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We design a p-aminothiophenol (pATP) modified Au/ITO chip to determine nitrite ions in lake water by a ratiometric surface-enhanced Raman scattering (SERS) method based on nitrite ions triggering the transformation of pATP to p,p'-dimercaptoazobenzene (DMAB). Intriguingly, by using the SERS peak (at 1008 cm-1) from benzoic ring deforming as an internal standard instead of the traditional peak at 1080 cm-1, the detection sensitivity of the method was improved 10 times.
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BACKGROUND: Pancreatic cancer is a common malignancy with poor prognosis and limited treatment. Here we aimed to investigate the role of host chromosomal instability (CIN) and tumor microbiome in the prognosis of pancreatic cancer patients. METHODS: One hundred formalin-fixed paraffin-embedded (FFPE) pancreatic cancer samples were collected. DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing (WGS) via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector. RESULTS: Samples are tested according to the procedure of ultrasensitive chromosomal aneuploidy detector (UCAD). We excluded 2 samples with failed quality control, 1 patient lost to follow-up and 6 dead in the perioperative period. The final 91 patients were admitted for the following analyses. Thirteen (14.3%) patients with higher CIN score had worse overall survival (OS) than those with lower CIN score. The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses. Patients with high human herpesvirus (HHV)-7 and HHV-5 DNA reads exhibited worse OS. Furthermore, we classified 91 patients into 3 subtypes. Patients with higher CIN score (n =13) had the worst prognosis (median OS 6.9 mon); patients with lower CIN score but with HHV-7/5 DNA load (n = 24) had worse prognosis (median OS 10.6 mon); while patients with lower CIN score and HHV-7/5 DNA negative (n = 54) had the best prognosis (median OS 21.1 mon). CONCLUSIONS: High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer. The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value.
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Enhancer of zeste homologue 2 (EZH2, also known as KMT6A) is found to be a member of the histone lysine methyltransferase family. An increasing number of studies have shown that in addition to methylating histones, EZH2 plays a vital role in a variety of ways. The methylated substrates of EZH2 also include GATA4, AR/AR-related proteins, STAT3, Talin protein, and RORα. Meanwhile, EZH2 has been reported to form complexes with some proteins to perform other important biological functions as well as methylation. These complexes include: the EZH2-RelA-RelB complex, EZH2-ER-ß-catenin complex, and ß-catenin-PAF-EZH2-Mediator complex. Herein, we focus on the classical and non-classical functions of EZH2, and summarize anti-EZH2 therapeutic strategies. Finally, we highlight that understanding the physiological and pathological functions of EZH2 in specific indications can help the development of inhibitors or degraders.
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Histonas , beta Catenina , N-Metiltransferasa de Histona-Lisina , Histonas/metabolismo , Metilación , beta Catenina/metabolismoRESUMEN
For real application, it is an urgent demand to fabricate stable and flexible surface-enhanced Raman scattering (SERS) substrates with high enhancement factors in a large-scale and facile way. Herein, by using the electrospinning technique, a hydrophobic and flexible poly(styrene-co-butadiene) (SB) fibrous membrane is obtained, which is beneficial for modification of silver nanoparticles (Ag NPs) colloid in a small region and then formation of more "hot spots" by drying; the final SERS substrate is designated as Ag/SB. Hydrophobic Ag/SB can efficiently capture heterocyclic molecules into the vicinity of hot spots of Ag NPs. Such Ag/SB films are used to quantitatively detect trace triazophos residue on fruit peels or in the juice, and the limit of detection (LOD) of 2.5 × 10-8 M is achieved. Ag/SB films possess a capability to resist heat. As a case, 6-mercaptopurine (6MP) that just barely dissolves in 90 °C water is picked for conducting Ag/SB-film-based experiments.
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OBJECTIVE: To study the characteristics of pulmonary function in children with pertussis-like coughing caused by different pathogen infections. METHODS: The data on etiology and tidal breathing pulmonary function were collected from 95 hospitalized infants and young children with pertussis-like coughing. The tidal breathing pulmonary function was compared between these children and 67 healthy children. According to the type of pathogen, the children with pertussis-like coughing were classified to 6 groups: pertussis (n=17), viral infection (n=23), tuberculosis infection (n=6), Mycoplasma infection (n=9), other bacterial infection (n=8), and unknown pathogen (n=32). RESULTS: Among the 95 children with pertussis-like coughing, 15 (16%) had mild obstructive ventilatory dysfunction, 30 (32%) had moderate obstructive ventilatory dysfunction, and 22 (23%) had severe obstructive ventilatory dysfunction. Compared with the normal control group, the children with pertussis-like coughing had significant reductions in inspiratory-to-expiratory time ratio, ratio of time to peak tidal expiratory flow to total expiratory time (tPF%tE), and ratio of volume to peak tidal expiratory flow to total expiratory volume (vPF%vE) (P<0.05). The tuberculosis infection and Mycoplasma infection groups had a significantly lower tidal volume than the normal control group (P<0.05). All pathogen infection groups except the tuberculosis infection group had significantly lower tPF%tE and vPF%vE than the normal control group (P<0.05). The pertussis group had significantly lower tPF%tE and vPF%vE than the other infection groups (P<0.05). CONCLUSIONS: Most of children with pertussis-like coughing have abnormal pulmonary functions. The children with Bordetella pertussis infection have the most severe pulmonary function impairment. Tidal breathing pulmonary function test may provide a reference for pathogen analysis of children with pertussis-like coughing.
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Tos Ferina , Niño , Preescolar , Humanos , Lactante , Pulmón , Respiración , Pruebas de Función Respiratoria , Volumen de Ventilación PulmonarRESUMEN
BACKGROUND: Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The study aimed to illustrate characteristics of contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder adenoma. METHODS: Thirty-seven patients with 39 gallbladder adenomatoid lesions (maximal diameter ≥10 mm and without metastasis) were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individually among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. RESULTS: Adenoma lesions showed iso-echogenicity in ultrasound, and an eccentric enhancement pattern, "fast-in and synchronous-out" contrast enhancement pattern and homogeneous at peak-time enhancement in CEUS. The homogenicity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion (100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively). The characteristic of the eccentric enhancement pattern had the highest diagnostic ability in differentiating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively. CONCLUSIONS: CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps (≥10 mm in diameter). Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.
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Adenocarcinoma/diagnóstico por imagen , Adenoma/diagnóstico por imagen , Medios de Contraste , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Vesícula Biliar/patología , Pólipos/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Colesterol/metabolismo , Diagnóstico Diferencial , Femenino , Vesícula Biliar/diagnóstico por imagen , Humanos , Hiperplasia/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Ultrasonografía , Adulto JovenRESUMEN
Folliculin interacting protein 1 (FNIP1), a novel folliculin interacting protein 1, is a key regulatory factor for mitochondrial function. FNIP1 mainly responds to energy signal transduction through physical interactions with 5'-AMP activated protein kinase (AMPK). Simultaneously, it affects the transcription of mitochondria-associated genes by regulating the lysosomal localization of mechanistic target of rapamycin kinase (mTORC1). This article takes FNIP1 as the core and first introduces its involvement in the development of B cells and invariant natural killer T (iNKT) cells, muscle fiber type conversion, and the thermogenic remodeling of adipocytes by regulating mitochondrial function. In addition we discuss the detailed impact of upstream regulatory factors of FNIP1 on its function. Finally, the impact of FNIP1 on the prognosis and treatment of clinically related metabolic diseases is summarized, aiming to provide a new theoretical basis and treatment plans for the diagnosis and treatment of such diseases.
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Mitocondrias , Humanos , Mitocondrias/metabolismo , Animales , Proteínas Portadoras/metabolismo , Transducción de Señal , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Enfermedades Metabólicas/metabolismoRESUMEN
The PHB2 gene is located on chromosome 12p13 and encodes prohibitin 2, a highly conserved protein of 37 kDa. PHB2 is a dimer with antiparallel coils, possessing a unique negatively charged region crucial for its mitochondrial molecular chaperone functions. Thus, PHB2 plays a significant role in cell life activities such as mitosis, mitochondrial autophagy, signal transduction, and cell death. This review discusses how PHB2 inhibits transcription factors or nuclear receptors to maintain normal cell functions; how PHB2 in the cytoplasm or membrane ensures normal cell mitosis and regulates cell differentiation; how PHB2 affects mitochondrial structure, function, and cell apoptosis through mitochondrial intimal integrity and mitochondrial autophagy; how PHB2 affects mitochondrial stress and inhibits cell apoptosis by regulating cytochrome c migration and other pathways; how PHB2 affects cell growth, proliferation, and metastasis through a mitochondrial independent mechanism; and how PHB2 could be applied in disease treatment. We provide a theoretical basis and an innovative perspective for a comprehensive understanding of the role and mechanism of PHB2 in cell function regulation.
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Mitocondrias , Prohibitinas , Diferenciación Celular/fisiología , Proliferación Celular , Mitocondrias/metabolismo , Transducción de Señal/fisiología , HumanosRESUMEN
Avena sterilis L. (A. sterilis) and Avena ludoviciana Dur. (A. ludoviciana) are extremely invasive weeds with strong competitive ability and multiple transmission routes. Both species can invade a variety of dryland crops, including wheat, corn, and beans. Asia, as the world's major food-producing continent, will experience significant losses to agricultural production if it is invaded by these weeds on a large scale. This study used the MaxEnt model and ArcGIS to map the distribution of suitable habitats of the two species in Asia under climate change conditions. The constructed model comprised four levels, with a total of 25 index-level indicator factors used to evaluate the invasion risk of the two species. The results showed that the distribution of suitable habitats for both Avena species was highly dependent on precipitation and temperature. Under climate warming conditions, although overall the total suitable area is predicted to decrease compared to the current period, there are still moderately or highly suitable areas. Asian countries need to provide early warning for areas with significant increases in moderate and highly suitable zones for these two species of weeds under the background of climate change. If there is already an invaded area or if the suitability of the original area is increased, this should be closely monitored, and control measures should be taken to prevent further spread and deterioration.
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Avena , Cambio Climático , Especies Introducidas , Malezas , Asia , Ecosistema , Productos AgrícolasRESUMEN
Mildewed tobacco leaves seriously impact on cigarette product quality and pose a health risk to person. However, early moldy tobacco leaves are hardly found by naked eyes in the workshop. In this work, we self-assemble AuAg nanoalloys on silicon wafers to construct Si/AuAg chips. The headspace-surface enhanced Raman scattering (SERS) protocol is developed to monitor volatile 1,2-dichloro-3-methoxybenzene (2,3-DCA) and 2,4,6-trichloroanisole (2,4,6-TCA) released from postharvest tobacco. Consequently, the visualization of the SERS peak at 1592 cm-1 assigned to ν(CC) after headspace collection for 10 min and the SERS intensity ratio of 1054 and 1035 cm-1 from 2,3-DCA and 2,4,6-TCA less than 0.5 could be used as indicators to predict early moldy tobacco. Additionally, with headspace collection time prolonging to 2 h, a SERS band at 682 cm-1 due to ν(CCl) of 2,4,6-TCA occurs, confirming the mildew of leaves. The headspace-SERS protocol paves a path for rapid and on-site inspection of the quality of tobacco leaves and cigarettes during storage with a portable Raman system.
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Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D) culture model, closely mimics tissues or organs in vivo. Insulin-secreting islet organoid, derived from stem cells induced in vitro with 3D structures, has emerged as a potential alternative for islet transplantation and as a possible disease model that mirrors the human body's in vivo environment, eliminating species difference. This technology has gained considerable attention for its potential in diabetes treatment. Despite advances, the process of stem cell differentiation into islet organoid and its cultivation demonstrates deficiencies, prompting ongoing efforts to develop more efficient differentiation protocols and 3D biomimetic materials. At present, the constructed islet organoid exhibit limitations in their composition, structure, and functionality when compared to natural islets. Consequently, further research is imperative to achieve a multi-tissue system composition and improved insulin secretion functionality in islet organoid, while addressing transplantation-related safety concerns, such as tumorigenicity, immune rejection, infection, and thrombosis. This review delves into the methodologies and strategies for constructing the islet organoid, its application in diabetes treatment, and the pivotal scientific challenges within organoid research, offering fresh perspectives for a deeper understanding of diabetes pathogenesis and the development of therapeutic interventions.
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Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Organoides , Humanos , Organoides/metabolismo , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/citología , Animales , Trasplante de Islotes Pancreáticos/métodos , Diabetes Mellitus/terapia , Diabetes Mellitus/patología , Diferenciación CelularRESUMEN
BACKGROUND: Early allograft dysfunction (EAD) is a common complication after liver transplantation (LT) and is associated with poor prognosis. Graft itself plays a major role in the development of EAD. We aimed to reveal the EAD-specific molecular profiles to assess graft quality and establish EAD predictive models. METHODS: A total of 223 patients who underwent LT were enrolled and divided into training ( n =73) and validation ( n =150) sets. In the training set, proteomics was performed on graft biopsies, together with metabolomics on paired perfusates. Differential expression, enrichment analysis, and protein-protein interaction network were used to identify the key molecules and pathways involved. EAD predictive models were constructed using machine learning and verified in the validation set. RESULTS: A total of 335 proteins were differentially expressed between the EAD and non-EAD groups. These proteins were significantly enriched in triglyceride and glycerophospholipid metabolism, neutrophil degranulation, and the MET-related signaling pathway. The top 12 graft proteins involved in the aforementioned processes were identified, including GPAT1, LPIN3, TGFB1, CD59, and SOS1. Moreover, downstream metabolic products, such as lactate dehydrogenase, interleukin-8, triglycerides, and the phosphatidylcholine/phosphorylethanolamine ratio in the paired perfusate displayed a close relationship with the graft proteins. To predict the occurrence of EAD, an integrated model using perfusate metabolic products and clinical parameters showed areas under the curve of 0.915 and 0.833 for the training and validation sets, respectively. It displayed superior predictive efficacy than that of currently existing models, including donor risk index and D-MELD scores. CONCLUSIONS: We identified novel biomarkers in both grafts and perfusates that could be used to assess graft quality and provide new insights into the etiology of EAD. Herein, we also offer a valid tool for the early prediction of EAD.
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Trasplante de Hígado , Metabolómica , Proteómica , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Disfunción Primaria del Injerto/metabolismo , Disfunción Primaria del Injerto/etiología , Disfunción Primaria del Injerto/diagnóstico , Aloinjertos , Biomarcadores/metabolismo , Biomarcadores/análisisRESUMEN
OBJECTIVE: To evaluate pancreatic tissue stiffness and provide a normal reference shear wave velocity (SWV) value of pancreas from healthy adults by Virtual Touch Imaging Quantification (VTIQ) measurements. METHODS: Healthy adult volunteers without known history of hepatobiliary or pancreatic diseases were included. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used. SWV values were measured at the cephalic, corpus and tail of pancreas and replicated different operators' obtained data. Subgroups were classified according to the volunteers' gender, age, body mass index (BMI), depth of measurements and the echogenicity of the pancreas. RESULTS: From February 2023 to July 2023, 33 healthy adult volunteers were included. The success rate of VTIQ measurements in cephalic, corpus and tail regions was 90.90 % (30/33), 96.97 % (32/33) and 90.90 % (30/33) respectively. The color elastograms of healthy adult pancreas showed uniform blue or simultaneously blue and green. The average SWV values were 0.97±0.26âm/s for cephalic, 0.91±0.24âm/s for corpus and 0.97±0.25âm/s for pancreatic tail respectively (Pâ=â0.198). The mean SWV values of pancreas did not show significant difference with age, gender or depth (Pâ>â0.05). BMI was an influence factor in the measurements of SWV values of cephalic and tail of pancreas (Pâ<â0.05). Pancreas with hyperechoic parenchyma showed higher mean SWV values (Pâ<â0.05). The intra-observer (ICCâ=â0.938 [95% CI: 0.869-0.971]) and the inter-observer (ICCâ=â0.887 [95% CI: 0.760-0.947]) agreements of VTIQ measurements were excellent. CONCLUSIONS: The mean SWV value of the pancreas in healthy adults was 0.96±0.20âm/s (range: 0.52-1.74âm/s). VTIQ technique can be used in pancreatic stiffness measurements with good reliability.
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Diagnóstico por Imagen de Elasticidad , Páncreas , Humanos , Diagnóstico por Imagen de Elasticidad/métodos , Masculino , Femenino , Adulto , Páncreas/diagnóstico por imagen , Persona de Mediana Edad , Voluntarios Sanos , Adulto JovenRESUMEN
Objectives: Serous microcystic adenoma (SMA), a primary benign pancreatic tumor which can be clinically followed-up instead of undergoing surgery, are sometimes mis-distinguished as pancreatic neuroendocrine tumor (pNET) in regular preoperative imaging examinations. This study aimed to analyze preoperative contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) features of SMAs in comparison to pNETs. Material and methods: In this retrospective study, patients with imaging-diagnosed pancreatic lesions were screened between October 2020 to October 2022 (ethical approval No. B2020-309R). Performing by a Siemens Sequoia (Siemens Medical Solutions, Mountain View, CA, USA) equipped with a 5C-1 curved array transducer (3.0-4.5 MHz), CEUS examination was conducted to observe the microvascular perfusion patterns of pancreatic lesions in arterial phase, venous/late phases (VLP) using SonoVue® (Bracco Imaging Spa, Milan, Italy) as the contrast agent. Virtual touch tissue imaging and quantification (VTIQ) - SWE was used to measure the shear wave velocity (SWV, m/s) value to represent the quantitative stiffness of pancreatic lesions. Multivariate logistic regression was performed to analyze potential ultrasound and clinical features in discriminating SMAs and pNETs. Results: Finally, 30 SMA and 40 pNET patients were included. All pancreatic lesions were pathologically proven via biopsy or surgery. During the arterial phase of CEUS, most SMAs and pNETs showed iso- or hyperenhancement (29/30, 97 % and 31/40, 78 %), with a specific early honeycomb enhancement pattern appeared in 14/30 (47 %) SMA lesions. During the VLP, while most of the SMA lesions remained iso- or hyperenhancement (25/30, 83 %), nearly half of the pNET lesions revealed an attenuated hypoenhancement (17/40, 43 %). The proportion of hypoenhancement pattern during the VLP of CEUS differed significantly between SMAs and pNETs (P = 0.021). The measured SWV value of SMAs was significantly higher than pNETs (2.04 ± 0.70 m/s versus 1.42 ± 0.44 m/s, P = 0.002). Taking a SWV value > 1.83 m/s as a cutoff in differentiating SMAs and pNETs, the area under the receiver operating characteristic curve (AUROC) was 0.825, with sensitivity, specificity and likelihood ratio (+) of 85.71 %, 72.73 % and 3.143, respectively. Multivariate logistic regression revealed that SWV value (m/s) of the pancreatic lesion was an independent variable in discriminating SMA and pNET. Conclusion: By comprehensively evaluating CEUS patterns and SWE features, SMA and pNET may be well differentiated before the operation. While SMA typically presents as harder lesion in VTIQ-SWE, exhibiting a specific honeycomb hyperenhancement pattern during the arterial phase of CEUS, pNET is characterized by relative softness, occasionally displaying a wash-out pattern during the VLP of CEUS.
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At present, China has become one of the fastest growing countries in terms of junk food consumption. However, there has been less previous evidence for the effect of endowment insurance on dietary health. Using the data China Family Panel Studies (CFPS) from 2014, this paper exploits a policy, the New Rural Pension System (NRPS), that only the older adults who have reached 60 years old can receive pensions and conduct a fuzzy regression discontinuity (FRD) to address endogeneity and examine the causal effect of the NRPS on the intake of junk food among rural older adults in China. We find that the NRPS can significantly reduce junk food intake among them, which remains robust after a series of robustness tests. In addition, heterogeneity analysis shows that the female, low-educated, unemployed, and low-income groups are more sensitive to the pension shock from the NRPS. The result of our study provides insights to effectively improve people's dietary quality and related policy formulation.
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Pensiones , Pobreza , Humanos , Femenino , Anciano , Persona de Mediana Edad , Dieta , Población Rural , ChinaRESUMEN
CD8+ T cells are an important component of the body's adaptive immune response. During viral or intracellular bacterial infections, CD8+ T cells are rapidly activated and differentiated to exert their immune function by producing cytokines. Alterations in the glycolysis of CD8+ T cells have an important effect on their activation and function, while glycolysis is important for CD8+ T cell functional failure and recovery. This paper summarizes the importance of CD8+ T cell glycolysis in the immune system. We discuss the link between glycolysis and CD8+ T cell activation, differentiation, and proliferation, and the effect of altered glycolysis on CD8+ T cell function. In addition, potential molecular targets to enhance and restore the immune function of CD8+ T cells by affecting glycolysis and the link between glycolysis and CD8+ T cell senescence are summarized. This review provides new insights into the relationship between glycolysis and CD8+ T cell function, and proposes novel strategies for immunotherapy by targeting glycolysis.
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Linfocitos T CD8-positivos , Citocinas , Citocinas/metabolismo , Glucólisis , Diferenciación Celular , Activación de LinfocitosRESUMEN
Under conditions of oxygen sufficiency, tumor cells supply themselves with energy through glycolysis, which is one of the causes of their rapid proliferation, metastasis and acquisition of drug resistance. Tumorassociated macrophages (TAMs) are transformed from peripheral blood monocytes and are among the immunerelated cells that constitute the tumor microenvironment (TME). Altered glycolysis levels in TAMs have an important impact on their polarization and function. The cytokines secreted by TAMs, and phagocytosis in different polarization states, affect tumorigenesis and development. Furthermore, changes in glycolysis activity of tumor cells and other immunerelated cells in the TME also affect the polarization and function of TAMs. Studies on the relationship between glycolysis and TAMs have received increasing attention. The present study summarized the link between glycolysis of TAMs and their polarization and function, as well as the interaction between changes in glycolysis of tumor cells and other immuneassociated cells in the TME and TAMs. The present review aimed to provide a comprehensive understanding of the effects of glycolysis on the polarization and function of TAMs.
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Macrófagos , Macrófagos Asociados a Tumores , Humanos , Macrófagos/patología , Monocitos , Glucólisis , Microambiente TumoralRESUMEN
OBJECTIVE: This study aimed to evaluate the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) with a propagation map in evaluating the degree of hepatic fibrosis in patients with liver tumors before resection. METHODS AND MATERIALS: From January 2020 to April 2021, 128 patients with liver tumors were prospectively enrolled, including 20 benign liver tumors and 108 malignant liver tumors. 2D-SWE with a propagation map technology was used to measure the stiffness of liver parenchyma 2 cm away from the tumor. The median value of five measurements was used in this study. The stage of hepatic fibrosis was graded in accordance with Scheuer standard. Spearman correlation was used to analyze the correlation between liver fibrosis stage and the liver stiffness. Univariate and multivariate linear regression analyses were used to determine significant affecting factors for liver stiffness value. The diagnostic performance of 2D-SWE with a propagation map in predicting fibrosis stage was evaluated by receiver operating characteristic curve analysis. RESULTS: The median liver stiffness value in patients with benign liver tumors was lower than that in patients with malignant liver tumors (6.0âkPa vs. 9.4âkPa, pâ<â0.05). The median liver stiffness values in patients with primary liver cancer were higher than that in patients with benign liver tumors and other types of malignant liver tumors (9.6âkPa vs. 6.0âkPa, pâ<â0.05). The liver stiffness measured by 2D-SWE was highly correlated with the fibrosis stage confirmed by postoperative pathology (râ=â0.834, pâ<â0.05). For the liver stiffness value, PLT,TB,ALB and fibrosis stage are significantly associated with liver stiffness. The median liver stiffness values in stages S0-S4 of fibrosis were 6.0, 7.2, 8.0, 9.4, and 12.6âkPa, respectively. The areas under the ROC curve of S≥1, S≥2, S≥3, and Sâ=â4 as predicted by SWE were 0.932, 0.945, 0.945, and 0.916, respectively. According to the Youden index, the optimal critical values for predicting fibrosis S≥1, S≥2, S≥3, and Sâ=â4 were 6.8 (sensitivity of 89.69% and specificity of 93.55%), 7.5 (sensitivity of 87.50 % and specificity of 95.00 %), 8.3 (sensitivity of 87.14 % and specificity of 87.93 %) and 9.8 (sensitivity of 79.55 % and specificity of 86.90 %) kPa. CONCLUSION: 2D-SWE with a propagation map could noninvasively and accurately predict the staging of liver fibrosis in patients with liver tumors before resection.
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Carcinoma Hepatocelular , Diagnóstico por Imagen de Elasticidad , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Hígado/diagnóstico por imagenRESUMEN
PRMT6 is a member of the protein arginine methyltransferase family, which is involved in a variety of physiological processes and plays an important role in the occurrence and development of tumors. Due to the high homology of type â PRMTs and the two close binding sites of the SAM pocket and the substrate pocket, selective PRMT6 inhibitors have rarely been reported. In this study, a series of (5-phenylpyridin-3-yl)methanamine derivatives were designed and synthesized, which could form hydrogen bonding interactions with the unique Glu49 of PRMT6, thereby improving the selectivity of the compounds for PRMT6. Among them, a25 had the best activity and selectivity, with more than 25-fold selectivity for PRMT1/8 and more than 50-fold selectivity for PRMT3/4/5/7, which was superior to these reported SAM competitive and substrate competitive PRMT6 inhibitors. Importantly, a25 could significantly inhibit the proliferation of various tumor cells and effectively induce apoptosis of cancer cells. Our data clarified that a25 is a promising selective PRMT6 inhibitor for cancer therapy which is worthy of further evaluation.
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Neoplasias , Proteínas Nucleares , Humanos , Proteínas Nucleares/metabolismo , Metilación , Proteína-Arginina N-Metiltransferasas , Proteínas Represoras/metabolismoRESUMEN
The cytoplasmic dynein 1, a minus end-directed motor protein, is an essential microtubule-based molecular motor that mediates the movement of molecules to intracellular destinations in eukaryotes. However, the role of dynein in the pathogenesis of Magnaporthe oryzae is unknown. Here, we identified cytoplasmic dynein 1 intermediate-chain 2 genes in M. oryzae and functionally characterized it using genetic manipulations, and biochemical approaches. We observed that targeted the deletion of MoDYNC1I2 caused significant vegetative growth defects, abolished conidiation, and rendered the ΔModync1I2 strains non-pathogenic. Microscopic examinations revealed significant defects in microtubule network organization, nuclear positioning, and endocytosis ΔModync1I2 strains. MoDync1I2 is localized exclusively to microtubules during fungal developmental stages but co-localizes with the histone OsHis1 in plant nuclei upon infection. The exogenous expression of a histone gene, MoHis1, restored the homeostatic phenotypes of ΔModync1I2 strains but not pathogenicity. These findings could facilitate the development of dynein-directed remedies for managing the rice blast disease.