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1.
Plant Dis ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587792

RESUMO

Euphorbia lathyris L. is a biennial herb in the Euphorbiaceae that has been used as a medicinal plant. It is distributed or cultivated worldwide, and the seeds of E. lathyris are the main source of ingenol, which is the precursor of Picato, the first medicine approved by USFDA for the treatment of solar keratosis (Abramovits et al. 2013). However, the production of E. lathyris can be severely hampered by the occurrence of plant diseases. Between 2020-2022 (specifically in October-November of each year), anthracnose-like symptoms were observed on E. lathyris in fields (E 118°49'50″, N 32°3'33″) in Nanjing, Jiangsu Province, China. The incidence of E. lathyris with disease symptoms was between 25%-30% (n = 100). The lesions on the leaves were evident initially as dark brown spots, which expanded into larger necrotic spots, finally resulting in leaves withering and dropping off. In severe cases, stem wilting was also observed. To determine the causal agent, we collected diseased leaf samples (n = 20) from different E. lathyris plants in the field (~ 1800 m2). After cleaning, the junctions of the diseased and healthy parts were excised and sterilized in 75% ethanol for 20-25 seconds, and rinsed with sterile water. After that, they were transferred onto potato sucrose agar (PSA) plates and placed at 25℃ for 3-4 days, until fungal growth was evident. The fungus was purified by recovering single conidia and growing them on PSA (Hu et al. 2015). A consistent fungal colony, based on morphological characteristics, was recovered from 17 samples. The colony color was initially white, green in the middle, and gradually changed into gray green as the colony matured. Conidia were transparent and cylindrical (22-28 µm × 7-9 µm, n = 50). Five loci informative (ITS, TUB, ACT, GAPDH, and CHS-1) (Weir et al. 2012) for Colletotrichum spp. identification were sequenced from two isolates ELC-1 and ELC-2 obtained from different plant individuals. Compared with a reference isolate (Colletotrichum gloeosporioides ZH3), the GAPDH, CHS-1, and TUB2 sequences of ELC-1 and ELC-2 showed 95% (263 bp out of 275 bp), 98% (295 bp out of 299 bp), and 99% (711 bp out of 712 bp and 717 bp out of 719 bp) similarity, respectively. The ITS sequence identities were 100% (577 bp out of 577 bp) and 99% (594 bp out of 597 bp), while the ACT sequence identities were 100% (281 bp out of 281 bp) and 98% (279 bp out of 284 bp). All sequences have been deposited in Genbank database (OR865865-OR865866 and OR873625-OR873632). After performing phylogenetic analysis with Mega 11, the pathogen was confirmed as C. gloeosporioides. To fulfil Koch's postulates, we sprayed six-week-old healthy plants with a conidia suspension of C. gloeosporioides (106 spores/mL) or sterile water (serve as control). The inoculated plants were placed at 25℃, 100% relative humidity, and 12-h photoperiod (Zhang et al. 2021). Six plants were inoculated for each treatment, and the experiment was repeated three times. After 6-8 days, the plants inoculated with C. gloeosporioides showed similar symptoms to those observed on diseased plants in the field, while the control plants remained healthy and free of disease. The pathogens were then re-isolated and identified as C. gloeosporioides. To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on E. lathyris. Anthracnose may cause significant yield losses in E. lathyris production, and our results will provide experimental and theoretical basis for the management of the disease.

2.
Huan Jing Ke Xue ; 45(5): 2926-2938, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629554

RESUMO

With the rapid urbanization and industrialization, heavy metal contamination in urban soil and surface dust has received particular attention due to its negative effects on the eco-environment and human health. Contamination and spatio-temporal characteristics, contamination sources, and source apportionment methods, as well as the ecological and health risks of heavy metals in urban soil and surface dust were reviewed. The knowledge gaps in current research and prospects of future works were proposed. Four key points were presented, including improving the research on the interaction mechanism of heavy metals in urban soil and surface dust under complex conditions, enriching verification methods to improve the source apportionment reliability of anthropogenic metals by receptor models, strengthening the research on chemical forms of heavy metals from different sources and their short-term accumulation processes in surface dust, and raising the credibility of ecological and health risk forecast of heavy metals by integrating the improved exposure parameters and chemical forms.

3.
Planta ; 259(5): 115, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589536

RESUMO

MAIN CONCLUSION: A member of the rice GT61 clade B is capable of transferring both 2-O-xylosyl and 2-O-arabinosyl residues onto xylan and another member specifically catalyses addition of 2-O-xylosyl residue onto xylan. Grass xylan is substituted predominantly with 3-O-arabinofuranose (Araf) as well as with some minor side chains, such as 2-O-Araf and 2-O-(methyl)glucuronic acid [(Me)GlcA]. 3-O-Arabinosylation of grass xylan has been shown to be catalysed by grass-expanded clade A members of the glycosyltransferase family 61. However, glycosyltransferases mediating 2-O-arabinosylation of grass xylan remain elusive. Here, we performed biochemical studies of two rice GT61 clade B members and found that one of them was capable of transferring both xylosyl (Xyl) and Araf residues from UDP-Xyl and UDP-Araf, respectively, onto xylooligomer acceptors, whereas the other specifically catalysed Xyl transfer onto xylooligomers, indicating that the former is a xylan xylosyl/arabinosyl transferase (named OsXXAT1 herein) and the latter is a xylan xylosyltransferase (named OsXYXT2). Structural analysis of the OsXXAT1- and OsXYXT2-catalysed reaction products revealed that the Xyl and Araf residues were transferred onto O-2 positions of xylooligomers. Furthermore, we demonstrated that OsXXAT1 and OsXYXT2 were able to substitute acetylated xylooligomers, but only OsXXAT1 could xylosylate GlcA-substituted xylooligomers. OsXXAT1 and OsXYXT2 were predicted to adopt a GT-B fold structure and molecular docking revealed candidate amino acid residues at the predicted active site involved in binding of the nucleotide sugar donor and the xylohexaose acceptor substrates. Together, our results establish that OsXXAT1 is a xylan 2-O-xylosyl/2-O-arabinosyl transferase and OsXYXT2 is a xylan 2-O-xylosyltransferase, which expands our knowledge of roles of the GT61 family in grass xylan synthesis.


Assuntos
Arabidopsis , Oryza , Glicosiltransferases/análise , Oryza/metabolismo , Xilanos/metabolismo , Arabidopsis/metabolismo , Simulação de Acoplamento Molecular , 60613 , Poaceae/metabolismo , Parede Celular/metabolismo
4.
Acta Biomater ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599439

RESUMO

During physiological and pathological processes, cells experience significant morphological alterations with the re-arrangement of cytoskeletal filaments, resulting in anisotropic viscoelasticity. Here, a structure-based cell model is proposed to study the anisotropic viscoelastic mechanical behaviors of living cells. We investigate how cell shape affects its creep responses in longitudinal and perpendicular directions. It is shown that cells exhibit power-law rheological behavior in both longitudinal and perpendicular directions under step stress, with a more solid-like behavior along the longitudinal direction. We reveal that the cell volume and cytoskeletal filament orientation, which have been neglected in most existing models, play a critical role in regulating cellular anisotropic viscoelasticity. The stiffness of the cell in both directions increases linearly with increasing its aspect ratio, due to the decrease of cell volume. Moreover, the increase in the cell's aspect ratio produces the aggregation of cytoskeletal filaments along the longitudinal direction, resulting in higher stiffness in this direction. It is also shown that the increase in cell's aspect ratio corresponds to a process of cellular ordering, which can be quantitatively characterized by the orientational entropy of cytoskeletal filaments. In addition, we present a simple yet robust method to establish the relationship between cell's aspect ratio and cell volume, thus providing a theoretical framework to capture the anisotropic viscoelastic behavior of cells. This study suggests that the structure-based cell models may be further developed to investigate cellular rheological responses to external mechanical stimuli and may be extended to the tissue scale. STATEMENT OF SIGNIFICANCE: The viscoelastic behaviors of cells hold significant importance in comprehending the roles of mechanical forces in embryo development, invasion, and metastasis of cancer cells. Here, a structure-based cell model is proposed to study the anisotropic viscoelastic mechanical behaviors of living cells. Our study highlights the crucial role of previously neglected factors, such as cell volume and cytoskeletal filament orientation, in regulating cellular anisotropic viscoelasticity. We further propose an orientational entropy of cytoskeletal filaments to quantitatively characterize the ordering process of cells with increasing aspect ratios. Moreover, we derived the analytical interrelationships between cell aspect ratio, cell stiffness, cell volume, and cytoskeletal fiber orientation. This study provides a theoretical framework to describe the anisotropic viscoelastic mechanical behavior of cells.

5.
Oncol Lett ; 27(5): 192, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38495833

RESUMO

As a novel tyrosine kinase inhibitor (TKI), pyrotinib can irreversibly block dual pan-ErbB receptors and has been used in the treatment of advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, there are limited data on the use of pyrotinib in early breast cancer. Therefore, the present meta-analysis was conducted to evaluate the safety and efficacy of pyrotinib in the neoadjuvant setting for patients with early-stage or locally advanced HER2-positive breast cancer. Online databases (Pubmed, Web of Science, Embase and Cochrane Library) were comprehensively searched for eligible prospective clinical trials on August 17, 2023. The primary endpoint was the treatment-related adverse events (TRAEs), and the secondary endpoint was pathological complete response (pCR) rate. In total, seven trials with a total enrolment of 407 patients were included. A total of seven studies evaluated pyrotinib in combination with trastuzumab and chemotherapy in the neoadjuvant setting. The median age ranged from 47-50 years. The most common TRAEs were diarrhea [98% of patients; 95% confidence interval (CI): 92-100%], followed by anemia (71%; 95% CI: 55-89%), vomiting (69%; 95% CI: 55-82%), and leucopenia (66%; 95% CI: 35-91%). No treatment-related deaths occurred. The pooled pCR rate was 57% (95% CI: 47-68%). It was concluded that pyrotinib-containing neoadjuvant therapy could be an effective treatment strategy in patients with early-stage or locally advanced HER2-positive breast cancer; however, the management of adverse events should be a key consideration. The management of adverse events should be paid great attention to, during pyrotinib therapy, although pyrotinib-contained neoadjuvant therapy could be an effective treatment for patients with early-stage or locally advanced HER2-positive breast cancer. Head-to-head randomized clinical trials are warranted to further confirm the benefits and risks associated with pyrotinib therapy in patients with breast cancer.

6.
Chem Commun (Camb) ; 60(28): 3858-3861, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38497365

RESUMO

Herein, we describe a copper-catalyzed intramolecular dearomative amination of indoles via a formal aza-Wacker reaction. This protocol provides an efficient method to access aza-polycyclic indoline molecules bearing exocyclic CC bonds in moderate to excellent yields in the presence of molecular oxygen as an oxidant. It is worth noting that indolin-3-ones are achieved when employing C3-non-substituted indoles as substrates.

7.
Front Endocrinol (Lausanne) ; 15: 1345203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469143

RESUMO

Background: Tyrosine kinase inhibitors (TKIs) contribute to the treatment of patients with anaplastic thyroid cancer (ATC). Although prospective clinical studies of TKIs exhibit limited efficacy, whether ATC patients benefit from TKI treatment in real-world clinical practice may enlighten future explorations. Therefore, we conducted this effective analysis based on real-world retrospective studies to illustrate the efficacy of TKI treatment in ATC patients. Methods: We systematically searched the online databases on September 03, 2023. Survival curves were collected and reconstructed to summarize the pooled curves. Responses were analyzed by using the "meta" package. The primary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: 12 studies involving 227 patients were enrolled in the study. Therapeutic strategies included: anlotinib, lenvatinib, dabrafenib plus trametinib, vemurafenib, pembrolizumab plus dabrafenib and trametinib, pembrolizumab plus lenvatinib, pembrolizumab plus trametinib, and sorafenib. The pooled median OS and PFS were 6.37 months (95% CI 4.19-10.33) and 5.50 months (95% CI 2.17-12.03). The integrated ORR and DCR were 32% (95% CI 23%-41%) and 40% (95% CI 12%-74%). Conclusion: In real-world clinical practice, ATC patients could benefit from TKI therapy. In future studies, more basic experiments and clinical explorations are needed to enhance the effects of TKIs in the treatment of patients with ATC.


Assuntos
Imidazóis , Oximas , Compostos de Fenilureia , Quinolinas , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Estudos Retrospectivos , Estudos Prospectivos , Neoplasias da Glândula Tireoide/tratamento farmacológico
8.
Molecules ; 29(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474571

RESUMO

The Euodia genus comprises numerous untapped medicinal plants that warrant thorough evaluation for their potential as valuable natural sources of herbal medicine or food flavorings. In this study, untargeted metabolomics and in vitro functional methods were employed to analyze fruit extracts from 11 significant species of the Euodia genus. An investigation of the distribution of metabolites (quinolone and indole quinazoline alkaloids) in these species indicated that E. rutaecarpa (Euodia rutaecarpa) was the most widely distributed species, followed by E. compacta (Euodia compacta), E. glabrifolia (Euodia glabrifolia), E. austrosinensis (Euodia austrosinensis), and E. fargesii (Euodia fargesii). There have been reports on the close correlation between indole quinazoline alkaloids and their anti-tumor activity, especially in E. rutaecarpa fruits which exhibit effectiveness against various types of cancer, such as SGC-7901, Hela, A549, and other cancer cell lines. Additionally, the E. rutaecarpa plant contains indole quinazoline alkaloids, which possess remarkable antibacterial properties. Our results offer novel insights into the utilization of Euodia resources in the pharmaceutical industry.


Assuntos
Alcaloides , Evodia , Plantas Medicinais , Quinolonas , Rutaceae , Humanos , Extratos Vegetais , Alcaloides Indólicos , Células HeLa , Quinazolinas
9.
Org Lett ; 26(6): 1224-1228, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38305744

RESUMO

The semipinacol rearrangement is a powerful and versatile method for constructing all-carbon quaternary stereocenters. The development of catalytic asymmetric semipinacol rearrangements using multifunctionalizable electrophiles remains highly sought-after in organic synthesis. In this study, a catalytic enantioselective allylic cation-induced semipinacol rearrangement reaction was presented that enables the simultaneous construction of two skipped chiral carbon centers. Chiral Ir(I)-(P,olefin) and Sc(OTf)3 catalysts cooperatively initiate the asymmetric allylic alkylation of alkenyl cyclobutanols with allylic alcohols, triggering ring expansion of the cyclobutanol moiety through a stereoselective 1,2-alkyl migration. The reaction afforded a range of cyclopentanones bearing an α-quaternary carbon that is adjacent to a chiral allyl scaffold. The products were applied to synthesize enantioenriched fused tricyclopentanoids bearing four stereogenic carbon centers.

10.
Adv Sci (Weinh) ; 11(15): e2306139, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342634

RESUMO

Despite its high potential, non-viral gene therapy of cancer remains challenging due to inefficient nucleic acid delivery. Ultrasound (US) with microbubbles (MB) can open biological barriers and thus improve DNA and mRNA passage. Polymeric MB are an interesting alternative to clinically used lipid-coated MB because of their high stability, narrow size distribution, and easy functionalization. However, besides choosing the ideal MB, it remains unclear whether nanocarrier-encapsulated mRNA should be administered separately (co-administration) or conjugated to MB (co-formulation). Therefore, the impact of poly(n-butyl cyanoacrylate) MB co-administration with mRNA-DOTAP/DOPE lipoplexes or their co-formulation on the transfection of cancer cells in vitro and in vivo is analyzed. Sonotransfection improved mRNA delivery into 4T1 breast cancer cells in vitro with co-administration being more efficient than co-formulation. In vivo, the co-administration sonotransfection approach also resulted in higher transfection efficiency and reached deeper into the tumor tissue. On the contrary, co-formulation mainly promoted transfection of endothelial and perivascular cells. Furthermore, the co-formulation approach is much more dependent on the US trigger, resulting in significantly lower off-site transfection. Thus, the findings indicate that the choice of co-administration or co-formulation in sonotransfection should depend on the targeted cell population, tolerable off-site transfection, and the therapeutic purpose.


Assuntos
Embucrilato , Neoplasias , Humanos , Microbolhas , Neoplasias/terapia , Transfecção , Ultrassonografia
11.
J Org Chem ; 89(6): 4085-4097, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394366

RESUMO

A palladium-catalyzed annulative π-extension reaction of bay-iodinated triphenylenes with aryl iodides/o-chloroaromatic carboxylic acids was developed. This approach enabled the synthesis of diverse polycyclic aromatic compounds, including dibenzo[fg,op]tetracenes, azadibenzo[fg,op]tetracenes, and tribenzo[a,g,m]coronenes. Initial studies indicate that the resulting product, 2,3,8,9,14,15-hexakis(decyloxy)tribenzo[a,g,m]coronene, exhibits good liquid-crystalline properties.

12.
Target Oncol ; 19(2): 203-212, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38289445

RESUMO

BACKGROUND: Immunotherapy has revolutionized the treatment of hepatocellular carcinoma (HCC). However, whether adding immunotherapy to antiangiogenic therapy benefits patients with unresectable HCC (uHCC) more in the first-line setting remains controversial. OBJECTIVE: In this analysis, we compared the clinical outcomes of lenvatinib monotherapy with atezolizumab plus bevacizumab combination therapy in advanced uHCC in real-world clinical practice. METHODS: The MEDLINE, Embase, and Cochrane CENTRAL databases were systematically searched on 23 April 2023. The "metaSurvival" and "meta" packages of the R software (version 4.2.2) were used to summarize the survival curves and meta-analyze the survival data. Overall survival (OS) and progression-free survival (PFS) were defined as dual primary endpoints. Secondary endpoints included the objective response rate (ORR) and disease control rate (DCR). RESULTS: Overall, the pooled median OS was 18.4 months in the lenvatinib group versus 18.5 months in the atezolizumab plus bevacizumab group; the pooled median PFS was 6.9 months in the lenvatinib group versus 7.3 months in the atezolizumab plus bevacizumab group. Lenvatinib therapy showed similar OS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.55-1.52, p = 0.72] and PFS (HR: 0.79, 95% CI: 0.56-1.12, p = 0.19) compared with atezolizumab plus bevacizumab therapy. In addition, a comparable ORR [odds ratio (OR): 0.89, 95% CI: 0.65-1.20, p = 0.44) was observed between lenvatinib and atezolizumab plus bevacizumab. CONCLUSIONS: Comprehensive analysis suggested that lenvatinib monotherapy exhibited survival outcomes comparable to those of atezolizumab plus bevacizumab combination therapy, which may provide useful insights for clinicians in future clinical practice.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico
13.
BJOG ; 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168494

RESUMO

OBJECTIVE: To assess pelvic floor muscle (PFM) strength and influencing factors among healthy women at different life stages. DESIGN: Multicentre cross-sectional study. SETTING: Fourteen hospitals in China. POPULATION: A total of 5040 healthy women allocated to the following groups (with 1680 women per group): premenopausal nulliparous, premenopausal parous and postmenopausal. METHODS: The PFM strength was evaluated by vaginal manometry. Multivariate logistic regression was used to determine the influencing factors for low PFM strength. MAIN OUTCOME MEASURES: Maximum voluntary contraction pressure (MVCP). RESULTS: The median MVCP values were 36, 35 and 35 cmH2 O in premenopausal nulliparous (aged 19-51 years), premenopausal parous (aged 22-61 years), and postmenopausal (aged 40-86 years) women, respectively. In the premenopausal nulliparous group, physical work (odds ratio, OR 2.05) was the risk factor for low PFM strength, which may be related to the chronic increased abdominal pressure caused by physical work. In the premenopausal parous group, the number of vaginal deliveries (OR 1.28) and diabetes (OR 2.70) were risk factors for low PFM strength, whereas sexual intercourse (<2 times per week vs. none, OR 0.55; ≥2 times per week vs. none, OR 0.56) and PFM exercise (OR 0.50) may have protective effects. In the postmenopausal group, the number of vaginal deliveries (OR 1.32) and family history of pelvic organ prolapse (POP) (OR 1.83) were risk factors for low PFM strength. CONCLUSIONS: Physical work, vaginal delivery, diabetes and a family history of POP are all risk factors for low PFM strength, whereas PFM exercises and sexual life can have a protective effect. The importance of these factors varies at different stages of a woman's life.

14.
Plant Biotechnol J ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38194521

RESUMO

Wolfberry is a plant with medicinal and food values. However, its bioactive ingredients and the corresponding genetic bases have not been determined. Here, we de novo generated a chromosome-level genome assembly for wolfberry, yielding a genome sequence of ~1.77 Gb with contig N50 of 50.55 Mb and 39 224 predicted gene models. A variation map, using 307 re-sequenced accessions, was called based on this genome assembly. Furthermore, the fruit metabolome of these accessions was profiled using 563 annotated metabolites, which separated Lycium barbarum L. and non-L. barbarum L. The flavonoids, coumarins, alkaloids and nicotinic acid contents were higher in the former than in the latter. A metabolite-based genome-wide association study mapped 156 164 significant single nucleotide polymorphisms corresponding to 340 metabolites. This included 19 219 unique lead single nucleotide polymorphisms in 1517 significant association loci, of which three metabolites, flavonoids, betaine and spermidine, were highlighted. Two candidate genes, LbUGT (evm.TU.chr07.2692) and LbCHS (evm.TU.chr07.2738), with non-synonymous mutations, were associated with the flavonoids content. LbCHS is a structural gene that interacts with a nearby MYB transcription factor (evm.TU.chr07.2726) both in L. barbarum and L. ruthenicum. Thus, these three genes might be involved in the biosynthesis/metabolism of flavonoids. LbSSADH (evm.TU.chr09.627) was identified as possibly participating in betaine biosynthesis/metabolism. Four lycibarbarspermidines (E-G and O) were identified, and only the lycibarbarspermidines O content was higher in L. barbarum varieties than in non-L. barbarum varieties. The evm.TU.chr07.2680 gene associated with lycibarbarspermidines O was annotated as an acetyl-CoA-benzylalcohol acetyltransferase, suggesting that it is a candidate gene for spermidine biosynthesis. These results provide novel insights into the specific metabolite profile of non-L. barbarum L. and the genetic bases of flavonoids, betaine and spermidine biosynthesis/metabolism.

15.
Int J Mol Sci ; 25(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38256166

RESUMO

Prostate cancer (PCa) has been known as the most prevalent cancer disease and the second leading cause of cancer mortality in men almost all over the globe. There is an urgent need for establishment of PCa models that can recapitulate the progress of genomic landscapes and molecular alterations during development and progression of this disease. Notably, several organoid models have been developed for assessing the complex interaction between PCa and its surrounding microenvironment. In recent years, PCa organoids have been emerged as powerful in vitro 3D model systems that recapitulate the molecular features (such as genomic/epigenomic changes and tumor microenvironment) of PCa metastatic tumors. In addition, application of organoid technology in mechanistic studies (i.e., for understanding cellular/subcellular and molecular alterations) and translational medicine has been recognized as a promising approach for facilitating the development of potential biomarkers and novel therapeutic strategies. In this review, we summarize the application of PCa organoids in the high-throughput screening and establishment of relevant xenografts for developing novel therapeutics for metastatic, castration resistant, and neuroendocrine PCa. These organoid-based studies are expected to expand our knowledge from basic research to clinical applications for PCa diseases. Furthermore, we also highlight the optimization of PCa cultures and establishment of promising 3D organoid models for in vitro and in vivo investigations, ultimately facilitating mechanistic studies and development of novel clinical diagnosis/prognosis and therapies for PCa.


Assuntos
Medicina de Precisão , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/genética , Próstata , Organoides , Epigenômica , Microambiente Tumoral
16.
Chem Asian J ; 19(3): e202301080, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38214422

RESUMO

Two isomeric series of compounds with "inverted" chains' substitution patterns, 7,10-dialkoxy-1,2,3,4-tetrafluoro-6,11-dimethoxytriphenylene and 6,11-dialkoxy-1,2,3,4-tetrafluoro-7,10-dimethoxytriphenylene, labelled respectively p-TPFn and m-TPFn, and two non-fluorinated homologous isomers, 3,6-dibutoxy-2,7-dimethoxytriphenylene and 2,7-dibutoxy-3,6-dimethoxytriphenylene, p-TP4 and m-TP4, respectively, were synthesized in three steps and obtained in good yields by the efficient transition-metal-free, fluoroarene nucleophilic substitution via the reaction of appropriate 2,2'-dilithium biphenylenes with either perfluorobenzene, C6 F6 , to yield p-TPFn and m-TPFn, or o-difluorobenzene, C6 H4 F2 , for p-TP4 and m-TP4, respectively. The single-crystal structures of p-TPF4, m-TPF4 and p-TP4, unequivocally confirmed that the cyclization reactions occurred at the expected positions, and that the fluorinated molecules stack up into columns with short separation, a propitious situation for the emergence of columnar mesophases. The mesomorphous properties were found to be greatly affected by both chains' length and positional isomerism: a Colhex phase is found for p-TPF4 and m-TPF4, but mesomorphism vanishes in p-TPF6, and changes for the isomeric homologs m-TPFn, with the induction for n≥6 of a lamello-columnar phase, LamColrec . As expected, both non-fluorinated compounds are deprived of mesomorphism. These compounds emit blue-violet colour in solution, independently of the chains' substitution pattern, and the absolute fluorescence quantum yields can reach up to 46 %. In thin films, fluorescence is slightly redshifted.

17.
Pest Manag Sci ; 80(3): 1228-1239, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37897133

RESUMO

BACKGROUND: Phytophthora capsici is an extremely destructive phytopathogenic oomycete that causes huge economic losses. However, due to the drug resistance risk and environmental threat of chemical fungicides, it is necessary to develop environmentally friendly biocontrol alternatives. Rhein is a major medicinal ingredient of traditional Chinese herbs, and it is widely used in the medical field. However, its inhibitory effect against phytopathogens is unknown. Herein, the antifungal spectrum of rhein and its possible action mechanism against P. capsici were investigated. RESULTS: Rhein possessed broad-spectrum antifungal activity against phytopathogens, particularly P. capsici, Phytophthora infestans, Helminthosporium maydis, and Rhizoctonia solani. Rhein inhibited the mycelial growth as well as the spore germination of P. capsici with mean 50% effective concentration (EC50 ) values of 4.68 µg mL-1 and 6.57 µg mL-1 against 117 P. capsici isolates, respectively. Rhein effectively suppressed the occurrence and spread of Phytophthora blight and significantly destroyed the cell membrane permeability and integrity of P. capsici, corroded its cell wall integrity, and damaged its morphology and ultrastructure. Moreover, rhein caused a considerable reduction in the phospholipid and cellulose contents. Genome-wide transcriptional profiling of P. capsici in response to rhein indicated significant reduction in the expression levels of genes participating in glycerolipid metabolism and starch and sucrose metabolism. Additionally, rhein strengthened the disease defense system of pepper by enhancing related enzyme activities. CONCLUSION: This study demonstrated that rhein could effectively inhibit P. capsici using multiple mechanisms of action. Rhein has the potential to be an efficient alternative to control diseases caused by P. capsici. © 2023 Society of Chemical Industry.


Assuntos
Fungicidas Industriais , Phytophthora infestans , Antifúngicos/farmacologia , Fungicidas Industriais/farmacologia , Antraquinonas , Doenças das Plantas/microbiologia
18.
J Synchrotron Radiat ; 31(Pt 1): 55-64, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37930257

RESUMO

X-ray photon correlation spectroscopy (XPCS) holds strong promise for observing atomic-scale dynamics in materials, both at equilibrium and during non-equilibrium transitions. Here an in situ XPCS study of the relaxor ferroelectric PbMg1/3Nb2/3O3 (PMN) is reported. A weak applied AC electric field generates strong response in the speckle of the diffuse scattering from the polar nanodomains, which is captured using the two-time correlation function. Correlated motions of the Bragg peak are also observed, which indicate dynamic tilting of the illuminated volume. This tilting quantitatively accounts for the observed two-time speckle correlations. The magnitude of the tilting would not be expected solely from the modest applied field, since PMN is an electrostrictive material with no linear strain response to the field. A model is developed based on non-uniform static charging of the illuminated surface spot by the incident micrometre-scale X-ray beam and the electrostrictive material response to the combination of static and dynamic fields. The model qualitatively explains the direction and magnitude of the observed tilting, and predicts that X-ray-induced piezoresponse could be an important factor in correctly interpreting results from XPCS and nanodiffraction studies of other insulating materials under applied AC field or varying X-ray illumination.

19.
Angew Chem Int Ed Engl ; : e202317433, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38086770

RESUMO

Transition metal-catalyzed annulations of four-membered rings via C-C activation are powerful tools to construct complex fused and bridged ring systems. Despite significant progress in (4+1), (4+2) and (4+4) annulations, the (4+3) annulation remains unexplored. Herein, we develop an asymmetric Rh-catalyzed intramolecular (4+3) annulation of α-arylalkene-tethered benzocyclobutenols for the synthesis of dihydrofuran-annulated dibenzocycloheptanols with two discontinuous chiral carbon centers via a C-C and C-H activation cascade. The reaction features excellent diastereo- and enantioselectivities and 100 % atom economy, and is applicable to late-stage modification of complex molecules.

20.
Sci Rep ; 13(1): 22393, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38104140

RESUMO

The stability of coal pillar is extremely important to the control of rock strata movement and surface subsidence. It is of great significance for mining design to analyze the stability and failure characteristics of coal and rock pillars left after mining and to study the failure characteristics and rheological properties of coal and rock with different shapes. In this paper, based on uniaxial compression and rheological tests on rock samples, the rheological properties of rock samples with different shapes were discussed by using the nonlinear theoretical mechanics and damage theory, and the rheological mechanical characteristics of coarse yellow sandstone samples under the action of different free surface areas and the same loading contact area were investigated by means of experimental research, theoretical analysis and numerical simulation. The following conclusions were drawn: the failure characteristics and dynamic change process of rock samples with different shapes under the same loading contact area are obtained by uniaxial compression test and multi-stage rheological loading. The uniaxial compressive strengths of rock samples with the same loading contact surface area and different free surface areas are inversely proportional to their free surface areas. For the round sample, the stress level in the rheological test is obviously lower than the instantaneous peak uniaxial compression strength, while for the other samples, the stress level in the rheological test is close to the instantaneous peak uniaxial compression strength. For rock all these samples, both the ratio of steady-state rheological time to final failure time and the deformation degree decrease with the increase of free surface area.

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