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1.
J Agric Food Chem ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34842424

RESUMO

The increasingly serious resistance of Tetranychus cinnabarinus Boisduval to a wide range of insecticides/acaricides poses a major challenge to their control. The citrus processing industry generates a huge quantity of various wastes that contain many limonoids. To effectively utilize these byproducts and discover more potent green acaricidal molecules as sustainable alternatives for traditional resistant pesticides, various limonoid-type derivatives (halogenated/seven-membered lactam derivatives of obacunone and halogenated/oxime esters/oxime ethers/seven-membered lactam derivatives of limonin) were synthesized based on a diversity-oriented synthetic strategy. The key steric configurations of 10 derivatives were further confirmed by X-ray crystallography. Compound 9m, which displayed greater than 9.7-fold potent acaricidal activity of limonin, was of preeminence. In addition, some interesting structure-activity relationships were observed. Moreover, a biocompatible O/W nanoemulsion delivery system was used to prepare the limonin-based agronanoacaricide, which exhibited pronounced control efficiency against T. cinnabarinus Boisduval in the greenhouse. This systematic investigation will provide valuable information and guidance for future value-added applications of novel eco-friendly natural product-based nanopesticides.

2.
J Magn Reson Imaging ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611963

RESUMO

BACKGROUND: In experimental animal models, implantation location might influence the heterogeneity and overall development of the tumor, leading to an interpretation bias. PURPOSE: To investigate the effects of implantation location in experimental tumor model using magnetic resonance imaging (MRI) and pathological findings. STUDY TYPE: Prospective. SUBJECTS: Forty-five breast cancer-bearing mice underwent orthotopic (N = 15) and heterotopic (intrahepatic [N = 15] and subcutaneous [N = 15]) implantation. FIELD STRENGTH/SEQUENCE: Sequences including: T1-weighted turbo spin echo sequence, T2-weighted blade sequence, diffusion-weighted imaging, pre- and post-contrast T1 mapping, multi-echo T2 mapping at 3.0 T. ASSESSMENT: MRI was performed at 7, 14, and 21 days after implantation. Native T1, post-contrast T1, T2, and apparent diffusion coefficient (ADC) of tumors, the tumor volume and necrosis volume within tumor were obtained. Lymphocyte cells from H&E staining, Ki67-positive, and CD31-positive cells from immunohistochemistry were determined. STATISTICAL TESTS: One-way analysis of variance and Spearman's rank correlation were performed. P value <0.05 was considered statistically significant. RESULTS: The tumor volume (intrahepatic vs. orthotopic vs. subcutaneous: 587.50 ± 77.62 mm3 vs. 814.00 ± 43.85 mm3 vs. 956.13 ± 119.22 mm3 ), necrosis volume within tumor (89.10 ± 26.60 mm3 vs. 292.41 ± 57.92 mm3 vs. 179.91 ± 31.73 mm3 , respectively), ADC at day 21 (543.41 ± 42.28 vs. 542.92 ± 99.67 vs. 369.83 ± 42.90, respectively), and post-contrast T1 at all timepoints (day 7: 442.00 ± 11.52 vs. 435.00 ± 22.90 vs. 394.33 ± 29.95; day 14: 459.00 ± 26.11 vs. 436.83 ± 26.01 vs. 377.00 ± 27.83; day 21: 463.50 ± 23.49 vs. 458.00 ± 34.28 vs. 375.00 ± 30.55) were significantly different between three groups. Necrosis volumes of subcutaneous and intrahepatic tumors were significantly lower than those of orthotopic tumors. The CD31-positive rate in the intrahepatic implantation was significantly higher than in orthotopic and subcutaneous groups. Necrosis volume (r = -0.71), ADC (r = -0.85), and post-contrast T1 (r = -0.75) were strongly correlated with vascular invasion index. DATA CONCLUSION: Orthotopic and heterotopic tumors have their unique growth kinetics, necrosis volume, and vascular invasion. Non-invasive MR quantitative parameters, including ADC and post-contrast T1, may reflect vascular invasion in mice. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

3.
Mol Med ; 27(1): 139, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717544

RESUMO

BACKGROUND: Cancer-associated fibroblasts (CAFs) in the tumour microenvironment are associated with poor prognosis and chemoresistance in multiple solid tumours. However, there is a lack of universal measures of CAFs in colorectal cancer (CRC). The aim of this study was to assess the utility of a fibroblast-related gene signature (FRGS) for predicting patient outcomes and reveal its relevant mechanism. METHODS: The GSE39582 dataset, which includes 316 CRC patients who did not receive adjuvant chemotherapy was used as a discovery cohort to identify the prognostic fibroblast-related genes (FRGs). A total of 1352 CRC patients were divided into one training cohort (GSE39582, n = 461) and two validation cohorts (TCGA, n = 338; meta-validation, n = 553) for the construction of the FRGS and the verification of its prognostic value in stage II/III CRC patients. Functional annotation and analysis were performed to explore the underlying mechanism. The ability of the FRGS to predict immunotherapy response was further tested in a clear cell renal cell carcinoma (ccRCC) cohort. RESULTS: An 11-gene signature that had prognostic value for stage II/III CRC patients in both validation cohorts was developed (TCGA cohort: HR = 1.90, 95% CI 1.16-3.12, P < 0.01; meta-validation cohort: HR = 1.95, 95% CI 1.39-2.73, P < 0.001). A high level of CAFs was correlated with worse prognosis in CRC patients who did not receive adjuvant chemotherapy (HR = 3.63, 95% CI 2.24-5.88, P < 0.001). Importantly, patients in the low-risk group were found to be benefit from chemotherapy (P < 0.01), but not in the high CAF group (P > 0.05). Similar results were found in the TCGA cohort. Integrated with clinical characteristics, the FRGS was confirmed to be an independent prognostic factor in the multivariate analysis after adjustment for tumour TNM stage (GSE39582 cohort: HR = 3.19, 95% CI 1.88-5.41, P < 0.001; TCGA cohort: HR = 5.00, 95% CI 1.58-15.85, P = 0.007; meta-validation cohort: HR = 2.99, 95% CI 1.44-6.21, P = 0.003). Furthermore, the enrichment analysis found that the antitumour immune response was suppressed and the infiltration of CD4 T cells and M1 macrophages was depressed in the high CAF group. The FRGS was also found to have value in predicting for immunotherapy response in the ccRCC cohort. CONCLUSIONS: The 11-gene FRGS had independent prognostic value for CRC patients, as well as utility in the prediction of benefit from chemotherapy. CAFs in the tumour microenvironment might have an impact on the prognosis of CRC patients via inhibiting immune response.

4.
Arch Virol ; 166(12): 3333-3341, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34591172

RESUMO

The 2014 Ebola outbreak in West Africa resulted in more than 11,000 deaths, highlighting the need for a vaccine. A phase I clinical trial of a human adenovirus type 5 vector-based Ebola virus (EBOV) vaccine (HAdV-5-MakGP) showed that a homologous prime-boost regimen with HAdV-5 vaccine elicited a robust humoral response but a weak cellular immune response. Due to pre-existing anti-vector immunity, boosting with the same vaccine did not increase the magnitude of the cellular immune response, which contributes significantly to protection against EBOV infection. Here, we generated a recombinant Newcastle disease virus (NDV), based on the LaSota vaccine strain, expressing the GP protein of the EBOV variant Makona (rLS/EB-GP) using reverse genetics technology. The humoral and cellular immune responses to this vaccine candidate in mice immunized using a homologous prime-boost regimen or a heterologous prime-boost regimen with the HAdV-5-vectored Ebola vaccine were assessed using ELISA and ELISPOT assays. The ELISA and ELISPOT results showed that mice primed with rLS/EB-GP and boosted with HAdV-5-MakGP (NDV+HAdV-5) or, reversed, primed with HAdV-5-MakGP and boosted with rLS/EB-GP (HAdV-5+NDV) exhibited more-potent EBOV GP-specific antibody and cellular immune responses than those receiving the same vaccine twice. The most robust EBOV GP-specific antibody and T-cell responses were detected in the HAdV-5-MakGP-primed and rLS/EB-GP-boosted (HAdV-5+NDV) mice. These results suggest that the HAdV-5 prime-NDV boost regimen is more effective in stimulating EBOV-specific immunity than homologous regimens alone, indicating the potential boosting ability of the NDV vector in human vaccine use.

5.
J Magn Reson Imaging ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34545977

RESUMO

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL: Established PBDL models. POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

6.
Bioorg Med Chem Lett ; 50: 128350, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34478839

RESUMO

To develop new potential pesticide candidates from low value-added natural bioactive products, a series of new cholesterol-matrine conjugates (I(a-e)-IV(a-e)) were prepared from two lead compounds cholesterol and matrine. Against Mythimna separata Walker, compound IVa exhibited 3.0 and 2.6 folds promising insecticidal activity of cholesterol and matrine, respectively; against Aphis citricola Van der Goot, compound IVd showed 4.3 and 2.2 folds potent aphicidal activity of their precursors; notably, it also showed good control effects in the greenhouse; against Plutella xylostella Linnaeus at a dose of 20 µg/nymph, compound IIIe exhibited 2.8 and 2.0 folds oral toxicity of cholesterol and matrine, respectively. Compounds IIIe, IVd and IVe can be used as the leads for further structural optimization as the insecticidal and aphicidal agents.

7.
Bioorg Med Chem Lett ; 51: 128356, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520882

RESUMO

In order to increase the agricultural properties of matrine, a series of novel matrine-type alkaloidscontaining spiro-1,2,4-oxadiazoline fragment at the C-15 position were prepared. Eight target molecules were elucidated by X-ray single-crystal diffraction. The antifeedant activities of Ig and IIIh against Mythimna separata Walker were>1.7 folds of the precursor matrine. The acaricidal activities of Ij, IIe, IIg, IIi and IIIa against Tetranychus cinnabarinus Boisduval were 2.6-3.7 folds of matrine. Especially IIg (R1 = R2 = 4-Cl) and IIi (R1 = 4-Cl; R2 = 4-Br) exhibited the pronounced antifeedant and acaricidal activities. SARs showed that their pesticidal activities were related to the substitutents and their positions on the phenyl rings at the C-3 and N-4 positions of 1,2,4-oxadiazoline skeleton.

8.
Bioorg Med Chem Lett ; 48: 128246, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34233221

RESUMO

To discover non-food renewable forest bioactive products as new potential pesticidal alternatives for crop protection, a series of C15-imines alkaloids were obtained by structural modification of matrine and oxymatrine. Compounds Id, Ih, Ii and IIg (>2-3 folds of their precursors) showed the most potent antifeedant activity against armyworm. Against red spider mite, compounds Ie, Il, IIb, IIc and IIg displayed 1.8-3.1 folds acaricidal activity of their precursors. Notably, compound IIg exhibiting the most pronounced pesticidal activities, can be used as a promising bio-sourced agrochemical agent. The study of stress responses showed that the nAChR subunit α5 and VGSC might be the targets of action of matrine, oxymatrine and IIg against red spider mite.

9.
Appl Opt ; 60(20): 5819-5825, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34263800

RESUMO

A wavelength-tunable Q-switched erbium-doped fiber laser based on a digital micromirror device (DMD) is experimentally demonstrated. The Q-switched pulses are generated by incorporating a saturable absorption device made of graphene oxide. Stable Q-switched pulses at 1.5 µm band are obtained at a low threshold of 20 mW, corresponding to the pulse width of 7.1 µs and the repetition rate of 43.3 kHz. The maximum output power and the maximum pulse energy of the Q-switched pulses are 260.1 µW and 3.97 nJ, respectively. By controlling the DMD, the center wavelength of the Q-switched pulses can be tuned from 1528.2 to 1559.3 nm, with a tuning range of about 31 nm. The fine tunable accuracy can reach 0.08 nm by precisely controlling the DMD. Combining the filtering characteristics of the DMD with the saturable absorption characteristics of nanomaterials, the Q-switched laser with tunable wavelength is realized, which, we believe, is reported for the first time and has broad application prospects.

10.
Front Med (Lausanne) ; 8: 686885, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211990

RESUMO

Background: Hypoxia is associated with a poorer clinical outcome and resistance to chemotherapy in solid tumors; identifying hypoxic-related colorectal cancer (CRC) and revealing its mechanism are important. The aim of this study was to assess hypoxia signature for predicting prognosis and analyze relevant mechanism. Methods: Patients without chemotherapy were selected for the identification of hypoxia-related genes (HRGs). A total of six independent datasets that included 1,877 CRC patients were divided into a training cohort and two validation cohorts. Functional annotation and analysis were performed to reveal relevant mechanism. Results: A 12-gene signature was derived, which was prognostic for stage II/III CRC patients in two validation cohorts [TCGA, n = 509, hazard ratio (HR) = 2.14, 95% confidence interval (CI) = 1.18 - 3.89, P = 0.01; metavalidation, n = 590, HR = 2.46, 95% CI = 1.59 - 3.81, P < 0.001]. High hypoxic risk was correlated with worse prognosis in CRC patients without adjuvant chemotherapy (HR = 5.1, 95% CI = 2.51 - 10.35, P < 0.001). After integration with clinical characteristics, hypoxia-related gene signature (HRGS) remained as an independent prognostic factor in multivariate analysis. Furthermore, enrichment analysis found that antitumor immune response was suppressed in the high hypoxic group. Conclusions: HRGS is a promising system for estimating disease-free survival of stage II/III CRC patients. Hypoxia tumor microenvironment may be via inhibiting immune response to promote chemoresistance in stage II/III CRC patients.

11.
J Agric Food Chem ; 69(29): 8098-8109, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34278787

RESUMO

To explore natural-product-based pesticidal candidates and high value-added application of cholesterol in agriculture, oximinoether derivatives of cholesterol-containing isoxazoline/isoxazole fragments (I-1∼I-16 and II-1∼II-18) were semiprepared by structural optimization of cholesterol. Their structures were characterized by optical rotation, high-resolution mass spectrometry (HRMS), IR, and 1H NMR spectroscopy. Particularly, the Z configurations of oxime fragments at the C-7 position of target compounds were undoubtedly determined by X-ray crystallography. Against Mythimna separata Walker, compounds 3e, I-8, I-14, and II-3 showed 2.4-2.7-fold growth inhibitory activity of the precursor cholesterol. Against Plutella xylostella Linnaeus, compounds I-6, I-7, and I-9 showed 2.4-2.7-fold oral toxicity of cholesterol. Against Aphis citricola Van der Goot, compounds 2e and II-15 exhibited 4.9 and 5.8-fold aphicidal activity of cholesterol, respectively. Notably, they showed good control effects (3.0-5.0-fold promising control efficiency of 1) against A. citricola in the greenhouse. Structure-activity relationships (SARs) suggested that the C-3 hydroxyl group and the C-7 position of cholesterol are two important modification sites. It will pave the way for future structural optimization and application of cholesterol derivatives as potential pesticidal agents in agriculture.


Assuntos
Inseticidas , Mariposas , Agricultura , Animais , Colesterol , Éter , Inseticidas/farmacologia , Isoxazóis/farmacologia , Estrutura Molecular , Oximas/farmacologia , Relação Estrutura-Atividade
12.
Sci Total Environ ; 792: 148417, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34144237

RESUMO

The widespread occurrence of tire particles (TPs) in soils has attracted considerable attention due to their potential threats. The assemblage of bacteria and associated antibiotic resistant genes (ARGs) on TPs is yet largely unknown, especially under the stress of soil pollutants. In the present study, TPs were incubated in soils with or without the stress of heavy metal (Cu2+) or/and antibiotic (tetracycline), and bacterial community and ARG profile on TPs and in soils were explored using high-throughput sequencing and high-throughput quantitative PCR. Results indicated that bacterial community structure on TPs was significantly different from the surrounding soils, with a lower diversity, and significantly shifted by heavy metal and antibiotic exposure. Additionally, a diverse set of ARGs were detected on TPs, and their abundances were significantly increased under the stress of heavy metal and antibiotic, revealing a strong synergistic effect. Moreover, a good fit was observed for the correlation between bacterial community and ARG profile on TPs. Taken together, this study, for the first time, demonstrates that TPs can provide a novel niche for soil bacteria and soil resistome, and heavy metal and antibiotic exposure may potentially increase the abundance of ARGs on TPs, threatening soil ecosystems and human health.


Assuntos
Metais Pesados , Solo , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Ecossistema , Genes Bacterianos , Humanos , Metais Pesados/toxicidade , Microbiologia do Solo
13.
J Agric Food Chem ; 69(23): 6465-6474, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34077224

RESUMO

Here, we prepared a series of novel osthole-type ester derivatives modified in the lactone ring of osthole, which is isolated from Cnidium monnieri. The positions of H-3 and H-4 of the representative compound 4z were determined by a 1H-1H COSY spectrum. By opening the lactone ring of osthole, the double bonds at the C-3 and C-4 positions of diol 3 and esters 4a-4z, 4a', and 4b' were still retained as a Z configuration. That is, H-3 and H-4 of compounds 3 and 4a-4z, 4a', and 4b' were all in the cis relationship. The steric configurations of 4k, 4v, and 4z were further undoubtedly determined by single-crystal X-ray diffraction. Against Tetranychus cinnabarinus Boisduval, four aliphatic esters 4c (R = n-C3H7; LC50: 0.31 mg/mL), 4d (R = CH3(CH2)10; LC50: 0.24 mg/mL), 4a' (R = CH3(CH2)9; LC50: 0.28 mg/mL), and 4b' (R = CH3(CH2)12; LC50: 0.32 mg/mL) showed the most promising acaricidal activity, and compounds 4c, 4d, and 4a' also exhibited a potent control efficiency. Especially, compound 4d exhibited greater than fivefold acaricidal activity of the precursor osthole (LC50: 1.22 mg/mL). Against Mythimna separata Walker, compounds 4g, 4l, and 4m displayed 1.6-1.8-fold potent insecticidal activity of osthole. It demonstrated that the lactone ring of osthole is not necessary for the agricultural activities, thiocarbonylation of osthole was not beneficial for the agricultural activities, introduction of R as an aliphatic chain is vital for the acaricidal activity, notably, the length of the aliphatic chain is related to the acaricidal activity, 4d could be further studied as a lead acaricidal agent, and to the aromatic series, R containing the fluorine atom(s) is important for the insecticidal activity.


Assuntos
Inseticidas , Praguicidas , Animais , Cumarínicos , Ésteres , Inseticidas/farmacologia , Lactonas , Estrutura Molecular , Praguicidas/farmacologia , Relação Estrutura-Atividade
14.
Arch Gynecol Obstet ; 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34128125

RESUMO

OBJECTIVE: To develop prediction models for the chance of successful external cephalic version (ECV) and delivery outcome. STUDY DESIGN: This is a single-center retrospective study including 350 pregnant women with a singleton non-cephalic pregnancy at or after 36 weeks of gestational age. We selected 22 factors for ECV prediction and 21 for delivery outcome after successful ECV prediction as candidate predictors. Multivariable logistic regression with a stepwise backward selection procedure was used to construct a prediction model for the chance of successful ECV and the other for the delivery outcome. The discrimination and calibration of the models were assessed and internal validation was done with bootstrapping. RESULTS: ECV was successfully performed in 232 cases (66.3%) among 343 women. Eight predictive factors were identified to be associated with a successful ECV: Gestational week at ECV < 39 weeks, multiparous, BMI before pregnancy < 22 kg/m3, palpable fetal head, breech engagement, larger AFI, larger BPD and posterior placenta. This model showed good calibration and good discrimination (c-statistic = 0.82, 95% CI 0.76-0.88). Six predictive factors were identified to be associated with vaginal delivery after successful ECV: age < 35, multiparous, BMI before pregnancy < 22 kg/m3, anterior placenta, lateral placenta and none-front fetal spine position. This model showed fair discrimination (c-statistic = 0.79, 95% CI 0.72-0.85). However, its calibration was not so satisfactory especially when the predicted probability was low. CONCLUSION: We validated a prediction model for ECV and delivery outcome, showing that the model's overall performance is good. This can be used in clinical practice after external validation.

15.
Front Genet ; 12: 661296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968137

RESUMO

Dendrobium officinale is a kind of traditional Chinese herbal medicine. Its flowers could be used as health care tea for its aroma flavor and medicinal value. Most recent studies demonstrated that terpenoids are the main components of the aromatic compounds in the flowers, but the biosynthesis of terpenoids is poorly understood in D. officinale. In the experiment, the flowers from two cultivars of D. officinale with different smells were collected. The transcriptome analysis and combined volatile terpenoids determination were performed to identify the genes related to the biosynthesis of the terpenoids. The results showed that the different products of volatile terpenoids are α-thujene, linalool, α-terpineol, α-phellandrene, γ-muurolene, α-patchoulene, and δ-elemene in two cultivar flowers. The transcriptome analysis detected 25,484 genes in the flowers. And 18,650 differentially expressed genes were identified between the two cultivars. Of these genes, 253 genes were mapped to the terpenoid metabolism pathway. Among these genes, 13 terpene synthase (TPS) genes may have correlations with AP2/ERF, WRKY, MYB, bHLH, and bZIP transcription factors by weighted gene co-expression network analysis (WGCNA). The transcription factors have regulatory effects on TPS genes. These results may provide ideas for the terpenoid biosynthesis and regulatory network of D. officinale flowers.

16.
J Clin Transl Hepatol ; 9(2): 194-202, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-34007801

RESUMO

Background and Aims: In Europeans, variants in the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene impact liver histology in metabolic-associated fatty liver disease (MAFLD). The impact of these variants in ethnic Chinese is unknown. The aim of this study was to investigate the potential associations in Chinese patients. Methods: In total, 427 Han Chinese with biopsy-confirmed MAFLD were enrolled. Two single nucleotide polymorphisms in HSD17B13 were genotyped: rs72613567 and rs6531975. Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology. Results: In our cohort, the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis [odds ratio (OR): 2.93 (1.20-7.17), p=0.019 for the additive model; OR: 3.32 (1.39-7.91), p=0.007 for the recessive model], representing an inverse association as compared to the results from European cohorts. In contrast, we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant [OR: 0.48 (0.24-0.98), p=0.043 for the additive model; OR: 0.62 (0.40-0.94), p=0.025 for the dominant model]. HSD17B13 variants were only associated with fibrosis but no other histological features. Furthermore, HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis. Conclusions: HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans. These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.

17.
Vaccine ; 39(25): 3428-3434, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33965257

RESUMO

BACKGROUND: The widespread use of pneumococcal conjugate vaccines (PCVs) has significantly decreased pneumococcal disease worldwide. However, China has not adopted PCVs in their national immunization schedules and had only approved these vaccines for children aged 2-15 months by 2020. METHODS: In an open-label trial, enrolled healthy children aged 2-5 years old were randomized 1:1 and divided into a 7-valent pneumococcal conjugate vaccine (PCV7) group and a Haemophilus influenzae type b conjugate vaccine (Hib) group. Children in the PCV7 group received a single dose of PCV7, and the Hib group received a single dose of Hib vaccine. Blood samples were collected before and 6 months after vaccination. Immunogenicity and safety of PCV7 were assessed at prespecified time points. RESULTS: Six months after a single dose of PCV7, children in the PCV7 group for all 7 serotypes, IgG mean concentrations (GMCs) and opsonophagocytic geometric mean titres (GMTs) were significantly higher (P < .001) than at baseline, and the proportion of IgG ≥ 0.35 µg/mL ranged from 90.0% to 100%. Although the antibody level increased with age, preexisting antibodies did not induce hyporesponsiveness to PCV7. In the Hib group, the antibody levels were not significantly different or had changed slightly at 6 months. PCV7 was well tolerated in all age groups, and no serious adverse events (AEs) emerged during this study. CONCLUSIONS: A single dose of PCV7 was immunogenic and safe for Chinese children aged 2-5 years, and the preexisting antibodies against the PCV7 serotypes did not change the response to vaccination. The findingssupported the effectiveness of PCV7 in this age group. PCVs with broader serotype coverage are expected to expand pneumococcal disease protection.


Assuntos
Infecções Pneumocócicas , Vacinas Pneumocócicas , Anticorpos Antibacterianos , Criança , Pré-Escolar , China , Humanos , Esquemas de Imunização , Lactente , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/efeitos adversos , Vacinas Conjugadas/efeitos adversos
18.
Bioorg Med Chem Lett ; 43: 128104, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33984477

RESUMO

To explore natural-product-based insecticide candidates, and high value-added application of natural plants in agriculture, a series of twin compounds were prepared from two natural products podophyllotoxin and cytisine, which are isolated from the plants Podophyllum hexandrum and Thermopsis lanceolata, respectively. Compounds IIa (X = Cl, Y = R1 = R2 = H), IIIc (X = Y = R1 = R2 = Cl) and IVd (X = R1 = R2 = Br, Y = H) exhibited >2-fold potent insecticidal activity of podophyllotoxin against armyworm with FMRs greater than 60%. SARs were also observed. It is noteworthy that the idea of twin insecticides was addressed for the first time. We hope this idea will be conducive to design new twin insecticidal agents, and lay the foundation for future high value-added application of the plants P. hexandrum and T. lanceolata as potentially botanical pesticides in agriculture.


Assuntos
Alcaloides/farmacologia , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Podofilotoxina/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Azocinas/química , Azocinas/isolamento & purificação , Azocinas/farmacologia , Relação Dose-Resposta a Droga , Fabaceae/química , Inseticidas/química , Inseticidas/isolamento & purificação , Estrutura Molecular , Podofilotoxina/química , Podofilotoxina/isolamento & purificação , Podophyllum/química , Quinolizinas/química , Quinolizinas/isolamento & purificação , Quinolizinas/farmacologia , Relação Estrutura-Atividade
19.
Asian J Surg ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33893031

RESUMO

Testis-sparing surgery (TSS) has been increasingly used for treating a variety of testicular tumors (TTs) in children. However, the indications and feasibility associated with TSS remain uncertain. This study aimed to present the clinical outcomes of TSS in children with TTs. The PubMed, Cochrane Library, and Embase databases were reviewed for relevant articles on the clinical outcomes of TSS in children. Recurrence rate, benign rate, rate of TSS and its 95% confidence interval (CI) were calculated. A total of nine relevant studies with 320 patients were included in this study. The recurrence rate was 5.8% (95% CI: 2.3%-14.1%), benign rate was 70.9% (95% CI: 56.3%-82.1%), the rate of TSS (RTSS) was 36.2% (95% CI: 26.1%-47.8%), RTSS in benign tumor was 48.4% (95% CI: 34.3%-62.9%) and rate of elevated AFP was 29.3% (95% CI: 19.7%-41.3%) in children with TTs. Regarding the distribution of TTs, 159 (49.6%) were teratomas, 74 (23.1%) were yolk sac tumors, 36 (11.3%) were epidermoid cysts, 3 (0.9%) were rhabdomyosarcomas, 7 (2.2%) were leydig cell tumor, 6 (1.8%) were sex-cord stromal tumor, 8(2.5%) were mixed malignant germ cell tumors, 3(0.9%) were hemangioma, and 4(1.3%) were adrenal rest tumors. The findings of this meta-analysis suggested that most of the TTs in children were benign, and the most common histologic subtype was teratoma. TSS should be provided to children with benign lesions. This study confirmed that very low rates of tumor recurrence were observed in children with TTs.

20.
Bioorg Med Chem Lett ; 40: 127962, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33741463

RESUMO

Osthole, a coumarin-type natural product, is isolated from Chinese traditional herbal medicine Cnidium monnieri. In order to improve the pesticidal activity of osthole, and high value-added application of the plant Cnidium monnieri, a series of new derivatives containing hydrazone/acylhydrazone/sulfonylhydrazone skeletons at the C-8 position of osthole were regioselectively semi-prepared. The steric structure of 3c was determined by the X-ray crystal structure. Against Mythimna separata Walker, benzoylhydrazone 3b (R1 = 4-CH3Ph) showed 1.6 folds potent insecticidal activity of the precursor osthole. Introduction of the acylhydrazones on the 3'-methyl-2'-butylenyl fragment at the C-8 position of osthole can improve the insecticidal activity. These will provide a foundation for future structural modifications of osthole as pesticidal agents.


Assuntos
Cumarínicos/farmacologia , Hidrazonas/farmacologia , Inseticidas/farmacologia , Animais , Cumarínicos/síntese química , Hidrazonas/síntese química , Inseticidas/síntese química , Estrutura Molecular , Mariposas/efeitos dos fármacos , Testes de Toxicidade
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