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1.
PeerJ ; 12: e17987, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39224818

RESUMO

Background: Understanding the reproductive biology of weeds is crucial for managing them effectively. Diplachne fusca (Poaceae) is a widely distributed weed species that poses significant challenges to agricultural productivity. Nevertheless, it remains unclear how the soil seed bank of D. fusca responds to environmental shifts, and whether a dormancy cycle is present in this species. Methods: We investigated how seed dormancy in D. fusca is broken and how it responds to natural environmental changes. The impact of incubation temperature, light exposure, cold stratification at 4 °C, and gibberellic acid (GA3) on seed germination/dormancy-break was investigated, along with assessing seasonal changes in germinability through monthly excavation and laboratory incubation of buried seeds over 2 years. Results: Results indicated that newly ripened seeds of D. fusca were dormant, with germination facilitated by GA3, cold stratification, and after-ripening at ambient room conditions. Exposure to darkness inhibited germination. Seasonal patterns of germination were observed, with peak germination occurring in cooler months and a marked decline during the hot summer months. After 2 years of being buried, approximately 40% of the seeds remained viable. Conclusion: In summary, seeds of D. fusca exhibit non-deep physiological dormancy and maintain a persistent soil seed bank. Seeds buried in the soil undergo a yearly dormancy/non-dormancy cycle. This dormancy cycle prevents seed germination and seedling emergence in autumn, which boosts the survival of seedlings in less favorable seasons, yet it also makes it more challenging to eradicate this weed.


Assuntos
Germinação , Dormência de Plantas , Plantas Daninhas , Estações do Ano , Sementes , Dormência de Plantas/fisiologia , Germinação/fisiologia , Plantas Daninhas/fisiologia , Sementes/crescimento & desenvolvimento , Sementes/fisiologia , Poaceae/fisiologia , Giberelinas/metabolismo , Temperatura
2.
Small ; : e2402874, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162119

RESUMO

Using orthogonal click chemistries for efficient nanoscale self-assembly, a new antibody-directing antibody conjugate (ADAC) nanogel is generated. In this system, one of the antibodies is displayed on the nanogel surface to specifically recognize cell-surface epitopes while the other antibody is encapsulated inside the nanogel core. The system is programmed to release the latter antibody in its functional form in the cytosolic environment of a specific cell to engage intracellular targets. ADACs offer a potential solution to harness the advantages seen with antibody-drug conjugates (ADCs) to deliver therapeutic cargos to specific tissues, but with the added capability of carrying biologics as the cargo. In this manuscript, this potential is demonstrated through delivery of antibodies against intracellular targets in specific cells. This platform offers new avenues for precise therapeutic interventions and the potential to address previously "undruggable" cellular targets.

3.
DNA Res ; 31(4)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946223

RESUMO

Tamarix austromongolica is endemic to the Yellow River Basin and has adapted to diverse ecological settings in the region, including the arid areas of northwestern China and the saline soil regions of the Yellow River Delta. However, the genetic basis of its local adaptation remains unclear. We report a chromosome-level assembly of the T. austromongolica genome based on PacBio high-fidelity sequencing and Hi-C technology. The 12 pseudochromosomes cover 98.44% of the 1.32 Gb assembly, with a contig N50 of 52.57 Mb and a BUSCO score of 98.2%. The genome comprises 913.6 Mb (68.83%) of repetitive sequences and 22,374 protein-coding genes. Genome evolution analyses suggest that genes under positive selection and significantly expanded gene families have facilitated T. austromongolica's adaptability to diverse environmental factors and high resistance to diseases. Using genotyping-by-sequencing, we conducted population structure and selection analyses of 114 samples from 15 sites. Two genetic groups were identified, and 114 and 289 candidate genes were assigned to the populations of the northwestern and eastern parts of the Yellow River, respectively. Furthermore, we discovered numerous candidate genes associated with high-altitude adaptability and salt tolerance. This research provides valuable genomic resources for the evolutionary study and genetic breeding of tamarisk.


Assuntos
Genoma de Planta , Tamaricaceae , Tamaricaceae/genética , China , Rios , Adaptação Fisiológica/genética , Evolução Molecular , Cromossomos de Plantas , Filogenia
4.
Talanta ; 277: 126355, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38838563

RESUMO

Acute liver injury (ALI) is a frequent and devastating liver disease that has been made more prevalent by the excessive use of chemicals, drugs, and alcohol in modern life. Hypochlorous acid (HClO), an important biomarker of oxidative stress originating mainly from the mitochondria, has been shown to be intimately connected to the development and course of ALI. Herein, a novel BODIPY-based NIR ratiometric fluorescent probe Mito-BS was constructed for the specific recognition of mitochondrial HClO. The probe Mito-BS can rapidly respond to HClO within 20 s with a ratiometric fluorescence response (from 680 nm to 645 nm), 24-fold fluorescence intensity ratio enhancement (I645/I680), a wide pH adaptation range (5-9) and the low detection limit (31 nM). The probe Mito-BS has been effectively applied to visualize endogenous and exogenous HClO fluctuations in living zebrafish and cells based on its low cytotoxicity and prominent mitochondria-targeting ability. Furthermore, the fluorescent probe Mito-BS makes it possible to achieve the non-invasive in-situ diagnosis of ALI through in mice, and provides a feasible strategy for early diagnosis and drug therapy of ALI and its complications.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Mitocôndrias , Peixe-Zebra , Ácido Hipocloroso/análise , Ácido Hipocloroso/metabolismo , Animais , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Camundongos , Mitocôndrias/metabolismo , Modelos Animais de Doenças , Humanos , Compostos de Boro/química , Imagem Óptica , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem
5.
J Hazard Mater ; 475: 134845, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38876016

RESUMO

Organophosphate esters (OPEs) are ubiquitous in surface soil, and atmospheric deposition is considered to be the major pollution source. However, the research on the environmental transport behaviors of OPEs between atmospheric deposition and soil is very limited. In this study, we investigated the contamination levels and seasonal variations of OPEs in atmospheric deposition samples (n = 33) collected from an area of South China every month between February 2021 and January 2022, and evaluated the contribution of OPEs in atmospheric deposition to soil. The concentrations of ∑21target-OPEs ranged from 3670 to 18,600 ng/g dry weight (dw), with a mean of 8200 ng/g dw (median: 7600 ng/g dw). ∑21target-OPEs concentrations in all atmospheric deposition samples exhibited significant seasonal differences (p < 0.05) with higher concentrations observed in winter and lower concentrations in summer. Tris(2,4-di-tert-butylphenyl) phosphate (TDTBPP) was the most dominant target OPE in atmospheric deposition (4870 ng/g dw), and its seasonal variation trend was consistent with ∑21OPEs (p < 0.05). Simultaneously, in order to further explore the effect of atmospheric deposition on the levels of OPEs in soil of the study region, input fluxes and accumulation increments were estimated. Ten OPEs (including seven target OPEs and three suspect OPEs) exhibited high input flux means and accumulation increments, indicating that these compounds are prone to accumulate in soil via atmospheric deposition. It is noteworthy that the non-target phosphonate analyte bis(2,4-di-tert-butylphenyl) dibutyl ethane-1,2-diylbis(phosphonate) (BDTBPDEDBP) was detected at highest median concentration (8960 ng/g dw) in atmospheric deposition. Correspondingly, the average input flux and accumulation increment of BDTBPDEDBP were higher than those of all target and suspect OPEs. Collectively, this study quantifies the environmental transport behavior of OPEs between atmospheric deposition and soil, and provides new evidences for the fact that atmospheric deposition is the important pollution source of OPEs in soil.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124522, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38838599

RESUMO

Detection of highly toxic mercury ions (Hg2+) in actual environmental and biological samples is of significant importance for protecting environment and human health. In this paper, a new ratiometric fluorescent probe BTIA was designed and synthesized from 3-pinone based on Internal Charge Transfer (ICT) mechanism. BTIA could selectively recognize Hg2+ over other competitive analytes with short reaction time (5 s), distinct ratiometric response, strong anti-interference ability, large Stokes shift (200 nm), and low detection limit (2.36 × 10-7 M). Furthermore, BTIA was applicable for detecting Hg2+ in actual water samples and it also performed an excellent imaging capability in living RAW264.7 cells, zebrafish and onion tissue.


Assuntos
Corantes Fluorescentes , Limite de Detecção , Mercúrio , Espectrometria de Fluorescência , Poluentes Químicos da Água , Peixe-Zebra , Animais , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Mercúrio/análise , Camundongos , Células RAW 264.7 , Poluentes Químicos da Água/análise , Cebolas/química , Água/química
7.
ACS Appl Mater Interfaces ; 16(21): 27898-27907, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38749009

RESUMO

Bubble dynamics significantly impact mass transfer and energy conversion in electrochemical gas evolution reactions. Micro-/nanostructured surfaces with extreme wettability have been employed as gas-evolving electrodes to promote bubble departure and decrease the bubble-induced overpotential. However, effects of the electrodes' wickability on the electrochemical reaction performances remain elusive. In this work, hydrogen evolution reaction (HER) performances are experimentally investigated using micropillar array electrodes with varying interpillar spacings, and effects of the electrodes' wettability, wickability as well as bubble adhesion are discussed. A deep learning-based object detection model was used to obtain bubble counts and bubble departure size distributions. We show that microstructures on the electrode have little effect on the total bubble counts and bubble size distribution characteristics at low current densities. At high current densities, however, micropillar array electrodes have much higher total bubble counts and smaller bubble departure sizes compared with the flat electrode. We also demonstrate that surface wettability is a critical factor influencing HER performances under low current densities, where bubbles exist in an isolated regime. Under high current densities, where bubbles are in an interacting regime, the wickability of the micropillar array electrodes emerges as a determining factor. This work elucidates the roles of surface wettability and wickability on enhancing electrochemical performances, providing guidelines for the optimal design of micro-/nanostructured electrodes in various gas evolution reactions.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124476, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38776670

RESUMO

Malononitrile is a very important chemical material and has wide application fields in production of medicines, pesticides, and extraction of gold. However, its nonnegligible hypertoxicity inspired researchers to develop more efficient analysis techniques to sensitively and selectively detect malononitrile. Nopinone derivatives initiated by our research group have been developed as a class of organic fluorescent chemosensors for identifying multiple analytes in recent years. Different heterocyclic compounds based on nopinone were designed and synthesized to be applied in the fields of environmental analysis, food detection and bioimaging. Nevertheless, the comparison research on the optical properties of fluorescent compounds containing the nopinyl matrix with other structural analogs including alkyl, cyclohexyl and phenyl groups was deficient. Herein, four 4-(1H-imidazol-2-yl)benzaldehyde-based ratiometric fluorescent chemosensors based on o-dimethyl cyclohexyl, phenyl and nopinyl units for recognizing malononitrile were designed and developed, and their differences in the optical properties and detection performances were investigated by using spectral analysis combined with theoretical calculations. Moreover, the nopinone-based 4-(1H-imidazol-2-yl)benzaldehyde fluorescent chemosensor NMZQ was successfully applied in the dual channel fluorescence bioimaging of malononitrile in living HeLa cells and zebrafish, which attributed to its outstanding spectral property and detection performance.

9.
Cells ; 13(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38727294

RESUMO

Information on long-term effects of postovulatory oocyte aging (POA) on offspring is limited. Whether POA affects offspring by causing oxidative stress (OS) and mitochondrial damage is unknown. Here, in vivo-aged (IVA) mouse oocytes were collected 9 h after ovulation, while in vitro-aged (ITA) oocytes were obtained by culturing freshly ovulated oocytes for 9 h in media with low, moderate, or high antioxidant potential. Oocytes were fertilized in vitro and blastocysts transferred to produce F1 offspring. F1 mice were mated with naturally bred mice to generate F2 offspring. Both IVA and the ITA groups in low antioxidant medium showed significantly increased anxiety-like behavior and impaired spatial and fear learning/memory and hippocampal expression of anxiolytic and learning/memory-beneficial genes in both male and female F1 offspring. Furthermore, the aging in both groups increased OS and impaired mitochondrial function in oocytes, blastocysts, and hippocampus of F1 offspring; however, it did not affect the behavior of F2 offspring. It is concluded that POA caused OS and damaged mitochondria in aged oocytes, leading to defects in anxiety-like behavior and learning/memory of F1 offspring. Thus, POA is a crucial factor that causes psychological problems in offspring, and antioxidant measures may be taken to ameliorate the detrimental effects of POA on offspring.


Assuntos
Comportamento Animal , Mitocôndrias , Oócitos , Estresse Oxidativo , Animais , Oócitos/metabolismo , Mitocôndrias/metabolismo , Feminino , Camundongos , Masculino , Ovulação , Ansiedade/metabolismo , Ansiedade/patologia , Antioxidantes/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Blastocisto/metabolismo , Senescência Celular , Memória
10.
FASEB J ; 38(7): e23591, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38572579

RESUMO

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Invasividade Neoplásica/genética , Neoplasias Pancreáticas/genética , RNA Circular/genética , RNA Circular/metabolismo
11.
Anal Methods ; 16(13): 1846-1855, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38497272

RESUMO

Toxic mercury ions (Hg2+) can cause serious environmental pollution and accumulate in living organisms via the food chain. Therefore, monitoring Hg2+ is crucial in ensuring the safety of ecosystems and organisms. In this work, a novel ratiometric fluorescent probe CMT (5-(4-(diphenylamino)phenyl)-1-(7-hydroxy-coumarin-3-yl)-4-pentene-1,3-dione) based on coumarin was developed for detecting Hg2+, which displayed obvious fluorescence changes, a low detection limit (2.24 × 10-7 M), good selectivity, and a large Stokes shift (255 nm). The CMT probe could detect Hg2+ in real environmental soil and water samples. Furthermore, the CMT probe enabled the naked-eye detection of Hg2+ using test paper experiments. CMT was also applied for fluorescence imaging in living zebrafish and plants. This work provides a highly efficient tool for monitoring Hg2+ in environmental samples and biological systems.


Assuntos
Corantes Fluorescentes , Mercúrio , Animais , Peixe-Zebra , Ecossistema , Mercúrio/análise , Cumarínicos
12.
J Chem Phys ; 160(9)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38426510

RESUMO

Molecular dynamics simulations have become increasingly important in understanding the microscopic mechanisms of various molecular systems. However, the high energy barriers in complicated molecules often make it difficult to observe events of interest within a reasonable timescale. To address this issue, researchers have developed a variety of enhanced sampling methods to explore configuration space by adding bias potentials along the slowly changing collective variables (CVs). In this study, we have developed a new tool that combines slow feature analysis and biasing-enhanced sampling methods to identify effective CVs and enhance the sampling efficiency of configuration space. We have demonstrated the effectiveness of this tool through three general examples.

13.
Theriogenology ; 220: 84-95, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490113

RESUMO

Understanding the mechanisms for oocyte maturation and optimizing the protocols for in vitro maturation (IVM) are greatly important for improving developmental potential of IVM oocytes. The miRNAs expressed in cumulus cells (CCs) play important roles in oocyte maturation and may be used as markers for selection of competent oocytes/embryos. Although a recent study from our group identified several new CCs-expressed miRNAs that regulate cumulus expansion (CE) and CC apoptosis (CCA) in mouse oocytes, validation of these findings and further investigation of mechanisms of action in other model species was essential before wider applications. By using both in vitro and in vivo pig oocyte models with significant differences in CE, CCA and developmental potential, the present study validated that miR-149 and miR-31 improved CE and developmental potential while suppressing CCA of pig oocytes. We demonstrated that miR-149 and miR-31 targeted SMAD family member 6 (SMAD6) and transforming growth factor ß2 (TGFB2), respectively, in the transforming growth factor-ß (TGF-ß) signaling. Furthermore, both miR-149 and miR-31 increased CE and decreased CCA via activating SMAD family member 2 (SMAD2) and increasing the expression of SMAD2 and SMAD family member 4. In conclusion, the present results show that miR-149 and miR-31 improved CE and developmental potential while suppressing CCA of pig oocytes by activating the TGF-ß signaling, suggesting that they might be used as markers for pig oocyte quality.


Assuntos
Células do Cúmulo , Técnicas de Maturação in Vitro de Oócitos , MicroRNAs , Oócitos , Animais , Feminino , Células do Cúmulo/fisiologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , MicroRNAs/genética , MicroRNAs/metabolismo , Oócitos/fisiologia , Suínos , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta/metabolismo
14.
BMC Surg ; 24(1): 31, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263014

RESUMO

BACKGROUND: Due to the great heterogeneity of gastric cancer (GC), the prognosis of patients within a stage is very different. Therefore, it is necessary to identify the high risk factors for postoperative recurrence and metastasis and take appropriate therapeutic strategies to improve the prognosis of patients. In this study, we aimed to explore the prognostic significance of preoperative and postoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19 - 9 (CA19-9) and carbohydrate antigen 72 - 4 (CA72-4) in patients with stage I, II and III GC who underwent radical gastrectomy. METHODS: A total of 580 patients who underwent curative surgical resection and had not received neoadjuvant chemotherapy were included in this study. The relationship between clinicopathological features and recurrence was analysed. Survival analysis was performed by Kaplan-Meier curve. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors in GC patients. RESULTS: Among patients with stage III GC, the recurrence free survival (RFS) and overall survival (OS) of patients with CA19-9>35 U/mL were significantly lower than those with CA19-9 ≤ 35 U/mL; CA19-9 was always a significant independent marker. CEA and CA72-4 were sometime useful to predict RFS or OS alternatively in the pre- or postoperative period. The only other independent significant factors for prognosis in our study were lymph node metastases for RFS and postoperative adjuvant chemotherapy for OS. CONCLUSION: Preoperative and postoperative CA19-9 values are independent risk factors for predicting prognosis in stage III GC after curative gastrectomy.


Assuntos
Antígeno CA-19-9 , Neoplasias Gástricas , Humanos , Prognóstico , Antígeno Carcinoembrionário , Gastrectomia
15.
Pediatr Neurol ; 152: 98-106, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242024

RESUMO

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is considered a demyelinating disease of the central nervous system, but an increasing number of encephalitis cases associated with MOG antibodies have been reported recently. METHODS: This was a single-center, retrospective study. All data for pediatric patients with MOGAD diagnosed at Beijing Children's Hospital from January 2017 to January 2022 were collected. Clinical characteristics and outcomes were analyzed, and treatment responses were compared between the rituximab (RTX) and mycophenolate mofetil (MMF) groups. RESULTS: A total of 190 patients (age range: 5 months to 16 years; median age: 7.2 years; females: 97) were included in this study. The phenotypes of the first attack included acquired demyelinating syndromes (105 [55%]), encephalitis other than acute disseminated encephalomyelitis (82 [43%]), and isolated meningitis (3 [2%]). After a median follow-up of 30.4 months (interquartile range: 14.8-43.7), 64 (34%) patients had relapses. Fifty-one of the 64 (80%) patients who had relapse received maintenance therapy, including MMF (41), RTX (11), maintenance intravenous immunoglobulin (two), and tocilizumab (two). The annualized relapse rates decreased significantly after treatment in both the RTX and MMF cohorts (P < 0.05); however, there were no significant differences between the two groups (P = 0.56). A total of 178 (94%) patients had complete (175 patients) or almost complete (three patients) recovery (modified Rankin scale [mRS] < 2), and 12 had moderate to severe deficits (mRS ≥ 2). CONCLUSIONS: The spectrum of pediatric MOGAD is broader than previously reported and includes demyelinating syndromes and encephalitis. Encephalitis is an important initial phenotype observed in pediatric patients with MOGAD.


Assuntos
Autoanticorpos , Encefalite , Feminino , Humanos , Criança , Lactente , Estudos de Coortes , Glicoproteína Mielina-Oligodendrócito , Estudos Retrospectivos , Encefalite/tratamento farmacológico , Rituximab/uso terapêutico , Recidiva , Ácido Micofenólico
18.
J Am Chem Soc ; 146(1): 33-38, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38147631

RESUMO

Inspired by the immune system's own strategy for macrophage activation, we describe here a simple self-assembly strategy for generating artificial immune complexes. The built-in recognition domains in the antibody, viz. the Fab and Fc domains, are judiciously leveraged for cargo conjugation to generate the nanoassembly and macrophage targeting, respectively. A responsive linker is engineered into the nanoassembly for releasing the protein cargo inside the macrophages, while ensuring stability during delivery. The design principles are simple and versatile to be applicable to a range of biologics, from small protein toxins to large enzymes, with high loading capacity. This self-assembly platform has the potential for delivering biologics to immune cells with implications in immunotherapy.


Assuntos
Produtos Biológicos , Epitopos , Proteínas , Anticorpos , Células Apresentadoras de Antígenos
19.
Mol Cancer ; 22(1): 195, 2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-38044421

RESUMO

BACKGROUND: Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer and chemoresistance. DNA damage repair contributes to the proliferation of cancer cells and resistance to chemotherapy-induced apoptosis. However, the role of circRNAs in the regulation of DNA damage repair needs clarification. METHODS: RNA sequencing analysis was applied to identify the differentially expressed circRNAs. qRT-PCR was conducted to confirm the expression of hsa_circ_0007919, and CCK-8, FCM, single-cell gel electrophoresis and IF assays were used to analyze the proliferation, apoptosis and gemcitabine (GEM) resistance of pancreatic ductal adenocarcinoma (PDAC) cells. Xenograft model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor growth and DNA damage in vivo. RNA sequencing and GSEA were applied to confirm the downstream genes and pathways of hsa_circ_0007919. FISH and nuclear-cytoplasmic RNA fractionation experiments were conducted to identify the cellular localization of hsa_circ_0007919. ChIRP, RIP, Co-IP, ChIP, MS-PCR and luciferase reporter assays were conducted to confirm the interaction among hsa_circ_0007919, FOXA1, TET1 and the LIG1 promoter. RESULTS: We identified a highly expressed circRNA, hsa_circ_0007919, in GEM-resistant PDAC tissues and cells. High expression of hsa_circ_0007919 correlates with poor overall survival (OS) and disease-free survival (DFS) of PDAC patients. Hsa_circ_0007919 inhibits the DNA damage, accumulation of DNA breaks and apoptosis induced by GEM in a LIG1-dependent manner to maintain cell survival. Mechanistically, hsa_circ_0007919 recruits FOXA1 and TET1 to decrease the methylation of the LIG1 promoter and increase its transcription, further promoting base excision repair, mismatch repair and nucleotide excision repair. At last, we found that GEM enhanced the binding of QKI to the introns of hsa_circ_0007919 pre-mRNA and the splicing and circularization of this pre-mRNA to generate hsa_circ_0007919. CONCLUSIONS: Hsa_circ_0007919 promotes GEM resistance by enhancing DNA damage repair in a LIG1-dependent manner to maintain cell survival. Targeting hsa_circ_0007919 and DNA damage repair pathways could be a therapeutic strategy for PDAC.


Assuntos
Carcinoma Ductal Pancreático , MicroRNAs , Neoplasias Pancreáticas , Humanos , Gencitabina , RNA Circular/genética , RNA Circular/metabolismo , Precursores de RNA , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Dano ao DNA , MicroRNAs/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Oxigenases de Função Mista/genética , Proteínas Proto-Oncogênicas/genética , Fator 3-alfa Nuclear de Hepatócito/genética
20.
Langmuir ; 39(45): 16101-16110, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37920930

RESUMO

Bubble nucleation has a significant influence on mass transfer and energy conversion in electrochemical gas-evolving reactions. In this work, we establish a theoretical model for bubble nucleation from gas cavities on gas-evolving surfaces. Based on analyses of transient gas diffusion within the concentration boundary layer and supersaturation equation for stable bubble nuclei, we determined the size ranges of effective nucleation cavities on gas-evolving surfaces under different levels of supersaturation conditions. In addition, a criterion for the incipience of bubble nucleation on gas-evolving surfaces is proposed. We investigate the effects of the contact angle, cone angle, concentration boundary layer thickness, ambient pressure, and temperature on the size ranges of effective nucleation cavities, respectively. We demonstrate that a larger contact angle or a smaller cone angle can broaden the size range of effective cavities, thereby promoting bubble nucleation from cavities. We also show that increasing the concentration boundary layer thickness causes larger cavities to become effective nucleation sites, which significantly expands the size range of effective cavities. In contrast, increasing the ambient pressure enables smaller cavities to become effective nucleation sites, resulting in an expansion in the size range of effective cavities. Results of this work will contribute to the manipulation of bubble nucleation densities and the optimal design of gas-evolving electrodes in various electrochemical gas-evolving reactions.

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