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1.
Nucleic Acids Res ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850159

RESUMEN

Genomic instability is one of the hallmarks of cancer. While loss of histone demethylase KDM6A increases the risk of tumorigenesis, its specific role in maintaining genomic stability remains poorly understood. Here, we propose a mechanism in which KDM6A maintains genomic stability independently on its demethylase activity. This occurs through its interaction with SND1, resulting in the establishment of a protective chromatin state that prevents replication fork collapse by recruiting of RPA and Ku70 to nascent DNA strand. Notably, KDM6A-SND1 interaction is up-regulated by KDM6A SUMOylation, while KDM6AK90A mutation almost abolish the interaction. Loss of KDM6A or SND1 leads to increased enrichment of H3K9ac and H4K8ac but attenuates the enrichment of Ku70 and H3K4me3 at nascent DNA strand. This subsequently results in enhanced cellular sensitivity to genotoxins and genomic instability. Consistent with these findings, knockdown of KDM6A and SND1 in esophageal squamous cell carcinoma (ESCC) cells increases genotoxin sensitivity. Intriguingly, KDM6A H101D & P110S, N1156T and D1216N mutations identified in ESCC patients promote genotoxin resistance via increased SND1 association. Our finding provides novel insights into the pivotal role of KDM6A-SND1 in genomic stability and chemoresistance, implying that targeting KDM6A and/or its interaction with SND1 may be a promising strategy to overcome the chemoresistance.

2.
J Biol Chem ; 299(9): 105177, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37611825

RESUMEN

Translational regulation is one of the decisive steps in gene expression, and its dysregulation is closely related to tumorigenesis. Eukaryotic translation initiation factor 3 subunit i (eIF3i) promotes tumor growth by selectively regulating gene translation, but the underlying mechanisms are largely unknown. Here, we show that eIF3i is significantly increased in colorectal cancer (CRC) and reinforces the proliferation of CRC cells. Using ribosome profiling and proteomics analysis, several genes regulated by eIF3i at the translation level were identified, including D-3-phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in the de novo serine synthesis pathway that participates in metabolic reprogramming of tumor cells. PHGDH knockdown significantly represses CRC cell proliferation and partially attenuates the excessive growth induced by eIF3i overexpression. Mechanistically, METTL3-mediated N6-methyladenosine modification on PHGDH mRNA promotes its binding with eIF3i, ultimately leading to a higher translational rate. In addition, knocking down eIF3i and PHGDH impedes tumor growth in vivo. Collectively, this study not only uncovered a novel regulatory mechanism for PHGDH translation but also demonstrated that eIF3i is a critical metabolic regulator in human cancer.


Asunto(s)
Neoplasias Colorrectales , Factor 3 de Iniciación Eucariótica , Regulación Neoplásica de la Expresión Génica , Fosfoglicerato-Deshidrogenasa , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/fisiopatología , Metiltransferasas/metabolismo , Fosfoglicerato-Deshidrogenasa/genética , Fosfoglicerato-Deshidrogenasa/metabolismo , ARN Mensajero/metabolismo , Factor 3 de Iniciación Eucariótica/genética , Factor 3 de Iniciación Eucariótica/metabolismo , Regulación hacia Arriba , Técnicas de Silenciamiento del Gen , Regulación Neoplásica de la Expresión Génica/genética , Animales , Ratones , Ratones Endogámicos BALB C , Femenino , Xenoinjertos
3.
Biochem Biophys Res Commun ; 694: 149403, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38147699

RESUMEN

Mounting studies have showed that tumor microenvironment (TME) is crucial for cervical cancer (CC), and cancer-related fibroblasts (CAFs) play a major role in it. Recently, exosomal miRNAs secreted by CAFs have been found to be potential targets for cancer diagnosis and therapy. In this paper, we aimed to investigate the function of CAFs-mediated exosome miR-18a-5p (CAFs-exo-miR-18a-5p) in CC. First, in combination with bioinformatic data analysis of the GEO database (GSE86100) and RT-qPCR of CC clinical tissue samples and cell lines, miR-18a-5p was discovered to be markedly up-regulated in CC. Next, CAFs-secreted exosomes were isolated and it was found that miR-18a-5p expression was dramatically promoted in CC cell lines when treated with CAFs-exos. The CAFs-exo-miR-18a-5p was then elucidated to stimulate the proliferation and migration and inhibit the apoptosis of CC cells. In order to clarify the underlying mechanism, we further screened the target genes of miR-18a-5p. TMEM170B was selected by bioinformatic data analysis of online databases combined with RT-qPCR of CC clinical tissues and cells. Luciferase reporter gene analysis combined with molecular biology experiments further elucidated that miR-18a-5p suppressed TMEM170B expression in CC. Finally, both cell and animal experiments demonstrated that TMEM170B over-expression attenuated the oncogenic effect of CAFs-exo-miR-18a-5p. In conclusion, our study indicates that CAFs-mediated exosome miR-18a-5p promotes the initiation and development of CC by suppressing TMEM170B signaling axis, which provides a possible direction for the diagnosis and therapy of CC.


Asunto(s)
Fibroblastos Asociados al Cáncer , Exosomas , MicroARNs , Neoplasias del Cuello Uterino , Humanos , Animales , Femenino , Exosomas/genética , Exosomas/metabolismo , Neoplasias del Cuello Uterino/patología , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Fibroblastos/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral
4.
Plant Biotechnol J ; 22(5): 1325-1334, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38213067

RESUMEN

Cytoplasmic male sterility (CMS), encoded by the mitochondrial open reading frames (ORFs), has long been used to economically produce crop hybrids. However, the utilization of CMS also hinders the exploitation of sterility and fertility variation in the absence of a restorer line, which in turn narrows the genetic background and reduces biodiversity. Here, we used a mitochondrial targeted transcription activator-like effector nuclease (mitoTALENs) to knock out ORF138 from the Ogura CMS broccoli hybrid. The knockout was confirmed by the amplification and re-sequencing read mapping to the mitochondrial genome. As a result, knockout of ORF138 restored the fertility of the CMS hybrid, and simultaneously manifested a cold-sensitive male sterility. ORF138 depletion is stably inherited to the next generation, allowing for direct use in the breeding process. In addition, we proposed a highly reliable and cost-effective toolkit to accelerate the life cycle of fertile lines from CMS-derived broccoli hybrids. By applying the k-mean clustering and interaction network analysis, we identified the central gene networks involved in the fertility restoration and cold-sensitive male sterility. Our study enables mitochondrial genome editing via mitoTALENs in Brassicaceae vegetable crops and provides evidence that the sex production machinery and its temperature-responsive ability are regulated by the mitochondria.


Asunto(s)
Brassica , Infertilidad Masculina , Masculino , Humanos , Brassica/genética , Nucleasas de los Efectores Tipo Activadores de la Transcripción , Fitomejoramiento , Mitocondrias/genética , Fertilidad/genética , Infertilidad Vegetal/genética
5.
Cancer Control ; 31: 10732748241255535, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38773761

RESUMEN

The current standard treatment for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) comprises concurrent radiotherapy (CRT) alongside platinum-based chemotherapy. However, innovative therapeutic alternatives are being evaluated in phase II/III randomized trials. This study employed a Bayesian network meta-analysis (NMA) using fixed effects to provide both direct and indirect comparisons of all existing treatment modalities for unresectable LASCCHN. METHODS: We referenced randomized controlled trials (RCTs) from January 2000 to July 2023 by extensively reviewing PubMed, EMBASE, and Web of Science databases, adhering to the Cochrane methodology. Relevant data, including summary estimates of overall survival (OS) and progression-free survival (PFS), were extracted from these selected studies and recorded in a predefined database sheet. Subsequently, we conducted a random effects network meta-analysis using a Bayesian framework. RESULTS: Based on the Surface Under the Cumulative Ranking (SUCRA) values, the league table organizes the various treatments for OS in the following order: IC + RT&MTT, MTT-CRT, IC + CRT&MTT, CRT, IC + CRT, MTT-RT, IC + MTT-RT, and RT. In a similar order, the treatments rank as follows according to the league table: IC + CRT&MTT, MTT-CRT, IC + CRT, IC + RT&MTT, CRT, IC + MTT-RT, MTT-RT, and RT. Notably, none of these treatments showed significant advantages over concurrent chemoradiotherapy. CONCLUSION: Despite concurrent chemoradiotherapy being the prevailing treatment for LASCCHN, our findings suggest the potential for improved outcomes when concurrent chemoradiotherapy is combined with targeted therapy or induction chemotherapy.


The current standard treatment for advanced head and neck cancer involves combining radiation therapy with chemotherapy. However, there are ongoing trials exploring alternative therapies. In this study, we conducted a comprehensive analysis of existing treatments using a statistical method called network meta-analysis. Our analysis included data from randomized controlled trials published between January 2000 and July 2023. We focused on overall survival and progression-free survival as key outcome measures. The results of our analysis showed that none of the alternative treatments demonstrated significant advantages over the standard concurrent chemoradiotherapy. Nevertheless, there is potential for improved outcomes when targeted therapy or induction chemotherapy is combined with concurrent chemoradiotherapy.


Asunto(s)
Neoplasias de Cabeza y Cuello , Metaanálisis en Red , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Quimioradioterapia/métodos , Teorema de Bayes , Ensayos Clínicos Controlados Aleatorios como Asunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
6.
Inorg Chem ; 63(8): 3835-3842, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38349821

RESUMEN

Optical thermometry has gained significant attention due to its remarkable sensitivity and noninvasive, rapid response to temperature changes. However, achieving both high absolute and relative temperature sensitivity in two-dimensional perovskites presents a substantial challenge. Here, we propose a novel approach to address this issue by designing and synthesizing a new narrow-band blue light-emitting two-dimensional perovskite named (C8H12NO2)2PbBr4 using a straightforward solution-based method. Under excitation of near-ultraviolet light, (C8H12NO2)2PbBr4 shows an ultranarrow emission band with the full width at half-maximum (FWHM) of only 19 nm. Furthermore, its luminescence property can be efficiently tuned by incorporating energy transfer from host excitons to Mn2+. This energy transfer leads to dual emission, encompassing both blue and orange emissions, with an impressive energy transfer efficiency of 38.3%. Additionally, we investigated the temperature-dependent fluorescence intensity ratio between blue emission of (C8H12NO2)2PbBr4 and orange emission of Mn2+. Remarkably, (C8H12NO2)2PbBr4:Mn2+ exhibited maximum absolute sensitivity and relative sensitivity values of 0.055 K-1 and 3.207% K-1, respectively, within the temperature range of 80-360 K. This work highlights the potential of (C8H12NO2)2PbBr4:Mn2+ as a promising candidate for optical thermometry sensor application. Moreover, our findings provide valuable insights into the design of narrow-band blue light-emitting perovskites, enabling the achievement of single-component dual emission in optical thermometry sensors.

7.
Inorg Chem ; 63(25): 11708-11715, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38865675

RESUMEN

Mixed-dimensional perovskite (MDP) heterostructures are promising optoelectronic semiconductors. Yet, the current preparation methods involve complex experimental procedures and material compatibility constraints, limiting their widespread applications. Here, we present a one-step room temperature solution-based approach to synthesize a range of 1D C4N2H14PbBr4 and 3D APbBr3 (A = Cs+, MA+, FA+) self-assembled MDP heterostructures exhibiting high-efficiency white light-emitting properties. The ultra-broadband emission results from the synergy between the self-captured blue broadband emission from 1D perovskites and the green emission of 3D perovskites, covering the entire visible-light spectrum with a full width at half-maximum exceeding 170 nm and a remarkable photoluminescence quantum yield of 26%. This work establishes a novel prototype for the preparation of highly luminescent MDP heterostructures, offering insights for future research and industrialization in the realm of white light LEDs.

8.
J Fluoresc ; 34(2): 765-774, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37358758

RESUMEN

Sensitive and convenient strategy of tyrosinase (TYR) and its inhibitor atrazine is in pressing demand for essential research as well as pragmatic application. In this work, an exquisite label-free fluorometric assay with high sensitivity, convenience and efficiency was described for detecting TYR and the herbicide atrazine on the basis of fluorescent nitrogen-doped carbon dots (CDs). The CDs were prepared via one-pot hydrothermal reaction starting from citric acid and diethylenetriamine. TYR catalyzed the oxidation of dopamine to dopaquinone derivative which could quench the fluorescence of CDs through a fluorescence resonance energy transfer (FRET) process. Thus, a sensitive and selective quantitative evaluation of TYR can be constructed on the basis of the relationship between the fluorescence of CDs and TYR activity. Atrazine, a typical inhibitor of TYR, inhibited the catalytic activity of TYR, leading to the reduced dopaquinone and the fluorescence was retained. The strategy covered a broad linear range of 0.1-150 U/mL and 4.0-80.0 nM for TYR and atrazine respectively with a low detection limit of 0.02 U/mL and 2.4 nM/mL. It is also demonstrated that the assay can be applied to detect TYR and atrazine in spiked complex real samples, which provides infinite potential in application of disease monitoring along with environmental analysis.


Asunto(s)
Atrazina , Dihidroxifenilalanina/análogos & derivados , Puntos Cuánticos , Monofenol Monooxigenasa/análisis , Carbono , Atrazina/análisis , Benzoquinonas , Colorantes Fluorescentes , Nitrógeno
9.
J Plant Res ; 137(2): 241-254, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38194204

RESUMEN

'Red Meat Honey Crisp (RMHC)' has been widely cultivated by growers in recent years due to its early maturity, and red meat type characteristics. As a bud variant of 'Super Red (SR)' peach, red flesh is the most distinctive characteristic of 'Red Meat Honey Crisp (RMHC)'. However, the mechanism of red flesh formation in 'RMHC' remains unclear. In this study, 79 differentially produced metabolites were identified by metabolomics analysis. The anthocyanin content in 'RMHC' was significantly higher than that in 'SR' during the same period, such as cyanidin O-syringic acid and cyanidin 3-O-glucoside. Other flavonoids also increased during the formation of red flesh, including flavonols (6-hydroxykaempferol-7-O-glucoside, hyperin), flavanols (protocatechuic acid, (+)-gallocatechin), and flavonoids (chrysoeriol 5-O-hexoside, tricetin). In addition, transcriptomic analysis and RT-qPCR showed that the expression levels of the flavonoid synthesis pathway transcription factor MYB75 and some structural genes, such as PpDFR, PpCHS, PpC4H, and PpLDOX increased significantly in 'RMHC'. Subcellular localization analysis revealed that MYB75 was localized to the nucleus. Yeast single hybridization assays showed that MYB75 bound to the cis-acting element CCGTTG of the PpDFR promoter region. The MYB75-PpDFR regulatory network was identified to be a key pathway in the reddening of 'RMHC' flesh. Moreover, this is the first study to describe the cause for red meat reddening in 'RMHC' compared to 'SR' peaches using transcriptomics, metabolomics and molecular methods. Our study identified a key transcription factor involved in the regulation of the flavonoid synthetic pathway and contributes to peach breeding-related efforts as well as the identification of genes involved in color formation in other species.


Asunto(s)
Miel , Prunus persica , Prunus persica/genética , Prunus persica/metabolismo , Antocianinas/metabolismo , Flavonoides/metabolismo , Perfilación de la Expresión Génica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas
10.
BMC Public Health ; 24(1): 1314, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750484

RESUMEN

BACKGROUND: Medical students are known to be at a greater risk of psychological disorders compared to the general population. However, their rate of help-seeking behavior is low. The purpose of this study was to explore the influencing factors of attitudes towards psychological help-seeking among Chinese medical students and to examine its gender differences. METHODS: A total of 3,453 medical students from three medical colleges in Hainan Province, China, completed anonymous questionnaires that included socio-demographic attributes, the Family APGAR Index, the General Health Questionnaire (GHQ-20), and the Attitudes Towards Seeking Professional Psychological Help Short Form (ATSPPH-SF). Associations between predictor variables and attitudes towards help-seeking were explored using multivariate linear regression, and regression models with interaction terms were employed to test gender difference. RESULTS: The mean score on ATSPPH-SF Scale was 15.04 ± 3.45, with males scoring significantly lower than females (14.34 vs. 15.64, P < 0.0001). For both male and female groups, psych knowledge, mental health status, family function and help-seeking utility perception significantly influenced attitudes toward psychological help-seeking. Furthermore, having more than once psycho-help experiences was positively correlated with women's attitudes. Significant interactions were found between gender and mental health status. CONCLUSION: Attitude towards seeking psychological help was relatively negative among Chinese medical students. The implementation of interventions should take into account the at-risk population, especially the males and individuals with poor mental health.


Asunto(s)
Estudiantes de Medicina , Humanos , Femenino , Estudiantes de Medicina/psicología , Estudiantes de Medicina/estadística & datos numéricos , Masculino , China , Factores Sexuales , Adulto Joven , Encuestas y Cuestionarios , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Adulto , Conducta de Búsqueda de Ayuda , Trastornos Mentales/psicología , Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Pueblos del Este de Asia
11.
Chem Soc Rev ; 52(1): 212-247, 2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36468561

RESUMEN

Recently, halide perovskites (HPs) and layered two-dimensional (2D) materials have received significant attention from industry and academia alike. HPs are emerging materials that have exciting photoelectric properties, such as a high absorption coefficient, rapid carrier mobility and high photoluminescence quantum yields, making them excellent candidates for various optoelectronic applications. 2D materials possess confined carrier mobility in 2D planes and are widely employed in nanostructures to achieve interfacial modification. HP/2D material interfaces could potentially reveal unprecedented interfacial properties, including light absorbance with desired spectral overlap, tunable carrier dynamics and modified stability, which may lead to several practical applications. In this review, we attempt to provide a comprehensive perspective on the development of interfacial engineering of HP/2D material interfaces. Specifically, we highlight the recent progress in HP/2D material interfaces considering their architectures, electronic energetics tuning and interfacial properties, discuss the potential applications of these interfaces and analyze the challenges and future research directions of interfacial engineering of HP/2D material interfaces. This review links the fields of HPs and 2D materials through interfacial engineering to provide insights into future innovations and their great potential applications in optoelectronic devices.

12.
J Environ Manage ; 365: 121618, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943747

RESUMEN

Transboundary lakes are shared by multiple administrative regions. The key to balance the development and protection of transboundary lakes is to properly measure the value of water resources. Most of previous studies on the measurement of lake water resources value have not fully considered the ecosystem service function. This paper proposes a new concept "composite water value" to measure the value of transboundary lakes by integrating the external runoff value and the internal runoff value of water resources. The study constructs a composite water value measurement system for transboundary lakes, further analyzes its influencing factors,and applies the system to the case of Nansi Lake, a representative transboundary lake in eastern China. The results show that: (1) The composite water value of lakes is influenced by various factors, including industrial structure, water withdrawal, and water use methods, which impact the external runoff water value; meanwhile, the composite water quality and fluctuations in lake level are closely associated with the internal runoff water value. From 2008 to 2021, the average annual composite water value of Nansi Lake was 39.628 billion yuan, exhibiting a "rising-falling-fluctuating rising" trend due to pollution control policies, reduced precipitation, and enhanced water-saving technologies successively. (2) From a long-term perspective, it is necessary to focus on the internal runoff water use value of lakes. The internal runoff water value of Nansi Lake has been over 75% of the composite water value, and flood storage and water conservation are important manifestations of its ecosystem service value. (3) The external runoff water value of lake is closely related to the internal runoff water value, and relevant departments need to consider the balance between the water withdrawal of multiple cities along the lake and the retained water volume of the lake to achieve the maximum benefit of composite water value.

13.
J Cell Mol Med ; 27(23): 3692-3705, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37830980

RESUMEN

Perineural invasion (PNI) has emerged as a key pathological feature and be considered as a poor prognostic factor in cervical cancer. However, the underlying molecular mechanisms are largely unknown. Here, PNI status of 269 cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) samples were quantified by using whole-slide diagnostic images obtained from The Cancer Genome Atlas. Integrated analyses revealed that PNI was an indicative marker of poorer disease-free survival for CESC patients. Among the differentially expressed genes, ADCYAP1 were identified. Clinical specimens supported that high expression of PACAP (encoded by ADCYAP1) contributed to PNI in CESC. Mechanistically, PACAP, secreted from cervical cancer cells, reversed myelin differentiation of Schwann cells (SCs). Then, dedifferentiated SCs promoted PNI by producing chemokine FGF17 and by degrading extracellular matrix through secretion of Cathepsin S and MMP-12. In conclusion, this study identified PACAP was associated with PNI in cervical cancer and suggested that tumour-derived PACAP reversed myelin differentiation of SCs to aid PNI.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Femenino , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Diferenciación Celular , Invasividad Neoplásica/patología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/genética , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Células de Schwann/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Comunicación Paracrina/genética
14.
Cancer Sci ; 114(5): 1958-1971, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36692137

RESUMEN

As one of the common malignant cancer types, gastric cancer (GC) is known for late-stage diagnosis and poor prognosis. Overexpression of the receptor tyrosine kinase MET is associated with poor prognosis among patients with advanced stage GC. However, no MET inhibitor has been used for GC treatment. Like other tyrosine kinase inhibitors that fit the "occupancy-driven" model, current MET inhibitors are prone to acquired resistance. The emerging proteolysis targeting chimera (PROTAC) strategy could overcome such limitations through direct degradation of the target proteins. In this study, we successfully transformed the MET-targeted inhibitor crizotinib into a series of PROTACs, recruiting cereblon/cullin 4A E3 ubiquitin ligase to degrade the MET proteins. The optimized lead PROTAC (PRO-6 E) effectively eliminated MET proteins in vitro and in vivo, inhibiting proliferation and motility of MET-positive GC cells. In the MKN-45 xenograft model, PRO-6 E showed pronounced antitumor efficacy with a well-tolerated dosage regimen. These results validated PRO-6 E as the first oral PROTAC for MET-dependent GC.


Asunto(s)
Neoplasias Gástricas , Humanos , Crizotinib/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteolisis , Quimera Dirigida a la Proteólisis , Neoplasias Gástricas/tratamiento farmacológico , Ubiquitina-Proteína Ligasas/metabolismo
15.
Opt Lett ; 48(13): 3415-3418, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37390144

RESUMEN

The cutting-edge imaging system exhibits low output resolution and high power consumption, presenting challenges for the RGB-D fusion algorithm. In practical scenarios, aligning the depth map resolution with the RGB image sensor is a crucial requirement. In this Letter, the software and hardware co-design is considered to implement a lidar system based on the monocular RGB 3D imaging algorithm. A 6.4 × 6.4-mm2 deep-learning accelerator (DLA) system-on-chip (SoC) manufactured in a 40-nm CMOS is incorporated with a 3.6-mm2 TX-RX integrated chip fabricated in a 180-nm CMOS to employ the customized single-pixel imaging neural network. In comparison to the RGB-only monocular depth estimation technique, the root mean square error is reduced from 0.48 m to 0.3 m on the evaluated dataset, and the output depth map resolution matches the RGB input.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Diseño de Equipo , Imagenología Tridimensional
16.
Cell Mol Biol (Noisy-le-grand) ; 69(13): 203-209, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38158665

RESUMEN

Ferroptosis is a new form of cell death that is unique and closely related to iron concentration, and reactive oxygen species (ROS) production. We investigated the indicators of ferroptosis between vulnerable plaque and stable plaque in atherosclerotic. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the expression of the ferroptosis-related genes and proteins and extracellular matrix stability-related genes and proteins (FN, CoL-1). Superoxide dismutase (SOD) activities, glutathione peroxidase (GSH) and malondialdehyde (MDA) were detected by ELISA. The commercially available kit was used to detect Fe2+ concentration in tissue. DCFH-DA fluorescent probe was used to detect the ROS levels. H&E stain, Masson trichrome stain, and Oil Red O stain were used to detect pathological states in vulnerable plaque and stable plaque. Tissue localization and positive rate of GPX4, SLC7A11, COX-2, FN, and COL-1 were evaluated by immunohistochemistry. The results showed a significant increase in the expression of COX2 and a significant decrease in the expression of GPX4 and SLC7A11 in genes related to ferroptosis in vulnerable plaque compared with stable plaque. Pathologic results showed vulnerable plaque with higher levels of inflammatory cell infiltration, more diffuse collagen fibers, and larger particles of lipid droplets. Concentrations of the antioxidant metabolites SOD and GSH were significantly reduced and concentrations of the oxidative metabolites MDA and Fe2+ were significantly increased in vulnerable plaque compared with stable plaque. The expression of FN and CoL-1 was significantly reduced in genes related to extracellular matrix stability in vulnerable plaque. Taken together, these findings indicate that the degree of ferroptosis in vulnerable plaque is higher than that in stable plaque, suggesting that changes in indicators of ferroptosis may affect carotid atherosclerotic plaque stability, target spot in the ferroptosis signaling pathway may provide further theoretical basis for the clinical treatment of carotid atherosclerosis.


Asunto(s)
Ferroptosis , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/genética , Ferroptosis/genética , Especies Reactivas de Oxígeno , Glutatión Peroxidasa/genética , Anticuerpos Monoclonales , Superóxido Dismutasa/genética
17.
J Nanobiotechnology ; 21(1): 344, 2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37741962

RESUMEN

Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Síndrome del Colon Irritable , Humanos , Animales , Ratones , Microesferas , Fermentación , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mesalamina , Alginatos , Fibras de la Dieta
18.
Appl Opt ; 62(17): 4673-4680, 2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37707165

RESUMEN

High-precision and high-sensitivity vibration acceleration sensors have been a research hotspot in engineering technology, which play an important role in engineering structural health monitoring, earthquakes, tsunamis, and geological exploration. A novel, to the best of our knowledge, fiber Bragg grating (FBG) acceleration sensor incorporating a mass block and flexible hinge was proposed against the low sensitivity and poor transverse interference resistance of existing FBG acceleration sensors. The FBG accelerometer with the multi-stage flexible hinge was modeled and theoretically analyzed, the structural parameters of the sensor were optimized and actual sensors were developed, and a sensor performance test experiment was carried out in the end. The result suggested that the sensor's natural frequency was as high as 1400 Hz, and its response was flat in the frequency range of 50-800 Hz; its sensitivity was 18.4 pm/g, linearity R 2 was 0.9983, and transverse interference immunity was below 3.2%. The research findings offered a new way of thinking about high-precision and high-sensitivity vibration measurement in engineering technology.

19.
Langenbecks Arch Surg ; 408(1): 322, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37594605

RESUMEN

PURPOSE: Anastomotic leakage (AL) is a common postoperative complication of rectal cancer, with an incidence of about 10%, and the efficacy of reinforced sutures for preventing AL remains contentious. This study investigated the safety and effectiveness of reinforcement sutures for preventing AL after rectal cancer surgery. METHODS: The present authors conducted a systematic search in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, Wanfang, VIP, and CNKI databases for randomized controlled trials (RCTs) and nonrandomized studies up to June 2023. We performed a meta-analysis to evaluate the efficacy of anastomotic reinforcement sutures after rectal cancer surgery. The primary outcome measures were AL, anastomotic bleeding, and infection rates. RESULTS: Eleven articles (1921 subjects) were analyzed, with 912 and 1009 cases in the reinforced and unreinforced suture groups, respectively. The reinforced suture group showed a lower AL incidence (odds ratio [OR]=0.25, 95% CI 0.17-0.37, P< 0.00001), lower infection rate (OR=0.41, 95%CI 0.19-0.89, P<0.05), shorter hospital stay (mean difference [MD]=-0.57, 95%CI -1.15-0.00, P≤0.05), and earlier anal exhaust (MD=-0.12, 95%CI -0.23-0.00, P<0.05). However, the operative time (MD=18.25, 95% CI 12.20-24.30, P<0.00001) was longer for reinforced sutures than for unreinforced sutures. There were no significant differences between the suture techniques in intraoperative blood loss MD=2.74, 95% CI -4.50-9.97, P>0.05), incidence of anastomotic bleeding (OR=0.49, 95%CI 0.12-1.97, P>0.05), and incidence of intestinal obstruction (OR=0.65, 95%CI 0.27-1.61, P>0.05). CONCLUSION: Existing articles indicate that anastomotic reinforcement sutures can significantly reduce AL incidence. However, this conclusion still requires confirmation based on multicentre, high-quality RCTs with large sample sizes.


Asunto(s)
Fuga Anastomótica , Neoplasias del Recto , Humanos , Fuga Anastomótica/epidemiología , Fuga Anastomótica/etiología , Fuga Anastomótica/prevención & control , Anastomosis Quirúrgica/efectos adversos , Neoplasias del Recto/cirugía , Suturas , Resultado del Tratamiento
20.
J Environ Manage ; 344: 118401, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37364487

RESUMEN

As the requirements for environmental protection and high-efficiency economies increase, grain production (GP) across the globe faces more stringent ecological constraints and economic pressure. Understanding the relationships between natural resources and economic and agricultural factors in grain-producing regions is paramount for ensuring global food security. This paper proposes a methodological framework to explore the relationships between water and soil resources (WSRs), economic input factors (EIFs), and GP. We employed the northeast region of China as a case study to advance our understanding of the factors driving the development of grain-producing capacity. We first constructed and calculated the region's water and soil comprehensive index (WSCI) to describe water-soil properties. We then used hotspot analysis to explore the spatial agglomeration characteristics of WSRs, EIFs, and GP. Finally, we used threshold regression analysis to understand the effects of EIFs and GP with the WSCI as the threshold variable. With the improvement of the WSCI, the positive impact of fertilizer and irrigation on GP shows a U-shaped curve in elasticity coefficients. The positive effect of agricultural machinery on GP decreases significantly, and the impact of labor input on GP is insignificant. These results provide new insights into the relationship between WSRs, EIFs, and GP and a reference for improving GP efficiency globally. This work thus contributes to advancing our capabilities to enable food security while considering aspects of sustainable agriculture in important grain-producing regions across the globe.


Asunto(s)
Suelo , Agua , Agricultura , Grano Comestible , Conservación de los Recursos Naturales/métodos , China , Recursos Hídricos
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