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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 290: 122312, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36608518

RESUMO

Scutellariae Radix (SR) is a common herb in Asia and Europe. In the clinical practice of traditional Chinese medicine, the raw SR is often stir-baked to partly scorch to reduce the side effects (stomach discomfort, diarrhea, etc.) but enhance some desired effects (such as the hemostatic activity). The scorching degree is crucial to assure the safety and efficacy of the scorched SR. Under-scorching is insufficient to adapt the adverse and favorable activities, while over-scorching can destroy all activities. Up to now, the scorching degree of SR is still determined by the manual observation of colors. Since the visual judgement is vulnerable to personal knowledge and experience, it is difficult to control the optimization and consistence of the scorching degree of SR. This research was designed to explore the potential indicators that can exactly reflect the scorching degree of SR and be measured objectively and quantitatively. A total of 15 morphological and chemical properties as well as Fourier transform infrared (FTIR) spectroscopy were included to profile the variations of the SR slices that were stir-baked at different temperatures for different times. According to the principal component analysis and statistical tests, 10 properties showed close relationships with the scorching degree of SR. As the increase of the heating time at the same heating temperature, the yield, L*, a*, b*, sucrose, baicalin and wogonoside decreased continuously and showed the monotone variation patterns. Meanwhile, 5-HMF, baicalein and wogonin showed the inflection variation patterns, which means these properties increased in the earlier stage but decreased in the later stage during the scorching process. FTIR spectra also revealed the variations of flavonoids and carbohydrates. The scorching degree of SR can be determined by the intuitive observation of FTIR spectral peaks at 1738 cm-1, 1705 cm-1, 1611 cm-1, 1586 cm-1, 1450 cm-1, 1410 cm-1 and 1023 cm-1. In summary, FTIR spectroscopy can be used for the rapid assessment of the scorching degree of SR, while the contents of flavonoid glycosides and aglycones may be used as the quality criteria of the scorched SR.

2.
Circulation ; 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36591786

RESUMO

BACKGROUND: Epsin endocytic adaptor proteins are implicated in the progression of atherosclerosis; however, the underlying molecular mechanisms have not yet been fully defined. In this study, we determined how epsins enhance endothelial-to-mesenchymal transition (EndoMT) in atherosclerosis and assessed the efficacy of a therapeutic peptide in a preclinical model of this disease. METHODS: Using single-cell RNA sequencing combined with molecular, cellular, and biochemical analyses, we investigated the role of epsins in stimulating EndoMT using knockout in Apoe-/- and lineage tracing/proprotein convertase subtilisin/kexin type 9 serine protease mutant viral-induced atherosclerotic mouse models. The therapeutic efficacy of a synthetic peptide targeting atherosclerotic plaques was then assessed in Apoe-/- mice. RESULTS: Single-cell RNA sequencing and lineage tracing revealed that epsins 1 and 2 promote EndoMT and that the loss of endothelial epsins inhibits EndoMT marker expression and transforming growth factor-ß signaling in vitro and in atherosclerotic mice, which is associated with smaller lesions in the Apoe-/- mouse model. Mechanistically, the loss of endothelial cell epsins results in increased fibroblast growth factor receptor-1 expression, which inhibits transforming growth factor-ß signaling and EndoMT. Epsins directly bind ubiquitinated fibroblast growth factor receptor-1 through their ubiquitin-interacting motif, which results in endocytosis and degradation of this receptor complex. Consequently, administration of a synthetic ubiquitin-interacting motif-containing peptide atheroma ubiquitin-interacting motif peptide inhibitor significantly attenuates EndoMT and progression of atherosclerosis. CONCLUSIONS: We conclude that epsins potentiate EndoMT during atherogenesis by increasing transforming growth factor-ß signaling through fibroblast growth factor receptor-1 internalization and degradation. Inhibition of EndoMT by reducing epsin-fibroblast growth factor receptor-1 interaction with a therapeutic peptide may represent a novel treatment strategy for atherosclerosis.

3.
Respir Res ; 24(1): 28, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698189

RESUMO

BACKGROUND: The Mesenchymal epithelial transition factor (MET) gene encodes a receptor tyrosine kinase with pleiotropic functions in cancer. MET exon 14 skipping alterations and high-level MET amplification are oncogenic and targetable genetic changes in patients with non-small-cell lung cancer (NSCLC). Resistance to tyrosine kinase inhibitors (TKIs) has been a major challenge for targeted therapies that impairs their clinical efficacies. METHODS: Eighty-six NSCLC patients were categorized into three cohorts based on the time of detecting MET tyrosine kinase domain (TKD) mutations (cohort 1: at baseline; cohort 2: after MET-TKI treatment; cohort 3: after EGFR-TKI treatment). Baseline and paired TKI treatment samples were analyzed by targeted next-generation sequencing. RESULTS: MET TKD mutations were highly prevalent in METex14-positive NSCLC patients after MET-TKI treatment, including L1195V, D1228N/H/Y/E, Y1230C/H/N/S, and a double-mutant within codons D1228 and M1229. Missense mutations in MET TKD were also identified at baseline and in post-EGFR-TKI treatment samples, which showed different distribution patterns than those in post-MET-TKI treatment samples. Remarkably, H1094Y and L1195F, absent from MET-TKI-treated patients, were the predominant type of MET TKD mutations in patients after EGFR-TKI treatment. D1228H, which was not found in treatment-naïve patients, also accounted for 14.3% of all MET TKD mutations in EGFR-TKI-treated samples. Two patients with baseline EGFR-sensitizing mutations who acquired MET-V1092I or MET-H1094Y after first-line EGFR-TKI treatment experienced an overall improvement in their clinical symptoms, followed by targeted therapy with MET-TKIs. CONCLUSIONS: MET TKD mutations were identified in both baseline and patients treated with TKIs. MET-H1094Y might play an oncogenic role in NSCLC and may confer acquired resistance to EGFR-TKIs. Preliminary data indicates that EGFR-mutated NSCLC patients who acquired MET-V1092I or MET-H1094Y may benefit from combinatorial therapy with EGFR-TKI and MET-TKI, providing insights into personalized medical treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Resistencia a Medicamentos Antineoplásicos/genética , Mutação/genética , Proteínas Tirosina Quinases/genética , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia
4.
Med Phys ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646444

RESUMO

BACKGROUND: MRI-guidance techniques that dynamically adapt radiation beams to follow tumor motion in real time will lead to more accurate cancer treatments and reduced collateral healthy tissue damage. The gold-standard for reconstruction of undersampled MR data is compressed sensing (CS) which is computationally slow and limits the rate that images can be available for real-time adaptation. PURPOSE: Once trained, neural networks can be used to accurately reconstruct raw MRI data with minimal latency. Here, we test the suitability of deep-learning-based image reconstruction for real-time tracking applications on MRI-Linacs. METHODS: We use automated transform by manifold approximation (AUTOMAP), a generalized framework that maps raw MR signal to the target image domain, to rapidly reconstruct images from undersampled radial k-space data. The AUTOMAP neural network was trained to reconstruct images from a golden-angle radial acquisition, a benchmark for motion-sensitive imaging, on lung cancer patient data and generic images from ImageNet. Model training was subsequently augmented with motion-encoded k-space data derived from videos in the YouTube-8M dataset to encourage motion robust reconstruction. RESULTS: AUTOMAP models fine-tuned on retrospectively acquired lung cancer patient data reconstructed radial k-space with equivalent accuracy to CS but with much shorter processing times. Validation of motion-trained models with a virtual dynamic lung tumor phantom showed that the generalized motion properties learned from YouTube lead to improved target tracking accuracy. CONCLUSION: AUTOMAP can achieve real-time, accurate reconstruction of radial data. These findings imply that neural-network-based reconstruction is potentially superior to alternative approaches for real-time image guidance applications.

5.
Exp Hematol Oncol ; 12(1): 7, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635765

RESUMO

BACKGROUND: Caspase-8 (Casp8) acts as an initiator in cell apoptosis signaling. However, the role of Casp8 in tuning the tumor immune microenvironment remains controversial due to the complicated crosstalk between immune-tolerogenic apoptotic cell death and immunogenic cell death cascades. METHODS: The Cancer Genome Atlas (TCGA) and publicly accessible immune checkpoint blockade (ICB)-treated cohorts were used to investigate the clinical relevance of Casp8. A tumor-bearing mouse model was used to characterize changes in the tumor microenvironment and to explore the efficacy of ICB treatment under Casp8 knockout conditions. RESULTS: By exploring TCGA datasets, we showed that the expression level of Casp8 was associated with an immuno-hot microenvironment across various solid tumor types. Casp8 deficiency leads to decreased CD8+ T cell infiltration and resistance to anti-PD-L1 therapy in a mouse model. Mechanistically, Casp8 deficiency or pharmacological disruption results in impaired ecto-calreticulin transition in tumor cells, which in turn hampers antigen presentation in draining lymph nodes. Furthermore, radiotherapy restored sensitivity to anti-PD-L1 treatment via elevated calreticulin surface expression. CONCLUSIONS: Our data revealed a causative role of Casp8 in modulating the immunogenicity of tumor cells and responsiveness to ICB immunotherapies and proposed radiotherapy as a salvage approach to overcome Casp8 deficiency-mediated ICB resistance.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36633015

RESUMO

BACKGROUND: Although Lesion size index (LSI) has been reported to highly predict radiofrequency lesion size in vitro, its accuracy in lesion size and steam pop estimation has not been well investigated for every possible scenario. METHODS: Initially, radiofrequency ablations were performed on porcine myocardial slabs at various power, CF, and time settings with blinded LSI. Subsequently, radiofrequency power at 20, 30, 40, 50, and 60 W was applied at CF values of 5, 10, 20, and 30 g to reach target LSIs of 4, 5, 6, and 7. Lesion size and steam pops were recorded for each ablation. RESULTS: Lesion size was positively correlated with LSI regardless of power settings (p< 0.001). The linear correlation coefficients of lesion size and LSI decreased at higher power settings. At high power combined with high CF settings (50 W/20 g), lesion depth and LSI showed an irrelevant correlation (p = 0.7855). High-power ablation shortened ablation time and increased the effect of resistive heating. LSI could predict the risk of steam pops at high-power settings with the optimal threshold of 5.65 (sensitivity, 94.1%; specificity, 46.1%). The ablation depth of the heavy heart was shallower than that of the light heart under similar ablation settings. CONCLUSIONS: LSI could predict radiofrequency lesion size and steam pops at high power settings in vitro, while synchronous high power and high CF should be avoided. Lighter hearts require relatively lower ablation settings to create appropriate ablation depth. This article is protected by copyright. All rights reserved.

7.
Sci Transl Med ; 15(679): eabn5029, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652534

RESUMO

Anti-PD-1/PD-L1 therapy, either by anti-PD-1 antibody or anti-PD-L1 antibody, has efficacy by reinvigorating tumor-infiltrating CD8+ T cells in a subset of patients with cancer, but it has unequal effects on heterogeneous CD8+ T cell populations. Hence, the subset crucial to efficacious PD-1 blockade therapy remains elusive. Here, we found an increase in tumor-infiltrating CD200+ cytotoxic T lymphocytes (CTLs) upon PD-1/PD-L1 blockade, with higher proportions of CD200+ T cells positively related to a favorable clinical outcome to anti-PD-1/PD-L1 therapy in three independent cohorts of patients with cancer. Using multiple mouse tumor models, we demonstrated that CD200+ CTLs are essential for efficacious anti-PD-L1 therapy. Mechanistically, we observed a unique chromatin landscape in CD200+ CTLs and found that these cells are enriched for tumor antigen-specific CTLs and have antitumor effector functions. Coinoculation of CD200+ CTLs with tumor cells led to robust tumor regression in two transplanted mouse models. Clinically, we found that infiltration of CD200+ CTLs into tumors could predict immunotherapy efficacy in six patient cohorts. Together, our findings reveal that CD200+ CTLs in the tumor microenvironment are crucial for efficacious anti-PD-1/PD-L1 therapy and could serve as a predictor of successful immunotherapy in the clinic.


Assuntos
Neoplasias , Linfócitos T Citotóxicos , Animais , Camundongos , Linfócitos T CD8-Positivos , Microambiente Tumoral , Neoplasias/terapia , Imunoterapia , Antígeno B7-H1 , Linfócitos do Interstício Tumoral
8.
BMC Med ; 21(1): 11, 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36617560

RESUMO

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This phase IIa study was part of a phase I/IIa study (NCT03386955), aimed to evaluate the efficacy and safety of rezivertinib as the first-line treatment for patients with locally advanced or metastatic/recurrent EGFR mutated non-small cell lung cancer (NSCLC). METHODS: Patients received the first-line treatment of 180 mg rezivertinib orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: From Jun 12, 2019, to Oct 17, 2019, 43 patients were enrolled. At the data cutoff date on Dec 23, 2021, the ORR by BICR was 83.7% (95% CI: 69.3-93.2%). The median DoR was 19.3 (95% CI: 15.8-25.0) months. The median PFS by BICR was 20.7 (95% CI: 13.8-24.8) months and 22.0 (95% CI: 16.8-26.3) months by investigators. Data on OS was immature. Totally, 40 (93.0%) patients had at least one treatment-related adverse event while 4 (9.3%) of them were grade ≥ 3. CONCLUSIONS: Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation in the first-line setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03386955.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Antineoplásicos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Receptores ErbB/genética , Receptores ErbB/uso terapêutico , Mutação
9.
Curr Microbiol ; 80(2): 73, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622432

RESUMO

The presence and diversity of endophytic fungi associated with host plants are important not just for host plant growth and defense, but also impact the production of medicinal secondary metabolites. However, the correlation between endophytic fungi and crocin production in Crocus sativus (CS) remains underexplored. Here, we explore the relationship between endophytic fungal diversity and crocin content among different CS tissues and field sites. Specifically, we isolated endophytic fungi from five different field sites (Shanghai, Jiande, Huzhou, Anhui, and Hebei) and five different tissues (corm, scape, leaf, petal, and stigma) and analyzed fungal community diversity, richness, and evenness. We identified a total of 32 endophytic fungal taxa, assigned to 7 orders within 4 classes (Eurotiomycetes, Agaricomycetes, Dothideomycetes, and Sordariomycetes). The most dominant order was Eurotiales, and the most dominant genera were Penicillium and Talaromyces. Species richness tended to be highest in belowgrown tissues, such as corm and scape. Additionally, several fungal taxa were found to be either site- or tissue-specific. Three genera in particular were correlated with crocin content: Penicillium, Sistotrema, and Bjerkandera. Given the fact that endophytic microorganisms can both promote the production of secondary metabolites in host plants and potentially produce secondary metabolites themselves, further study is required to understand the mechanistic relationship between these and other fungal genera and crocin production.


Assuntos
Ascomicetos , Crocus , Penicillium , Fungos , Endófitos , China , Penicillium/genética
10.
Sci Rep ; 13(1): 1608, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709211

RESUMO

Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disease occurring during pregnancy that is characterized by disordered bile acid (BA) metabolism. It is related to adverse clinical outcomes in both the mother and fetus. Our aim was to evaluate the BA metabolism profiles in different types of ICP and investigate the association between specific BAs and perinatal complications in ICP patients. We consecutively evaluated 95 patients with ICP, in which 53 patients were diagnosed with early-onset ICP (EICP) and 42 patients were diagnosed with late-onset ICP (LICP). Concentrations of 15 BA components were detected using high-performance liquid chromatography tandem mass spectrometry. Clinical information was abstracted from the medical records. The percentage of conjugated bile acids increased in ICP patients. Specifically, taurocholic acid (TCA) accumulated in LICP patients, and glycocholic acid (GCA) predominated in EICP patients. A higher preterm birth incidence was observed among ICP patients. Albumin, total bile acids, total bilirubin and GCA percentage values at ICP diagnosis predicts 83.5% of preterm birth in EICP, and the percentage of TCA in total bile acids at ICP diagnosis predicts 93.2% of preterm birth in LICP. This analysis showed that the BA metabolism profiles of EICP and LICP were distinct. Increased hepatic load was positively correlated with preterm birth in EICP. An elevated TCA percentage in total bile acids provides a biomarker to predict preterm birth in LICP.


Assuntos
Colestase Intra-Hepática , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Humanos , Recém-Nascido , Ácidos e Sais Biliares , Nascimento Prematuro/epidemiologia , Complicações na Gravidez/epidemiologia , Colestase Intra-Hepática/diagnóstico , Resultado da Gravidez
11.
Inorg Chem ; 62(3): 1156-1164, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36625518

RESUMO

Iridium/nickel (Ir/Ni) metallaphotoredox dual catalysis overcomes the challenging reductive elimination (RE) of Ni(II) species and has made a breakthrough progress to construct a wide range of C-X (X = C, N, S, and P) bonds. However, the corresponding reaction mechanisms are still ambiguous and controversial because the systematic research on the nature of this synergistic catalysis is not sufficient. Herein, IrIII/NiII and IrIII/Ni0 metallaphotoredox catalysis have been theoretically explored taking the aryl esterification reaction of benzoic acid and aryl bromide as an example by a combination of density functional theory (DFT), molecular dynamics, and time-dependent DFT computations. It is found that an electron-transfer mechanism is applicable to IrIII/NiII metallaphotoredox catalysis, but an energy-transfer mechanism is applicable to IrIII/Ni0 combination. The IrIII/NiII metallaphotoredox catalysis succeeds to construct a NiI-NiIII catalytic cycle to avoid the challenging RE of Ni(II) species, while the RE occurs from triplet excited-state Ni(II) species in the IrIII/Ni0 metallaphotoredox catalysis. In addition, the lower lowest unoccupied molecular orbital energy level of Ni(III) species than that of Ni(II) species accelerates RE from Ni(III) one. The triplet excited-state Ni(II) species can resemble a Ni(III) center, considering the metal-to-ligand charge transfer character to promote the RE.


Assuntos
Elétrons , Transporte de Elétrons
12.
Arthrosc Tech ; 11(11): e2003-e2011, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36457404

RESUMO

Recurrent anterior shoulder dislocations accompanied by severe glenoid bone defects are typically treated with arthroscopy. Until now, autologous iliac grafting has been reported with excellent results, and different techniques of bone fixation have been introduced by numerous scholars. In this article, we introduce a specially designed guide that can achieve accurate positioning of the bone graft and a nonrigid graft fixation technique with a single EndoButton (Smith & Nephew). Using this technique, we greatly simplify the arthroscopic procedure and avoid the use of screws.

13.
Environ Pollut ; : 120771, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36455767

RESUMO

A large number of synthetic fibers found in the environment have aroused public conern about microfiber pollution. However, more studies have found that the number of natural fibers and regenerated cellulose fibers in the environment is much higher than that of synthetic fibers. If humans are exposed to excessive amounts of these two types of fibers for a long time, they may also suffer physiological injury. However, this is often ignored by previous research on microfiber pollution. Recently, some publications attributed the dominating amounts of natural fiber and regenerated cellulosic fibers in the environment to the past yield advantage and low durability compared to synthetic fibers. This correspondence supports that view and further discusses the main reasons for the domination of natural and regenerated cellulosic fibers: their physicochemical properties, material sources, manufacturing processes (staple yarn and filament) and applications. This correspondence aims to arouse attention to the potential impact of natural fibers and regenerated cellulose fibers.

14.
Front Microbiol ; 13: 1044676, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36578566

RESUMO

The HIV-1 Rev response element (RRE) is a cis-acting RNA element that facilitates the nuclear export of mRNA-containing introns by binding specifically to the Rev protein, enabling a critical step in the viral replication cycle. This study aims to determine the subtype-specific loci of HIV-1 subtype B RRE circulating in China and to analyze their effects on Rev-RRE function and HIV-1 replication. We amplified 71 HIV-1 subtype B RRE full-length sequences from the HIV patients' blood samples collected in China, analyzed the subtype-specific loci on them by comparing them with subtype B in the United States, and predicted their RNA secondary structures. Rev-RRE activity assay was used to test the binding activity of Rev and different RREs. Infectious clones were mutated to test the effect of the subtype-specific loci on replication capacity. In this study, two sites were determined to be the subtype-specific loci of HIV-1 subtype B RRE circulating in China. Both site 186 and site 56-57insAAC can significantly increase the viral mRNA transcription and Rev-RRE activity, but only the site 186 can significantly improve viral replication ability. Collectively, the subtype-specific loci of subtype B RRE circulating in China have a significant effect on the Rev-RRE activity and viral replication. This study investigates the subtype-specific loci of RRE, which are unique to retroviruses and essential for viral replication, and will help to explore the reasons why subtype B circulating in China is more widespread and persistent than American subtype B in China at the genetic level, and will provide theoretical support for the development of more inclusive detection and treatment methods for subtype B circulating in China. At the same time, it will also provide insight into the impact of different subtype HIV-1 genetic characteristics on viral replication.

15.
Front Plant Sci ; 13: 1045147, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36483959

RESUMO

Introduction: Several microorganisms in the plant root system, especially in the rhizosphere, have their own compositions and functions. Corm rot is the most severe disease of Crocus sativus, leading to more than 50% mortality in field production. Methods: In this study, metagenomic sequencing was used to analyze microbial composition and function in the rhizosphere of C. sativus for possible microbial antagonists against pathogenic Fusarium oxysporum. Results: The microbial diversity and composition were different in the C. sativus rhizosphere from different habitats. The diversity index (Simpson index) was significantly lower in the C. sativus rhizospheric soil from Chongming (Rs_CM) and degenerative C. sativus rhizospheric soil from Chongming (RsD_CM) than in others. Linear discriminant analysis effect size results showed that differences among habitats were mainly at the order (Burkholderiales, Micrococcales, and Hypocreales) and genus (Oidiodendron and Marssonina) levels. Correlation analysis of the relative lesion area of corm rot showed that Asanoa was the most negatively correlated bacterial genus (ρ = -0.7934, p< 0.001), whereas Moniliophthora was the most negatively correlated fungal genus (ρ = -0.7047, p< 0.001). The relative lesion area result showed that C. sativus from Qiaocheng had the highest resistance, followed by Xiuzhou and Jiande. C. sativus groups with high disease resistance had abundant pathogen resistance genes, such as chitinase and ß-1,3-glucanase genes, from rhizosphere microorganisms. Further, 13 bacteria and 19 fungi were isolated from C. sativus rhizosphere soils, and antagonistic activity against pathogenic F. oxysporum was observed on potato dextrose agar medium. In vivo corm experiments confirmed that Trichoderma yunnanense SR38, Talaromyces sp. SR55, Burkholderia gladioli SR379, and Enterobacter sp. SR343 displayed biocontrol activity against corm rot disease, with biocontrol efficiency of 20.26%, 31.37%, 39.22%, and 14.38%, respectively. Discussion: This study uncovers the differences in the microbial community of rhizosphere soil of C. sativus with different corm rot disease resistance and reveals the role of four rhizospheric microorganisms in providing the host C. sativus with resistance against corm rot. The obtained biocontrol microorganisms can also be used for application research and field management.

16.
PLoS Genet ; 18(12): e1010318, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36520929

RESUMO

Growth differentiation factor 9 (GDF9) was the first oocyte-specific growth factor identified; however, most information about GDF9 functions comes from studies in the mouse model. In this study, we created a mutant for Gdf9 gene (gdf9-/-) in zebrafish using TALEN approach. The loss of Gdf9 caused a complete arrest of follicle development at primary growth (PG) stage. These follicles eventually degenerated, and all mutant females gradually changed to males through sex reversal, which could be prevented by mutation of the male-promoting gene dmrt1. Interestingly, the phenotypes of gdf9-/- could be rescued by simultaneous mutation of inhibin α (inha-/-) but not estradiol treatment, suggesting a potential role for the activin-inhibin system or its signaling pathway in Gdf9 actions. In gdf9-null follicles, the expression of activin ßAa (inhbaa), but not ßAb (inhbab) and ßB (inhbb), decreased dramatically; however, its expression rebounded in the double mutant (gdf9-/-;inha-/-). These results indicate clearly that the activation of PG follicles to enter the secondary growth (SG) requires intrinsic factors from the oocyte, such as Gdf9, which in turn works on the neighboring follicle cells to trigger follicle activation, probably involving activins. In addition, our data also support the view that estrogens are not involved in follicle activation as recently reported.


Assuntos
Fator 9 de Diferenciação de Crescimento , Peixe-Zebra , Camundongos , Feminino , Animais , Masculino , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Fator 9 de Diferenciação de Crescimento/genética , Fator 9 de Diferenciação de Crescimento/metabolismo , Inibinas/genética , Inibinas/metabolismo , Folículo Ovariano/metabolismo , Ativinas/genética , Ativinas/metabolismo
17.
Evol Appl ; 15(12): 2028-2042, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36540636

RESUMO

Genomic prediction (GP) based on haplotype alleles can capture quantitative trait loci (QTL) effects and increase predictive ability because the haplotypes are expected to be in linkage disequilibrium (LD) with QTL. In this study, we constructed haploblocks using LD-based and the fixed number of single nucleotide polymorphisms (fixed-SNP) methods with Illumina BovineHD chip in beef cattle. To evaluate the performance of different haplotype block partitioning methods, we constructed haploblocks based on LD thresholds (from r 2 > 0.2 to r 2 > 0.8) and the number of fixed-SNPs (5, 10, 20). The performance of predictive methods for three carcass traits including liveweight (LW), dressing percentage (DP), and longissimus dorsi muscle weight (LDMW) was evaluated using three approaches (GBLUP and BayesB model based on the SNP, GHBLUP, and BayesBH models based on the haploblock, and GHBLUP+GBLUP and BayesBH+BayesB models based on the combined haploblock and the nonblocked SNPs, which were located between blocks). In this study, we found the accuracies of LD-based and fixed-SNP haplotype Bayesian methods outperformed the Bayesian models (up to 8.54 ± 7.44% and 5.74 ± 2.95%, respectively). GHBLUP showed a high improvement (up to 11.29 ± 9.87%) compared with GBLUP. The Bayesian models have higher accuracies than BLUP models in most scenarios. The average computing time of the BayesBH+BayesB model can reduce by 29.3% compared with the BayesB model. The prediction accuracies using the LD-based haplotype method showed higher improvements than the fixed-SNP haplotype method. In addition, to avoid the influence of rare haplotypes generated from haplotype construction, we compared the performance of GP by filtering four types of minor haplotype allele frequency (MHAF) (0.01, 0.025, 0.05, and 0.1) under different conditions (LD levels were set at r 2 > 0.3, and the fixed number of SNPs was 5). We found the optimal MHAF threshold for LW was 0.01, and the optimal MHAF threshold for DP and LDMW was 0.025.

18.
Angew Chem Int Ed Engl ; : e202215616, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36573021

RESUMO

Herein, an I2 -catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom-economy. This protocol not only represents the first molecular-iodine-catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine-ynamides involving distinctively different C(sp3 )-C(sp3 ) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I2 . Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5-exo-dig cyclization/rearrangement process.

19.
J Vis Exp ; (189)2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36533829

RESUMO

To determine the salt tolerance and physiological mechanism of pepper (Capsicum annuum L.) at the germination stage, the Hongtianhu 101 and Xinxiang 8 varieties, which have large differences in salt tolerance, are employed as the study materials. Six mixed salt concentrations of 0, 3, 5, 10, 15, and 20 g/L derived using equal molar ratios of Na2CO3, NaHCO3, NaCl, CaCl2, MgCl2, MgSO4, and Na2SO4 are used. To determine their effects, the related indexes of seed germination, seedling growth, and physiology are measured, and salt tolerance is comprehensively evaluated using membership function analysis. The results show that as the mixed salt concentration increases, the germination potential, germination index, germination rate, seed germination vigor index, root length, and root fresh weight of the two cultivars significantly decrease, whereas the relative salt rate gradually increases. The hypocotyl length and fresh weight aboveground increase first and then decrease, while the malondialdehyde (MDA), proline (Pro) content, catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activity decrease and then increase. The germination potential, germination index, germination rate, seed germination vigor index, root length, root fresh weight, MDA and Pro content, and CAT activity of the Hongtianhu 101 seeds are higher than those of Xinxiang 8 for all salt concentrations employed here. However, hypocotyl length, fresh weight aboveground, and relative salt rate are lower in Hongtianhu 101 than in Xinxiang 8. The comprehensive evaluation of salt tolerance reveals that the total weighted values of the two membership function indexes increase first and then decrease as the mixed salt concentration increases. Compared with 5 g/L, which has the highest membership function value, the index under salt concentrations of 3 g/L, 10 g/L, and 15 g/L decreases by 4.7%-11.1%, 25.3%-28.3%, and 41.4%-45.1%, respectively. This study provides theoretical guidance for the breeding of salt-tolerant varieties of pepper and an analysis of the physiological mechanisms involved in salt tolerance and salt-tolerant cultivation.


Assuntos
Capsicum , Germinação , Germinação/fisiologia , Tolerância ao Sal , Sementes , Melhoramento Vegetal , Plântula
20.
Front Endocrinol (Lausanne) ; 13: 999154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440200

RESUMO

Objective: To explore the effect of maternal body mass index (BMI) on steroid hormone profiles in women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT). Methods: We enrolled 79 women with NGT and 80 women with GDM who had a gestational age of 24-28 weeks. The participants were grouped according to their BMI. We quantified 11 steroid hormones profiles by liquid chromatography-tandem mass spectrometry and calculated the product-to-precursor ratios in the steroidogenic pathway. Results: Women with GDM and BMI<25kg/m2 showed higher concentrations of dehydroepiandrosterone (DHEA) (p<0.001), testosterone (T) (p=0.020), estrone (E1) (p=0.010) and estradiol (E2) (p=0.040) and lower Matsuda index and HOMA-ß than women with NGT and BMI<25kg/m2. In women with GDM, concentrations of E1 (p=0.006) and E2 (p=0.009) declined, accompanied by reduced E2/T (p=0.008) and E1/androstenedione (A4) (p=0.010) in the BMI>25 kg/m2 group, when compared to that in the BMI<25 kg/m2 group. The values of E2/T and E1/A4 were used to evaluate the cytochrome P450 aromatase enzyme activity in the steroidogenic pathway. Both aromatase activities negatively correlated with the maternal BMI and positively correlated with the Matsuda index in women with GDM. Conclusions: NGT women and GDM women with normal weight presented with different steroid hormone profiles. Steroidogenic pathway profiling of sex hormones synthesis showed a significant increase in the production of DHEA, T, E1, and E2 in GDM women with normal weight. Additionally, the alteration of steroid hormone metabolism was related to maternal BMI in women with GDM, and GDM women with overweight showed reduced estrogen production and decreased insulin sensitivity compared with GDM women with normal weight.


Assuntos
Diabetes Gestacional , Gravidez , Feminino , Humanos , Lactente , Diabetes Gestacional/metabolismo , Índice de Massa Corporal , Aromatase , Insulina , Estradiol , Desidroepiandrosterona
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