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1.
BMC Genomics ; 25(1): 572, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844832

RESUMO

KNOXs, a type of homeobox genes that encode atypical homeobox proteins, play an essential role in the regulation of growth and development, hormonal response, and abiotic stress in plants. However, the KNOX gene family has not been explored in sweet potato. In this study, through sequence alignment, genomic structure analysis, and phylogenetic characterization, 17, 12 and 11 KNOXs in sweet potato (I. batatas, 2n = 6x = 90) and its two diploid relatives I. trifida (2n = 2x = 30) and I. triloba (2n = 2x = 30) were identified. The protein physicochemical properties, chromosome localization, phylogenetic relationships, gene structure, protein interaction network, cis-elements of promoters, tissue-specific expression and expression patterns under hormone treatment and abiotic stresses of these 40 KNOX genes were systematically studied. IbKNOX4, -5, and - 6 were highly expressed in the leaves of the high-yield varieties Longshu9 and Xushu18. IbKNOX3 and IbKNOX8 in Class I were upregulated in initial storage roots compared to fibrous roots. IbKNOXs in Class M were specifically expressed in the stem tip and hardly expressed in other tissues. Moreover, IbKNOX2 and - 6, and their homologous genes were induced by PEG/mannitol and NaCl treatments. The results showed that KNOXs were involved in regulating growth and development, hormone crosstalk and abiotic stress responses between sweet potato and its two diploid relatives. This study provides a comparison of these KNOX genes in sweet potato and its two diploid relatives and a theoretical basis for functional studies.


Assuntos
Diploide , Regulação da Expressão Gênica de Plantas , Ipomoea batatas , Família Multigênica , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Ipomoea batatas/genética , Ipomoea batatas/crescimento & desenvolvimento , Ipomoea batatas/metabolismo , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Genoma de Planta , Perfilação da Expressão Gênica , Regiões Promotoras Genéticas
2.
Antimicrob Agents Chemother ; 68(1): e0094823, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38051047

RESUMO

Candida albicans is responsible for conditions ranging from superficial infections such as oral or vaginal candidiasis to potentially fatal systemic infections. It produces pathogenic factors contributing to its virulence. Iturin A, a lipopeptide derived from Bacillus sp., exhibits a significant inhibitory effect against C. albicans. However, its exact mechanism in mitigating the pathogenic factors of C. albicans remains to be elucidated. This study aimed to explore the influence of iturin A on several pathogenic attributes of C. albicans, including hypha formation, cell membrane permeability, cell adhesion, biofilm formation, and therapeutic efficacy in an oral C. albicans infection model in mice. The minimal inhibitory concentration of iturin A against C. albicans was determined to be 25 µg/mL in both YEPD and RPMI-1640 media. Iturin A effectively inhibited C. albicans hyphal formation, decreased cell viability within biofilms, enhanced cell membrane permeability, and disrupted cell adhesion in vitro. Nonetheless, iturin A did not significantly affect the phospholipase activity or hydrophobicity of C. albicans. A comparative study with nystatin demonstrated the superior therapeutic efficacy of iturin A in a mouse model of oral C. albicans infection, significantly decreasing C. albicans count and inhibiting both fungal hypha formation and tongue surface adhesion. High-dose iturin A treatment (25 µg/mL) in mice had no significant effects on blood indices, tongue condition, or body weight, indicating the potential for iturin A in managing oral infections. This study confirmed the therapeutic potential of iturin A and provided valuable insights for developing effective antifungal therapies targeting C. albicans pathogenic factors.


Assuntos
Candida albicans , Candidíase , Feminino , Camundongos , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fatores de Virulência , Candidíase/tratamento farmacológico , Biofilmes
3.
Oncologist ; 29(6): e837-e842, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38159086

RESUMO

The presence of mutations in the BRCA1 gene (MIM: 113705) is widely recognized as a significant genetic predisposition for ovarian cancer. This study investigated the genomic mutations in a Chinese family with a history of ovarian, breast, and rectal adenocarcinoma. A novel germline mutation (Phe1695Val) in BRCA1 was identified through whole-exome sequencing. Subsequently, we performed whole-genome sequencing to identify somatic mutations and analyze mutational signatures in individuals carrying the novel germline mutation. Our findings revealed a correlation between somatic mutational signatures and the BRCA1 germline mutation in the proband with ovarian cancer, while no such association was observed in the tumor tissue from the patient with breast cancer. Furthermore, distinct somatic driver mutations were identified, a truncated mutation in the TP53 gene in the ovarian tumor tissue, and a hotspot mutation in the PIK3CA gene in the breast cancer. According to our findings, the BRCA1 F1695V mutation is linked to ovarian cancer susceptibility in the family and causes specific somatic mutational profiles.


Assuntos
Proteína BRCA1 , Neoplasias da Mama , Mutação em Linhagem Germinativa , Neoplasias Ovarianas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína BRCA1/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , População do Leste Asiático/genética , Predisposição Genética para Doença , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Linhagem , Idoso
4.
Anal Chem ; 96(10): 4224-4231, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38421217

RESUMO

The detection of physiological phosphates (PPs) is of great importance due to their essential roles in numerous biological processes, but the efficient detection of different PPs simultaneously remains challenging. In this work, we propose a fluorescence sensor array for detecting PPs based on metal-ion-regulated gold nanoclusters (AuNCs) via an indicator-displacement assay. Zn2+ and Eu3+ are selected to assemble with two different AuNCs, resulting in quenching or enhancing their fluorescence. Based on the competitive interaction of metal ions with AuNCs and PPs, the fluorescence of AuNCs will be recovered owing to the disassembly of AuNC-metal ion ensembles. Depending on different PPs' distinct fluorescence responses, a four-channel sensor array was established. The array not only exhibits good discrimination capability for eight kinds of PPs (i.e., ATP, ADP, AMP, GTP, CTP, UTP, PPi, and Pi) via linear discriminant analysis but also enables quantitative detection of single phosphate (e.g., ATP) in the presence of interfering PPs mixtures. Moreover, potential application of the present sensor array for the discrimination of different PPs in real samples (e.g., cell lysates and serum) was successfully demonstrated with a good performance. This work illustrates the great potential of a metal ion-regulated sensor array as a new and efficient sensing platform for differential sensing of phosphates as well as other disease-related biomolecules.


Assuntos
Ouro , Nanopartículas Metálicas , Corantes Fluorescentes , Espectrometria de Fluorescência/métodos , Fosfatos , Trifosfato de Adenosina
5.
Small ; 20(32): e2312253, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38501846

RESUMO

Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (Vmax) 3.4 times higher than that of AuNPs for the catalytic reaction of H2O2. Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases.


Assuntos
Anfotericina B , Antifúngicos , Candida albicans , Ouro , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Ouro/química , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/uso terapêutico , Anfotericina B/farmacologia , Anfotericina B/química , Anfotericina B/uso terapêutico , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Candida albicans/efeitos dos fármacos , Animais , Saccharomyces cerevisiae/efeitos dos fármacos , Camundongos
6.
J Med Virol ; 96(5): e29634, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38682578

RESUMO

Metabolic reprogramming induced by Epstein-Barr virus (EBV) often mirrors metabolic changes observed in cancer cells. Accumulating evidence suggests that lytic reactivation is crucial in EBV-associated oncogenesis. The aim of this study was to explore the role of metabolite changes in EBV-associated malignancies and viral life cycle control. We first revealed that EBV (LMP1) accelerates the secretion of the oncometabolite D-2HG, and serum D-2HG level is a potential diagnostic biomarker for NPC. EBV (LMP1)-driven metabolite changes disrupts the homeostasis of global DNA methylation and demethylation, which have a significantly inhibitory effect on active DNA demethylation and 5hmC content. We found that loss of 5hmC indicates a poor prognosis for NPC patients, and that 5hmC modification is a restriction factor of EBV reactivation. We confirmed a novel EBV reactivation inhibitor, α-KG, which inhibits the expression of EBV lytic genes with CpG-containing ZREs and the latent-lytic switch by enhancing 5hmC modification. Our results demonstrate a novel mechanism of which metabolite abnormality driven by EBV controls the viral lytic reactivation through epigenetic modification. This study presents a potential strategy for blocking EBV reactivation, and provides potential targets for the diagnosis and therapy of NPC.


Assuntos
Metilação de DNA , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Ativação Viral , Humanos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiologia , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/complicações , Proteínas da Matriz Viral/metabolismo , Proteínas da Matriz Viral/genética , Epigênese Genética , Progressão da Doença
7.
Am J Nephrol ; 55(3): 273-283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38104542

RESUMO

INTRODUCTION: This study aimed to investigate the relationship between circulating soluble Klotho concentration and all-cause mortality in individuals with chronic kidney disease (CKD). METHODS: We conducted a prospective cohort study involving 2,456 participants with CKD from the National Health and Nutrition Examination Survey (NHANES) cycles spanning from 2007 to 2016. Complex sampling-weighted multivariate Cox proportional hazards models were used to estimate the association between serum Klotho level and all-cause mortality, presenting hazard ratios (HRs) and 95% confidence intervals (CIs). Additionally, a restricted cubic spline analysis was performed to explore potential nonlinear associations. RESULTS: During a median of 82 months of follow-up, 550 (22.40%) all-cause deaths were recorded. The median serum Klotho concentration was 760 pg/mL (interquartile ranges, 624, 958). After adjusting for potential covariates, the risk of all-cause mortality decreased by 4% for every 100 pg/mL increase in Klotho (HR = 0.96, 95% CI, 0.92, 0.99). The HR for the fourth quartile of Klotho compared to the first quartile was 0.73 (95% CI, 0.56, 0.96). The restricted cubic spline model revealed a distinctive "L"-shaped association between serum Klotho and all-cause mortality among patients with CKD, with a Klotho concentration of 760 pg/mL at the inflection point. When Klotho concentration was less than 760 pg/mL, a significant negative correlation between Klotho and all-cause mortality was observed (HR per 100 pg/mL increase in Klotho = 0.86, 95% CI, 0.78, 0.95). CONCLUSION: This study documented a distinctive "L"-shaped association between serum Klotho levels and all-cause mortality among individuals with CKD. Further research is needed to validate these findings.


Assuntos
Causas de Morte , Proteínas Klotho , Insuficiência Renal Crônica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos de Coortes , Proteínas Klotho/sangue , Mortalidade , Inquéritos Nutricionais , Modelos de Riscos Proporcionais , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/mortalidade
8.
Langmuir ; 40(15): 7781-7790, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38572817

RESUMO

The distinct features of nanoparticles have provided a vast opportunity of developing new diagnosis and therapy strategies for miscellaneous diseases. Although a few nanomedicines are available in the market or in the translation stage, many important issues are still unsolved. When entering the body, nanomaterials will be quickly coated by proteins from their surroundings, forming a corona on their surface, the so-called protein corona. Studies have shown that the protein corona has many important biological implications, particularly at the in vivo level. For example, they can promote the immune system to rapidly clear these outer materials and prevent nanoparticles from playing their designed role in therapy. In this Perspective, the available techniques for characterizing protein-nanoparticle interactions are critically summarized. Effects of nanoparticle properties and environmental factors on protein corona formation, which can further regulate the in vivo fate of nanoparticles, are highlighted and discussed. Moreover, recent progress on the biomedical application of protein corona-engineered nanoparticles is introduced, and future directions for this important yet challenging research area are also briefly discussed.


Assuntos
Nanopartículas , Coroa de Proteína , Coroa de Proteína/metabolismo , Nanopartículas/metabolismo , Proteínas/metabolismo , Nanomedicina , Ligação Proteica
9.
Environ Res ; 244: 117841, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38065390

RESUMO

Olefin industry as a vital part in economic development is facing a problem of high CO2 emission. In this work, for the global and China's olefin industry under different development scenario, the carbon emission is predicted after the revealing of carbon footprint in different olefin routes. The results show that the carbon footprint of the natural gas liquids (NGLs)-derived route is highly lower than that of the oil- and coal-derived routes. The carbon emission from the global olefin industry in 2015 is 553 million ton CO2 (MtCO2). In 2030, it will be ranged between 739 and 924 MtCO2 under different scenarios. Under sustainable development scenario, 15% reduction space is existed, whereas 6% growth is observed under the hybrid-development scenario compared to the business-as-usual situation. In the case of China, its carbon emission is 120 MtCO2 in 2015. Its potential carbon emission in 2030 will increase to 264-925 MtCO2, depending on the rest new capacity from low-carbon or high-carbon routes. The large gap implies the significant influence of the development route choice. However, if most new capacity is from the existed planned olefin projects, the carbon emission will be ranged between 390 and 594 MtCO2. Finally, the low-carbon roadmaps as well as polices are proposed for sustainable development of olefin industry.


Assuntos
Dióxido de Carbono , Carbono , Dióxido de Carbono/análise , Carbono/análise , Alcenos , Carvão Mineral , Gás Natural , China , Desenvolvimento Econômico
10.
J Obstet Gynaecol Res ; 50(9): 1655-1666, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38936810

RESUMO

AIM: To investigate the DNA damage response (DDR) in a cyclophosphamide (CTX)-induced mouse model of premature ovarian failure (POF). METHODS: The POF model was established by injecting mice with CTX. The body, ovarian weights, the estrus cycle, and pathological changes of the ovaries were recorded. The serum levels of 17 ß-estradiol (E2) and follicle-stimulating hormone (FSH) were measured. The expression of Ki67, ß-galactosidase (ß-gal), p21, p53, γH2AX, and pATM in ovarian tissues was detected by immunohistochemistry. The expression of ß-gal, γH2AX, and pATM was analyzed by immunofluorescence staining of primary cultured granulosa cells (GCs). RESULTS: The body and ovarian weights decreased, the estrus cycles were erratic, and the FSH level increased, whereas the E2 level decreased in POF mice compared to controls. The pathological consequences of POF revealed an increase in atretic follicles, corpus luteum, and primordial follicles and a decrease in the number of primary, secondary, and tertiary follicles. Ki67 expression was reduced, ß-gal, p21, p53, γH2AX, and pATM expression were elevated in the ovaries of POF mice. The expression of ß-gal, γH2AX, and pATM increased in GCs with the concentration in a time-dependent manner. CONCLUSION: In total, CTX induced POF in mice, which was mediated by the DDR pathway of ATM-P53-P21.


Assuntos
Ciclofosfamida , Dano ao DNA , Modelos Animais de Doenças , Insuficiência Ovariana Primária , Animais , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/metabolismo , Feminino , Ciclofosfamida/efeitos adversos , Camundongos , Dano ao DNA/efeitos dos fármacos , Ovário/metabolismo , Ovário/efeitos dos fármacos , Ovário/patologia , Estradiol/sangue
11.
Ren Fail ; 46(1): 2319324, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38390735

RESUMO

BACKGROUND: Renal impairment has been previously linked to peripheral eosinophil count (PEC), prompting an investigation into its potential relationship with chronic kidney disease (CKD). This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) to comprehensively explore the association between PEC and CKD. METHODS: Survey-weighted generalized multivariate linear regression was employed to evaluate the associations between PEC, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), with meticulous adjustment for potential covariates. To assess non-linear correlations, a restricted cubic spline analysis was conducted. Sensitivity analysis was performed to test the stability of results. RESULTS: The study included a total of 9224 participants with non-dialysis CKD. In the multivariate linear regression model, after comprehensive adjustment for potential covariates, PEC showed a negative association with eGFR (ß per 100 cells/uL increase in PEC, -0.71; 95% CI, -1.04, -0.37), while demonstrating a positive trend with UACR (ß per 100 cells/uL increase in PEC, 10.21; 95% CI, 1.37, 19.06). The restrictive cubic spline curve analysis suggested that these associations occurred within the range of 0 to 400 cells/uL for PEC. Sensitivity analysis supported the stability of the observed results. CONCLUSIONS: Circulating eosinophil levels are negatively correlated with eGFR and demonstrate a positive trend with UACR, when PEC falls within the range of less than 400 cells/uL among adults with CKD. Further research is warranted to validate these findings.


Assuntos
Eosinófilos , Insuficiência Renal Crônica , Adulto , Humanos , Inquéritos Nutricionais , Estudos Transversais , Creatinina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Taxa de Filtração Glomerular , Albuminúria
12.
Angew Chem Int Ed Engl ; 63(11): e202318989, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38221223

RESUMO

As bulky pollutants in industrial and agricultural wastewater, nitrate and formaldehyde pose serious threats to the human health and ecosystem. Current purification technologies including chemical and bio-/photo-/electro-chemical methods, are generally high-cost, time-consuming, or energy-intensive. Here, we report a novel formaldehyde-nitrate battery by pairing anodic formaldehyde oxidation with cathodic nitrate reduction, which simultaneously enables wastewater purification, electricity generation, and the production of high-value-added ammonia and formate. As a result, the formaldehyde-nitrate battery remarkably exhibits an open-circuit voltage of 0.75 V, a peak power density of 3.38 mW cm-2 and the yield rates of 32.7 mg h-1 cm-2 for ammonia and 889.4 mg h-1 cm-2 for formate. In a large-scale formaldehyde-nitrate battery (25 cm2 ), 99.9 % of nitrate and 99.8 % of formaldehyde are removed from simulated industrial wastewater and the electricity of 2.03 W⋅h per day is generated. Moreover, the design of such a multi-functional battery is universally applicable to the coupling of NO3 - or NO2 - reduction with various aldehyde oxidization, paving a new avenue for wastewater purification and chemical manufacturing.

13.
BMC Genomics ; 24(1): 781, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102559

RESUMO

BACKGROUND: Odorant-binding proteins (OBPs) are essential in insect's daily behaviors mediated by olfactory perception. Megachile saussurei Radoszkowski (Hymenoptera, Megachilidae) is a principal insect pollinating alfalfa (Medicago sativa) in Northwestern China. The olfactory function have been less conducted, which provides a lot of possibilities for our research. RESULTS: Our results showed that 20 OBPs were identified in total. Multiple sequence alignment analysis indicated MsauOBPs were highly conserved with a 6-cysteine motif pattern and all belonged to the classic subfamily, coding 113-196 amino acids and sharing 41.32%-99.12% amino acid identity with known OBPs of other bees. Phylogenetic analysis indicated there were certain homologies existed among MsauOBPs and most sequences were clustered with that of Osmia cornuta (Hymenoptera, Megachilidae). Expression analysis showed the identified OBPs were mostly enriched in antennae instead of other four body parts, especially the MsauOBP2, MsauOBP3, MsauOBP4, MsauOBP8, MsauOBP11 and MsauOBP17, in which the MsauOBP2, MsauOBP4 and MsauOBP8 presented obvious tissue-biased expression pattern. Molecular docking results indicated MsauOBP4 might be the most significant protein in recognizing alfalfa flower volatile 3-Octanone, while MsauOBP13 might be the most crucial protein identifying (Z)-3-hexenyl acetate. It was also found the lysine was a momentous hydrophilic amino acid in docking simulations. CONCLUSION: In this study, we identified and analyzed 20 OBPs of M. saussurei. The certain homology existed among these OBPs, while some degree of divergence could also be noticed, indicating the complex functions that different MsauOBPs performed. Besides, the M. saussurei and Osmia cornuta were very likely to share similar physiological functions as most of their OBPs were clustered together. MsauOBP4 might be the key protein in recognizing 3-Octanone, while MsauOBP13 might be the key protein in binding (Z)-3-hexenyl acetate. These two proteins might contribute to the alfalfa-locating during the pollination process. The relevant results may help determine the highly specific and effective attractants for M. saussurei in alfalfa pollination and reveal the molecular mechanism of odor-evoked pollinating behavior between these two species.


Assuntos
Himenópteros , Receptores Odorantes , Abelhas , Animais , Himenópteros/metabolismo , Odorantes , Sequência de Aminoácidos , Filogenia , Simulação de Acoplamento Molecular , Perfilação da Expressão Gênica , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Aminoácidos/metabolismo , Proteínas de Insetos/metabolismo , Antenas de Artrópodes/metabolismo , Transcriptoma
14.
Breast Cancer Res ; 25(1): 144, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968653

RESUMO

BACKGROUND: Breast cancer stem cells (BCSCs) are resistant to standard therapies, facilitate tumor dissemination, and contribute to relapse and progression. Super-enhancers are regulators of stemness, and BET proteins, which are critical for super-enhancer function, are a potential therapeutic target. Here, we investigated the effects of BET proteins on the regulation of breast cancer stemness using the pan-BET degrader ZBC260. METHODS: We evaluated the effect of ZBC260 on CSCs in TNBC cell lines. We assessed the effect of ZBC260 on cellular viability and tumor growth and measured its effects on cancer stemness. We used RNA sequencing and stemness index to determine the global transcriptomic changes in CSCs and bulk cells and further validated our findings by qPCR, western blot, and ELISA. RESULTS: ZBC260 potently inhibited TNBC growth both in vitro and in vivo. ZBC260 reduced stemness as measured by cell surface marker expression, ALDH activity, tumorsphere number, and stemness index while increasing differentiated cells. GSEA analysis indicated preferential downregulation of stemness-associated and inflammatory genes by ZBC260 in ALDH+ CSCs. CONCLUSIONS: The BET degrader ZBC260 is an efficient degrader of BET proteins that suppresses tumor progression and decreases CSCs through the downregulation of inflammatory genes and pathways. Our findings support the further development of BET degraders alone and in combination with other therapeutics as CSC targeting agents.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/patologia , Proteínas/metabolismo , Proteínas/farmacologia , Proteínas/uso terapêutico , Transformação Celular Neoplásica/metabolismo , Diferenciação Celular/genética , Células-Tronco Neoplásicas/patologia
15.
Anal Chem ; 95(20): 8077-8087, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37170069

RESUMO

Transition metal chalcogenide quantum dots (QDs), especially MoS2 QDs, are an emerging class of novel optical probes for versatile bioanalytical applications owing to their distinct physicochemical properties. However, the reasonable use of these QDs for biological imaging has been largely restricted due to the challenge of controllable surface functionalization. In this work, we report a new strategy to engineer the surface of MoS2 QDs by taking advantage of cyclodextrin (CD)-based host-guest chemistry. The prepared ß-CD-modified QDs (ß-CD-MoS2 QDs) exhibit enhanced fluorescence properties, excellent biocompatibility, and good stability, making them promising as novel optical probes for bioimaging. Cellular imaging experiments revealed that these ß-CD-MoS2 QDs can enter living cells through multiple internalization pathways, which differs significantly from pristine QDs. Particularly, we observed that the intracellular accumulation of MoS2 QDs in lipid droplets was enhanced owing to the specific binding of ß-CD to cholesterol, which was then harnessed for monitoring the lipid metabolism in living cells via fluorescence imaging. Furthermore, we also demonstrated the potential use of ß-CD-MoS2 QDs for targeted cell imaging and microplate-based cell recognition, which can be easily achieved via bioconjugation with functional motifs (e.g., folate acid) through host-guest chemistry. Altogether, these results illustrate the great potential of engineering the surface of MoS2 QDs and other analogous materials via CD-based host-guest chemistry for advancing their cell imaging applications.


Assuntos
Ciclodextrinas , Pontos Quânticos , Pontos Quânticos/química , Molibdênio/química , Fluorescência , Diagnóstico por Imagem
16.
Anal Chem ; 95(32): 12104-12112, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37525420

RESUMO

Adenosine triphosphate (ATP) participates in the regulation of most biological processes, and the ATP level is closely associated with many diseases. However, it still remains challenging to achieve on-site monitoring of ATP in an equipment-free and efficient way. Microneedles, a minimally invasive technology that can extract biomarkers from liquid biopsies, have recently emerged as useful tools for early diagnosis of a broad range of diseases. In this work, we developed hydrogel microneedles that are loaded with ATP-specific dual-emitting gold nanoclusters (RhE-AuNCs) for fast sampling and on-needle detection of ATP. These RhE-AuNCs were photo-crosslinked to the hydrogel matrix to form a fluorescent microneedle patch. Based on the ATP-induced Förster resonance energy transfer in RhE-AuNCs, a highly selective, sensitive, and reliable ATP sensor was developed. Moreover, simultaneous capture and visual detection of ATP was achieved by the AuNC-loaded microneedle sensing platform, which exhibits promising sensing performance. This work provides a new approach to design a point-of-care ATP sensing platform, which also holds great potential for the further development of microneedle-based analytical devices.


Assuntos
Nanopartículas Metálicas , Ouro , Trifosfato de Adenosina , Corantes Fluorescentes , Hidrogéis
17.
Small ; 19(49): e2304857, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37590390

RESUMO

Despite great advances in understanding the biological behaviors of chiral materials, the effect of chirality-configured nanoparticles on tissue regeneration-related biological processes remains poorly understood. Herein, the chirality of MoS2 quantum dots (QDs) is tailored by functionalization with l-/d-penicillamine, and the profound chiral effects of MoS2 QDs on cellular activities, angiogenesis, and tissue regeneration are thoroughly investigated. Specifically, d-MoS2 QDs show a positive effect in promoting the growth, proliferation, and migration of human umbilical vein endothelial cells. The expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and fibroblast growth factor (FGF) in d-MoS2 QDs group is substantially up-regulated, resulting in enhanced tube formation activity. This distinct phenomenon is largely due to the higher internalization efficiency of d-MoS2 QDs than l-MoS2 QDs and chirality-dependent nano-bio interactions. In vivo angiogenic assay shows the expression level of angiogenic markers in newly-formed skin tissues of d-MoS2 QDs group is higher than that in l-MoS2 QDs group, leading to an accelerated re-epithelialization and improved skin regeneration. The findings of chirality-dependent angiogenesis activity of MoS2 QDs provide new insights into the biological activity of MoS2 nanomaterials, which also opens up a new path to the rational design of chiral nanomaterials for tissue regeneration application.


Assuntos
Pontos Quânticos , Humanos , Molibdênio , Fator A de Crescimento do Endotélio Vascular , Células Endoteliais da Veia Umbilical Humana
18.
Theor Appl Genet ; 136(3): 45, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36905488

RESUMO

KEY MESSAGE: Leaf senescence in sorghum is primarily controlled by the progression, but not by the onset of senescence. The senescence-delaying haplotypes of 45 key genes accentuated from landraces to improved lines. Leaf senescence is a genetically programmed developmental process and plays a central role for plant survival and crop production by remobilising nutrients accumulated in senescent leaves. In theory, the ultimate outcome of leaf senescence is determined by the onset and progression of senescence, but how these two processes contribute to senescence is not fully illustrated in crops and the genetic basis for them is not well understood. Sorghum (Sorghum bicolor), which is known for the remarkable stay-green trait, is ideal for dissecting the genomic architecture underlying the regulation of senescence. In this study, a diverse panel of 333 sorghum lines was explored for the onset and progression of leaf senescence. Trait correlation analysis showed that the progression of leaf senescence, rather than the onset of leaf senescence, significantly correlated with variations of the final leaf greenness. This notion was further supported by GWAS, which identified 31 senescence-associated genomic regions containing 148 genes, of which 124 were related to the progression of leaf senescence. The senescence-delaying haplotypes of 45 key candidate genes were enriched in lines with extremely prolonged senescence duration, while senescence-promoting haplotypes in those with extremely accelerated senescence. Haplotype combinations of these genes could well explain the segregation of the senescence trait in a recombinant inbred population. We also demonstrated that senescence-delaying haplotypes of candidate genes were under strong selection during sorghum domestication and genetic improvement. Together, this research advanced our understanding of crop leaf senescence and provided a suite of candidate genes for functional genomics and molecular breeding.


Assuntos
Sorghum , Sorghum/genética , Senescência Vegetal , Locos de Características Quantitativas , Fenótipo , Grão Comestível/genética , Genômica
19.
Sensors (Basel) ; 23(16)2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37631596

RESUMO

The ultrasonic guided lamb wave approach is an effective non-destructive testing (NDT) method used for detecting localized mechanical damage, corrosion, and welding defects in metallic pipelines. The signal processing of guided waves is often challenging due to the complexity of the operational conditions and environment in the pipelines. Machine learning approaches in recent years, including convolutional neural networks (CNN) and long short-term memory (LSTM), have exhibited their advantages to overcome these challenges for the signal processing and data classification of complex systems, thus showing great potential for damage detection in critical oil/gas pipeline structures. In this study, a CNN-LSTM hybrid model was utilized for decoding ultrasonic guided waves for damage detection in metallic pipelines, and twenty-nine features were extracted as input to classify different types of defects in metallic pipes. The prediction capacity of the CNN-LSTM model was assessed by comparing it to those of CNN and LSTM. The results demonstrated that the CNN-LSTM hybrid model exhibited much higher accuracy, reaching 94.8%, as compared to CNN and LSTM. Interestingly, the results also revealed that predetermined features, including the time, frequency, and time-frequency domains, could significantly improve the robustness of deep learning approaches, even though deep learning approaches are often believed to include automated feature extraction, without hand-crafted steps as in shallow learning. Furthermore, the CNN-LSTM model displayed higher performance when the noise level was relatively low (e.g., SNR = 9 or higher), as compared to the other two models, but its prediction dropped gradually with the increase of the noise.

20.
J Am Chem Soc ; 144(40): 18175-18194, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36162119

RESUMO

Mineral-based bulk structural materials (MBSMs) are known for their long history and extensive range of usage. The inherent brittleness of minerals poses a major problem to the performance of MBSMs. To overcome this problem, design principles have been extracted from natural biominerals, in which the extraordinary mechanical performance is achieved via the hierarchical organization of minerals and organics. Nevertheless, precise and efficient fabrication of MBSMs with bioinspired hierarchical structures under mild conditions has long been a big challenge. This Perspective provides a panoramic view of an emerging fabrication strategy, matrix-directed mineralization, which imitates the in vivo growth of some biominerals. The advantages of the strategy are revealed by comparatively analyzing the conventional fabrication techniques of artificial hierarchically structured MBSMs and the biomineral growth processes. By introducing recent advances, we demonstrate that this strategy can be used to fabricate artificial MBSMs with hierarchical structures. Particular attention is paid to the mass transport and the precursors that are involved in the mineralization process. We hope this Perspective can provide some inspiring viewpoints on the importance of biomimetic mineralization in material fabrication and thereby spur the biomimetic fabrication of high-performance MBSMs.


Assuntos
Materiais Biomiméticos , Biomimética , Materiais Biomiméticos/química , Biomimética/métodos , Minerais/química
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