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1.
Cell Death Dis ; 15(5): 346, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769124

RESUMEN

Exploring novel diagnostic and therapeutic biomarkers is extremely important for osteosarcoma. YME1 Like 1 ATPase (YME1L), locating in the mitochondrial inner membrane, is key in regulating mitochondrial plasticity and metabolic activity. Its expression and potential functions in osteosarcoma are studied in the present study. We show that YME1L mRNA and protein expression is significantly elevated in osteosarcoma tissues derived from different human patients. Moreover, its expression is upregulated in various primary and immortalized osteosarcoma cells. The Cancer Genome Atlas database results revealed that YME1L overexpression was correlated with poor overall survival and poor disease-specific survival in sarcoma patients. In primary and immortalized osteosarcoma cells, silencing of YME1L through lentiviral shRNA robustly inhibited cell viability, proliferation, and migration. Moreover, cell cycle arrest and apoptosis were detected in YME1L-silenced osteosarcoma cells. YME1L silencing impaired mitochondrial functions in osteosarcoma cells, causing mitochondrial depolarization, oxidative injury, lipid peroxidation and DNA damage as well as mitochondrial respiratory chain complex I activity inhibition and ATP depletion. Contrarily, forced YME1L overexpression exerted pro-cancerous activity and strengthened primary osteosarcoma cell proliferation and migration. YME1L is important for Akt-S6K activation in osteosarcoma cells. Phosphorylation of Akt and S6K was inhibited after YME1L silencing in primary osteosarcoma cells, but was strengthened with YME1L overexpression. Restoring Akt-mTOR activation by S473D constitutively active Akt1 mitigated YME1L shRNA-induced anti-osteosarcoma cell activity. Lastly, intratumoral injection of YME1L shRNA adeno-associated virus inhibited subcutaneous osteosarcoma xenograft growth in nude mice. YME1L depletion, mitochondrial dysfunction, oxidative injury, Akt-S6K inactivation, and apoptosis were detected in YME1L shRNA-treated osteosarcoma xenografts. Together, overexpressed YME1L promotes osteosarcoma cell growth, possibly by maintaining mitochondrial function and Akt-mTOR activation.


Asunto(s)
Neoplasias Óseas , Proliferación Celular , Ratones Desnudos , Osteosarcoma , Osteosarcoma/patología , Osteosarcoma/genética , Osteosarcoma/metabolismo , Humanos , Animales , Línea Celular Tumoral , Ratones , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/genética , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Apoptosis/genética , Movimiento Celular/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , ATPasas Asociadas con Actividades Celulares Diversas/genética , Ratones Endogámicos BALB C , Masculino , Serina-Treonina Quinasas TOR/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Femenino
2.
Clin Cancer Res ; : OF1-OF13, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619278

RESUMEN

PURPOSE: The inherent genetic heterogeneity of acute myeloid leukemia (AML) has challenged the development of precise and effective therapies. The objective of this study was to elucidate the genomic basis of drug resistance or sensitivity, identify signatures for drug response prediction, and provide resources to the research community. EXPERIMENTAL DESIGN: We performed targeted sequencing, high-throughput drug screening, and single-cell genomic profiling on leukemia cell samples derived from patients with AML. Statistical approaches and machine learning models were applied to identify signatures for drug response prediction. We also integrated large public datasets to understand the co-occurring mutation patterns and further investigated the mutation profiles in the single cells. The features revealed in the co-occurring or mutual exclusivity pattern were further subjected to machine learning models. RESULTS: We detected genetic signatures associated with sensitivity or resistance to specific agents, and identified five co-occurring mutation groups. The application of single-cell genomic sequencing unveiled the co-occurrence of variants at the individual cell level, highlighting the presence of distinct subclones within patients with AML. Using the mutation pattern for drug response prediction demonstrates high accuracy in predicting sensitivity to some drug classes, such as MEK inhibitors for RAS-mutated leukemia. CONCLUSIONS: Our study highlights the importance of considering the gene mutation patterns for the prediction of drug response in AML. It provides a framework for categorizing patients with AML by mutations that enable drug sensitivity prediction.

3.
J Behav Addict ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38598290

RESUMEN

Background and aims: Impaired inhibitory control accompanied by enhanced craving is hallmark of addiction. This study investigated the effects of transcranial direct current stimulation (tDCS) on response inhibition and craving in Internet gaming disorder (IGD). We examined the brain changes after tDCS and their correlation with clinical variables. Methods: Twenty-four males with IGD were allocated randomly to an active or sham tDCS group, and data from 22 participants were included for analysis. Participants self-administered bilateral tDCS over the dorsolateral prefrontal cortex (DLPFC) for 10 sessions. Stop-signal tasks were conducted to measure response inhibition and participants were asked about their cravings for Internet gaming at baseline and post-tDCS. Functional magnetic resonance imaging data were collected at pre- and post-tDCS, and group differences in resting-state functional connectivity (rsFC) changes from the bilateral DLPFC and nucleus accumbens were examined. We explored the relationship between changes in the rsFC and behavioral variables in the active tDCS group. Results: A significant group-by-time interaction was observed in response inhibition. After tDCS, only the active group showed a decrease in the stop-signal reaction time (SSRT). Although craving decreased, there were no significant group-by-time interactions or group main effects. The anterior cingulate cortex (ACC) showed group differences in post- versus pre-tDCS rsFC from the right DLPFC. The rsFC between the ACC and left middle frontal gyrus was negatively correlated with the SSRT. Discussion and conclusion: Our study provides preliminary evidence that bilateral tDCS over the DLPFC improves inhibitory control and could serve as a therapeutic approach for IGD.

4.
J Orthop Translat ; 45: 247-255, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38601198

RESUMEN

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

5.
Cell ; 187(8): 1907-1921.e16, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38552624

RESUMEN

Hydroxyproline-rich glycoproteins (HRGPs) are a ubiquitous class of protein in the extracellular matrices and cell walls of plants and algae, yet little is known of their native structures or interactions. Here, we used electron cryomicroscopy (cryo-EM) to determine the structure of the hydroxyproline-rich mastigoneme, an extracellular filament isolated from the cilia of the alga Chlamydomonas reinhardtii. The structure demonstrates that mastigonemes are formed from two HRGPs (a filament of MST1 wrapped around a single copy of MST3) that both have hyperglycosylated poly(hydroxyproline) helices. Within the helices, O-linked glycosylation of the hydroxyproline residues and O-galactosylation of interspersed serine residues create a carbohydrate casing. Analysis of the associated glycans reveals how the pattern of hydroxyproline repetition determines the type and extent of glycosylation. MST3 possesses a PKD2-like transmembrane domain that forms a heteromeric polycystin-like cation channel with PKD2 and SIP, explaining how mastigonemes are tethered to ciliary membranes.


Asunto(s)
Chlamydomonas reinhardtii , Cilios , Glicoproteínas , Cilios/química , Glicoproteínas/química , Glicosilación , Hidroxiprolina/química , Plantas/metabolismo , Chlamydomonas reinhardtii/química
6.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38446740

RESUMEN

Protein annotation has long been a challenging task in computational biology. Gene Ontology (GO) has become one of the most popular frameworks to describe protein functions and their relationships. Prediction of a protein annotation with proper GO terms demands high-quality GO term representation learning, which aims to learn a low-dimensional dense vector representation with accompanying semantic meaning for each functional label, also known as embedding. However, existing GO term embedding methods, which mainly take into account ancestral co-occurrence information, have yet to capture the full topological information in the GO-directed acyclic graph (DAG). In this study, we propose a novel GO term representation learning method, PO2Vec, to utilize the partial order relationships to improve the GO term representations. Extensive evaluations show that PO2Vec achieves better outcomes than existing embedding methods in a variety of downstream biological tasks. Based on PO2Vec, we further developed a new protein function prediction method PO2GO, which demonstrates superior performance measured in multiple metrics and annotation specificity as well as few-shot prediction capability in the benchmarks. These results suggest that the high-quality representation of GO structure is critical for diverse biological tasks including computational protein annotation.


Asunto(s)
Benchmarking , Biología Computacional , Ontología de Genes , Aprendizaje , Anotación de Secuencia Molecular
7.
Artículo en Inglés | MEDLINE | ID: mdl-38456596

RESUMEN

Most cells tightly control the length of their cilia. The regulation likely involves intraflagellar transport (IFT), a bidirectional motility of multi-subunit particles organized into trains that deliver building blocks into the organelle. In Chlamydomonas, the anterograde IFT motor kinesin-2 consists of the motor subunits FLA8 and FLA10 and the nonmotor subunit KAP. KAP dissociates from IFT at the ciliary tip and diffuses back to the cell body. This observation led to the diffusion-as-a-ruler model of ciliary length control, which postulates that KAP is progressively sequestered into elongating cilia because its return to the cell body will require increasingly more time, limiting motor availability at the ciliary base, train assembly, building block supply, and ciliary growth. Here, we show that Chlamydomonas FLA8 also returns to the cell body by diffusion. However, more than 95% of KAP and FLA8 are present in the cell body and, at a given time, just ~1% of the motor participates in IFT. After repeated photobleaching of both cilia, IFT of fluorescent kinesin subunits continued indicating that kinesin-2 cycles from the large cell-body pool through the cilia and back. Furthermore, growing and full-length cilia contained similar amounts of kinesin-2 subunits and the size of the motor pool at the base changed only slightly with ciliary length. These observations are incompatible with the diffusion-as-a-ruler model, but rather support an "on-demand model," in which the cargo load of the trains is regulated to assemble cilia of the desired length.

8.
World J Hepatol ; 16(2): 146-151, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38495283

RESUMEN

We read with interest the article by Xing Wang, which was published in the recent issue of the World Journal of Hepatology 2023; 15: 1294-1306. This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis (LC), prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma (HCC), and management strategies. The etiology of cirrhosis varies according to geographical, economic, and population factors. Viral hepatitis is the dominant cause in China. Vaccination and effective treatment have reduced the number of people with viral hepatitis, but the overall number is still large. Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage. The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease (MASLD)-associated LC and alcoholic liver disease in the future. Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development. These changing trends indicate a need for greater emphasis on tackling obesity and diabetes, and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD. In an effort to help cope with these changing trends, the authors further proposed countermeasures for healthcare authorities doctors, and patients.

9.
Open Med (Wars) ; 19(1): 20240899, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38463525

RESUMEN

Background: N6-methyladenosine (m6A) is the most frequently occurring interior modification in eukaryotic messenger RNA (mRNA), and abnormal mRNA modifications can affect many biological processes. However, m6A's effect on the metabolism of antiplatelet drugs for the prevention of ischemic stroke (IS) remains largely unclear. Methods: We analyzed the m6A enzymes and m6A methylation in peripheral blood samples of IS patients with/without clopidogrel resistance (CR), and the peripheral blood and liver of rat models with/without CR. We also compared the effect of m6A methylation on the expression of the drug-metabolizing enzymes (CYP2C19 and CYP2C6v1) in CR and non-CR samples. Results: Methyltransferase-like 3 (METTL3), an m6A enzyme, was highly expressed in the peripheral blood of patients with CR, and in both the peripheral blood and liver of rats with CR. This enzyme targets CYP2C19 or CYP2C6v1 mRNA through m6A methylation, resulting in low expression of CYP2C19 or CYP2C6v1 mRNA. Consequently, this leads to decreased clopidogrel metabolism and CR. Conclusion: The METTL3-mediated methylation of CYP2C19 mRNA may aggravate CR in IS patients.

10.
Fungal Genet Biol ; 172: 103886, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38485049

RESUMEN

Plant-derived sugars and lipids are key nutritional sources for plant associated fungi. However, the relationship between utilization of host-derived sugars and lipids during development of the symbiotic association remains unknown. Here we show that the fungus Metarhizium robertsii also needs plant-derived lipids to develop symbiotic relationship with plants. The fatty acid binding proteins FABP1 and FABP2 are important for utilization of plant-derived lipids as the deletion of Fabp1 and Fabp2 significantly reduced the ability of M. robertsii to colonize rhizoplane and rhizosphere of maize and Arabidopsis thaliana. Deleting Fabp1 and Fabp2 increased sugar utilization by upregulating six sugar transporters, and this explains why deleting the monosaccharide transporter gene Mst1, which plays an important role in utilization of plant-derived sugars, had no impact on the ability of the double-gene deletion mutant ΔFabp1::ΔFabp2 to colonize plant roots. FABP1 and FABP2 were also found in other plant-associated Metarhizium species, and they were highly expressed in the medium using the tomato root exudate as the sole carbon and nitrogen source, suggesting that they could be also important for these species to develop symbiotic relationship with plants. In conclusion, we discovered that utilization of plant-derived sugars and lipids are coupled during colonization of rhizoplane and rhizosphere by M. robertsii.

11.
BMJ ; 384: e078581, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443074

RESUMEN

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.


Asunto(s)
Endoscopía Capsular , Várices Esofágicas y Gástricas , Várices , Adulto , Humanos , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Cirrosis Hepática/complicaciones , Estudios Prospectivos
12.
Zhongguo Zhong Yao Za Zhi ; 49(2): 509-517, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38403326

RESUMEN

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.


Asunto(s)
Alcaloides , Piperidinas , Alcamidas Poliinsaturadas , Benzodioxoles , Absorción Intestinal
13.
PhytoKeys ; 238: 11-31, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38344432

RESUMEN

Recent research has indicated that the Phyllagathis (raphides) clade (Sonerileae, Melastomataceae) is only distantly related to the type of Phyllagathis and should be separated as a distinct genus. Phylogeny of this clade is here reconstructed with expanded taxon sampling. Four strongly supported subclades have been identified. The possible affinities of taxa that were not sampled in the analysis are discussed, based on morphological data. Perilimnastes is resurrected as the generic name of the Phyllagathis (raphides) clade. A generic description, colour figures, map of distribution, a list of included species and a key are provided for Perilimnastes. Fifteen new combinations are made plus the description of a new species. As interpreted here, Perilimnastes consists of twenty species and two varieties.

14.
Nutrients ; 16(4)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38398816

RESUMEN

Objective: the aim of this study was to identify plasma metabolomic markers of Dietary Approaches to Stop Hypertension (DASH) dietary patterns in pregnant women. Methods: This study included 186 women who had both dietary intake and metabolome measured from a nested case-control study within the NICHD Fetal Growth Studies-Singletons cohort (FGS). Dietary intakes were ascertained at 8-13 gestational weeks (GW) using the Food Frequency Questionnaire (FFQ) and DASH scores were calculated based on eight food and nutrient components. Fasting plasma samples were collected at 15-26 GW and untargeted metabolomic profiling was performed. Multivariable linear regression models were used to examine the association of individual metabolites with the DASH score. Least absolute shrinkage and selection operator (LASSO) regression was used to select a panel of metabolites jointly associated with the DASH score. Results: Of the total 460 known metabolites, 92 were individually associated with DASH score in linear regressions, 25 were selected as a panel by LASSO regressions, and 18 were identified by both methods. Among the top 18 metabolites, there were 11 lipids and lipid-like molecules (i.e., TG (49:1), TG (52:2), PC (31:0), PC (35:3), PC (36:4) C, PC (36:5) B, PC (38:4) B, PC (42:6), SM (d32:0), gamma-tocopherol, and dodecanoic acid), 5 organic acids and derivatives (i.e., asparagine, beta-alanine, glycine, taurine, and hydroxycarbamate), 1 organic oxygen compound (i.e., xylitol), and 1 organoheterocyclic compound (i.e., maleimide). Conclusions: our study identified plasma metabolomic markers for DASH dietary patterns in pregnant women, with most of being lipids and lipid-like molecules.


Asunto(s)
Enfoques Dietéticos para Detener la Hipertensión , Hipertensión , Humanos , Femenino , Embarazo , Enfoques Dietéticos para Detener la Hipertensión/métodos , Mujeres Embarazadas , Patrones Dietéticos , Estudios de Casos y Controles , Lípidos , Biomarcadores
15.
Stud Health Technol Inform ; 310: 1548-1549, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38269739

RESUMEN

The purpose of this research was to construct a Markov model of digital therapeutics to predict the lifetime costs and consequences that would be incurred by a hypothetical group of adult smokers in Korea who only made a single attempt to stop smoking. To determine the efficacy of DTx, we created an annual cycle Markov model. The result shows that the NRT strategy is determined as the dominant strategy. Digital therapeutics acts as a complement to pharmacotherapy and is a low-cost option.


Asunto(s)
Cese del Hábito de Fumar , Adulto , Humanos , Análisis Costo-Beneficio , Fumar
16.
Cell Death Dis ; 15(1): 57, 2024 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-38228583

RESUMEN

Osteosarcoma (OS) is a highly aggressive form of bone cancer that predominantly affects adolescents and young adults. In this study, we have undertaken an investigation into the potential anti-OS cell activity of IMT1 (inhibitor of mitochondrial transcription 1), a first-in-class inhibitor of RNA polymerase mitochondrial (POLRMT). IMT1 exhibited a profound inhibitory effect on cell survival, proliferation, cell cycle progression, and migration in primary and immortalized OS cells. Furthermore, this POLRMT inhibitor elicited apoptosis in the OS cells, without, however, inducing cytotoxicity in human osteoblasts or osteoblastic cells. IMT1 disrupted mitochondrial functions in OS cells, resulting in mitochondrial depolarization, oxidative injury, lipid peroxidation, and ATP reduction in OS cells. Silencing POLRMT using targeted shRNA closely mimicked the actions of IMT1 and exerted potent anti-OS cell activity. Importantly, IMT1's effectiveness was diminished in POLRMT-silenced OS cells. Subsequent investigations revealed that IMT1 suppressed the activation of the Akt-mammalian target of rapamycin (mTOR) cascade in OS cells. IMT1 treatment or POLRMT silencing in primary OS cells led to a significant reduction in Akt1-S6K-S6 phosphorylation. Conversely, it was enhanced upon POLRMT overexpression. The restoration of Akt-mTOR activation through the introduction of a constitutively active S473D mutant Akt1 (caAkt1) mitigated IMT1-induced cytotoxicity in OS cells. In vivo, oral administration of IMT1 robustly curtailed the growth of OS xenografts in nude mice. Furthermore, IMT1 suppressed POLRMT activity, impaired mitochondrial function, repressed Akt-mTOR activation, and induced apoptosis within xenograft tissues. Collectively, these findings underscore the potent growth-inhibitory effects attributed to IMT1 via targeted POLRMT inhibition. The utilization of this POLRMT inhibitor carries substantial therapeutic promise in the context of OS treatment.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Animales , Ratones , Adolescente , Adulto Joven , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones Desnudos , Línea Celular Tumoral , Serina-Treonina Quinasas TOR/metabolismo , Osteosarcoma/genética , Sirolimus/farmacología , Apoptosis , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Proliferación Celular , Mitocondrias/metabolismo , Mamíferos , ARN Polimerasas Dirigidas por ADN
17.
J Pediatr Orthop B ; 33(2): 174-177, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36943689

RESUMEN

The purpose of this study was to compare outcomes between percutaneous K-wire reduction cast immobilization (PKRC) and percutaneous K-wire reduction elastic intramedullary nailing combined with cast immobilization (PKRNC) for the treatment of radial neck fractures in children. This was a retrospective analysis of 62 radial neck fractures in children treated with PKRC or PKRNC. Thirty-one children were treated with percutaneous K-wire reduction, K-wire removal after reduction, and cast immobilization while 31 radial neck fractures in controls were managed using PKRNC. There were no significant differences between PKRC and PKRNC with regard to preoperative angulation ( P  = 0.556). The operation time in the PKRC group was significantly shorter than that of the PKRNC group ( P  = 0.023). There was no significant difference in the displacement angle when compared between the two groups on the first day and 1 month after surgery ( P  = 0.617, 0.72). The Mayo elbow performance score of the elbow joint function did not differ significantly between the two groups ( P  = 0.587). Although the hospital stay was not significantly different between groups (4.81 ±â€…1.07 vs. 4.16 ±â€…1.59 days; P  = 0.067), the PKRNC group required a second hospitalization to remove the elastic intramedullary nail 3 months after the operation. PKRC and PKRNC both achieved satisfactory outcomes for radial neck fractures in children. The operation time in the PKRC group was significantly lower than in the PKRNC group. PKRC does not require reoperation to remove internal fixation. Therefore, PKRC is recommended for radial neck fractures in children.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas Radiales de Cabeza y Cuello , Fracturas del Radio , Niño , Humanos , Codo , Estudios Retrospectivos , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/cirugía , Resultado del Tratamiento , Hilos Ortopédicos
18.
Talanta ; 269: 125484, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38043338

RESUMEN

Ethylene is a hormone for fruit ripening control, and for the purpose of maintaining plant quality, ethylene monitoring is crucial. Due to the simple structure and limited functionality, the technical realization of ethylene detection by an artificial sensor remains a challenge. In this paper, we present a metal-organic frameworks (MOFs) array based electronic nose (e-nose) for rapid and accurate determination of ethylene. Six zirconium-based MOFs with systematically modified pore sizes and π-π binding sites have been prepared and fabricated into a sensor array using quartz crystal microbalance (QCM) technology. By virtue of the synergistic features of six MOF sensors, selectivity detection of ethylene has been achieved. The detection limit reaches to 0.27 ± 0.02 ppm, and high selectivity and stability (98.29 % ± 0.88 %) could also be confirmed. By submitting data to machine learning algorithm, an e-nose system could be established for discriminating ethylene from mixtures with a qualitative accuracy of 90.30 % and quantitative accuracy of 98.89 %. Practical evaluation suggests that the e-nose could index the fruit quality based on the accurate detection of ethylene released during fruit ripeness. This work demonstrates the promising potential of fabricating MOFs based e-nose systems for practical monitoring applications by selectively detecting challengeable target molecules.

19.
Adv Mater ; 36(14): e2307690, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38145556

RESUMEN

Ti-series oxide ceramics in the form of aerogels, such as TiO2, SrTiO3, BaTiO3, and CaCu3Ti4O12, hold tremendous potential as functional materials owing to their excellent optical, dielectric, and catalytic properties. Unfortunately, these inorganic aerogels are usually brittle and prone to pulverization owing to weak inter-particulate interactions, resulting in restricted application performance and serious health risks. Herein, a novel strategy is reported to synthesize an elastic form of an aerogel-like, highly porous structure, in which activity-switchable Ti-series oxide sols transform from the metastable state to the active state during electrospinning, resulting in condensation and solidification at the whipping stage to obtain curled nanofibers. These curled nanofibers are further entangled when flying in the air to form a physically interlocked, elastic network mimicking the microstructure of high-elasticity hydrogels. This strategy provides a library of Ti-series oxide nanofiber sponges with unprecedented stretchability, compressibility, and bendability, possessing extensive opportunities for greener, safer, and broader applications as integrated or wearable functional devices. As a proof-of-concept demonstration, a new, elastic form of TiO2, composed of both "white" and "black" TiO2 nanofiber sponges, is constructed as spontaneous air-conditioning textiles in smart clothing, buildings, and vehicles, with unique bidirectional regulation of radiative cooling in summer and solar heating in winter.

20.
Nanomaterials (Basel) ; 13(21)2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37947729

RESUMEN

The nanotribological properties of aluminum gallium nitride (AlxGa1-xN) epitaxial films grown on low-temperature-grown GaN/AlN/Si substrates were investigated using a nanoscratch system. It was confirmed that the Al compositions played an important role, which was directly influencing the strength of the bonding forces and the shear resistance. It was verified that the measured friction coefficient (µ) values of the AlxGa1-xN films from the Al compositions (where x = 0.065, 0.085, and 0.137) were in the range of 0.8, 0.5, and 0.3, respectively, for Fn = 2000 µN and 0.12, 0.9, and 0.7, respectively, for Fn = 4000 µN. The values of µ were found to decrease with the increases in the Al compositions. We concluded that the Al composition played an important role in the reconstruction of the crystallites, which induced the transition phenomenon of brittleness to ductility in the AlxGa1-xN system.

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