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1.
Front Plant Sci ; 15: 1348182, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571712

RESUMO

Pollen analysis, a crucial tool in botany and ecology for examining historical biotic dynamics, has elicited debate owing to its complex link with vegetation. The challenge lies in discerning the ecological significance of pollen data. In this study, we conducted detailed quadrat surveys on Jinhua Mountain, subtropical China, analyzing topsoil pollen to determine whether pollen signals accurately reflect key ecological components in the forests and shrublands. We performed direct comparisons between pollen and plant compositions and calculated pollen percentages and plant Important Values (IVs) for each quadrat. The results indicate greater homogeneity in pollen composition across the study area compared to plant composition, particularly in the high percentage of Pinus pollen. However, distinct plant communities exhibited significantly different pollen compositions, as evidenced by the multi-response permutation test. This divergence aligns with variations in the dominant plant species across different communities. There were significant correlations between pollen percentages and plant IVs, with correlation coefficients of 0.55 (p < 0.001) at the quadrat level and 0.78 (p < 0.001) at the taxon level. These results support the utility of pollen analysis for representing ecologically significant values in subtropical Chinese forests and shrublands. Such correlations might also be extrapolated to pollen-based paleoecological studies.

2.
Food Funct ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38590246

RESUMO

Cereals are the main source of energy in the human diet. Compared to refined grains, whole grains retain more beneficial components, including dietary fiber, polyphenols, proteins, vitamins, and minerals. Dietary fiber and bound polyphenols (biounavailable) in cereals are important active substances that can be metabolized by the gut microorganisms and affect the intestinal environment. There is a close relationship between the gut microbiota structures and various disease phenotypes, although the consistency of this link is affected by many factors, and the specific mechanisms are still unclear. Remodeling unfavorable microbiota is widely recognized as an important way to target the gut and improve diseases. This paper mainly reviews the interaction between the gut microbiota and cereal-derived dietary fiber and polyphenols, and also summarizes the changes to the gut microbiota and possible molecular mechanisms of related glycolipid metabolism. The exploration of single active ingredients in cereals and their synergistic health mechanisms will contribute to a better understanding of the health benefits of whole grains. It will further help promote healthier whole grain foods by cultivating new varieties with more potential and optimizing processing methods.

3.
Plant Mol Biol ; 114(3): 46, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630415

RESUMO

Peach fruit rapidly soften after harvest, a significant challenge for producers and marketers as it results in rotting fruit and significantly reduces shelf life. In this study, we identified two tandem genes, PpNAC1 and PpNAC5, within the sr (slow ripening) locus. Phylogenetic analysis showed that NAC1 and NAC5 are highly conserved in dicots and that PpNAC1 is the orthologous gene of Non-ripening (NOR) in tomato. PpNAC1 and PpNAC5 were highly expressed in peach fruit, with their transcript levels up-regulated at the onset of ripening. Yeast two-hybrid and bimolecular fluorescence complementation assays showed PpNAC1 interacting with PpNAC5 and this interaction occurs with the tomato and apple orthologues. Transient gene silencing experiments showed that PpNAC1 and PpNAC5 positively regulate peach fruit softening. Yeast one-hybrid and dual luciferase assays and LUC bioluminescence imaging proved that PpNAC1 and PpNAC5 directly bind to the PpPGF promoter and activate its transcription. Co-expression of PpNAC1 and PpNAC5 showed higher levels of PpPGF activation than expression of PpNAC1 or PpNAC5 alone. In summary, our findings demonstrate that the tandem transcription factors PpNAC1 and PpNAC5 synergistically activate the transcription of PpPGF to regulate fruit softening during peach fruit ripening.


Assuntos
Prunus persica , Solanum lycopersicum , Prunus persica/genética , Frutas/genética , Filogenia , Saccharomyces cerevisiae , Solanum lycopersicum/genética , Fatores de Transcrição/genética
4.
Front Immunol ; 15: 1354040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529273

RESUMO

Introduction: Taraxacum mongolicum (TM) is a kind of medicinal and edible homologous plant which is included in the catalogue of feed raw materials in China. It is rich in polyphenols, flavonoids, polysaccharides and other active substances, and shows many benefits to livestock, poultry and aquatic products. The study aimed to assess the potential of TM aqueous extract (TMAE) as a substitute for poultry AGPs. Methods: A total of 240 one-day-old Arbor Acker broilers were randomly assigned to four groups and fed a basal diet (Con) supplemented with 500, 1000, and 2000 mg/kg TMAE (Low, Medium, and High groups). The growth performance of the broilers was measured on day 21 and day 42. At the end of the trial, the researchers measured slaughter performance and collected serum, liver, spleen, ileum, and intestinal contents to investigate the effects of TMAE on serum biochemistry, antioxidant capacity, immune function, organ coefficient, intestinal morphology, flora composition, and short-chain fatty acids (SCFAs). Results: The results showed that broilers treated with TMAE had a significantly higher average daily gain from 22 to 42 days old compared to the Con group. Various doses of TMAE resulted in different levels of improvement in serum chemistry. High doses increased serum alkaline phosphatase and decreased creatinine. TMAE also increased the antioxidant capacity of serum, liver, and ileum in broilers. Additionally, middle and high doses of TMAE enhanced the innate immune function of the liver (IL-10) and ileum (Occludin) in broilers. Compared to the control group, the TMAE treatment group exhibited an increase in the ratio of villi length to villi crypt in the duodenum. TMAE increased the abundance of beneficial bacteria, such as Alistipes and Lactobacillus, while reducing the accumulation of harmful bacteria, such as Colidextracter and Sellimonas. The cecum's SCFAs content increased with a medium dose of TMAE. Supplementing broiler diets with TMAE at varying doses enhanced growth performance and overall health. The most significant benefits were observed at a dose of 1000 mg/kg, including improved serum biochemical parameters, intestinal morphology, antioxidant capacity of the liver and ileum, immune function of the liver and ileum, and increased SCFAs content. Lactobacillus aviarius, norank_f_norank_o__Clostridia_UCG-014, and Flavonifractor are potentially dominant members of the intestinal microflora. Conclusion: In conclusion, TMAE is a promising poultry feed additive and 1000 mg/kg is an effective reference dose.


Assuntos
Antioxidantes , Taraxacum , Animais , Antioxidantes/farmacologia , Galinhas/microbiologia , Suplementos Nutricionais , Ácidos Graxos Voláteis , Aves Domésticas
5.
Science ; 383(6690): 1434-1440, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38547259

RESUMO

The emergence of SARS-CoV-2 variants and drug-resistant mutants calls for additional oral antivirals. The SARS-CoV-2 papain-like protease (PLpro) is a promising but challenging drug target. We designed and synthesized 85 noncovalent PLpro inhibitors that bind to a recently discovered ubiquitin binding site and the known BL2 groove pocket near the S4 subsite. Leads inhibited PLpro with the inhibitory constant Ki values from 13.2 to 88.2 nanomolar. The co-crystal structures of PLpro with eight leads revealed their interaction modes. The in vivo lead Jun12682 inhibited SARS-CoV-2 and its variants, including nirmatrelvir-resistant strains with EC50 from 0.44 to 2.02 micromolar. Oral treatment with Jun12682 improved survival and reduced lung viral loads and lesions in a SARS-CoV-2 infection mouse model, suggesting that PLpro inhibitors are promising oral SARS-CoV-2 antiviral candidates.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Proteases Semelhantes à Papaína de Coronavírus , Inibidores de Protease de Coronavírus , Desenho de Fármacos , SARS-CoV-2 , Animais , Camundongos , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores , Proteases Semelhantes à Papaína de Coronavírus/química , Modelos Animais de Doenças , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Inibidores de Protease de Coronavírus/administração & dosagem , Inibidores de Protease de Coronavírus/química , Inibidores de Protease de Coronavírus/farmacologia , Administração Oral , Cristalografia por Raios X , Relação Estrutura-Atividade , Carga Viral/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos BALB C
6.
J Sci Food Agric ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459923

RESUMO

BACKGROUND: Solid-state fermentation (SSF) has been widely used in the processing of sorghum grain (SG) because it can produce products with improved sensory characteristics. To clarify the influence of different microbial strains on the SSF of SG, especially on the polyphenols content and composition, Lactiplantibacillus plantarum, Saccharomyces cerevisiae, Rhizopus oryzae, Aspergillus oryzae, and Neurospora sitophila were used separately and together for SSF of SG. Furthermore, the relationship between the dynamic changes in polyphenols and enzyme activity closely related to the metabolism of polyphenols has also been measured and analyzed. Microstructural changes observed after SSF provide a visual representation of the SSF on the SG. RESULTS: After SSF, tannin content (TC) and free phenolic content (FPC) were decreased by 56.36% and 23.48%, respectively. Polyphenol oxidase, ß-glucosidase and cellulase activities were increased 5.25, 3.27, and 45.57 times, respectively. TC and FPC were negatively correlated with cellulase activity. A positive correlation between FPC and xylanase activity after 30 h SSF became negative after 48 h SSF. The SG surface was fragmented and porous, reducing the blocking effect of cortex. CONCLUSION: Cellulase played a crucial role in promoting the degradation of tannin (antinutrient) and phenolic compounds. Xylanase continued to release flavonoids while microbial metabolism consumed them with the extension of SSF time. SSF is an effective way to improve the bioactivity and processing characteristics of SG. © 2024 Society of Chemical Industry.

7.
Protoplasma ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38418654

RESUMO

Transient transformation is extremely useful for rapid in vivo assessment of gene function, especially for fruit-related genes. Grape berry, while an important fruit crop, is recalcitrant to transient transformation, due to the high turgor pressure in its mesocarp cells that limits the ability of Agrobacterium to penetrate into the tissue. It is urgent to establish a simple transient transformation system for rapid analysis of gene function. In this study, different injection methods, grape genotypes, and developmental stages were tested in order to develop a rapid and efficient Agrobacterium-mediated transient transformation methodology for grape berries. Two injection methods, namely punch injection and direct injection, were evaluated using the ß-glucuronidase (GUS) gene and by x-gluc tissue staining and 4-methylumbelliferyl-ß-D-glucuronide fluorescence analysis. The results indicated that there were no significant differences on transformation effects between the two methods, but the latter was more suitable because of its simplicity and convenience. Six grape cultivars ('Hanxiangmi', 'Moldova', 'Zijixin', 'Jumeigui', 'Shine-Muscat', and 'A17') were tested for transient transformation. 'Hanxiangmi', 'Moldova', and 'Zijixin' grape berries were not suitable for agroinfiltration due to frequently fruit cracking, browning, and formation of scar skin. The fruit integrity rates of 'Jumeigui', 'Shine-Muscat', and 'A17' berries were all above 80%, and GUS activity was detected in the berries of the three cultivars 3-14 days after injection with the Agrobacterium culture, while higher GUS activities were observed in the 'Jumeigui' berries. The levels of GUS activity in injected berries at 7-8 weeks after full blooming (WAFB) were more than twice at 6 WAFB. In subsequent assays, the over-expression of MYB transcription factor VvMYB44 via transient transformation accelerated the anthocyanin accumulation and fruit coloring through raising the expression levels of VvLAR1, VvUFGT, VvLDOX, VvANS, and VvDFR, which verified the effectiveness of this transformation system. These experiments finally identified the reliable grape cultivars and suitable operational approach for transient transformation and further indicated that this Agrobacterium-mediated transient transformation system was efficient and suitable for the elucidation of gene function in grape berries.

8.
Dalton Trans ; 53(9): 4342, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38353276

RESUMO

Correction for 'The {Cu2I2} cluster bearing metal organic frameworks: crystal structures and fluorescence detecting performances towards cysteine and explosive molecules' by Jiang Jiang et al., Dalton Trans., 2024, 53, 706-714, https://doi.org/10.1039/d3dt03363e.

9.
J Food Sci ; 89(4): 2397-2409, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38391005

RESUMO

Soybean paste, a traditional fermented condiment, exhibits distinct quality attributes by its microbial communities. This study employed Illumina sequencing and LC-MS to scrutinize the bacterial biota and metabolome of highly preserved (HP) and easily spoiled (ES) soybean pastes. Firmicutes were prevalent in both pastes, with HP showcasing greater microbial α-diversity compared to ES pastes. Bacillus predominated in HP pastes, whereas Lactobacillus was most abundant in ES pastes. Significant metabolic differences were observed between HP and ES samples in lipids, peptides, nucleic acids, secondary metabolite biosynthesis, protein digestion, amino acid metabolism, inflammatory mediator regulation, and neomycin, kanamycin, and gentamicin biosynthesis. Lactobacillus exhibited positive associations with daidzein and 3,4,5-trihydroxypentanoylcarnitine, whereas Bacillus showed negative correlations with 1,n6-ethenoadenosine, 2-deoxy-2,3-dehydro-n-acetyl-neuraminic acid, 3,4,5-trihydroxypentanoyl carnitine, and fructosyl valine. These findings highlight the collaborative impact of bacterial communities and metabolites on soybean paste quality attributes. This research enhances our comprehension of preservation mechanisms in fermented foods, particularly soybean pastes. PRACTICAL APPLICATION: The investigation would provide insights into the soybean pastes fermentation, safe and quality control methods, bio-preservative development strategies, and so on of soybean pastes for related studies and the consumers. Bacteria and their metabolites could be used to optimize the fermentation processes for the preservative and safe regulations.


Assuntos
Bacillus , Alimentos Fermentados , Soja , Bactérias/genética , Fermentação
10.
Int J Biol Macromol ; 262(Pt 2): 130180, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38360239

RESUMO

Ferroptosis represents a novel form of programmed cell death. Pan-cancer bioinformatics analysis indicates that identifying and modulating ferroptosis offer innovative approaches for preventing and treating diverse tumor pathologies. However, the precise detection of ferroptosis-related proteins via conventional wet-laboratory techniques remains a formidable challenge, largely due to the constraints of existing methodologies. These traditional approaches are not only labor-intensive but also financially burdensome. Consequently, there is an imperative need for the development of more sophisticated and efficient computational tools to facilitate the detection of these proteins. In this paper, we presented a XGBoost and multi-view features-based machine learning prediction method for predicting ferroptosis-related proteins, which was referred to as FRP-XGBoost. In this study, we explored four types of protein feature extraction methods and evaluated their effectiveness in predicting ferroptosis-related proteins using six of the most commonly used traditional classifiers. To enhance the representational power of the hybrid features, we employed a two-step feature selection technique to identify the optimal subset of features. Subsequently, we constructed a prediction model using the XGBoost algorithm. The FRP-XGBoost achieved an accuracy of 96.74 % in 10-fold cross-validation and a further accuracy of 91.52 % in an independent test. The implementation source code of FRP-XGBoost is available at https://github.com/linli5417/FRP-XGBoost.


Assuntos
Ferroptose , Algoritmos , Apoptose , Biologia Computacional , Domínios Proteicos
11.
Inflammation ; 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38401019

RESUMO

Mitochondrial dysfunction is considered one of the major pathogenic mechanisms of sepsis-induced cardiomyopathy (SIC). Pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of mitochondrial metabolism, is essential for maintaining mitochondrial function. However, its specific role in SIC remains unclear. To investigate this, we established an in vitro model of septic cardiomyopathy using lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Our study revealed a significant increase in PDK4 expression in LPS-treated H9C2 cardiomyocytes. Inhibiting PDK4 with dichloroacetic acid (DCA) improved cell survival, reduced intracellular lipid accumulation and calcium overload, and restored mitochondrial structure and respiratory capacity while decreasing lactate accumulation. Similarly, Oxamate, a lactate dehydrogenase inhibitor, exhibited similar effects to DCA in LPS-treated H9C2 cardiomyocytes. To further validate whether PDK4 causes cardiomyocyte and mitochondrial damage in SIC by promoting lactate production, we upregulated PDK4 expression using PDK4-overexpressing lentivirus in H9C2 cardiomyocytes. This resulted in elevated lactate levels, impaired mitochondrial structure, and reduced mitochondrial respiratory capacity. However, inhibiting lactate production reversed the mitochondrial dysfunction caused by PDK4 upregulation. In conclusion, our study highlights the pathogenic role of PDK4 in LPS-induced cardiomyocyte and mitochondrial damage by promoting lactate production. Therefore, targeting PDK4 and its downstream product lactate may serve as promising therapeutic approaches for treating SIC.

12.
Horm Metab Res ; 56(3): 197-205, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242159

RESUMO

Recent studies have confirmed that tumor immune cell infiltration (ICI) is associated with sensitivity of ovarian cancer (OC) immunotherapy and disease progression of OC patients. However, studies related to immune infiltration in OC, has not been elucidated. Two algorithms are used to analyze the OC data in the TCGA and GEO databases. After combining the two data sets, the immune cell content of the sample was estimated by Cell-type Identification By Estimate Relative Subsets of RNA Transcripts (CIBERSORT method). An unsupervised consistent clustering algorithm was used to analyze ICI subtypes and their differentially expressed genes (DEGs). Two subgroups and three ICI gene clusters were identified by unsupervised consensus clustering algorithm. The ICI score was obtained by analyzing the gene characteristics through principal component analysis (PCA). The ICI score ranged from -15.8132 to 18.7211, which was associated with the prognosis of OC patients with immunotherapy. The Toll-like receptor pathway, B-cell receptor pathway, antigen processing and presentation pathway, NK-cell-mediated cytotoxicity pathway, and arginine-proline metabolism pathway were activated in the high ICI score group, suggesting that immune cells in the high ICI score group were activated, thus leading to a better prognosis in this group of patients. Patients with G3-G4 in the high ICI rating group were more sensitive to immunotherapy and had a better prognosis in patients with high tumor mutation burden (TMB). This study suggests that ICI scores can be used as a feasible auxiliary indicator for predicting the prognosis of patients with OC.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Biologia Computacional , Algoritmos , Imunoterapia , Prognóstico
13.
Mol Biol Rep ; 51(1): 67, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38170368

RESUMO

BACKGROUND: HucMSCs had shown promising efficacy in treating childhood diseases, but oxidative stress induced by the poor microenvironment at the site of damage resulted in low cell survival after transplantation, thus preventing the cells from maximizing therapeutic efficacy. Therefore, this study aimed to investigate the role and mechanism of keap1 in oxidative stress injury of human umbilical cord mesenchymal stem cells (hucMSCs), and to provide theoretical support for improving the efficacy of stem cell therapy. METHODS: The hucMSCs were treated with hypoxic low-sugar-free serum (GSDH) to mimic the damaged site microenvironment after implantation. Adenoviral overexpression of keap1 gene of hucMSCs was performed in vitro, and cell proliferation ability was detected by CCK8 assay, crystal violet staining assay, and cell cycle assay. Cellular redox level was assessed by Amplex Red, MDA, and GSH/GSSG kit. Mitochondrial morphology was evaluated by mitotracker Red staining. ATP production was estimated by ATP detection kit. The mRNA and protein expression levels were tested by western blotting and RT-qPCR. RESULTS: GSDH treatment substantially upregulated keap1 expression. Subsequently, we found that overexpression of keap1 notably inhibited cell proliferation and caused cells to stagnate in G1 phase. At the same time, overexpression of keap1 induced the production of large amounts of H2O2 and the accumulation of MDA, but suppressed the GSH/GSSG ratio and the expression of antioxidant proteins NQO1 and SOD1, which caused oxidative stress damage. Overexpression of keap1 induced cells to produce a large number of dysfunctional mitochondria resulting in reduced ATP production. Moreover, Overexpression of keap1 significantly decreased the IKKß protein level, while upregulating IkB mRNA levels and downregulating P50 mRNA levels. CONCLUSIONS: Overexpression of keap1 may induce oxidative stress injury in hucMSCs by down-regulating IKKß expression and inhibiting NF-κB pathway activation. This implies the importance of keap1 in hucMSCs and it may be a potential gene for genetic modification of hucMSCs.


Assuntos
Peróxido de Hidrogênio , Células-Tronco Mesenquimais , Criança , Humanos , Trifosfato de Adenosina , Dissulfeto de Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Quinase I-kappa B/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo , Cordão Umbilical
14.
BMC Cancer ; 24(1): 110, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254159

RESUMO

BACKGROUNDS: Lymphoplasmacyte-rich meningioma(LPM) is a rare subtype of meningioma with a low degree of malignancy and an overall preferable prognosis. The purpose of this article is to increase the understanding of the disease, reduce misdiagnosis, and improve prognosis. METHODS: A search was conducted in the PubMed database for English articles published from 1993 to 2023. The keywords were "lymphoplasmacyte-rich (all fields) and meningioma (all fields) and English (lang)" and "lymphoplasmacyte-rich meningioma (title/abstract) and English (lang)".We further analyzed the clinical manifestations, imaging manifestations, pathological features, treatment strategies, and prognosis of LPM.The possible prognostic indicators were analyzed by the log-rank test and Pearson's chi-squared test. RESULTS: Fourteen reports with 95 LPM patients were included in this report, including 47 males and 48 females who were diagnosed between the ages of 9 and 79, with an average age of 45 years. The most common clinical manifestations are headache and limb movement disorders. In most cases, the tumor occurred on the convex portion of the brain. All tumors showed significant enhancement, with homogeneous enhancement being more common, and most patients showed peritumoral edema. Postoperative pathological EMA, LCA, and vimentin positivity were helpful for the final diagnosis of the patient. Log-rank tests showed a correlation between complete resection and better prognosis and recurrence. CONCLUSION: There is a lack of significant differences in the clinical symptoms and imaging manifestations of LPM compared to other diseases that need to be differentiated, and a clear diagnosis requires pathological examination. After standardized surgical treatment, the recurrence rate and mortality rate of LPM are both low. Complete surgical resection of tumors is associated with a better prognosis and lower recurrence rate.


Assuntos
Neoplasias Meníngeas , Meningioma , Feminino , Masculino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Meningioma/diagnóstico , Meningioma/epidemiologia , Prognóstico , Encéfalo , Bases de Dados Factuais , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/epidemiologia
15.
Nat Chem ; 16(3): 408-416, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38062248

RESUMO

The umpolung functionalization of imines bears vast synthetic potential, but polarity inversion is less efficient compared with the carbonyl counterparts. Strong nucleophiles are often required to react with the N-electrophiles without catalytic and stereochemical control. Here we show an effective strategy to realize umpolung of imines promoted by organocatalytic aromatization. The attachment of strongly electron-withdrawing groups to imines could enhance the umpolung reactivity by both electronegativity and aromatic character, enabling the direct amination of (hetero)arenes with good efficiencies and stereoselectivities. Additionally, the application of chiral Brønsted acid catalyst furnishes (hetero)aryl C-N atropisomers or enantioenriched aliphatic amines via dearomative amination from N-electrophilic aromatic precursors. Control experiments and density functional theory calculations suggest an ionic mechanism for the umpolung reaction of imines. This disconnection expands the options to forge C-N bonds stereoselectively on (hetero)arenes, which represents an important synthetic pursuit, especially in medicinal chemistry.

16.
Phytopathology ; 114(1): 200-210, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37435950

RESUMO

Plant-pathogenic phytoplasmas secrete specific virulence proteins into a host plant to modulate plant function for their own benefit. Identification of phytoplasmal effectors is a key step toward clarifying the pathogenic mechanisms of phytoplasma. In this study, Zaofeng3, also known as secreted jujube witches' broom phytoplasma protein 3 (SJP3), was a homologous effector of SAP54 and induced a variety of abnormal phenotypes, such as phyllody, malformed floral organs, witches' broom, and dwarfism in Arabidopsis thaliana. Zaofeng3 can also induce small leaves, dwarfism, and witches' broom in Ziziphus jujuba. Further experiments showed that the three complete α-helix domains predicted in Zaofeng3 were essential for induction of disease symptoms in jujube. Yeast two-hybrid library screening showed that Zaofeng3 mainly interacts with proteins involved in flower morphogenesis and shoot proliferation. Bimolecular fluorescence complementation assays confirmed that Zaofeng3 interacted with these proteins in the whole cell. Overexpression of zaofeng3 in jujube shoot significantly altered the expression patterns of ZjMADS19, ZjMADS47, ZjMADS48, ZjMADS77, and ZjTCP7, suggesting that overexpressing zaofeng3 might induce floral organ malformation and witches' broom by altering the expression of the transcriptional factors involved in jujube morphogenesis.


Assuntos
Arabidopsis , Cytisus , Nanismo , Phytoplasma , Ziziphus , Phytoplasma/genética , Doenças das Plantas/genética , Plantas , Proliferação de Células
17.
Eur J Med Chem ; 264: 116011, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38065031

RESUMO

The COVID-19 pandemic is caused by SARS-CoV-2, an RNA virus with high transmissibility and mutation rate. Given the paucity of orally bioavailable antiviral drugs to combat SARS-CoV-2 infection, there is a critical need for additional antivirals with alternative mechanisms of action. Papain-like protease (PLpro) is one of the two SARS-CoV-2 encoded viral cysteine proteases essential for viral replication. PLpro cleaves at three sites of the viral polyproteins. In addition, PLpro antagonizes the host immune response upon viral infection by cleaving ISG15 and ubiquitin from host proteins. Therefore, PLpro is a validated antiviral drug target. In this study, we report the X-ray crystal structures of papain-like protease (PLpro) with two potent inhibitors, Jun9722 and Jun9843. Subsequently, we designed and synthesized several series of analogs to explore the structure-activity relationship, which led to the discovery of PLpro inhibitors with potent enzymatic inhibitory activity and antiviral activity against SARS-CoV-2. Together, the lead compounds are promising drug candidates for further development.


Assuntos
COVID-19 , Papaína , Humanos , Papaína/química , Papaína/genética , Papaína/metabolismo , SARS-CoV-2/metabolismo , Pandemias , Antivirais/farmacologia , Antivirais/química , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química
18.
Dalton Trans ; 53(2): 706-714, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38084056

RESUMO

Two {Cu2I2} cluster-bearing metal organic frameworks (MOFs) of {[Eu(CuI)2(INA)3DMF]·0.95DMF}n (Eu-CuI-INA) and {K[(CH3)2NH2]Sr4(INA)2(DMF)2{(Cu2I2)2(INA)8}·2H2O}n (Sr-K-CuI-INA, HINA = isonicotinic acid, DMF = N,N-dimethyl formamide) were prepared and characterized in this work. Both materials feature a three-dimensional (3-D) structure, in which the {Cu2I2} clusters and Eu3+ (or Sr2+) metal ions are coordinated by INA- ligands with pyridine and carboxylic groups, respectively. Impressively, Sr-K-CuI-INA exhibits sensitive fluorescence sensing behaviors towards cysteine and nitro-bearing molecules, demonstrating potential FL sensing applications for bio and explosive molecules. This work would provide a good reference for designing fluorescent MOF probes containing CuI molecules.

19.
ChemMedChem ; 19(3): e202300619, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38103004

RESUMO

Naturally occurring resistances diminish the effectiveness of antibiotics, and present significant challenges to human health. Human activities are usually considered as the main drivers of the dissemination of antibiotic resistance, however, the origin of the clinical antibiotic resistance can be traced to the environmental microbes, and the clinically relevant resistance determinants have already pre-existed in nature before the antibiotics come into clinic. In this concept, we present the naturally occurring and widespread resistance determinants recently discovered during the biosynthesis study of bioactive compounds. These widely prevalent resistances in environmental microbes, including antibiotic producers and non-producers, advance the understanding of the origin of resistance, and provide prediction for the clinically relevant resistance to aid in the rational design of more effective drug analogues to combat resistance.


Assuntos
Produtos Biológicos , Humanos , Produtos Biológicos/farmacologia , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos
20.
Eur J Surg Oncol ; 50(2): 107930, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159390

RESUMO

BACKGROUND: Gallbladder adenoma represents a precancerous lesion of gallbladder cancer. However, distinguishing it from cholesteryl polyps of the gallbladder before surgery is challenging. Thus, we aimed to comprehensively explore various risk factors contributing to the formation of gallbladder adenoma to facilitate an informed diagnosis and treatment by clinicians. METHODS: We conducted a retrospective analysis of patients who had undergone cholecystectomy at the Affiliated Hospital of Qingdao University between January 2015 and December 2022. Following postoperative pathological examination, patients were categorized into cholesterol polyp and adenoma groups. We analyzed their baseline characteristics, ultrasound imaging variables, and biochemical data using logistic, lasso, and stepwise regression. Subsequently, we constructed a preoperative prediction model based on the independent risk factors. RESULTS: Regression analysis of 520 gallbladder polyps and 288 gallbladder adenomas in the model group revealed that age, gallbladder wall thickness, polyp size, echogenicity, pedunculation, and adenosine deaminase (ADA) levels were independent predictors of gallbladder adenoma, all with P < 0.05. Using these indicators, we established a regression equation: Logistic (P) = -5.615 + 0.018 ∗ age - 4.64 ∗ gallbladder wall thickness + 1.811 ∗ polyp size + 2.855 ∗ polyp echo + 0.97∗ pedunculation + 0.092 ∗ ADA. The resulting area under the curve (AUC) value was 0.894 (95 % CI: 0.872-0.917, P < 0.01), with a sensitivity of 89.20 %, specificity of 79.40 %, and overall accuracy of 84.41 % for adenoma detection. CONCLUSION: Age, polyp size, gallbladder wall thickness, polyp echogenicity, pedunculation, and ADA levels emerge as independent risk factors for gallbladder adenoma.


Assuntos
Adenoma , Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Pólipos , Humanos , Pré-Escolar , Estudos Retrospectivos , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/cirurgia , Ultrassonografia/métodos , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Pólipos/diagnóstico por imagem , Pólipos/cirurgia
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