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1.
Sci Rep ; 14(1): 15346, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961201

RESUMO

Rock mass deformation and failure are macroscopic manifestations of crack initiation, propagation, and coalescence. However, simulating the transition of rocks from continuous to discontinuous media under cyclic dynamic loading remains challenging. This study proposes a hybrid finite-discrete element method (HFDEM) to model crack propagation, incorporating a frequency-dependent cohesive-zone model. The mechanical properties of standard sandy mudstone under quasi-static and cyclic dynamic loading were simulated using HFDEM, and the method's reliability was verified through experimental comparison. The comparative analysis demonstrates that HFDEM successfully captures crack interaction mechanisms and accurately simulates the overall failure behavior of specimens. Additionally, the effects of pre-existing flaw inclination angle and dynamic loading frequency on rock failure mechanisms were investigated. The numerical results reveal that rock samples exhibit significantly higher compressive strength under dynamic loading compared to quasi-static loading, with compressive strength increasing with higher cyclic dynamic load frequencies. Furthermore, by analyzing the strength characteristics, crack propagation, and failure modes of the samples, insights into the failure mechanisms of rocks under different frequency loads were obtained. This study provides valuable insights into crack development and failure of rocks under seismic loads, offering guidance for engineering practices.

2.
Anal Bioanal Chem ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38981911

RESUMO

Rapid, efficient, versatile, easy-to-use, and non-expensive analytical approaches are globally demanded for food analysis. Many ambient ionization approaches based on electrospray ionization (ESI) have been developed recently for the rapid molecular characterization of food products. However, those approaches mainly suffer from insufficient signal duration for comprehensive chemical characterization by tandem MS analysis. Here, a commercially available disposable gel loading tip is used as a low-cost emitter for the direct ionization of untreated food samples. The most important advantages of our approach include high stability, and durability of the signal (> 10 min), low cost (ca. 0.1 USD per run), low sample and solvent consumption, prevention of tip clogging and discharge, operational simplicity, and potential for automation. Quantitative analysis of sulfapyridine, HMF (hydroxymethylfurfural), and chloramphenicol in real sample shows the limit-of-detection 0.1 µg mL-1, 0.005 µg mL-1, 0.01 µg mL-1; the linearity range 0.1-5 µg mL-1, 0.005-0.25 µg mL-1, 0.01-1 µg mL-1; and the linear fits R2 ≥ 0.980, 0.991, 0.986. Moreover, we show that tip-ESI can also afford sequential molecular ionization of untreated viscous samples, which is difficult to achieve by conventional ESI. We conclude that tip-ESI-MS is a versatile analytical approach for the rapid chemical analysis of untreated food samples.

3.
Microbiol Spectr ; : e0049624, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041815

RESUMO

Omadacycline and eravacycline are gradually being used as new tetracycline antibiotics for the clinical treatment of Gram-negative pathogens. Affected by various tetracycline-inactivating enzymes, there have been reports of resistance to eravacycline and omadacycline in recent years. We isolated a strain carrying the mobile tigecycline resistance gene tet(X4) from the feces of a patient in Zhejiang Province, China. The strain belongs to the rare ST485 sequence type. The isolate was identified as Klebsiella pneumoniae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The MICs of antimicrobial agents were determined using either the agar dilution method or the micro broth dilution method. The result showed that the isolate was resistant to eravacycline (MIC = 32 mg/L), omadacycline (MIC > 64 mg/L), and tigecycline (MIC > 32 mg/L). Whole-genome sequencing revealed that the tet(X4) resistance gene is located on the IncFII(pCRY) conjugative plasmid. tet(X4) is flanked by ISVsa3, and we hypothesize that this association contributes to the spread of the resistance gene. Plasmids were analyzed by S1-nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blotting, and electrotransformation experiment. We successfully transferred the plasmid carrying tet(X4) to the recipient bacteria by electrotransformation experiment. Compared with the DH-5α, the MICs of the transformant L3995-DH5α were increased by eight-fold for eravacycline and two-fold higher for omadacycline. Overall, the emergence of plasmid-borne tet(X4) resistance gene in a clinical isolate of K. pneumoniae ST485 underscores the essential requirement for the ongoing monitoring of tet(X4) to prevent and control its further dissemination in China.IMPORTANCEThere are still limited reports on Klebsiella pneumoniae strains harboring tetracycline-resistant genes in China, and K. pneumoniae L3995hy adds a new example to those positive for the tet(X4) gene. Importantly, our study raises concerns that plasmid-mediated resistance to omadacycline and eravacycline may spread further to a variety of ecological and clinical pathogens, limiting the choice of medication for extensively drug-resistant bacterial infections. Therefore, it is important to continue to monitor the prevalence and spread of tet(X4) and other tetracyclines resistance genes in K. pneumoniae and diverse bacterial populations.

4.
Cell Death Dis ; 15(7): 520, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039052

RESUMO

Aldehyde dehydrogenases superfamily (ALDHs), which are ubiquitously present in various organisms with diverse subcellular localizations, play a crucial role in regulating malignant tumor progression; Nevertheless, their involvement in clear cell renal cell carcinoma (ccRCC) has not been elucidated. In this study, we performed comprehensive bioinformatics analyses on the 19 ALDHs genes, and identified ALDH9A1 as a key contributor in ccRCC. Expression patterns and clinical relevance of ALDH9A1 were determined using bioinformatics analyses, real-time PCR, western blotting, and immunohistochemistry. To explore the underlying mechanism behind the tumor suppressor role of ALDH9A1, RNA sequencing, methylated RNA immunoprecipitation, luciferase reporter assay, mass spectroscopy, immunoprecipitation, mutational studies and immunofluorescence were employed. The impact of ALDH9A1 in ccRCC progression and metabolic programming was assessed through both in vitro and in vivo. Here, this study revealed ALDH9A1 as a tumor suppressor gene in ccRCC. The fat mass and obesity associated protein (FTO) was identified as a demethylase for ALDH9A1 mRNA, resulting in its reduced stability and expression levels in ccRCC. Functional experiments demonstrated that the deficiency of ALDH9A1 in ccRCC promoted tumor proliferation, invasion, migration and lipid accumulation. Mechanistic insights illustrated that the diminished levels of ALDH9A1 resulted in the failure to sequester nucleophosmin 1 (NPM1) within cytoplasm, thereby suppressing the transcription of IQ motif containing the GTPase-activating protein 2 (IQGAP2), subsequently activating the AKT-mTOR signaling, ultimately fostering tumor progression and lipid accumulation. In conclusion, the present study highlights the robust prognostic significance of ALDH9A1 and delivers a comprehensive understanding of ALDH9A1-NPM1-IQGAP2-AKT axis in ccRCC. These findings established a solid research foundation for novel therapeutic strategies for ccRCC patients.


Assuntos
Adenosina , Carcinoma de Células Renais , Neoplasias Renais , Nucleofosmina , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Progressão da Doença , Linhagem Celular Tumoral , Camundongos , Camundongos Nus , Proliferação de Células , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/genética , Masculino , Feminino
5.
Nat Commun ; 15(1): 5881, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-38997250

RESUMO

Carbon chain elongation (CCE) is normally carried out using either chemical catalysts or bioenzymes. Herein we demonstrate a catalyst-free approach to promote demethylation C-C coupling reactions for advanced CCE constructed with functional groups under ambient conditions. Accelerated by the electric field, two organic cations containing a methyl group (e.g., ketones, acids, and aldehydes) approach each other with such proximity that the energy of the repulsive Coulomb interaction between these two cations exceeds the bond energy of the methyl group. This results in the elimination of a methyl cation and the coupling of the residual carbonyl carbon groups. As confirmed by high-resolution mass spectrometry and isotope-labeling experiments, the C-C coupling reactions (yields up to 76.5%) were commonly observed in the gas phase or liquid phase, for which the mechanism was further studied using molecular dynamics simulations and stationary-point calculations, revealing deep insights and perspectives of chemistry.

6.
Cancer Lett ; 598: 217118, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39002690

RESUMO

Recent studies have highlighted palmitoylation, a novel protein post-translational modification, as a key player in various signaling pathways that contribute to tumorigenesis and drug resistance. Despite this, its role in bladder cancer (BCa) development remains inadequately understood. In this study, ZDHHC9 emerged as a significantly upregulated oncogene in BCa. Functionally, ZDHHC9 knockdown markedly inhibited tumor proliferation, promoted tumor cell apoptosis, and enhanced the efficacy of gemcitabine (GEM) and cisplatin (CDDP). Mechanistically, SP1 was found to transcriptionally activate ZDHHC9 expression. ZDHHC9 subsequently bound to and palmitoylated the Bip protein at cysteine 420 (Cys420), thereby inhibiting the unfolded protein response (UPR). This palmitoylation at Cys420 enhanced Bip's protein stability and preserved its localization within the endoplasmic reticulum (ER). ZDHHC9 might become a novel therapeutic target for BCa and could also contribute to combination therapy with GEM and CDDP.

7.
Plants (Basel) ; 13(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38999601

RESUMO

The ramet system is a typical structural type in the life history of clonal plants. This massive structure is formed by many similar ramets connected by underground rhizomes, which are independent and mutually influential. Therefore, the ramet system is unique to bamboo forests, and its role in the construction, maintenance, and productivity of bamboo populations is irreplaceable. Mulch management is a high-level cultivation model for bamboo forests that is used to cultivate bamboo shoots. However, the basic conditions of bamboo ramet systems in this managed model are poorly understood. This study analyzed the underground rhizome morphology, bud bank, and branching of bamboo ramets in a Phyllostachys praecox C.D. Chu et C.S. Chao 'Prevernalis' forest to explore the growth patterns of bamboo ramets in high-level management fields. In mulched bamboo forests, the bamboo rhizomes, distributed in intermediate positions of the bamboo ramet system, were long with many lateral buds and branches, and those at the initial and distal ends were short with few lateral buds and branches. The initial end of the ramet system reduced the ramet system, the intermediate part expanded the ramet system, and the distal end promoted ramet system regeneration. Owing to the continuous reduction, expansion, and renewal of ramet systems, the bamboo rhizome system demonstrates mobility and adaptability. This study found that a higher level of bamboo forest management increased the possibility of artificial fragmentation of the ramet system and that improving the efficiency of the ramet system was beneficial for maintaining its high vitality. Thus, this study provides a crucial reference for guiding the precise regulation of bamboo ramet systems in artificial bamboo forests.

8.
Environ Res ; 258: 119488, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925468

RESUMO

Medical waste incineration fly ash (MWI FA) is classified as a hazardous solid waste. Therefore, the development of recycling technologies to convert MWI FA into useful products is necessary and challenging. In this study, we developed a sustainable approach for preparing a catalyst through the pyrolysis of water-washed MWI FA (WW FA-x, where x corresponds to the pyrolysis temperature). Subsequently, it was applied as a potent peroxydisulfate (PDS) activator to remove tetracycline (TC) from water. The results showed that the WW FA-800 exhibited remarkable adsorption performance as well as highly efficient catalytic activation of PDS, with a 115 mg/g maximum TC adsorption capacity and 93.5% (reaction kinetic rate = 315 µmol/g/h) TC removal within 60 min. A synergistic effect was achieved by adsorption and PDS activation. TC degradation was primarily driven by non-radical (1O2 and electron transfer) processes. WW FA-800 possesses multiple active sites, including defects, π-π*, O-CO groups, Fe0, and Cu(I). Three possible pathways for TC decomposition have been proposed, with the majority of intermediates exhibiting less toxicity than TC. Furthermore, the WW FA/PDS system exhibited an excellent anti-interference ability, and universality in the degradation of various organic contaminants. Notably, energy consumption was minimal, approximately 2.80 kWh/(g·TC), and the leachability of heavy metals in the WW FA-800 was within acceptable limits. This study provides a MWI FA recycling route for the development of highly active catalysts.

9.
Front Plant Sci ; 15: 1348080, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855466

RESUMO

Clonal plants are widely distributed in the riparian zone and play a very important role in the maintenance of wetland ecosystem function. Flooding is an environmental stress for plants in the riparian zone, and the response of plants varies according to the depth and duration of flooding. However, there is a lack of research on the growth response of clonal plants during flooding, and the endogenous hormone response mechanism of clonal plants is still unclear. In the present study, Alternanthera philoxeroides, a clonal plant in the riparian zone, was used to investigate the time-dependent stem elongation, the elongation of different part of the immature internodes, and the relationship between growth elongation and the phytohormone gibberellin (GA) under a series of submergence depths (0 m, 2 m, 5 m, and 9 m). The results showed that stem elongation occurred under all treatments, however, compared to 0 m (control), plants grew more under 2 m and 5 m submergence depth, while grew less under 9 m water depth. Additionally, basal part elongation of the immature internode was the predominant factor contributing to the stem growth of A. philoxeroides under different submergence depths. The phytohormone contents in basal part of the mature and immature internodes showed that GA induced the differential elongation of internode. Plant submerged at depth of 2 m had the highest GA accumulation, but plant submerged at depth of 9 m had the lowest GA concentration. These data suggested that GA biosynthesis are essential for stem elongation in A. philoxeroides, and the basal part of the immature internode was the main position of the GA biosynthesis. This study provided new information about the rapid growth and invasion of the clonal plant A. philoxeroides around the world, further clarified the effects of submergence depth and duration on the elongation of the stem, and deepened our understanding of the growth response of terrestrial plants in deeply flooded environments.

10.
Materials (Basel) ; 17(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38893874

RESUMO

In order to investigate the influence of a hot-pressing process on the mechanical properties of ultra-high molecular weight polyethylene (UHMWPE) fiber non-woven fabrics with stretch and in-plane shear, UHMWPE non-woven fabric samples were prepared by adjusting the temperature, time, and pressure of the hot-pressing process, and mechanical property tests were carried out so as to clarify the influence of the hot-pressing process on the mechanical properties of the samples. The results show that the hot-pressing process mainly affects the silk-glue bonding strength of the samples; in the test range, with the increase in hot-pressing temperature and time, the tensile strength and in-plane shear strength of the samples increase and then decrease, and the best mechanical properties are obtained at 130 °C and 7 min of hot pressing, respectively; at 130 °C, the in-plane shear strength is 39.94 MPa and the tensile strength is 595.43 MPa; at 7 min, the in-plane shear strength is 63.0 MPa and the tensile strength is 643.30 MPa; with the increase in the hot-pressing pressure, the in-plane shear strength of the samples increases and then decreases, and the highest is 52.60 MPa, achieved at 8 MPa; in the range of 5-8 MPa, the tensile strength of the specimens did not change significantly, and increased significantly at 9 MPa, reaching a maximum strength of 674.55 MPa.

11.
Langmuir ; 40(24): 12512-12525, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38833532

RESUMO

g-C3N4/Ag-ZnO (CAZ) composite photocatalysts were synthesized successfully by the hydrothermal method. The photocatalytic performance of photocatalysts was assessed through experiments measuring both hydrogen (H2) production and the degradation of methylene blue (MB). The H2 production rate of 60% CAZ reached 2.450 mmol·g-1·h-1, which was 8.5 times that of g-C3N4. 25% CAZ degraded 99.14% of MB dye within 40 min, and its degradation rate constant was 12.4 times that of g-C3N4. CAZ composite photocatalysts have good synergistic properties in degradation and hydrogen production and exhibit better photocatalytic performance. A Z-scheme photocatalytic system mechanism of CAZ has been proposed for the enhanced H2 production and photocatalytic degradation rate.

12.
Exp Gerontol ; 194: 112496, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38897394

RESUMO

PURPOSE: Osteoporosis is linked to impaired function of osteoblasts, and decreased expression of METTL14 may result in abnormal differentiation of these bone-forming cells. However, the specific impact of METTL14 on osteoblast differentiation and its underlying mechanisms are not yet fully understood. METHODS AND RESULTS: This study discovered a positive correlation between METTL14 expression and bone formation in specimens from osteoporosis patients and ovariectomized (OVX) mice. Additionally, METTL14 targeting of SLC25A3 contributed to the restoration of mitochondrial ROS levels and mitochondrial membrane potential in osteoblasts and promoted osteoblast differentiation. Moreover, in vivo experiments showed that METTL14 enhanced bone formation, and therapeutic introduction of METTL14 countered the decrease in bone formation in OVX mice. CONCLUSIONS: Overall, these findings emphasize the crucial role of the METTL14/SLC25A3 signaling axis in osteoblast activity, suggesting that this axis could be a potential target for improving osteoporosis.

13.
Medicine (Baltimore) ; 103(23): e38418, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847680

RESUMO

BACKGROUND: Previous findings on the effect of general versus spinal anesthesia on postoperative delirium in elderly people with hip fractures are somewhat controversial. This article included the latest randomized controlled study for meta-analysis to evaluate the effect of general anesthesia (GA) and spinal anesthesia (SA) on delirium after hip fracture surgery in the elderly, so as to guide the clinical. METHODS: Cochrane Library, PubMed, Web Of Science, and Embase were searched from inception up to January 16, 2024. Randomized controlled trial (RCT) was included to evaluate the postoperative results of GA and SA in elderly patients (≥50 years old) undergoing hip fracture surgery. Two researchers independently screened for inclusion in the study and extracted data. Heterogeneity was assessed by the I²and Chi-square tests, and P < .1 or I² ≥ 50% indicated marked heterogeneity among studies. The Mantel-Haenszel method was used to estimate the combined relative risk ratio (RR) and the corresponding 95% confidence interval (CI) for the binary variables. RESULTS: Nine randomized controlled trials were included. There was no significant difference (RR = 0.93, 95% CI = 0.774-1.111, P > .05) in the incidence of postoperative delirium between the GA group and the SA group. In intraoperative blood transfusion (RR = 1.0, 95% CI = 0.77-1.28, Z = 0.04, P = .971), pulmonary embolism (RR = 0.795, 95% CI = 0.332-1.904, Z = 0.59, P = .606), pneumonia (RR = 1.47, 95% CI = 0.75-2.87, P = .675), myocardial infarction (RR = 0.97, 95% CI = 0.24-3.86, Z = 0.05, P = .961), heart failure (RR = 0.80, 95% CI = 0.26-2.42, Z = 0.40, P = .961), urinary retention (RR = 1.42, 95% CI = 0.77-2.61, Z = 1.11, P = .267) were similar between the 2 anesthetic techniques. CONCLUSION: There is no significant difference in the effect of GA and SA on postoperative delirium in elderly patients with hip fracture, and their effects on postoperative complications are similar.


Assuntos
Anestesia Geral , Raquianestesia , Delírio , Fraturas do Quadril , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Raquianestesia/efeitos adversos , Raquianestesia/métodos , Delírio/etiologia , Delírio/epidemiologia , Delírio/prevenção & controle , Delírio do Despertar/epidemiologia , Delírio do Despertar/prevenção & controle , Delírio do Despertar/etiologia , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Pessoa de Meia-Idade
14.
J Nanobiotechnology ; 22(1): 224, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702709

RESUMO

Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer.


Assuntos
Carbocianinas , Mitocôndrias , Recidiva Local de Neoplasia , Terapia Fototérmica , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Terapia Fototérmica/métodos , Humanos , Animais , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Linhagem Celular Tumoral , Carbocianinas/química , Imagem Óptica/métodos , Camundongos , Cirurgia Assistida por Computador/métodos , Corantes Fluorescentes/química , Camundongos Nus , Camundongos Endogâmicos BALB C , Raios Infravermelhos , Verde de Indocianina/química , Verde de Indocianina/uso terapêutico , Verde de Indocianina/farmacologia
15.
Front Microbiol ; 15: 1372403, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694797

RESUMO

Introduction: Bamboo can be used in the phytoremediation of heavy metal pollution. However, the characteristics of the bamboo rhizosphere archaeal community in Cr-contaminated soil under field conditions remain unclear. Methods: In this study, high-throughput sequencing was used to examine the rhizosphere soil archaeal communities of Lei bamboo (Phyllostachys precox) plantations along a Cr pollution gradient. Results: The results revealed U-shaped relationships between Cr [total Cr (TCr) or HCl-extractable Cr (ACr)] and two alpha indices (Chao1 and Shannon) of archaea. We also established that high Cr concentrations were associated with a significant increase in the abundance of Thaumarchaeota and significant reductions in the abundances of Crenarchaeota and Euryarchaeota. The archaeal co-occurrence networks reduced in complexity with Cr pollution, decreasing the community's resistance to environmental disturbance. Candidatus nitrosotalea and Nitrososphaeraceae_unclassified (two genera of Thaumarchaeota) were identified as keystone taxa. The community structure of soil archaeal communities was also found to be affected by TCr, ACr, pH, total organic C, and available nutrient (N, P, and K) concentrations, with pH being identified as the most reliable predictor of the archaeal community in assessed soils. Discussion: These findings enhance our understanding of microbial responses to Cr pollution and provide a basis for developing more refined approaches for the use of bamboo in the remediation of Cr-contaminated soils.

16.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38701415

RESUMO

N4-acetylcytidine (ac4C) is a modification found in ribonucleic acid (RNA) related to diseases. Expensive and labor-intensive methods hindered the exploration of ac4C mechanisms and the development of specific anti-ac4C drugs. Therefore, an advanced prediction model for ac4C in RNA is urgently needed. Despite the construction of various prediction models, several limitations exist: (1) insufficient resolution at base level for ac4C sites; (2) lack of information on species other than Homo sapiens; (3) lack of information on RNA other than mRNA; and (4) lack of interpretation for each prediction. In light of these limitations, we have reconstructed the previous benchmark dataset and introduced a new dataset including balanced RNA sequences from multiple species and RNA types, while also providing base-level resolution for ac4C sites. Additionally, we have proposed a novel transformer-based architecture and pipeline for predicting ac4C sites, allowing for highly accurate predictions, visually interpretable results and no restrictions on the length of input RNA sequences. Statistically, our work has improved the accuracy of predicting specific ac4C sites in multiple species from less than 40% to around 85%, achieving a high AUC > 0.9. These results significantly surpass the performance of all existing models.


Assuntos
Citidina , Citidina/análogos & derivados , RNA , Citidina/genética , RNA/genética , RNA/química , Humanos , Biologia Computacional/métodos , Animais , Software , Algoritmos
17.
BMC Cancer ; 24(1): 611, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773399

RESUMO

RNA interactomes and their diversified functionalities have recently benefited from critical methodological advances leading to a paradigm shift from a conventional conception on the regulatory roles of RNA in pathogenesis. However, the dynamic RNA interactomes in adenoma-carcinoma sequence of human CRC remain unexplored. The coexistence of adenoma, cancer, and normal tissues in colorectal cancer (CRC) patients provides an appropriate model to address this issue. Here, we adopted an RNA in situ conformation sequencing technology for mapping RNA-RNA interactions in CRC patients. We observed large-scale paired RNA counts and identified some unique RNA complexes including multiple partners RNAs, single partner RNAs, non-overlapping single partner RNAs. We focused on the antisense RNA OIP5-AS1 and found that OIP5-AS1 could sponge different miRNA to regulate the production of metabolites including pyruvate, alanine and lactic acid. Our findings provide novel perspectives in CRC pathogenesis and suggest metabolic reprogramming of pyruvate for the early diagnosis and treatment of CRC.


Assuntos
Adenoma , Neoplasias Colorretais , MicroRNAs , Ácido Pirúvico , RNA Longo não Codificante , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Ácido Pirúvico/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Reprogramação Metabólica
18.
J Adv Res ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38702028

RESUMO

INTRODUCTION: Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system and accounts for more than 90 % of all renal tumors. Resistance to targeted therapy has emerged as a pivotal factor that contributes to the progressive deterioration of patients with advanced RCC. Metabolic reprogramming is a hallmark of tumorigenesis and progression, with an increasing body of evidence indicating that abnormal lipid metabolism plays a crucial role in the advancement of renal clear cell carcinoma. OBJECTIVES: Clarify the precise mechanisms underlying abnormal lipid metabolism and drug resistance. METHODS: Bioinformatics screening and analyses were performed to identify hub gene. qRT-PCR, western blot, chromatin immunoprecipitation (ChIP) assays, and other biological methods were used to explore and verify related pathways. Various cell line models and animal models were used to perform biological functional experiments. RESULTS: In this study, we identified Mesoderm induction early response 2 (MIER2) as a novel biomarker for RCC, demonstrating its role in promoting malignancy and sunitinib resistance by influencing lipid metabolism in RCC. Mechanistically, MIER2 facilitated P53 deacetylation by binding to HDAC1. Acetylation modification augmented the DNA-binding stability and transcriptional function of P53, while deacetylation of P53 hindered the transcriptional process of PGC1A, leading to intracellular lipid accumulation in RCC. Furthermore, Trichostatin A (TSA), an inhibitor of HDAC1, was found to impede the MIER2/HDAC1/P53/PGC1A pathway, offering potential benefits for patients with sunitinib-resistant renal cell cancer. CONCLUSION: Our findings highlight MIER2 as a key player in anchoring HDAC1 and inhibiting PGC1A expression through the deacetylation of P53, thereby inducing lipid accumulation in RCC and promoting drug resistance. Lipid-rich RCC cells compensate for energy production and sustain their own growth in a glycolysis-independent manner, evading the cytotoxic effects of targeted drugs and ultimately culminating in the development of drug resistance.

19.
Biomater Sci ; 12(10): 2480-2503, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38592730

RESUMO

Prostate cancer (PCa) is a leading cause of cancer-related death in men, and most PCa patients treated with androgen deprivation therapy will progress to metastatic castration-resistant prostate cancer (mCRPC) due to the lack of efficient treatment. Recently, lots of research indicated that photothermal therapy (PTT) was a promising alternative that provided an accurate and efficient prostate cancer therapy. A photothermic agent (PTA) is a basic component of PPT and is divided into organic and inorganic PTAs. Besides, the combination of PTT and other therapies, such as photodynamic therapy (PDT), immunotherapy (IT), chemotherapy (CT), etc., provides an more efficient strategy for PCa therapy. Here, we introduce basic information about PTT and summarize the PTT treatment strategies for prostate cancer. Based on recent works, we think the combination of PPT and other therapies provides a novel possibility for PCa, especially CRPC clinical treatment.


Assuntos
Terapia Fototérmica , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Animais , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Imunoterapia , Fototerapia/métodos
20.
J Biol Chem ; 300(5): 107260, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582447

RESUMO

Thoracic aortic dissection (TAD) is a highly dangerous cardiovascular disorder caused by weakening of the aortic wall, resulting in a sudden tear of the internal face. Progressive loss of the contractile apparatus in vascular smooth muscle cells (VSMCs) is a major event in TAD. Exploring the endogenous regulators essential for the contractile phenotype of VSMCs may aid the development of strategies to prevent TAD. Krüppel-like factor 15 (KLF15) overexpression was reported to inhibit TAD formation; however, the mechanisms by which KLF15 prevents TAD formation and whether KLF15 regulates the contractile phenotype of VSMCs in TAD are not well understood. Therefore, we investigated these unknown aspects of KLF15 function. We found that KLF15 expression was reduced in human TAD samples and ß-aminopropionitrile monofumarate-induced TAD mouse model. Klf15KO mice are susceptible to both ß-aminopropionitrile monofumarate- and angiotensin II-induced TAD. KLF15 deficiency results in reduced VSMC contractility and exacerbated vascular inflammation and extracellular matrix degradation. Mechanistically, KLF15 interacts with myocardin-related transcription factor B (MRTFB), a potent serum response factor coactivator that drives contractile gene expression. KLF15 silencing represses the MRTFB-induced activation of contractile genes in VSMCs. Thus, KLF15 cooperates with MRTFB to promote the expression of contractile genes in VSMCs, and its dysfunction may exacerbate TAD. These findings indicate that KLF15 may be a novel therapeutic target for the treatment of TAD.


Assuntos
Aneurisma da Aorta Torácica , Dissecção da Aorta Torácica , Fatores de Transcrição Kruppel-Like , Miócitos de Músculo Liso , Fatores de Transcrição , Animais , Humanos , Masculino , Camundongos , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Aneurisma da Aorta Torácica/metabolismo , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/patologia , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Contração Muscular/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Fenótipo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
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