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1.
Microsc Res Tech ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39351968

RESUMEN

Lymph-node status is important in decision-making during early gastric cancer (EGC) treatment. Currently, endoscopic submucosal dissection is the mainstream treatment for EGC. However, it is challenging for even experienced endoscopists to accurately diagnose and treat EGC. Multiphoton microscopy can extract the morphological features of collagen fibers from tissues. The characteristics of collagen fibers can be used to assess the lymph-node metastasis status in patients with EGC. First, we compared the accuracy of four deep learning models (VGG16, ResNet34, MobileNetV2, and PVTv2) in training preprocessed images and test datasets. Next, we integrated the features of the best-performing model, which was PVTv2, with manual and clinical features to develop a novel model called AutoLNMNet. The prediction accuracy of AutoLNMNet for the no metastasis (Ly0) and metastasis in lymph nodes (Ly1) stages reached 0.92, which was 0.3% higher than that of PVTv2. The receiver operating characteristics of AutoLNMNet in quantifying Ly0 and Ly1 stages were 0.97 and 0.97, respectively. Therefore, AutoLNMNet is highly reliable and accurate in detecting lymph-node metastasis, providing an important tool for the early diagnosis and treatment of EGC.

2.
Plant J ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240190

RESUMEN

The lenticel is a channel-like structure that facilitates oxygen, carbon dioxide, and water vapor exchange on secondary growth tissue, such as a tree stem. Although the structure of lenticel has been described, there is limited understanding regarding the impact of this secondary structure on secondary growth as well as the cellular and metabolic processes underlying its formation. The study reveals the essential role of the lenticel in the process of tree secondary growth and the cellular and metabolic processes that take place during its formation. Under the stomata, lenticel development occurs when cells divide and differentiate into a structure of disconnected cells with air spaces between them. During lenticel formation, specific metabolic pathways and wax biosynthesis are activated. The SERK (somatic embryogenesis receptor kinase) gene controls lenticel density, and serk1serk3serk5 triple mutants enhance lenticel initiation. The findings shed light on the cellular and metabolic processes involved in lenticel formation, laying the groundwork for further mechanistic elucidation of their development, function, and genetic regulation in trees.

3.
Heliyon ; 10(18): e37736, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39315160

RESUMEN

In recent years, there has been a significant increase in the release of cadmium-containing pollutants into the environment from mining, industrial emissions, wastewater irrigation and the use of chemical fertilizers and pesticides. This leads to the degradation of soil quality and poses a threat to human health. Chemical leaching remediation technology is an effective method for controlling Cd contamination in soil. However, the leaching agent has a low removal efficiency of heavy metals. In order to find more suitable environmentally friendly new leaching agents, this study investigates the effects of three biodegradable chelating agents PMAS, EDTMPS and GLDA on the removal of heavy metal Cd in soil in the single factor soil leaching experiment. The concentration of the chelating agents, the leaching time and the pH of the leaching solution were varied to study their effects. The Box-Behnken (BBD) effect based on RSM was used to design the experimental conditions to optimize the leaching process of three biodegradable chelating agents. The optimum conditions for Cd removal by PMAS, EDTMPS and GLDA were obtained as follows: concentration 7 %, pH = 3.61, reaction time 180 min; concentration 4.94 %, pH = 3.0, reaction time 180 min; and concentration 4.96 %, pH = 3.0, reaction time 180 min. The validation test results showed that the deviation from the experimental value is less than 3 % under the theoretically optimal washing conditions, confirming the reliability and accuracy of the response surface methodology optimization process, which provides a reference for the development of efficient, environmentally friendly and low-cost leaching agents.

4.
Chem Sci ; 15(30): 12017-12025, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39092128

RESUMEN

Herein, we present an attractive organocatalytic asymmetric addition of P-nucleophiles to five-membered cyclic N-sulfonyl imines facilitated by phosphonium salt catalysis, enabling the highly enantioselective synthesis of tri- and tetra-substituted cyclic phosphorus-containing benzosultams. With this protocol, various cyclic α-aminophosphonates were efficiently synthesized with high yields and exceptional enantioselectivities (up to >99% ee) under mild reaction conditions. The utility and practicality of this method were demonstrated through gram-scale reactions and straightforward elaborations. Notably, the success of this approach relies on the deliberate selection of a synergistic organocatalytic system, which helps circumvent foreseeable side effects while handling secondary phosphine oxides (SPOs). Systematic mechanistic studies, incorporating experiments and DFT calculations, have revealed the critical importance of judiciously selecting bifunctional phosphonium salt catalysts for effectively activating P-nucleophiles while stereoselectively controlling the P-attack process.

5.
PLoS One ; 19(7): e0306892, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39008494

RESUMEN

Accurately predicting traffic flow is crucial for optimizing traffic conditions, reducing congestion, and improving travel efficiency. To explore spatiotemporal characteristics of traffic flow in depth, this study proposes the MFSTBiSGAT model. The MFSTBiSGAT model leverages graph attention networks to extract dynamic spatial features from complex road networks, and utilizes bidirectional long short-term memory networks to capture temporal correlations from both past and future time perspectives. Additionally, spatial and temporal information enhancement layers are employed to comprehensively capture traffic flow patterns. The model aims to directly extract original temporal features from traffic flow data, and utilizes the Spearman function to extract hidden spatial matrices of road networks for deeper insights into spatiotemporal characteristics. Historical traffic speed and lane occupancy data are integrated into the prediction model to reduce forecasting errors and enhance robustness. Experimental results on two real-world traffic datasets demonstrate that MFSTBiSGAT successfully extracts and captures spatiotemporal correlations in traffic networks, significantly improving prediction accuracy.


Asunto(s)
Análisis Espacio-Temporal , Humanos , Conducción de Automóvil , Modelos Teóricos , Predicción/métodos
6.
J Biophotonics ; 17(9): e202400200, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38955356

RESUMEN

Ovarian cancer is among the most common gynecological cancers and the eighth leading cause of cancer-related deaths among women worldwide. Surgery is among the most important options for cancer treatment. During surgery, a biopsy is generally required to screen for lesions; however, traditional case examinations are time consuming and laborious and require extensive experience and knowledge from pathologists. Therefore, this study proposes a simple, fast, and label-free ovarian cancer diagnosis method that combines second harmonic generation (SHG) imaging and deep learning. Unstained fresh human ovarian tissues were subjected to SHG imaging and accurately characterized using the Pyramid Vision Transformer V2 (PVTv2) model. The results showed that the SHG imaged collagen fibers could quantify ovarian cancer. In addition, the PVTv2 model could accurately differentiate the 3240 SHG images obtained from our imaging collection into benign, normal, and malignant images, with a final accuracy of 98.4%. These results demonstrate the great potential of SHG imaging techniques combined with deep learning models for diagnosing the diseased ovarian tissues.


Asunto(s)
Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/patología , Procesamiento de Imagen Asistido por Computador/métodos , Microscopía de Generación del Segundo Armónico
7.
Inorg Chem ; 63(28): 13031-13038, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38957956

RESUMEN

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

8.
Front Plant Sci ; 15: 1394337, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903430

RESUMEN

Background: Cannabidiol (CBD), as an important therapeutic property of the cannabis plants, is mainly produced in the flower organs. Auxin response factors (ARFs) are play a crucial role in flower development and secondary metabolite production. However, the specific roles of ARF gene family in cannabis remain unknown. Methods: In this study, various bioinformatics analysis of CsARF genes were conducted using online website and bioinformatics, quantitative real time PCR technology was used to investigate the expression patterns of the CsARF gene family in different tissues of different cannabis varieties, and subcellular localization analysis was performed in tobacco leaf. Results: In this study, 22 CsARF genes were identified and found to be unevenly distributed across 9 chromosomes of the cannabis genome. Phylogenetic analysis revealed that the ARF proteins were divided into 4 subgroups. Duplication analysis identified one pair of segmental/whole-genome duplicated CsARF, and three pairs of tandemly duplicated CsARF. Collinearity analysis revealed that two CsARF genes, CsARF4 and CsARF19, were orthologous in both rice and soybean. Furthermore, subcellular localization analysis showed that CsARF2 was localized in the nucleus. Tissue-specific expression analysis revealed that six genes were highly expressed in cannabis male flowers, and among these genes, 3 genes were further found to be highly expressed at different developmental stages of male flowers. Meanwhile, correlation analysis between the expression level of CsARF genes and CBD content in two cultivars 'H8' and 'Y7' showed that the expression level of CsARF13 was negatively correlated with CBD content, while the expression levels of six genes were positively correlated with CBD content. In addition, most of CsARF genes were responsive to IAA treatment. Conclusion: Our study laid a foundation for the further studies of CsARFs function in cannabis, and provides candidate genes for breeding varieties with high CBD yield in cannabis production.

9.
Angew Chem Int Ed Engl ; 63(33): e202407510, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-38774971

RESUMEN

Plastic pollution is an emerging global threat due to lack of effective methods for transforming waste plastics into useful resources. Here, we demonstrate a direct oxidative upcycling of polyethylene into high-value and high-volume saturated dicarboxylic acids in high carbon yield of 85.9 % in which the carbon yield of long chain dicarboxylic (C10-C20) acids can reach 58.9% over cobalt-doped MCM-41 molecular sieves, in the absence of any solvent or precious metal catalyst. The distribution of the dicarboxylic acids can be controllably adjusted from short-chain (C4-C10) to long-chain ones (C10-C20) through changing cobalt loading of MCM-41 under nanoconfinement. Highly and sparsely dispersed cobalt along with confined space of mesoporous structure enables complete degradation of polyethylene and high selectivity of dicarboxylic acid in mild condition. So far, this is the first report on highly selective one-step preparation of long chain dicarboxylic acids. The approach provides an attractive solution to tackle plastic pollution and a promising alternative route to long chain diacids.

10.
Redox Biol ; 73: 103174, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38701646

RESUMEN

Ribosomes mediate protein synthesis, which is one of the most energy-demanding activities within the cell, and mitochondria are one of the main sources generating energy. How mitochondrial morphology and functions are adjusted to cope with ribosomal defects, which can impair protein synthesis and affect cell viability, is poorly understood. Here, we used the fission yeast Schizosaccharomyces Pombe as a model organism to investigate the interplay between ribosome and mitochondria. We found that a ribosomal insult, caused by the absence of Rpl2702, activates a signaling pathway involving Sty1/MAPK and mTOR to modulate mitochondrial morphology and functions. Specifically, we demonstrated that Sty1/MAPK induces mitochondrial fragmentation in a mTOR-independent manner while both Sty1/MAPK and mTOR increases the levels of mitochondrial membrane potential and mitochondrial reactive oxygen species (mROS). Moreover, we demonstrated that Sty1/MAPK acts upstream of Tor1/TORC2 and Tor1/TORC2 and is required to activate Tor2/TORC1. The enhancements of mitochondrial membrane potential and mROS function to promote proliferation of cells bearing ribosomal defects. Hence, our study reveals a previously uncharacterized Sty1/MAPK-mTOR signaling axis that regulates mitochondrial morphology and functions in response to ribosomal insults and provides new insights into the molecular and physiological adaptations of cells to impaired protein synthesis.


Asunto(s)
Potencial de la Membrana Mitocondrial , Mitocondrias , Proteínas Ribosómicas , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Transducción de Señal , Serina-Treonina Quinasas TOR , Serina-Treonina Quinasas TOR/metabolismo , Mitocondrias/metabolismo , Proteínas Ribosómicas/metabolismo , Proteínas Ribosómicas/genética , Schizosaccharomyces/metabolismo , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Ribosomas/metabolismo , Sistema de Señalización de MAP Quinasas
11.
BMC Cancer ; 24(1): 318, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454386

RESUMEN

BACKGROUND: The histological grade is an important factor in the prognosis of invasive breast cancer and is vital to accurately identify the histological grade and reclassify of Grade2 status in breast cancer patients. METHODS: In this study, data were collected from 556 invasive breast cancer patients, and then randomly divided into training cohort (n = 335) and validation cohort (n = 221). All patients were divided into actual low risk group (Grade1) and high risk group (Grade2/3) based on traditional histological grade, and tumor-infiltrating lymphocyte score (TILs-score) obtained from multiphoton images, and the TILs assessment method proposed by International Immuno-Oncology Biomarker Working Group (TILs-WG) were also used to differentiate between high risk group and low risk group of histological grade in patients with invasive breast cancer. Furthermore, TILs-score was used to reclassify Grade2 (G2) into G2 /Low risk and G2/High risk. The coefficients for each TILs in the training cohort were retrieved using ridge regression and TILs-score was created based on the coefficients of the three kinds of TILs. RESULTS: Statistical analysis shows that TILs-score is significantly correlated with histological grade, and is an independent predictor of histological grade (odds ratio [OR], 2.548; 95%CI, 1.648-3.941; P < 0.0001), but TILs-WG is not an independent predictive factor for grade (P > 0.05 in the univariate analysis). Moreover, the risk of G2/High risk group is higher than that of G2/Low risk group, and the survival rate of patients with G2/Low risk is similar to that of Grade1, while the survival rate of patients with G2/High risk is even worse than that of patients with G3. CONCLUSION: Our results suggest that TILs-score can be used to predict the histological grade of breast cancer and potentially to guide the therapeutic management of breast cancer patients.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/patología , Linfocitos Infiltrantes de Tumor/patología , Pronóstico , Distribución Aleatoria
12.
Aging (Albany NY) ; 16(6): 5288-5310, 2024 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-38461439

RESUMEN

INTRODUCTION: Regulatory T cells (Tregs) play important roles in tumor immunosuppression and immune escape. The aim of the present study was to construct a novel Tregs-associated biomarker for the prediction of tumour immune microenvironment (TIME), clinical outcomes, and individualised treatment in hepatocellular carcinoma (HCC). METHODS: Single-cell sequencing data were obtained from the three independent cohorts. Cox and LASSO regression were utilised to develop the Tregs Related Scoring System (TRSSys). GSE140520, ICGC-LIRI and CHCC cohorts were used for the validation of TRSSys. Kaplan-Meier, ROC, and Cox regression were utilised for the evaluation of TRSSys. The ESTIMATE, TIMER 2.0, and ssGSEA algorithm were utilised to determine the value of TRSSys in predicting the TIME. GSVA, GO, KEGG, and TMB analyses were used for mechanistic exploration. Finally, the value of TRSSys in predicting drug sensitivity was evaluated based on the oncoPredict algorithm. RESULTS: Comprehensive validation showed that TRSSys had good prognostic predictive efficacy and applicability. Additionally, ssGSEA, TIMER and ESTIMATE algorithm suggested that TRSSys could help to distinguish different TIME subtypes and determine the beneficiary population of immunotherapy. Finally, the oncoPredict algorithm suggests that TRSSys provides a basis for individualised treatment. CONCLUSIONS: TRSSys constructed in the current study is a novel HCC prognostic prediction biomarker with good predictive efficacy and stability. Additionally, risk stratification based on TRSSys can help to identify the TIME landscape subtypes and provide a basis for individualized treatment options.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Linfocitos T Reguladores , Neoplasias Hepáticas/terapia , Pronóstico , Microambiente Tumoral , Biomarcadores
13.
J Biol Chem ; 300(3): 105754, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38360270

RESUMEN

KDELR (Erd2 [ER retention defective 2] in yeasts) is a receptor protein that retrieves endoplasmic reticulum (ER)-resident proteins from the Golgi apparatus. However, the role of the KDELR-mediated ER-retrieval system in regulating cellular homeostasis remains elusive. Here, we show that the absence of Erd2 triggers the unfolded protein response (UPR) and enhances mitochondrial respiration and reactive oxygen species in an UPR-dependent manner in the fission yeast Schizosaccharomyces pombe. Moreover, we perform transcriptomic analysis and find that the expression of genes related to mitochondrial respiration and the tricarboxylic acid cycle is upregulated in a UPR-dependent manner in cells lacking Erd2. The increased mitochondrial respiration and reactive oxygen species production is required for cell survival in the absence of Erd2. Therefore, our findings reveal a novel role of the KDELR-Erd2-mediated ER-retrieval system in modulating mitochondrial functions and highlight its importance for cellular homeostasis in the fission yeast.


Asunto(s)
Retículo Endoplásmico , Mitocondrias , Schizosaccharomyces , Respuesta de Proteína Desplegada , Retículo Endoplásmico/genética , Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico , Mitocondrias/genética , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo
14.
Biochem Soc Trans ; 52(1): 99-110, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38288744

RESUMEN

Mitochondria are the powerhouse of the cell. They undergo fission and fusion to maintain cellular homeostasis. In this review, we explore the intricate regulation of mitochondrial fission at various levels, including the protein level, the post-translational modification level, and the organelle level. Malfunctions in mitochondrial fission can have detrimental effects on cells. Therefore, we also examine the association between mitochondrial fission with diseases such as breast cancer and cardiovascular disorders. We anticipate that a comprehensive investigation into the control of mitochondrial fission will pave the way for the development of innovative therapeutic strategies.


Asunto(s)
Enfermedades Cardiovasculares , Dinámicas Mitocondriales , Humanos , Dinámicas Mitocondriales/fisiología , Mitocondrias/metabolismo , Procesamiento Proteico-Postraduccional , Enfermedades Cardiovasculares/metabolismo , Proteínas Mitocondriales/metabolismo
15.
Angew Chem Int Ed Engl ; 62(49): e202309515, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-37845782

RESUMEN

The catalytic asymmetric synthesis of phosphorus-containing helicenes remains a formidable challenge, presumably due to the lack of rational design of substrates, right choice of reactions together with highly effective catalysis systems. Herein, we disclosed an efficient and practical DKR-involving (dynamic kinetic resolution) cascade strategy toward synthesizing a novel family of phosphorus-installing helicenes by peptide-mimic phosphonium salt (PPS) catalysis. The sequential process of PPS-catalyzed phospha-Michael attack and copper salt-facilitated aromatization led to the formation of unprecedented phosphorus-containing oxa[5]helicene scaffolds. A wide variety of substrates bearing an assortment of functional groups were compatible with this protocol, furnishing the expected helical compounds in high yields and excellent stereoselectivities. Additionally, the helical products could be conveniently elaborated to promising phosphine ligands with perfectly retained helical chirality, which turned out to be highly efficient chiral ligands in transition metal-catalyzed reactions. These findings not only expand the current library of phosphorus-containing helicenes but also offer insights to explore other challenging scaffolds with molecular chirality.

16.
Front Pediatr ; 11: 1165477, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37547102

RESUMEN

Background: Birth defects (BDs) are associated with many potential risk factors, and its causes are complex. Objectives: This study aimed to explore the epidemiological characteristics of BDs in Guangxi of China and the associated risk factors of BDs. Methods: BDs data of perinatal infants (PIs) were obtained from the Guangxi birth defects monitoring network between 2016 and 2020. Univariate Poisson regression was used to calculate the prevalence-rate ratios (PRR) to explore the changing trends of BDs prevalence by year and the correlation between the regarding of characteristics of BDs (including infant gender, maternal age, and quarter) and BDs. Clinical characteristics of PIs with BDs and general characteristics of their mothers were documented, and Spearman correlation analysis was used to explore the potential associated risk factors of BDs. Results: Between 2016 and 2020, 44,146 PIs with BDs were monitored, with an overall BDs prevalence of 121.71 (95% CI: 120.58-122.84) per 10,000 PIs, showing a significant increase trend (PRR = 1.116, 95% CI: 1.108-1.123), especially the prevalence of congenital heart defects (CHDs) that most significantly increased (PRR = 1.300, 95% CI: 1.283-1.318). The 10 most common BDs were CHDs, polydactyly, congenital talipes equinovarus, other malformation of external ear, syndactyly, hypospadias, cleft lip with cleft palate, cleft lip, hemoglobin Bart's hydrops fetalis syndrome (BHFS), and congenital atresia of the rectum and anus. BDs were positively correlated with pregnant women's age (R = 0.732, P < 0.01) and education level (R = 0.586, P < 0.05) and having pre-gestational diabetes mellitus (PGDM)/gestational diabetes mellitus (GDM) (R = 0.711, P < 0.01), while when the pregnant women had a family history of a dead fetus (R = -0.536, P < 0.05) and a birth of a fetus with BDs (R = -0.528, P < 0.05) were negatively correlated with BDs. Conclusion: A significant increase in the prevalence of BDs was detected between 2016 and 2020 in Guangxi, especially the prevalence of CHDs that most significantly increased. Older maternal age, higher maternal education level, and having PGDM before pregnancy or GDM in early pregnancy were the risk factors for BDs.

17.
Nat Commun ; 14(1): 5050, 2023 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-37598233

RESUMEN

The precise and efficient construction of axially chiral scaffolds, particularly toward the aryl-alkene atropoisomers with impeccably full enantiocontrol and highly structural diversity, remains greatly challenging. Herein, we disclose an organocatalytic asymmetric nucleophilic aromatic substitution (SNAr) reaction of aldehyde-substituted styrenes involving a dynamic kinetic resolution process via a hemiacetal intermediate, offering a novel and facile way to significant axial styrene scaffolds. Upon treatment of the aldehyde-containing styrenes bearing (o-hydroxyl)aryl unit with commonly available fluoroarenes in the presence of chiral peptide-phosphonium salts, the SNAr reaction via an exquisite bridged biaryl lactol intermediate undergoes smoothly to furnish a series of axially chiral aldehyde-containing styrenes decorated with various functionalities and bioactive fragments in high stereoselectivities (up to >99% ee) and complete E/Z selectivities. These resulting structural motifs are important building blocks for the preparation of diverse functionalized axial styrenes, which have great potential as efficient and privileged chiral ligands/catalysts in asymmetric synthesis.

18.
PLoS Biol ; 21(8): e3002247, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37590302

RESUMEN

Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) and Mdv1 (the bridging protein between Fis1 and Dnm1), from mitochondria and reduces the localization of Dnm1 to mitochondria. The effect of Yta4 overexpression on Fis1 and Mdv1, but not Dnm1, depends on the ATPase and translocase activities of Yta4. Moreover, Yta4 interacts with Dnm1, Mdv1, and Fis1. In addition, Yta4 competes with Dnm1 for binding Mdv1 and decreases the affinity of Dnm1 for GTP and inhibits Dnm1 assembly in vitro. These findings suggest a model, in which Yta4 inhibits mitochondrial fission by inhibiting the function of the mitochondrial divisome composed of Fis1, Mdv1, and Dnm1. Therefore, the present work reveals an uncharacterized molecular mechanism underlying the inhibition of mitochondrial fission.


Asunto(s)
Demencia Frontotemporal , Schizosaccharomyces , Humanos , ATPasas Asociadas con Actividades Celulares Diversas/genética , Dinámicas Mitocondriales , Adenosina Trifosfatasas , Mitocondrias , Schizosaccharomyces/genética
19.
BMC Cancer ; 23(1): 530, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37296414

RESUMEN

BACKGROUND: Tumor necrosis (TN) was associated with poor prognosis. However, the traditional classification of TN ignored spatial intratumor heterogeneity, which may be associated with important prognosis. The purpose of this study was to propose a new method to reveal the hidden prognostic value of spatial heterogeneity of TN in invasive breast cancer (IBC). METHODS: Multiphoton microscopy (MPM) was used to obtain multiphoton images from 471 patients. According to the relative spatial positions of TN, tumor cells, collagen fibers and myoepithelium, four spatial heterogeneities of TN (TN1-4) were defined. Based on the frequency of individual TN, TN-score was obtained to investigate the prognostic value of TN. RESULTS: Patients with high-risk TN had worse 5-year disease-free survival (DFS) than patients with no necrosis (32.5% vs. 64.7%; P < 0.0001 in training set; 45.8% vs. 70.8%; P = 0.017 in validation set), while patients with low-risk TN had a 5-year DFS comparable to patients with no necrosis (60.0% vs. 64.7%; P = 0.497 in training set; 59.8% vs. 70.8%; P = 0.121 in validation set). Furthermore, high-risk TN "up-staged" the patients with IBC. Patients with high-risk TN and stage I tumors had a 5-year DFS comparable to patients with stage II tumors (55.6% vs. 62.0%; P = 0.565 in training set; 62.5% vs. 66.3%; P = 0.856 in validation set), as well as patients with high-risk TN and stage II tumors had a 5-year DFS comparable to patients with stage III tumors (33.3% vs. 24.6%; P = 0.271 in training set; 44.4% vs. 39.3%; P = 0.519 in validation set). CONCLUSIONS: TN-score was an independent prognostic factor for 5-year DFS. Only high-risk TN was associated with poor prognosis. High-risk TN "up-staged" the patients with IBC. Incorporating TN-score into staging category could improve its performance to stratify patients.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Pronóstico , Neoplasias de la Mama/diagnóstico , Estadificación de Neoplasias , Supervivencia sin Enfermedad , Estudios Retrospectivos
20.
Math Biosci Eng ; 20(4): 6498-6516, 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-37161116

RESUMEN

Digital economy is regarded as the main economic form following agricultural economy and industrial economy. And the digital transformation has given enterprises new development momentum. Can it reduce the equity capital cost? This paper uses text analysis obtained by crawling the annual reports from 2010 to 2021 and investigates the impact of digital transformation on the corporate equity capital cost. The results show that: 1) Digital transformation will reduce the equity capital cost; 2) The digital transformation has a heterogeneous impact on the equity capital cost of enterprises with different scales, natures and levels of leverage, which is more significant for large-scale enterprises, state-owned enterprises and highly leveraged enterprises; 3) Digital transformation mainly affects the equity capital cost by improving enterprise value, rather than by increasing analysts' attention and influencing the level of corporate risk bearing.

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