similar to Colletotrichum gigasporum identified and described by Rakotoniriana et al (Rakotoniriana et al., 2013). In order to accurately identify the isolates, the internal transcribed spacer region (ITS) of the rDNA, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the partial actin (ACT), the beta-tubulin (TUB2) and the calmodulin (CAL) genes were amplified and sequenced (Cannon et al., 2012). The nucleotide sequences were deposited into GenBank (accession numbers, ITS: OR017446 to OR017448, GAPDH: OR042810 to OR042812, ACT: OR042813 to OR042815, TUB2: OR042816 to OR042818, CAL: OR042819 to OR042821). Based on the BLASTn analysis, these sequences were more than 99% with the reference strain CBS 125476 of C. gigasporum sequences (ITS: MH863698, GAPDH: KF687833, ACT: KF687790, TUB2: KF687875, CAL: KF687814), respectively. The results of the multilocal phylogenetic analysis showed that the three isolates were C. gigasporum based on the Maximum Likelihood and Bayesian inference method. The pathogenicity test was performed by wounded with a sterile needle on the surface-sterilized papaya fruits. The mycelial discs (5 mm diameter) of three isolates were inoculated orderly on the same fruit, and the same inoculation was applied to non-wound papaya fruits. The control group were inoculated with sterilized PDA. Each treatment carried out with 9 fruits. The inoculated fruits were placed at 28 ℃ in plastic preservation boxes (32×22×11 cm) with sterilized distilled water to maintain high humidity. After 5 d of inoculation, typical anthracnose symptoms were observed on wound fruits and the non-wound fruits developed symptoms at 7 dpi, control fruits were symptomless. The fungi re-isolated from the inoculated fruits lesions after inoculation and identified by morphological characterization and molecular identification, fulfilling Koch's postulates. C. gigasporum has been reported causing leaf rot of Dalbergia odorifera in China (Wan et al., 2018). To our knowledge, this is the first report of anthracnose fruit rot of papaya caused by C. gigasporum in China.

5.
Plant Dis ; 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081633

RESUMO

Terminalia catappa belonging to the family Combretaceae, spreads in tropical and subtropical coastal areas. It mainly serves as shading and decorative tree (Anand et al, 2015). It is planted as roadside tree in Southern China. A leaf spot disease of T. catappa was observed at Wencheng Town (110.805323°E, 19.524567°N), Wenchang City, Hainan province, China in June, 2022. The disease incidence of leaves reached 10%. The occurrence of this leaf spot would reduce the ornamental value of T. catappa. The early symptoms of infected leaves were small, round, dark brown spots surrounded by irregular light halos, developing to larger irregular necrotic lesions and leaves withered. Twelve diseased leaves were collected from three survey trees. Symptomatic leaf samples were collected and cut into small pieces (3×3 mm). The pieces were surface sterilized with 2.5% sodium hypochlorite for 1 min, rinsed with sterile distilled water three times, placed on potato dextrose agar (PDA) medium and incubated at 28 ℃ in the dark for 3 days. Three hyphal tip isolates (DYLR-1, DYLR-2 and DYLR-3) were cultured on PDA. Colonies on PDA reached the edge of the 90 mm plates after 3 d and had fluffy mycelia with an uneven margin, initially creamy white, becoming light grey (5 d) to mouse grey (10 d) at the surface with the black globular cavity. To induce sporulation, the isolates were transferred to 2% water agar media with sterilised pine needles placed on the surface of the media. Conidia was hyaline, unicellular, thin-walled, smooth with granular contents, aseptate, narrowly fusiform, base subtruncate to bluntly rounded, 11.1 to 16.7 (14.5±1.4) × 4.6 to 7.6 (6.2±0.7) µm (n=50). Spermatia was hyaline, unicellular, aseptate, allantoid to rod-shaped, 3.2 to 6.9 (5.1±0.9) µm × 2.0 to 3.8 (2.5±0.4) µm (n=50). Pathogenicity tests were performed both in vitro and in vivo, and replicated twice. All three isolates were used for pathogenicity tests, with 18 detached leaves used for pathogenicity tests in vitro and 3 seedlings used for pathogenicity tests in vivo. A 5-mm-diameter agar plug containing mycelia were placed on the leaves both without and with wound. Sterile PDA plugs were used as controls. The leaves were moisturized with a clear plastic bag for 24 hours in a greenhouse under 90% ± 5% RH at 25 ℃. Brown spot symptoms were observed at 1 day post-inoculation (dpi) in vitro and 3 dpi in vivo. The same strains were reisolated from lesions of inoculated leaves. Control plants were symptomless. For molecular identification, internal transcribed spacer region and intervening 5.8S nrRNA gene (ITS; ITS1/ITS4 primers; White et al. 1990), translation elongation factor 1-alpha gene (tef1-α; EF1-728F/EF1-986R primers; Carbone and Kohn 1999), beta-tubulin gene (tub2; Bt2a/Bt2b primers; Glass and Donaldson 1995) and DNA directed RNA polymerase II second largest subunit gene (rpb2; RPB2bot6F/RPB2bot7R; Sakalidis et al. 2011) regions were PCR amplified from genomic DNA. The sequences (GenBank accessions numbers: OP435357 to OP435359 of ITS; OP535354 to OP535356 of tef1-α; OP535351 to OP535353 of tub2; OP535348 to OP535350 of rpb2) had 100%, 99.7%, 100%, 100% similar to the type strain of Neofusicoccum sinoeucalypti CERC2005 (GenBank accessions numbers: KX278061, KX278166, KX278270 and KX278290), respectively. Multi-locus phylogenetic tree (ITS, tef1-α, tub2 and rpb2) of Neofusicoccum spp. (Zhang et al. 2021) showed that those three isolates were sister to N. sinoeucalypti based on the maximum likelihood and bayesian inference methods. N. sinoeucalypti was first reported pathogen causing from Eucalyptus plantations and adjacent plants in China (Li et al. 2018). To our knowledge, this is the first report of Neofusicoccum sinoeucalypti causing leaf spot disease on Terminalia catappa in China. Neofusicoccum species, commonly cause diseases in woody plants worldwide, and identification of this pathogen is important for effective disease management and control.

6.
Small ; 18(16): e2106403, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35274455

RESUMO

Energy-storage materials can be assembled directly on the electrodes of a battery using electrochemical methods, this allowing sequential deposition, high structural control, and low cost. Here, a two-step approach combining electrophoretic deposition (EPD) and cathodic electrodeposition (CED) is demonstrated to fabricate multilayer hierarchical electrodes of reduced graphene oxide (rGO) and mixed transition metal sulfides (NiCoMnSx ). The process is performed directly on conductive electrodes applying a small electric bias to electro-deposit rGO and NiCoMnSx in alternated cycles, yielding an ideal porous network and a continuous path for transport of ions and electrons. A fully rechargeable alkaline battery (RAB) assembled with such electrodes gives maximum energy density of 97.2 Wh kg-1 and maximum power density of 3.1 kW kg-1 , calculated on the total mass of active materials, and outstanding cycling stability (retention 72% after 7000 charge/discharge cycles at 10 A g-1 ). When the total electrode mass of the cell is considered, the authors achieve an unprecedented gravimetric energy density of 68.5 Wh kg-1 , sevenfold higher than that of typical commercial supercapacitors, higher than that of Ni/Cd or lead-acid Batteries and similar to Ni-MH Batteries. The approach can be used to assemble multilayer composite structures on arbitrary electrode shapes.

7.
J Anim Physiol Anim Nutr (Berl) ; 106(5): 1097-1106, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34605078

RESUMO

This study was conducted to investigate whether the combination of garlic oil and cooked chilli oil is worth using for pigeon production in the context of a total ban on antibiotics in feed additives in China. Two hundred female white king pigeons aged 23 days were randomly divided into five groups with ten replicates (four birds each). In the 47 days trial, the control group was fed with a basal diet, treatment groups were given a basal diet supplemented with 20 mg/kg neomycin sulphate or 2 g/kg corresponding oil (garlic oil or cooked chilli oil or their mixture) respectively. The mixed oil showed obvious antibacterial activity against gram-positive bacterium and its minimal bactericidal concentration against St. aureus, Salmonella and Escherichia coli were all no more than 1.0 mg/ml. In the feeding experiment, pigeons feed with garlic oil with strong bacteriostatic activity had lower FCR and better protein metabolism, and chilli oil showed strong effects of promoting feed intake and weight gain on pigeons but increased serum glucose and lipid content. Compared with the control and the antibiotic group, the mixed oil got increased growth performance, less drip loss of meat, better protein metabolism promoting, and more complete intestinal structure of pigeon. In addition, the breast meat in the mixed oil group had higher total points in the sensory test. The mixed oil combined the strong bacteriostasis of garlic oil with the feeding promotion effect of cooked chilli oil, it improved the comprehensive performance of pigeons and had the feasibility to be popularized as a non-antibiotic strategy in pigeon production.


Assuntos
Compostos Alílicos , Capsicum , Columbidae , Dieta , Óleos de Plantas , Compostos Alílicos/farmacologia , Ração Animal/análise , Animais , Galinhas , Dieta/veterinária , Suplementos Nutricionais , Feminino , Sulfetos
8.
BMC Genomics ; 22(1): 298, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892645

RESUMO

BACKGROUND: Chloroplasts are important semi-autonomous organelles in plants and algae. Unlike higher plants, the chloroplast genomes of green algal linage have distinct features both in organization and expression. Despite the architecture of chloroplast genome having been extensively studied in higher plants and several model species of algae, little is known about the transcriptional features of green algal chloroplast-encoded genes. RESULTS: Based on full-length cDNA (Iso-Seq) sequencing, we identified widely co-transcribed polycistronic transcriptional units (PTUs) in the green alga Caulerpa lentillifera. In addition to clusters of genes from the same pathway, we identified a series of PTUs of up to nine genes whose function in the plastid is not understood. The RNA data further allowed us to confirm widespread expression of fragmented genes and conserved open reading frames, which are both important features in green algal chloroplast genomes. In addition, a newly fragmented gene specific to C. lentillifera was discovered, which may represent a recent gene fragmentation event in the chloroplast genome. With the newly annotated exon-intron boundary information, gene structural annotation was greatly improved across the siphonous green algae lineages. Our data also revealed a type of non-canonical Group II introns, with a deviant secondary structure and intronic ORFs lacking known splicing or mobility domains. These widespread introns have conserved positions in their genes and are excised precisely despite lacking clear consensus intron boundaries. CONCLUSION: Our study fills important knowledge gaps in chloroplast genome organization and transcription in green algae, and provides new insights into expression of polycistronic transcripts, freestanding ORFs and fragmented genes in algal chloroplast genomes. Moreover, we revealed an unusual type of Group II intron with distinct features and conserved positions in Bryopsidales. Our data represents interesting additions to knowledge of chloroplast intron structure and highlights clusters of uncharacterized genes that probably play important roles in plastids.


Assuntos
Clorófitas , RNA , Clorófitas/genética , Cloroplastos/genética , Íntrons/genética , Filogenia , Análise de Sequência de RNA
9.
Small ; 17(17): e2007242, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33719216

RESUMO

Lithium-sulfur (Li-S) batteries are considered one of the most promising energy storage technologies, possibly replacing the state-of-the-art lithium-ion (Li-ion) batteries owing to their high energy density, low cost, and eco-compatibility. However, the migration of high-order lithium polysulfides (LiPs) to the lithium surface and the sluggish electrochemical kinetics pose challenges to their commercialization. The interactions between the cathode and LiPs can be enhanced by the doping of the carbon host with heteroatoms, however with relatively low doping content (<10%) in the bulk of the carbon, which can hardly interact with LiPs at the host surface. In this study, the grafting of versatile functional groups with designable properties (e.g., catalytic effects) directly on the surface of the carbon host is proposed to enhance interactions with LiPs. As model systems, benzene groups containing N/O and S/O atoms are vertically grafted and uniformly distributed on the surface of expanded reduced graphene oxide, fostering a stable interface between the cathode and LiPs. The combination of experiments and density functional theory calculations demonstrate improvements in chemical interactions between graphene and LiPs, with an enhancement in the electrochemical kinetics, power, and energy densities.

10.
Faraday Discuss ; 227: 291-305, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33346768

RESUMO

The electrochemical exfoliation of graphite is one of the cheapest and most tunable industrial techniques to produce graphene nanosheets with a tunable degree of oxidation and solubility. Anodic oxidation allows high-yield production of electrochemically exfoliated graphene oxide (EGO) in either acid or salt solutions, with the key role played by ions electrochemically driven in between the graphene sheets. This chemical intercalation is followed by a mesoscale mechanical exfoliation process, which is key for the high yield of the process, but which is still poorly understood. In this work, we use Raman spectroscopy to simultaneously monitor the intercalation and oxidation processes taking place on the surface of highly ordered pyrolytic graphite (HOPG) during electrochemical exfoliation. The mechanism of EGO formation in either acidic (0.5 M H2SO4) or neutral (0.5 M Li2SO4) electrolytes through blistering and cracking steps is discussed and described. This process is also compared to the non-destructive intercalation of graphite in an organic electrolyte (1 M NaClO4 in acetonitrile). The results obtained show how high exfoliation yield and low defectivity can be achieved by the combination of efficient, non-destructive intercalation followed by chemical decomposition of the intercalants and gas production.

11.
Nature ; 527(7577): 245-8, 2015 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-26536115

RESUMO

It is estimated that more than 170 million people are infected with hepatitis C virus (HCV) worldwide. Clinical trials have demonstrated that, for the first time in human history, the potential exists to eradicate a chronic viral disease using combination therapies that contain only direct-acting antiviral agents. HCV non-structural protein 5A (NS5A) is a multifunctional protein required for several stages of the virus replication cycle. NS5A replication complex inhibitors, exemplified by daclatasvir (DCV; also known as BMS-790052 and Daklinza), belong to the most potent class of direct-acting anti-HCV agents described so far, with in vitro activity in the picomolar (pM) to low nanomolar (nM) range. The potency observed in vitro has translated into clinical efficacy, with HCV RNA declining by ~3-4 log10 in infected patients after administration of single oral doses of DCV. Understanding the exceptional potency of DCV was a key objective of this study. Here we show that although DCV and an NS5A inhibitor analogue (Syn-395) are inactive against certain NS5A resistance variants, combinations of the pair enhance DCV potency by >1,000-fold, restoring activity to the pM range. This synergistic effect was validated in vivo using an HCV-infected chimaeric mouse model. The cooperative interaction of a pair of compounds suggests that NS5A protein molecules communicate with each other: one inhibitor binds to resistant NS5A, causing a conformational change that is transmitted to adjacent NS5As, resensitizing resistant NS5A so that the second inhibitor can act to restore inhibition. This unprecedented synergistic anti-HCV activity also enhances the resistance barrier of DCV, providing additional options for HCV combination therapy and new insight into the role of NS5A in the HCV replication cycle.


Assuntos
Antivirais/farmacologia , Compostos de Bifenilo/farmacologia , Farmacorresistência Viral/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Imidazóis/farmacologia , Proteínas não Estruturais Virais/metabolismo , Regulação Alostérica/efeitos dos fármacos , Animais , Carbamatos , Linhagem Celular , Sinergismo Farmacológico , Quimioterapia Combinada , Hepacivirus/metabolismo , Hepatite C/virologia , Hepatócitos/transplante , Humanos , Camundongos , Modelos Moleculares , Conformação Proteica/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína/efeitos dos fármacos , Pirrolidinas , Reprodutibilidade dos Testes , Valina/análogos & derivados , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Replicação Viral/efeitos dos fármacos
12.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500776

RESUMO

Salinity gradient energy, as a type of blue energy, is a promising sustainable energy source. Its energy conversion efficiency is significantly determined by the selective membranes. Recently, nanofluidic membrane made by two-dimensional (2D) nanomaterials (e.g., graphene) with densely packed nanochannels has been considered as a high-efficient membrane in the osmotic power generation research field. Herein, the graphene oxide-cellulose acetate (GO-CA) heterogeneous membrane was assembled by combining a porous CA membrane and a layered GO membrane; the combination of 2D nanochannels and 3D porous structures make it show high surface-charge-governed property and excellent ion transport stability, resulting in an efficient osmotic power harvesting. A power density of about 0.13 W/m2 is achieved for the sea-river mimicking system and up to 0.55 W/m2 at a 500-fold salinity gradient. With different functions, the CA and GO membranes served as ion storage layer and ion selection layer, respectively. The GO-CA heterogeneous membrane open a promising avenue for fabrication of porous and layered platform for wide potential applications, such as sustainable power generation, water purification, and seawater desalination.

13.
Angew Chem Int Ed Engl ; 59(3): 1087-1092, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31553513

RESUMO

COF-1 has a structure with rigid 2D layers composed of benzene and B3 O3 rings and weak van der Waals bonding between the layers. The as-synthesized COF-1 structure contains pores occupied by solvent molecules. A high surface area empty-pore structure is obtained after vacuum annealing. High-pressure XRD and Raman experiments with mesitylene-filled (COF-1-M) and empty-pore COF-1 demonstrate partial amorphization and collapse of the framework structure above 12-15 GPa. The ambient pressure structure of COF-1-M can be reversibly recovered after compression up to 10-15 GPa. Remarkable stability of highly porous COF-1 structure at pressures at least up to 10 GPa is found even for the empty-pore structure. The bulk modulus of the COF-1 structure (11.2(5) GPa) and linear incompressibilities (k[100] =111(5) GPa, k[001] =15.0(5) GPa) were evaluated from the analysis of XRD data and cross-checked against first-principles calculations.

14.
Nanotechnology ; 30(2): 024001, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30378565

RESUMO

The use of sulfur as a cathode material for lithium-sulfur (Li-S) batteries has attracted significant attention due to its high theoretical specific capacity (1675 mA h g-1); however, practicality is hindered by a number of obstacles, including the shuttling effect of polysulfides and the low electrical conductivity of sulfur. Herein, ball milling sulfur with unzipped multiwalled carbon nanotubes (UMWNTs) was found to covalently immobilize sulfur nanoparticles to the UMWNTs and resulted in composites (designated as S@UMWNTs) with high electrical conductivity. The unzipping degree of MWNTs was first controlled to optimize the immobilization of sulfur nanoparticles to UMWNTs and the electrochemical performance of the resulting Li-S batteries. The presence of C-S covalent bonds between the UMWNTs and sulfur nanoparticles was verified using x-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy, and the formation of C-S bonds was ascribed to the reactions between the mechanically-induced sulfur radicals and the functional groups of UMWNTs. As a result, when used as a cathode material for Li-S batteries, the S@UMWNTs exhibited excellent electrochemical performance, including a good long-term cycling stability and low capacity decay (e.g., ca. 0.09% per cycle over 500 charge/discharge cycles at 1 C) due to the suppression of the shuttling effect by the C-S covalent bonds.

15.
Phys Chem Chem Phys ; 20(44): 27983-27991, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30382273

RESUMO

The most common methods to evaluate hydrogen sorption (volumetric and gravimetric) require significant experience and expensive equipment for providing reproducible results. Both methods allow one to measure excess uptake values which are used to calculate the total amount of hydrogen stored inside of a tank as required for applications. Here we propose an easy to use and inexpensive alternative approach which allows one to evaluate directly the weight of hydrogen inside a material-filled test tank. The weight of the same tank filled with compressed hydrogen in the absence of loaded material is used as a reference. We argue that the only parameter which is of importance for hydrogen storage applications is by how much the material improves the total weight of hydrogen inside of the given volume compared to compressed gas. This parameter which we propose to name Gain includes both volumetric and gravimetric characterization of the material; it can be determined directly without knowing the skeletal volume of the material or excess sorption. The feasibility of the Gravimetric Tank (GT) method was tested using several common carbon and Metal Organic Framework (MOF) materials. The best Gain value of ∼12% was found for the Cu-BTC MOF which means that the tank completely filled with this material stores a 12% higher amount of hydrogen compared to H2 gas at the same P-T conditions. The advantages of the GT method are its inexpensive design, extremely simple procedures and direct results in terms of tank capacity as required for industrial applications. The GT method could be proposed as a standard check for verification of the high hydrogen storage capacity of new materials. The GT method is expected to provide even better accuracy for evaluation of a material's performance for storage of denser gases like e.g. CO2 and CH4.

16.
Angew Chem Int Ed Engl ; 57(4): 1034-1038, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29210484

RESUMO

Hybrid 2D-2D materials composed of perpendicularly oriented covalent organic frameworks (COFs) and graphene were prepared and tested for energy storage applications. Diboronic acid molecules covalently attached to graphene oxide (GO) were used as nucleation sites for directing vertical growth of COF-1 nanosheets (v-COF-GO). The hybrid material has a forest of COF-1 nanosheets with a thickness of 3 to 15 nm in edge-on orientation relative to GO. The reaction performed without molecular pillars resulted in uncontrollable growth of thick COF-1 platelets parallel to the surface of GO. The v-COF-GO was converted into a conductive carbon material preserving the nanostructure of precursor with ultrathin porous carbon nanosheets grafted to graphene in edge-on orientation. It was demonstrated as a high-performance electrode material for supercapacitors. The molecular pillar approach can be used for preparation of many other 2D-2D materials with control of their relative orientation.

17.
Nanotechnology ; 28(39): 395404, 2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28726690

RESUMO

The morphology of electrode materials plays an important role in determining the performance of lithium-ion batteries (LIBs). However, studies on determining the most favorable morphology for high-performance LIBs have rarely been reported. In this study, a series of F-doped SnO x (F-SnO2 and F-SnO) materials with various morphologies was synthesized using ethylenediamine as a structure-directing agent in a facile hydrothermal process. During the hydrothermal process, the F-SnO x was embedded in situ into the three-dimensional (3D) architecture of reduced graphene oxide (RGO) to form F-SnO x @RGO composites. The morphologies and nanostructures of F-SnO x , i.e., F-SnO2 nanocrystals, F-SnO nanosheets, and F-SnO2 aggregated particles, were fully characterized using electron microscopy, x-ray diffraction, and x-ray photoelectron spectroscopy. Electrochemical characterization indicated that the F-SnO2 nanocrystals uniformly distributed in the 3D RGO architecture exhibited higher specific capacity, better rate performance, and longer cycling stability than the F-SnO x with other morphologies. These excellent electrochemical performances were attributed to the uniform distribution of the F-SnO2 nanocrystals, which significantly alleviated the volume changes of the electrode material and shortened the Li ion diffusion path during lithiation/delithiation processes. The F-SnO2@RGO composite composed of uniformly distributed F-SnO2 nanocrystals also exhibited excellent rate performance, as the specific capacities were measured to be 1158 and 648 mA h g-1 at current densities of 0.1 and 5 A g-1, respectively.

18.
Molecules ; 22(12)2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29210996

RESUMO

CF3CBrCH2 (2-bromo-3,3,3-trifluoropropene, 2-BTP) is a potential replacement for CF3Br; however, it shows conflicted inhibition and enhancement behaviors under different combustion conditions. To better understand the combustion chemistry of 2-BTP, a theoretical study has been performed on its reactions with OH and H radicals. Potential energy surfaces were exhaustively explored by using B3LYP/aug-cc-pVTZ for geometry optimizations and CCSD(T)/aug-cc-pVTZ for high level single point energy refinements. Detailed kinetics of the major pathways were predicted by using RRKM/master-equation methodology. The present predictions imply that the -C(Br)=CH2 moiety of 2-BTP is most likely to be responsible for its fuel-like property. For 2-BTP + OH, the addition to the initial adduct (CF3CBrCH2OH) is the dominant channel at low temperatures, while the substitution reaction (CF3COHCH2 + Br) and H abstraction reaction (CF3CBrCH + H2O) dominates at high temperatures and elevated pressures. For 2-BTP + H, the addition to the initial adduct (CF3CBrCH3) also dominates the overall kinetics at low temperatures, while Br abstraction reaction (CF3CCH2 + HBr) and ß-scission of the adduct forming CF3CHCH2 + Br dominates at high temperatures and elevated pressures. Compared to 2-BTP + OH, the 2-BTP + H reaction tends to have a larger effect on flame suppression, given the fact that it produces more inhibition species.


Assuntos
Alcenos/química , Hidrogênio/química , Radical Hidroxila/química , Modelos Químicos , Modelos Teóricos , Cinética , Modelos Moleculares
19.
Cell Immunol ; 302: 26-31, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26774852

RESUMO

Bone marrow-derived mesenchymal stem cells (MSCs) are promising candidate cells for therapeutic application in autoimmune diseases due to their immunomodulatory properties. Unused human umbilical cords (UC) offer an abundant and noninvasive source of MSCs without ethical issues and are emerging as a valuable alternative to bone marrow tissue for producing MSCs. We thus investigated the immunomodulation effect of umbilical cord-derived MSCs (UC-MSCs) on human peripheral blood mononuclear cells (PBMCs), T cells in particular, in a co-culture system. We found that UC-MSCs efficiently suppressed the proliferation of phytohaemagglutinin (PHA)-stimulated PBMCs (p<0.01). Kinetic analysis revealed that UC-MSCs primarily inhibited the division of generation 3 (G3) and 4 (G4) of PBMCs. In addition, UC-MSCs augmented the expression of CD127(+) and CD45RA(+) but reduced the expression of CD25(+) in PBMCs stimulated by PHA (p<0.05). Furthermore, UC-MSCs inhibited PHA-resulted increase in the frequency of CD4(+)CD25(+)CD127(low/-) Tregs significantly (p<0.01) but augmented PHA-resulted increase in the frequency of CD4(+)CD25(high)CD45RA(+) Tregs to about three times in PBMCs. The levels of anti-inflammatory cytokines, PEG2, TGF-ß, and IL-10 were greatly up-regulated, accompanied by a significant down-regulation of pro-inflammatory IFN-γ in the co-culture (p<0.01). Our results showed that UC-MSCs are able to suppress mitogen-induced PBMC activation and proliferation in vitro by altering T lymphocyte phenotypes, increasing the frequency of CD4(+)CD25(high)CD45RA(+) Tregs, and modulating the associated cytokine production. Further studies are warranted to investigate the therapeutic potential of UC-MSCs in immunologically-diseased conditions.


Assuntos
Antígenos CD/metabolismo , Citocinas/metabolismo , Linfócitos/citologia , Células-Tronco Mesenquimais/fisiologia , Linfócitos T/citologia , Cordão Umbilical/citologia , Antígenos CD4 , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Humanos , Subunidade alfa de Receptor de Interleucina-2 , Antígenos Comuns de Leucócito , Ativação Linfocitária , Linfócitos/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Fito-Hemaglutininas/farmacologia , Linfócitos T/imunologia
20.
Nature ; 465(7294): 96-100, 2010 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-20410884

RESUMO

The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people. Current therapy relies upon a combination of pegylated interferon-alpha and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus. The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B. Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC(50)) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log(10) reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors.


Assuntos
Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Imidazóis/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Adolescente , Adulto , Animais , Antivirais/sangue , Antivirais/química , Antivirais/uso terapêutico , Carbamatos , Linhagem Celular , Chlorocebus aethiops , Farmacorresistência Viral , Feminino , Genótipo , Células HeLa , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Imidazóis/sangue , Imidazóis/química , Concentração Inibidora 50 , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Fatores de Tempo , Valina/análogos & derivados , Células Vero , Carga Viral/efeitos dos fármacos , Adulto Jovem
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