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1.
Neural Regen Res ; 20(1): 6-20, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38767472

RESUMEN

The endoplasmic reticulum, a key cellular organelle, regulates a wide variety of cellular activities. Endoplasmic reticulum autophagy, one of the quality control systems of the endoplasmic reticulum, plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover, remodeling, and proteostasis. In this review, we briefly describe the endoplasmic reticulum quality control system, and subsequently focus on the role of endoplasmic reticulum autophagy, emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements. We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases. In summary, this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders. This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

2.
J Mol Biol ; : 168750, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39173734

RESUMEN

The final step in the de novo synthesis of cytidine 5'-triphosphate (CTP) is catalyzed by CTP synthase (CTPS), which can form cytoophidia in all three domains of life. Recently, we have discovered that CTPS binds to ribonucleotides (NTPs) to form filaments, and have successfully solved the structures of Drosophila melanogaster CTPS bound with NTPs. Previous biochemical studies have shown that CTPS can bind to deoxyribonucleotides (dNTPs) to produce 2'-deoxycytidine-5'-triphosphate (dCTP). However, the structural basis of CTPS binding to dNTPs is still unclear. In this study, we find that Drosophila CTPS can also form filaments with dNTPs. Using cryo-electron microscopy, we are able to solve the structure of Drosophila melanogaster CTPS bound to dNTPs with a resolution of up to 2.7 Å. By combining these structural findings with biochemical analysis, we compare the binding and reaction characteristics of NTPs and dNTPs with CTPS. Our results indicate that the same enzyme can act bifunctionally as CTP/dCTP synthase in vitro, and provide a structural basis for these activities.

4.
Kaohsiung J Med Sci ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177014

RESUMEN

Previous studies have supported a tumor-suppressive role of semaphorin 3A (SEMA3A) in several tumors including oral squamous cell carcinoma (OSCC). However, in-depth characterization of the role of SEMA3A in OSCC and the underlying molecular mechanisms is lacking. Gene and protein expressions were detected using quantitative real-time PCR, western blot assay, and immunohistochemistry. OSCC cell metastasis was evaluated using Transwell and angiogenesis of human umbilical vein endothelial cells (HUVECs) was determined using tube formation assay. The interactions among molecules were predicted using bioinformatics analysis and validated using luciferase activity experiment and RNA immunoprecipitation assay. Pulmonary metastasis was evaluated using hematoxylin and eosin staining after constructing a lung metastasis tumor model in mice. SEMA3A expression was decreased in OSCC cells and its overexpression led to suppression of epithelial-mesenchymal transition (EMT), migration, and invasion of OSCC cells and angiogenesis of HUVECs. miR-32-5p was identified as an upstream molecule of SEMA3A and long non-coding RNA NR2F2 antisense RNA 1 (NR2F2-AS1) was validated as an upstream gene of miR-32-5p. Further experiments revealed that the inhibitory effects of NR2F2-AS1 overexpression on EMT, migration, invasion of OSCC cells, and angiogenesis of HUVECs as well as tumor growth and metastasis in mice were mediated via the miR-32-5p/SEMA3A axis. To conclude, NR2F2-AS1 may attenuate OSCC cell metastasis and angiogenesis of HUVECs and suppress tumor growth and metastasis in mice via the miR-32-5p/SEMA3A axis.

5.
Heliyon ; 10(15): e35201, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39166047

RESUMEN

Background: Cardioembolic stroke is a type of ischemic stroke with high disability and mortality, a high recurrence rate and poor prognosis. miRNAs have been explored as potential noninvasive biomarkers in atrial fibrillation and ischemic stroke, but their expression profile in cardioembolic stroke still needs to be explored. This study will explore the differences in miRNA expression between cardioembolic stroke patients and healthy people through meta-analysis and attempt to analyze the target genes by bioinformatics analysis. Methods: Literature databases and gene expression databases were searched from the inception date to June 2022. The study reported the circulating miRNA expression profiles in cardioembolic stroke patients and healthy controls. miRNAs with significantly differential expression and their target genes were analyzed. Results: Three articles and one gene expression dataset were included in the analysis. The results showed that miR-21-5p (SMD: 2.16; 95 % CI: 1.57, 2.75; p < 0.001), miR-943, miR-145-3p, and miR-3148 were upregulated in cardioembolic stroke patients compared with controls. The downregulated miRNAs included miR-3136-5p, miR-2277-5p, and miR-2277-3p. The area under the receiver operating characteristic curve of miR-21-5p for cardioembolic stroke was 0.975 (0.933-0.989). For the enrichment results, the target genes of upregulated miRNAs were enriched in the MAPK signaling pathway, Ras signaling pathway, etc. The target genes of downregulated miRNAs were also enriched in the Ras signaling pathway. Conclusions: This study suggested that circulating miR-21-5p is upregulated in cardioembolic stroke patients compared to healthy controls. The Ras signaling pathway plays an important role in pathogenesis according to enrichment analysis.

6.
Cancer Res ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120596

RESUMEN

N6-methyladenosine (m6A) is the most prevalent RNA modification and is associated with various biological processes. Proteins that function as readers and writers of m6A modifications have been shown to play critical roles in human malignancies. Here, we identified KH-type splicing regulatory protein (KHSRP) as an m6A binding protein that contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). High KHSRP levels were detected in PDAC and predicted poor patient survival. KHSRP deficiency suppressed PDAC growth and metastasis in vivo. Mechanistically, KHSRP recognized and stabilized FAK pathway mRNAs, including MET, ITGAV and ITGB1, in an m6A-dependent manner, which led to activation of downstream FAK signaling that promoted PDAC progression. Targeting KHSRP with a PROTAC showed promising tumor suppressive effects in mouse models, leading to prolonged survival. Together, these findings indicate that KHSRP mediates FAK pathway activation in an m6A-dependent manner to support PDAC growth and metastasis, highlighting the potential of KHSRP as a therapeutic target in pancreatic cancer.

7.
Cell Death Dis ; 15(8): 591, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39143050

RESUMEN

Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.


Asunto(s)
Mitocondrias , Mitofagia , Neuronas , Receptores Acoplados a Proteínas G , Animales , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Neuronas/metabolismo , Mitocondrias/metabolismo , Ratones , Humanos , Fosforilación Oxidativa , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Especies Reactivas de Oxígeno/metabolismo , Ratones Noqueados , Neurogénesis
8.
Proc Natl Acad Sci U S A ; 121(33): e2406654121, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39116129

RESUMEN

Protein therapeutics play a critical role in treating a large variety of diseases, ranging from infections to genetic disorders. However, their delivery to target tissues beyond the liver, such as the lungs, remains a great challenge. Here, we report a universally applicable strategy for lung-targeted protein delivery by engineering Lung-Specific Supramolecular Nanoparticles (LSNPs). These nanoparticles are designed through the hierarchical self-assembly of metal-organic polyhedra (MOP), featuring a customized surface chemistry that enables protein encapsulation and specific lung affinity after intravenous administration. Our design of LSNPs not only addresses the hurdles of cell membrane impermeability of protein and nonspecific tissue distribution of protein delivery, but also shows exceptional versatility in delivering various proteins, including those vital for anti-inflammatory and CRISPR-based genome editing to the lung, and across multiple animal species, including mice, rabbits, and dogs. Notably, the delivery of antimicrobial proteins using LSNPs effectively alleviates acute bacterial pneumonia, demonstrating a significant therapeutic potential. Our strategy not only surmounts the obstacles of tissue-specific protein delivery but also paves the way for targeted treatments in genetic disorders and combating antibiotic resistance, offering a versatile solution for precision protein therapy.


Asunto(s)
Edición Génica , Pulmón , Nanopartículas , Animales , Edición Génica/métodos , Pulmón/metabolismo , Ratones , Nanopartículas/química , Perros , Conejos , Humanos , Sistemas CRISPR-Cas , Sistemas de Liberación de Medicamentos/métodos
9.
Adv Mater ; : e2408538, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39149779

RESUMEN

Hydrogel bioadhesives have emerged as a promising alternative to wound dressings for chronic wound management. However, many existing bioadhesives do not meet the functional requirements for efficient wound management through dynamically mechanical modulation, due to the reduced wound contractibility, frequent wound recurrence, incapability to actively adapt to external microenvironment variation, especially for those gradually-expanded chronic wounds. Here, a self-growing hydrogel bioadhesive (sGHB) patch that exhibits instant adhesion to biological tissues but also a gradual increase in mechanical strength and interfacial adhesive strength within a 120-h application is presented. The gradually increased mechanics of the sGHB patch could effectively mitigate the stress concentration at the wound edge, and also resist the wound expansion at various stages, thus mechanically contracting the chronic wounds in a programmable manner. The self-growing hydrogel patch demonstrated enhanced wound healing efficacy in a mouse diabetic wound model, by regulating the inflammatory response, promoting the faster re-epithelialization and angiogenesis through mechanical modulation. Such kind of self-growing hydrogel bioadhesives have potential clinical utility for a variety of wound management where dynamic mechanical modulation is indispensable.

10.
Clin Case Rep ; 12(8): e9230, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39091621

RESUMEN

Maxillary canines are often impacted, which can result in tooth disorders and adversely affect occlusal and facial development. The case report describes complete bilateral impaction of maxillary canines and significant root resorption of a central incisor. The multidisciplinary approach is the optimal strategy for addressing impacted maxillary canines.

11.
Bioorg Chem ; 151: 107684, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39094507

RESUMEN

Twenty-nine sesquiterpenoids, including pseudoguaiane-type (1-11), eudesmane-type (12-23), and carabrane-type (24-29), have been identified from the plant Carpesium abrotanoides. Of them, compounds 1-4, 12-15, and 24-27, namely carpabrotins A-L, are twelve previously undescribed ones. Compound 3 possessed a pseudoguaiane backbone with a rearrangement modification at C-11, C-12 and C-13, while compound 4 suffered a carbon bond break between the C-4 and C-5 to form a rare 4,5-seco-pseudoguaiane lactone. Compounds 1-3, 5, 13-16 and 25-27 exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 macrophages with IC50 values less than 40 µM, while compounds 1, 2, 5, 13, 14, 16, and 25-27 showed significant inhibitory activity comparable to that of dexamethasone. The anti-atopic dermatitis (AD) effects of compounds 5 and 16 were tested according to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in KM mice, and the results revealed that the major products 5 and 16 improved the histological features of AD-like skin lesions and mast cell infiltration in mice. This study suggested that sesquiterpenoids in C. abrotanoides should play a key role in its anti-inflammatory use.

12.
J Sci Food Agric ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39087633

RESUMEN

BACKGROUND: Research on the co-production of multiple enzymes by Bacillus velezensis as a novel species is still a topic that needs to be studied. This study aimed to investigate the fermentation characteristics of B. velezensis D6 co-producing α-amylase and protease and to explore their enzymatic properties and applications in fermentation. RESULTS: The maximum co-production of α-amylase and protease reached 13.13 ± 0.72 and 2106.63 ± 64.42 U mL-1, respectively, under the optimal fermented conditions (nutrients: 20.0 g L-1 urea, 20.0 g L-1 glucose, 0.7 g L-1 MnCl2; incubation conditions: initial pH 7.0, temperature 41 °C, 8% inoculation size and 30% working volume). Moreover, the genetic co-expression of α-amylase and protease increased from 0 to 24 h and then decreased after 36 h at the transcriptional level, which coincided with the growth trend of B. velezensis D6. The optimal reaction temperature of α-amylase was 55-60 °C, while that of protease was 35-40 °C. The activities of α-amylase and protease were retained by over 80% after thermal treatment (90 °C, 1 h), which indicated that two enzymes co-produced by B. velezensis D6 demonstrated excellent thermal stability. Moreover, the two enzymes were stable over a wide pH range (pH 4.0-8.0 for α-amylase; pH 4.0-9.0 for protease). Finally, the degrees of hydrolysis of corn, rice, sorghum and soybeans by α-amylase from B. velezensis D6 reached 44.95 ± 2.95%, 57.16 ± 2.75%, 52.53 ± 4.01% and 20.53 ± 2.42%, respectively, suggesting an excellent hydrolysis effect on starchy raw materials. The hydrolysis degrees of mackerel heads and soybeans by protease were 43.93 ± 2.19% and 26.38 ± 1.72%, respectively, which suggested that the protease from B. velezensis D6 preferentially hydrolyzed animal-based protein. CONCLUSION: This is a systematic study on the co-production of α-amylase and protease by B. velezensis D6, which is crucial in widening the understanding of this species co-producing multi-enzymes and in exploring its potential application. © 2024 Society of Chemical Industry.

13.
Front Immunol ; 15: 1405146, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947338

RESUMEN

Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Inmunoterapia , Aprendizaje Automático , Terapia Neoadyuvante , Tomografía Computarizada por Rayos X , Humanos , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/diagnóstico por imagen , Masculino , Femenino , Terapia Neoadyuvante/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Inmunoterapia/métodos , Nomogramas , Resultado del Tratamiento , Adulto , Radiómica
14.
mLife ; 3(2): 240-250, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38948148

RESUMEN

Cytidine triphosphate synthase (CTPS) plays a pivotal role in the de novo synthesis of cytidine triphosphate (CTP), a fundamental building block for RNA and DNA that is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: adenine triphosphate, uridine triphosphate, CTP, and guanidine triphosphate. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels. CTPS is considered a potential therapeutic target for combating invasions or infections by viral or prokaryotic pathogens. Utilizing cryo-electron microscopy, we determined the structure of Escherichia coli CTPS (ecCTPS) filament in complex with CTP, nicotinamide adenine dinucleotide (NADH), and the covalent inhibitor 6-diazo-5-oxo- l-norleucine (DON), achieving a resolution of 2.9 Å. We constructed a phylogenetic tree based on differences in filament-forming interfaces and designed a variant to validate our hypothesis, providing an evolutionary perspective on CTPS filament formation. Our computational analysis revealed a solvent-accessible ammonia tunnel upon DON binding. Through comparative structural analysis, we discern a distinct mode of CTP binding of ecCTPS that differs from eukaryotic counterparts. Combining biochemical assays and structural analysis, we determined and validated the synergistic inhibitory effects of CTP with NADH or adenine on CTPS. Our results expand our comprehension of the diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.

15.
Heliyon ; 10(12): e32621, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38975179

RESUMEN

Background: The exosome is a critical component of the intercellular communication., playing a vital role in regulating cell function. These small vesicles contain proteins, mRNAs, miRNAs, and lncRNAs, surrounded by lipid bilayer substances. Most cells in the human body can produce exosomes, released into various body fluids such as urine, blood, and cerebrospinal fluid. Bladder cancer is the most common tumor in the urinary system, with high recurrence and metastasis rates. Early diagnosis and treatment are crucial for improving patient outcomes. Methods: This study employed the PubMed search engine to retrieve publicly accessible data pertaining to urinary exosomes. Results: We summarize the origins and intricate biological characteristics of urinary exosomes, the introduction of research methodologies used in basic experiments to isolate and analyze these exosomes, the discussion of their applications and progress in the diagnosis and treatment of bladder cancer, and the exploration of the current limitations associated with using urinary exosomes as molecular biomarkers for diagnosing bladder cancer. Conclusion: Exosomes isolated from urine may be used as molecular biomarkers for early detection of bladder cancer.

16.
Plant J ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985498

RESUMEN

ERFs (ethylene-responsive factors) are known to play a key role in orchestrating cold stress signal transduction. However, the regulatory mechanisms and target genes of most ERFs are far from being well deciphered. In this study, we identified a cold-induced ERF, designated as PtrERF110, from trifoliate orange (Poncirus trifoliata L. Raf., also known as Citrus trifoliata L.), an elite cold-hardy plant. PtrERF110 is a nuclear protein with transcriptional activation activity. Overexpression of PtrERF110 remarkably enhanced cold tolerance in lemon (Citrus limon) and tobacco (Nicotiana tabacum), whereas VIGS (virus-induced gene silencing)-mediated knockdown of PtrERF110 drastically impaired the cold tolerance. RNA sequence analysis revealed that PtrERF110 overexpression resulted in global transcriptional reprogramming of a range of stress-responsive genes. Three of the genes, including PtrERD6L16 (early responsive dehydration 6-like transporters), PtrSPS4 (sucrose phosphate synthase 4), and PtrUGT80B1 (UDP-glucose: sterol glycosyltransferases 80B1), were confirmed as direct targets of PtrERF110. Consistently, PtrERF110-overexpressing plants exhibited higher levels of sugars and sterols compared to their wild type counterparts, whereas the VIGS plants had an opposite trend. Exogenous supply of sucrose restored the cold tolerance of PtrERF110-silencing plants. In addition, knockdown of PtrSPS4, PtrERD6L16, and PtrUGT80B1 substantially impaired the cold tolerance of P. trifoliata. Taken together, our findings indicate that PtrERF110 positively modulates cold tolerance by directly regulating sugar and sterol synthesis through transcriptionally activating PtrERD6L16, PtrSPS4, and PtrUGT80B1. The regulatory modules (ERF110-ERD6L16/SPS4/UGT80B1) unraveled in this study advance our understanding of the molecular mechanisms underlying sugar and sterol accumulation in plants subjected to cold stress.

17.
Plant Biotechnol J ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39024414

RESUMEN

Polyamines (PAs) are pleiotropic bioorganic molecules. Cellular PA contents are determined by a balance between PA synthesis and degradation. PAs have been extensively demonstrated to play vital roles in the modulation of plant developmental processes and adaptation to various environmental stresses. In this review, the latest advances on the diverse roles of PAs in a range of developmental processes, such as morphogenesis, organogenesis, growth and development, and fruit ripening, are summarized and discussed. Besides, the crosstalk between PAs and phytohormones or other signalling molecules, including H2O2 and NO, involved in these processes is dwelled on. In addition, the attempts made to improve the yield and quality of grain and vegetable crops through altering the PA catabolism are enumerated. Finally, several other vital questions that remain unanswered are proposed and discussed. These include the mechanisms underlying the cooperative regulation of developmental processes by PAs and their interplaying partners like phytohormones, H2O2 and NO; PA transport for maintaining homeostasis; and utilization of PA anabolism/catabolism for generating high-yield and good-quality crops. This review aims to gain new insights into the pleiotropic role of PAs in the modulation of plant growth and development, which provides an alternative approach for manipulating and engineering valuable crop varieties that can be used in the future.

18.
MedComm (2020) ; 5(7): e623, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38988495

RESUMEN

This study aimed to identify the role of chromothripsis as a novel biomarker in the prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms (pNENs). We conducted next-generation gene sequencing in a cohort of 30 patients with high-grade (G3) pNENs. As a reference, a similar analysis was also performed on 25 patients with low-grade (G1/G2) pancreatic neuroendocrine tumors (pNETs). Chromothripsis and its relationship with clinicopathological features and prognosis were investigated. The results showed that DNA damage response and repair gene alteration and TP53 mutation were found in 29 and 11 patients, respectively. A total of 14 out of 55 patients had chromothripsis involving different chromosomes. Chromothripsis had a close relationship with TP53 alteration and higher grade. In the entire cohort, chromothripsis was associated with a higher risk of distant metastasis; both chromothripsis and metastasis (ENETS Stage IV) suggested a significantly shorter overall survival (OS). Importantly, in the high-grade pNENs group, chromothripsis was the only independent prognostic indicator significantly associated with a shorter OS, other than TP53 alteration or pathological pancreatic neuroendocrine carcinomas (pNECs) diagnosis. Chromothripsis can guide worse prognosis in pNENs, and help differentiate pNECs from high-grade (G3) pNETs.

19.
Biomed Environ Sci ; 37(6): 639-646, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38988114

RESUMEN

Objective: To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We designed, developed, and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection. The precision of the liquid transfer and temperature control was tested. A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The entire process, from SARS-CoV-2 nucleic acid extraction to amplification, was evaluated. Results: The precision of the syringe transfer volume was 19.2 ± 1.9 µL (set value was 20), 32.2 ± 1.6 (set value was 30), and 57.2 ± 3.5 (set value was 60). Temperature control in the amplification tube was measured at 60.0 ± 0.0 °C (set value was 60) and 95.1 ± 0.2 °C (set value was 95) respectively. SARS-Cov-2 nucleic acid extraction yield through the device was 7.10 × 10 6 copies/mL, while a commercial kit yielded 2.98 × 10 6 copies/mL. The mean time to complete the entire assay, from SARS-CoV-2 nucleic acid extraction to amplification detection, was 36 min and 45 s. The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion: The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test (POCT).


Asunto(s)
COVID-19 , Equipos Desechables , ARN Viral , SARS-CoV-2 , SARS-CoV-2/aislamiento & purificación , COVID-19/diagnóstico , COVID-19/virología , Humanos , ARN Viral/aislamiento & purificación , ARN Viral/análisis , Prueba de Ácido Nucleico para COVID-19/instrumentación , Prueba de Ácido Nucleico para COVID-19/métodos , Técnicas de Amplificación de Ácido Nucleico/instrumentación , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/instrumentación
20.
Mar Genomics ; 76: 101126, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39009497

RESUMEN

Isolated from intertidal sediment of the Yellow Sea, China, Bremerella sp. P1 putatively represents a novel species within the genus Bremerella of the family Pirellulaceae in the phylum Planctomycetota. The complete genome of strain P1 comprises a single circular chromosome with a size of 6,955,728 bp and a GC content of 55.26%. The genome contains 5772 protein-coding genes, 80 tRNA and 6 rRNA genes. A total of 147 CAZymes and 128 sulfatases have been identified from the genome of strain P1, indicating that the strain has the capability to degrade a wide range of polysaccharides. Moreover, a gene cluster related to bacterial microcompartments (BMCs) formation containing genes encoding the shell proteins and related enzymes to metabolize fucose or rhamnose is also found in the genome of strain P1. The genome of strain P1 represents the second complete one in the genus Bremerella, expanding the understanding of the physiological and metabolic characteristics, interspecies diversity, and ecological functions of the genus.


Asunto(s)
Genoma Bacteriano , Polisacáridos , Polisacáridos/metabolismo , Secuenciación Completa del Genoma , China
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