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Vascular endothelial growth factor A (VEGFA) plays a critical role as a potent angiogenesis factor and is highly expressed in hepatocellular carcinoma (HCC). Although the expression of VEGFA has been strongly linked to the aggressive nature of HCC, the specific posttranscriptional modifications that might contribute to VEGFA expression and HCC angiogenesis are not yet well understood. In this study, we aimed to investigate the epitranscriptome regulation of VEGFA in HCC. A comprehensive analysis integrating MeRIP-seq, RNA-seq, and crosslinking-immunprecipitation-seq data revealed that VEGFA was hypermethylated in HCC and identified the potential m6A regulators of VEGFA including a m6A methyltransferase complex component RBM15 and the two readers, YTHDF2 and IGF2BP3. Through rigorous cell and molecular biology experiments, RBM15 was validated as a key component of methyltransferase complex responsible for m6A methylation of VEGFA, which was subsequently recognized and stabilized by IGF2BP3 and YTHDF2, leading to enhanced VEGFA expression and VEGFA-related functions such as human umbilical vascular endothelial cells (HUVEC) migration and tube formation. In the HCC xenograft model, knockdown of RBM15, IGF2BP3, or YTHDF2 resulted in reduced expression of VEGFA, accompanied by significant inhibition of tumor growth closely associated with VEGFA expression and angiogenesis. Furthermore, our analysis of HCC clinical samples identified positive correlations between the expression levels of VEGFA and the regulators RBM15, IGF2BP3, and YTHDF2. Collectively, these findings offer novel insights into the posttranscriptional modulation of VEGFA and provide potential avenues for alternative approaches to antiangiogenesis therapy targeting VEGFA.
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With the development of deep learning, the Super-Resolution (SR) reconstruction of microscopic images has improved significantly. However, the scarcity of microscopic images for training, the underutilization of hierarchical features in original Low-Resolution (LR) images, and the high-frequency noise unrelated with the image structure generated during the reconstruction process are still challenges in the Single Image Super-Resolution (SISR) field. Faced with these issues, we first collected sufficient microscopic images through Motic, a company engaged in the design and production of optical and digital microscopes, to establish a dataset. Secondly, we proposed a Residual Dense Attention Generative Adversarial Network (RDAGAN). The network comprises a generator, an image discriminator, and a feature discriminator. The generator includes a Residual Dense Block (RDB) and a Convolutional Block Attention Module (CBAM), focusing on extracting the hierarchical features of the original LR image. Simultaneously, the added feature discriminator enables the network to generate high-frequency features pertinent to the image's structure. Finally, we conducted experimental analysis and compared our model with six classic models. Compared with the best model, our model improved PSNR and SSIM by about 1.5 dB and 0.2, respectively.
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BACKGROUND: Shortening is used widely in cookie preparation to improve quality and texture. However, large amounts of saturated and trans fatty acids present in shortening have adverse effects on human health, and much effort has been made to reduce the use of shortening. The use of oleogels might be a suitable alternative. In this study, the oleogels of high oleic sunflower oil with beeswax (BW), BW-glyceryl monopalmitate (BW-GMP), and BW-Span80 (BW-S80) were prepared and their suitability to replace shortening in cookie preparation was evaluated. RESULTS: The solid fat content of BW, BW-GMP, and BW-S80 oleogels was significantly lower than that of commercial shortening when the temperature was not higher than 35 °C. However, the oil-binding capacity of these oleogels was almost similar to that of shortening. The crystals in the shortening and oleogels were ß' form mainly; however, the morphology of crystal aggregates in these oleogels was different from that of shortening. The textural and rheological properties of doughs prepared with the oleogels were similar, and clearly different from those of dough with commercial shortening. The breaking strengths of cookies made with oleogels were lower than that of cookies prepared with shortening. However, cookies containing BW-GMP and BW-S80 oleogels were similar in density and color to those prepared with shortening. CONCLUSION: The textural properties and color of cookies with BW-GMP and BW-S80 oleogels were very similar to those of the cookies containing commercial shortening. The BW-GMP and BW-S80 oleogels could act as alternatives to shortening in the preparation of cookies. © 2023 Society of Chemical Industry.
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Alimentos , Aceite de Girasol/química , Culinaria , ReologíaRESUMEN
This brief presents an analog front-end (AFE) for the detection of electroencephalogram (EEG) signals. The AFE is composed of four sections, chopper-stabilized amplifiers, ripple suppression circuit, RRAM-based lowpass FIR filter, and 8-bit SAR ADC. This is the first time that an RRAM-based lowpass FIR filter has been introduced in an EEG AFE, where the bio-plausible characteristics of RRAM are utilized to analyze signals in the analog domain with high efficiency. The preamp uses the symmetrical OTA structure, reducing power consumption while meeting gain requirements. The ripple suppression circuit greatly improves noise characteristics and offset voltage. The RRAM-based low-pass filter achieves a 40 Hz cutoff frequency, which is suitable for the analysis of EEG signals. The SAR ADC adopts a segmented capacitor structure, effectively reducing the capacitor switching power consumption. The chip prototype is designed in 40 nm CMOS technology. The overall power consumption is approximately 13 µW, achieving ultra-low-power operation.
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Amplificadores Electrónicos , Electroencefalografía , Análisis de Secuencia por Matrices de Oligonucleótidos , Procesamiento de Señales Asistido por ComputadorRESUMEN
OBJECTIVE: To study the characteristics, location, and amino acid changes of novel mutations of the Dystrophin gene. METHODS: Twelve patients in whom no deletion or duplication of the Dystrophin gene was detected were analyzed with next-generation sequencing. Fifty healthy adult males were recruited as the controls. RESULTS: All patients were detected with mutations of the Dystrophin gene, which included c.33C>G, c.583C>T, c.1333C>T, c.2593C>T, c.5731A>T, c.7288G>T, c.2803+1G>T, c.10034G>A, c.4289A>G, c.1905_906delAG, c.5017delC, c.5768_5771delAAGA, and c.6261_6262insA. No similar mutations were found among the controls. CONCLUSION: Our data has enriched the mutation spectrum of the Dystrophin gene and may provide an important basis for genetic diagnosis.
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Distrofina/genética , Mutación , Niño , Preescolar , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , MasculinoRESUMEN
OBJECTIVE: To provide prenatal diagnosis for two couples who respectively carried heterozygous CD41-42 (-TCTT) and CD43 (G>T) mutations of the beta hemoglobin gene. METHODS: The mutations were simultaneously detected with reverse dot blot (two diagnostic kits), multi-color melting curve analysis and sequencing analysis. RESULTS: The fetus of family 1 was shown to be heterozygous for CD43 (G>T) by the three methods, while the fetus of family 2 was shown to be double heterozygous for CD41-42 (-TCTT) and CD43 (G>T) by multi-color melting curve analysis and sequencing analysis. The two diagnostic kits yielded different results by reverse dot blot, one as double heterozygous for CD41-42 (-TCTT) and CD43 (G>T), and another as homozygous for CD41-42 (-TCTT). CONCLUSION: For prenatal diagnosis of couples carrying mutations of beta hemoglobin gene such as CD41-42 (-TCTT) and CD43 (G>T), other methods such as Sanger sequencing should be used in order to avoid misdiagnosis.
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Errores Diagnósticos , Mutación , Diagnóstico Prenatal , Globinas beta/genética , Talasemia beta/genética , Femenino , Heterocigoto , Humanos , Masculino , Embarazo , Juego de Reactivos para Diagnóstico , Talasemia beta/diagnósticoRESUMEN
BACKGROUND: We explored the prevalence of and risk factors for type 2 diabetes in the adult population of Shanghai (China) with and without dyslipidemia. MATERIAL AND METHODS: We conducted a cross-sectional survey including 14 385 adults (aged 16 to 88 years) in Shanghai using a stratified, multistage cluster sampling approach. RESULTS: Type 2 diabetes and hyperlipidemia were found in 1456 (10.1%) and 4583 (31.9%) subjects, respectively. Type 2 diabetes was more common in males (11.4%) than in females (9.2%, P<0.01), in the elderly (> or =65 years, 22.5%) than in younger (<55 years, <10%, P<0.01) individuals, and in urban (12.8%) than in rural populations (5.2%, P<0.01). Diabetes incidence was higher among patients with hyperlipidemia than in controls (16.9% vs. 7.0%, P<0.01; OR=2.72, 95% CI 2.44-3.03). Compared with controls, the risk for diabetes in subjects with isolated hypertriglyceridemia, isolated hypercholesterolemia, and mixed hyperlipidemia increased 1.75-fold (95% CI 1.53-1.99), 1.53-fold (95% CI 1.17-2.01), and 2.93-fold (95% CI 2.37-3.63), respectively. The fasting plasma glucose (FPG) and 2h-postprandial plasma glucose (2h-PG) increased with age in both sexes. The age- and sex-adjusted FPG and 2h-PG levels in hyperlipidemia were significantly higher than in controls (P<0.01). CONCLUSIONS: A high prevalence of type 2 diabetes in hyperlipidemia patients exists in Shanghai. Hyperlipidemia is associated with elevated blood glucose levels and therefore requires prompt intervention for prevention and treatment of diabetes in patients with dyslipidemia.
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Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Hiperlipidemias/complicaciones , Adolescente , Adulto , Anciano , Glucemia/metabolismo , China/epidemiología , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Ayuno/sangre , Femenino , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/complicaciones , Hiperlipidemias/sangre , Hipertrigliceridemia/sangre , Hipertrigliceridemia/complicaciones , Lípidos/sangre , Masculino , Persona de Mediana Edad , Periodo Posprandial , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE To assess the application value of multiplex ligation-dependent probe amplification (MLPA) for the detection of gene deletion and prenatal diagnosis of α-thalassemia. METHODS MLPA was applied for 2 cases with α-thalassemia phenotype by whole blood cell counting and hemoglobin component detection but were ruled out by regular molecular diagnosis. Potential gene deletions and point mutations of α-thalassemia gene were detected with regular Gap-polymerase chain reaction (Gap-PCR) and reverse dot blotting (RDB) in 89 cases where one or both partners were carriers of α-thalassemia mutations. Meanwhile, MLPA was used for detecting α-globin gene deletion among the 89 samples. RESULTS For the 2 cases with α-thalassemia phenotype, no α globin gene deletion was detected by MLPA, but were subsequently confirmed as iron-deficiency anemia. The results of MLPA and Gap-PCR detection for the 88 cases were consistent, except for 1 fetal sample (chorionic villi) which could not be diagnosed by Gap-PCR and was confirmed to be - SEA/αα by MLPA. CONCLUSION MLPA can be applied to prenatal diagnosis of α-thalassemia as an effective supplement to Gap-PCR to reduce both misdiagnosis and missed diagnosis and improve the accuracy of prenatal diagnosis.
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Técnicas de Amplificación de Ácido Nucleico/métodos , Diagnóstico Prenatal/métodos , Talasemia alfa/diagnóstico , Adulto , Femenino , Humanos , Embarazo , Talasemia alfa/genéticaRESUMEN
BACKGROUND: This paper explores the evolution of schemes for rural finance in China as a case study of the long and complex process of health system development. It argues that the evolution of these schemes has been the outcome of the response of a large number of agents to a rapidly changing context and of efforts by the government to influence this adaptation process and achieve public health goals. METHODS: The study draws on several sources of data including a review of official policy documents and academic papers and in-depth interviews with key policy actors at national level and at a sample of localities. RESULTS: The study identifies three major transition points associated with changes in broad development strategy and demonstrates how the adaptation of large numbers of actors to these contextual changes had a major impact on the performance of the health system. Further, it documents how the Ministry of Health viewed its role as both an advocate for the interests of health facilities and health workers and as the agency responsible for ensuring that government health system objectives were met. It is argued that a major reason for the resilience of the health system and its ability to adapt to rapid economic and institutional change was the ability of the Ministry to provide overall strategy leadership. Additionally, it postulates that a number of interest groups have emerged, which now also seek to influence the pathway of health system development. CONCLUSIONS: This history illustrates the complex and political nature of the management of health system development and reform. The paper concludes that governments will need to increase their capacity to analyze the health sector as a complex system and to manage change processes.
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Atención a la Salud/organización & administración , Programas de Gobierno , Política de Salud , Salud Pública , Servicios de Salud Rural , Población Rural , Cambio Social , China , Salud , Humanos , Liderazgo , PolíticaRESUMEN
This study was conducted to synthesize a series of nanosized BiOI-TiO2 catalysts to photodegrade Bisphenol A solution. The BiOI-TiO2 nanoparticles were synthesized in the reverse microemulsions, consisting of cyclohexane, Triton X-100, n-hexanol, and aqueous salt solutions. The synthesized particles were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface analyzer, Fourier transform-infrared spectroscopy (FT-IR), ultraviolet-visible light (UV-Vis) absorption spectra and transmission electron microscope (TEM). The photodegradation of Bisphenol A (BPA) in aqueous suspension under visible light irradiation was investigated to explore the feasibility of using the photocatalytic method to treat BPA wastewater. The effects of different molar ratios of BiOI to TiO2 on the photocatalytic activity were discussed. The experimental results revealed that the photocatalytic effect of the BiOI-TiO2 particles was superior to the commercial P25 TiO2. The BPA degradation could be approached by a pseudo-first-order rate expression. The observed reaction rate constant (kobs) was related to nanoparticles dosage and initial solution pH.
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Bismuto/química , Técnicas de Química Sintética/métodos , Nanopartículas del Metal/química , Fotoquímica/métodos , Titanio/química , Catálisis , Emulsiones , Difracción de Rayos X/métodosRESUMEN
OBJECTIVE: To identify genomic aberrations underlying pathogenesis of split hand foot malformation (SHFM) in two Chinese families, and to provide genetic counseling and prenatal diagnosis for them. METHODS: Two sets of peripheral blood and amniotic fluid samples were collected from the patients. One was processed with routine culture and karyotype analysis. For another set, DNA was extracted and analyzed with array-based comparative genomic hybridization (array-CGH). RESULTS: Karyotype analysis of peripheral blood samples for both probands was normal. Karyotype analysis of the amniotic fluid from family 1 has found no abnormality. However, analysis of amniotic fluid samples from the second family showed del(7)(q21q22.1). By array-CGH analysis, both blood and amniotic fluid samples from the first family showed a 662.3 kb dup(10q24.31q24.32). Array-CGH analysis of the blood sample from the second family was normal, whilst analysis of amniotic fluid sample revealed a 19.97 Mb del(7q11.23q21.3). CONCLUSION: Array-CGH features high resolution, high accuracy and rapid diagnosis for unbalanced chromosomal aberration. The dup(10q24.31q24.32) and 19.97 Mb del(7q11.23q21.3) have been the cause of SHFM in the two families. Genetic counseling and prenatal diagnosis have been provided for both families in order to prevent this birth defect.
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Pueblo Asiatico/genética , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/genética , Deformidades Congénitas del Pie/genética , Deformidades Congénitas de la Mano/genética , Adulto , China , Deleción Cromosómica , Duplicación Cromosómica , Cromosomas Humanos Par 10/genética , Cromosomas Humanos Par 7/genética , Femenino , Deformidades Congénitas del Pie/diagnóstico , Deformidades Congénitas de la Mano/diagnóstico , Humanos , Recién Nacido , Masculino , Linaje , Embarazo , Diagnóstico PrenatalRESUMEN
BACKGROUND: Astrocytoma is a type of adult-type diffuse gliomas that includes diffuse astrocytoma (DA) and anaplastic astrocytoma (AA). However, comprehensive investigations into the risk assessment and prognosis of DA and AA using population-based studies remain noticeably scarce. METHODS: In this study, we developed 2 predictive nomograms to evaluate the susceptibility and prognosis associated with DA and AA. The study cohort comprised 3837 individuals diagnosed with DA or AA between 2010 and 2019 selected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent predictors were identified and used to construct the nomograms for overall death and cancer-specific death rates. The performance of the models was assessed using C-index, calibration curves, and receiver operating characteristic curve, and the clinical applicability was evaluated using decision curve analysis. RESULTS: The receiver operating characteristic curves in this study show excellent clinical applicability and predictive power. Notably, the area under the curves of the training and verification queues was higher than 0.80, thereby cementing the models' precision. Additionally, the calibration plots demonstrate that the anticipated mortality rates strikingly match the measured values. This alignment of figures is sustained in the validation cohort. Furthermore, the decision curve analysis corroborates the models' translational potential, reinforcing their relevance within real-world clinical settings. CONCLUSIONS: The presented nomograms have not only exhibited good predictive performance but also showcased pragmatic clinical utility in prognosticating patient outcomes. Significantly, this will undoubtedly serve as a valuable asset for oncologists, facilitating informed treatment decisions and meticulous follow-up planning.
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Astrocitoma , Neoplasias Encefálicas , Nomogramas , Programa de VERF , Humanos , Astrocitoma/epidemiología , Astrocitoma/mortalidad , Astrocitoma/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Adulto , Anciano , Pronóstico , Estudios de Cohortes , Curva ROC , Medición de Riesgo/métodosRESUMEN
OBJECTIVE: Alloimmunization against red blood cell (RBC) antigen is an important concern in myelodysplastic syndromes (MDSs) patients with chronic transfusion, causing potential risk for hemolytic reaction and limited supply of compatible blood. However, there is little data addressing RBC alloimmunization in this patient cohort among the Chinese population. This study aims to evaluate the incidence, specificity of antibodies, and RBC units transfused before antibody formation and its significance in a population of patients consistently receiving RhD-matched RBC units. METHODS: We retrospectively reviewed the transfusion and clinical information of all transfused patients with MDS enrolled in our hospital from 2012 to 2022. The cumulative incidence of alloimmunization was analyzed by a Kaplan-Meier plot. Alloimmunization incidence was compared based on different transfused RBC units using the log-rank test. RESULTS: A total of 103 patients with MDS were included in this study; alloantibody formed in 8 (7.8%) patients. Before reaching 32 RBC units, 87.5% of the alloimmunized patients had developed their alloantibodies. All but 1 of the alloantibodies developed were antibodies to Rh antigens. The RBC transfusion intensity and frequency were significantly higher following alloimmunization in the alloimmunized patients (P = .008, P = .008, respectively). CONCLUSION: The antibodies detected mostly involve the Rh system among MDS patients in China. The alloimmunization tended to occur early prior to reaching 32 RBC units in patients with MDS. Rh antigen matching should be considered early in the patient's transfusion history and completed before receiving 32 RBC units.
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BACKGROUND: Gliosarcoma (GSM) is a highly aggressive variant of brain cancer with an extremely unfavorable prognosis. Prognosis is not feasible by traditional methods because of a lack of staging criteria, and the present study aims to screen more detailed demographic factors to predict the prognostic factors of the tumors. METHODS: For this study, we extracted data of patients diagnosed with GSM from the SEER (Surveillance Epidemiology and End Results) database between 2000 and 2019. To account for the influence of competing risks, we used a Cumulative Incidence Function. Subsequently, univariate analysis was conducted to evaluate the individual variables under investigation. Specifically for patients with GSM, we generated cumulative risk curves for specific mortality outcomes and events related to competing risks. In addition, we used both univariate and multivariate Cox analysis to account for non-GSM-related deaths that may confound our research. RESULTS: The competing risk model showed that age, marital status, tumor size, and adjuvant therapy were prognostic factors in GSM-related death. The analysis results showed that older age (60-70 years, ≥71 years) and larger tumor size (≥5.3 cm) significantly increased the risk of GSM-related death. Conversely, surgical intervention, chemotherapy, and being single were identified as protective factors against GSM-related death. CONCLUSIONS: Our study using a competing risk model provided valuable insights into the prognostic factors associated with GSM-related death. Further research and clinical interventions targeted at minimizing these risk factors and promoting the use of protective measures may contribute to improved outcomes and reduced mortality for patients with GSM.
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Neoplasias Encefálicas , Gliosarcoma , Humanos , Pronóstico , Gliosarcoma/diagnóstico , Factores de Riesgo , Neoplasias Encefálicas/patología , Incidencia , Programa de VERFRESUMEN
BACKGROUND: To determine the carrier frequency of, and evaluate a carrier screening program for, spinal muscular atrophy (SMA) in reproductive age women in Shenzhen area. METHODS: A staged screening procedure was used to perform carrier screening for SMA in 22,913 Chinese reproductive age women between 2019 and 2022 in Shenzhen area of China. First, the copy number of exon 7 in the SMN1 gene were detected in women of reproductive age using real-time quantitative polymerase chain reaction. If SMA carriers were detected, their spouses were then recommended to test. Prenatal diagnosis was carried out in couples who were both carriers. RESULTS: A total of 389 women were found to be SMA carriers (1.70%, 95% CI: 1.53%-1.87%), indicating the carrier prevalence was approximately 1:59. Despite the proportion of nonpregnant women increased from 37.96% in 2019 to 58.18% in 2022 (p < 0.05) among the 22,913 reproductive age women, the recall rate of spouses was still not high (62.21%, 95% CI: 57.39%-67.03%). Eight partners were found to be SMA carriers and two fetuses were determined to have SMA with no copies of the SMN1 gene. CONCLUSION: Although the acceptability and awareness of SMA carrier screening in Chinese population has increased in recent years, it still fails to reach the ideal expectation. Our experience may provide a basis for and facilitate the popularization of SMA carrier screening in Shenzhen area.
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Atrofia Muscular Espinal , Embarazo , Humanos , Femenino , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/epidemiología , Atrofia Muscular Espinal/genética , Diagnóstico Prenatal/métodos , Exones , Reacción en Cadena en Tiempo Real de la Polimerasa , ChinaRESUMEN
Huntington disease (HD) is a neurodegenerative disease caused by the abnormal expansion of a polyglutamine tract resulting from a mutation in the HTT gene. Oxidative stress has been identified as a significant contributing factor to the development of HD and other neurodegenerative diseases, and targeting anti-oxidative stress has emerged as a potential therapeutic approach. CHCHD2 is a mitochondria-related protein involved in regulating cell migration, anti-oxidative stress, and anti-apoptosis. Although CHCHD2 is highly expressed in HD cells, its specific role in the pathogenesis of HD remains uncertain. We postulate that the up-regulation of CHCHD2 in HD models represents a compensatory protective response against mitochondrial dysfunction and oxidative stress associated with HD. To investigate this hypothesis, we employed HD mouse striatal cells and human induced pluripotent stem cells (hiPSCs) as models to examine the effects of CHCHD2 overexpression (CHCHD2-OE) or knockdown (CHCHD2-KD) on the HD phenotype. Our findings demonstrate that CHCHD2 is crucial for maintaining cell survival in both HD mouse striatal cells and hiPSCs-derived neurons. Our study demonstrates that CHCHD2 up-regulation in HD serves as a compensatory protective response against oxidative stress, suggesting a potential anti-oxidative strategy for the treatment of HD.
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Enfermedad de Huntington , Células Madre Pluripotentes Inducidas , Enfermedades Neurodegenerativas , Animales , Ratones , Humanos , Enfermedad de Huntington/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Regulación hacia Arriba/genética , Células Madre Pluripotentes Inducidas/metabolismo , Estrés Oxidativo , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The brain is dynamic, associative, and efficient. It reconfigures by associating the inputs with past experiences, with fused memory and processing. In contrast, AI models are static, unable to associate inputs with past experiences, and run on digital computers with physically separated memory and processing. We propose a hardware-software co-design, a semantic memory-based dynamic neural network using a memristor. The network associates incoming data with the past experience stored as semantic vectors. The network and the semantic memory are physically implemented on noise-robust ternary memristor-based computing-in-memory (CIM) and content-addressable memory (CAM) circuits, respectively. We validate our co-designs, using a 40-nm memristor macro, on ResNet and PointNet++ for classifying images and three-dimensional points from the MNIST and ModelNet datasets, which achieves not only accuracy on par with software but also a 48.1 and 15.9% reduction in computational budget. Moreover, it delivers a 77.6 and 93.3% reduction in energy consumption.
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Background: Lung adenocarcinoma (LUAD) kills millions of people every year. Recently, FDA and researchers proved the significance of high tumor mutational burden (TMB) in treating solid tumors. But no scholar has constructed a TMB-derived computing framework to select sensitive immunotherapy/chemotherapy for the LUAD population with different prognoses. Methods: The datasets were collected from TCGA, GTEx, and GEO. We constructed the TMB-derived immune lncRNA prognostic index (TILPI) computing framework based on TMB-related genes identified by weighted gene co-expression network analysis (WGCNA), oncogenes, and immune-related genes. Furthermore, we mapped the immune landscape based on eight algorithms. We explored the immunotherapy sensitivity of different prognostic populations based on immunotherapy response, tumor immune dysfunction and exclusion (TIDE), and tumor inflammation signature (TIS) model. Furthermore, the molecular docking models were constructed for sensitive drugs identified by the pRRophetic package, oncopredict package, and connectivity map (CMap). Results: The TILPI computing framework was based on the expression of TMB-derived immune lncRNA signature (TILncSig), which consisted of AC091057.1, AC112721.1, AC114763.1, AC129492.1, LINC00592, and TARID. TILPI divided all LUAD patients into two populations with different prognoses. The random grouping verification, survival analysis, 3D PCA, and ROC curve (AUC=0.74) firmly proved the reliability of TILPI. TILPI was associated with clinical characteristics, including smoking and pathological stage. Furthermore, we estimated three types of immune cells threatening the survival of patients based on multiple algorithms. They were macrophage M0, T cell CD4 Th2, and T cell CD4 memory activated. Nevertheless, five immune cells, including B cell, endothelial cell, eosinophil, mast cell, and T cell CD4 memory resting, prolonged the survival. In addition, the immunotherapy response and TIDE model proved the sensitivity of the low-TILPI population to immunotherapy. We also identified seven intersected drugs for the LUAD population with poor prognosis, which included docetaxel, gemcitabine, paclitaxel, palbociclib, pyrimethamine, thapsigargin, and vinorelbine. Their molecular docking models and best binding energy were also constructed and calculated. Conclusions: We divided all LUAD patients into two populations with different prognoses. The good prognosis population was sensitive to immunotherapy, while the people with poor prognosis benefitted from 7 drugs.
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Sepsis-induced acute lung injury (ALI) is a life-threatening syndrome with high mortality and morbidity, resulting in a heavy burden on family and society. As a key factor that maintains cellular homeostasis, autophagy is regarded as a self-digesting process by which damaged organelles and useless proteins are recycled for cell metabolism, and it thus plays a crucial role during physiological and pathological processes. Recent studies have indicated that autophagy is involved in the pathophysiological process of sepsis-induced ALI, including cell apoptosis, inflammation, and mitochondrial dysfunction, which indicates that regulating autophagy may be beneficial for this disease. However, the role of autophagy in the etiology and treatment of sepsis-induced ALI is not well characterized. This review summarizes the autophagy-related signaling pathways in sepsis-induced ALI, as well as focuses on the dual role of autophagy and its regulation by non-coding RNAs during disease progression, for the development of potential therapeutic strategies in this disease.
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Thyroid cancer (TC) is the most predominant malignancy of the endocrine system, with steadily growing occurrence and morbidity worldwide. Although diagnostic and therapeutic methods have been rapidly developed in recent years, the underlying molecular mechanisms in the pathogenesis of TC remain enigmatic. The N6-methyladenosine(m6A) RNA modification is designed to impact RNA metabolism and further gene regulation. This process is intricately regulated by a variety of regulators, such as methylases and demethylases. Aberrant m6A regulators expression is related to the occurrence and development of TC and play an important role in drug resistance. This review comprehensively analyzes the effect of m6A methylation on TC progression and the potential clinical value of m6A regulators as prognostic markers and therapeutic targets in this disease.