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1.
Cell Stem Cell ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39357516

RESUMEN

Mitochondrial adaptations dynamically reprogram cellular bioenergetics and metabolism and confer key properties for human cancers. However, the selective regulation of these mitochondrial responses remains largely elusive. Here, inspired by a genetic screening in acute myeloid leukemia (AML), we identify RAS effector RREB1 as a translational regulator and uncover a unique translation control system for nuclear-encoded mitochondrial proteins in human cancers. RREB1 deletion reduces mitochondrial activities and succinate metabolism, thereby damaging leukemia stem cell (LSC) function and AML development. Replenishing complex II subunit SDHD rectifies these deficiencies. Notably, inhibition of complex II re-sensitizes AML cells to venetoclax treatment. Mechanistically, a short RREB1 variant binds to a conserved motif in the 3' UTRs and cooperates with elongation factor eEF1A1 to enhance protein translation of nuclear-encoded mitochondrial mRNAs. Overall, our findings reveal a unique translation control mechanism for mitochondrial adaptations in AML pathogenesis and provide a potential strategy for targeting this vulnerability of LSCs.

2.
Sheng Wu Gong Cheng Xue Bao ; 40(9): 3103-3113, 2024 Sep 25.
Artículo en Chino | MEDLINE | ID: mdl-39319727

RESUMEN

The widespread use of non-naturally degradable plastics is causing increasingly serious harm to the environment. Reducing plastic pollutants has become the core of ecological and environment management. Biological methods such as enzymes demonstrate advantages in depolymerizing plastics with mild reaction conditions and recycling of depolymerization products. However, there are few reports on the biological depolymerization of polyamide plastics. In this study, by using 4-nitropropionanilide as the model substrate, we screened against our plastic depolymerase library and obtained a Meiothermus ruber-derived enzyme (MrABH) that can hydrolyze the polyamide bond. We expressed this enzyme in Escherichia coli and purified the protein by affinity chromatography. Furthermore, we investigated the catalytic properties, enzymatic properties, and catalytic products of this enzyme with polyamide as the substrate. MrABH had good stability at pH 8.0-10.0, with the optimal performance at pH 9.0 and 30 ℃. The catalytic performance of this enzyme for ester bonds and amide bonds was similar. MrABH can catalyze the depolymerization of PA6 and PA66 to produce monomers and oligomers, demonstrating the potential to be used in the depolymerization and recycling of polyamide.


Asunto(s)
Escherichia coli , Nylons , Nylons/química , Escherichia coli/genética , Escherichia coli/enzimología , Hidrolasas/metabolismo , Hidrolasas/química , Estabilidad de Enzimas , Biodegradación Ambiental , Concentración de Iones de Hidrógeno , Especificidad por Sustrato , Hidrólisis , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/biosíntesis
3.
Neuroreport ; 35(16): 1019-1029, 2024 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-39292953

RESUMEN

This study aims to investigate the effect of adipose-derived stem cells (ADSCs) transplantation on progranulin (PGRN) expression and functional recovery in rats with spinal cord injury (SCI). ADSCs were isolated from the inguinal adipose tissue of rats. A SCI model was created, and ADSCs were injected into the injured area. Various techniques were used to assess the effects of ADSCs transplantation, including hematoxylin-eosin staining, Masson staining, immunofluorescence staining, electron microscopy, MRI, and motor function assessment. The potential mechanisms of ADSC transplantation were investigated using gene expression analysis and protein analysis. Finally, the safety of this therapy was evaluated through hematoxylin-eosin staining and indicators of liver and kidney damage in serum. PGRN expression increased in the injured spinal cord, and ADSCs transplantation further enhanced PGRN levels. The group that received ADSCs transplantation showed reduced inflammation, decreased scar formation, increased nerve regeneration, and faster recovery of bladder function. Importantly, motor function significantly improved in the ADSC transplantation group. ADSCs transplantation enhances functional regeneration in SCI by upregulating PGRN expression, reducing inflammation and scar formation, and promoting nerve regeneration and myelin repair. These findings suggest that ADSC transplantation is a potential therapy for SCI.


Asunto(s)
Tejido Adiposo , Progranulinas , Ratas Sprague-Dawley , Recuperación de la Función , Traumatismos de la Médula Espinal , Regeneración de la Medula Espinal , Trasplante de Células Madre , Regulación hacia Arriba , Animales , Progranulinas/genética , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/metabolismo , Tejido Adiposo/citología , Trasplante de Células Madre/métodos , Regeneración de la Medula Espinal/fisiología , Recuperación de la Función/fisiología , Ratas , Masculino , Células Madre/metabolismo , Femenino , Modelos Animales de Enfermedad
4.
J Cancer Res Clin Oncol ; 150(9): 431, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39340570

RESUMEN

BACKGROUND: Extramedullary plasmacytoma (EMP) is a rare solitary malignancy that accounts for 3% of plasma cell neoplasms, and EMP with a primary occurrence in the palate is extremely uncommon. Owing to the long course of EMP and the limited available data on treatment outcomes, there are no definitive guidelines for its management, especially for high-risk patients who are more susceptible to early progression to multiple myeloma. CASE PRESENTATION: In this study, we review nine relevant studies and describe a 54-year-old woman who presented with an asymptomatic nonulcerative mass localized in the palate. After initial radical surgical resection of the lesion, the patient was definitively diagnosed with EMP with minimal plasmacytosis in the bone marrow, and adjuvant intensity-modulated radiation therapy with a minimum dose of 39.6 Gy was administrated in the surgical area. There was no evidence of local recurrence, nodal metastasis or progression to multiple myeloma (MM) during the seven-year follow-up period. CONCLUSION: Given the atypical clinical features of palate EMP reported in the literature and the encouraging results of our patient, sequential therapy involving surgery and adjuvant radiotherapy for primary palatal lesions in high-risk EMP patients without nodal involvement could be an effective treatment modality.


Asunto(s)
Plasmacitoma , Humanos , Femenino , Plasmacitoma/patología , Plasmacitoma/radioterapia , Plasmacitoma/terapia , Persona de Mediana Edad , Estudios de Seguimiento , Neoplasias Palatinas/patología , Neoplasias Palatinas/terapia , Neoplasias Palatinas/radioterapia , Neoplasias Palatinas/cirugía , Radioterapia de Intensidad Modulada/métodos , Radioterapia Adyuvante
5.
PLoS One ; 19(8): e0305233, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39133675

RESUMEN

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) are currently the most widely used anti-inflammatory medications, but their long-term use can cause damage to the gastrointestinal tract(GIT). One of the risk factors for GIT injury is exposure to a high-altitude hypoxic environment, which can lead to damage to the intestinal mucosal barrier. Taking NSAIDs in a high-altitude hypoxic environment can exacerbate GIT injury and impact gut microbiota. The aim of this study is to investigate the mechanisms by which resveratrol (RSV) intervention alleviates NSAID-induced intestinal injury in a high-altitude hypoxic environment, as well as its role in regulating gut microbiota. METHODS: Aspirin was administered orally to rats to construct a rat model of intestinal injury induced by NSAIDs. Following the induction of intestinal injury, rats were administered RSV by gavage, and the expression levels of TLR4, NF-κB,IκB as well as Zonula Occludens-1 (ZO-1) and Occludin proteins in the different treatment groups were assessed via Western blot. Furthermore, the expression of the inflammatory factors IL-10, IL-1ß, and TNF-α was evaluated using Elisa.16sRNA sequencing was employed to investigate alterations in the gut microbiota. RESULTS: The HCk group showed elevated expression of TLR4/NF-κB/IκB pathway proteins, increased expression of pro-inflammatory factors IL-1ß and TNF-α, decreased expression of the anti-inflammatory factor IL-10, and expression of intestinal mucosal barrier proteins ZO-1 and Occludin. The administration of NSAIDs drugs in the plateau hypoxic environment exacerbates intestinal inflammation and damage to the intestinal mucosal barrier. After treatment with RSV intervention, the expression of TLR4/NF-κB/IκB signaling pathway proteins would be reduced, thereby lowering the expression of inflammatory factors in the HAsp group. The results of HE staining directly show the damage to the intestines and the repair of intestinal mucosa after RSV intervention. 16sRNA sequencing results show significant differences (P<0.05) in Ruminococcus, Facklamia, Parasutterella, Jeotgalicoccus, Coprococcus, and Psychrobacter between the HCk group and the Ck group. Compared to the HCk group, the HAsp group shows significant differences (P<0.05) in Facklamia, Jeotgalicoccus, Roseburia, Psychrobacter, and Alloprevotella. After RSV intervention, Clostridium_sensu_stricto bacteria significantly increase compared to the HAsp group. CONCLUSION: Resveratrol can attenuate intestinal damage caused by the administration of NSAIDs at high altitude in hypoxic environments by modulating the TLR4/NF-κB/IκB signaling pathway and gut microbiota composition.


Asunto(s)
Altitud , Antiinflamatorios no Esteroideos , Microbioma Gastrointestinal , FN-kappa B , Ratas Sprague-Dawley , Resveratrol , Transducción de Señal , Receptor Toll-Like 4 , Animales , Resveratrol/farmacología , Receptor Toll-Like 4/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , FN-kappa B/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Ratas , Masculino , Transducción de Señal/efectos de los fármacos , Hipoxia/complicaciones , Hipoxia/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Proteínas I-kappa B/metabolismo , Aspirina/farmacología
6.
J Med Virol ; 96(8): e29794, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39101375

RESUMEN

Human herpesvirus 8 (HHV-8) infection shows obvious regional and ethnic differences. Although studies have shown that these differences may be associated with lipid metabolism, to date, no large-scale studies have explored this. This study explored the seropositivity rate of HHV-8 among 2516 residents from 10 regions of northwest China and then the correlates of HHV-8 infection with lipid profile. The HHV-8 serological positivity rate was 15.6% among all residents. The HHV-8 seroprevalence ranged 11.2-27.6% among different ethnicities. Across different BMI levels, the positive rates of HHV-8 were 27.6%, 16.9%, and 13.6% for a BMI < 18.5, 18.5-24.9, and ≥25, respectively. HHV-8 seropositivity rate was lower for hypertensive people (12.6%) than for non-hypertensive people (16.7%). Univariate logistic regression analyses revealed that age, hypertension, systolic blood pressure, BMI, total cholesterol, and high-density lipoprotein cholesterol (HDL-C) significantly correlated with HHV-8 seropositivity (p < 0.05). Multivariate logistic regression analysis after adjusting for confounding factors showed that HDL-C (odds ratio [OR]: 0.132, 95% confidence interval [CI], 0.082-0.212; p < 0.001) and BMI (OR: 0.959, 95% CI 0.933-0.986; p = 0.003) were associated with HHV-8 seropositivity. Subgroup analyses concerning ethnicity, sex, or age demonstrated a consistent relationship with HDL-C. The results of HHV-8 seropositivity and BMI were inconsistent in the subgroups. However, Spearman's correlation analysis between HHV-8 serum antibody titer and HDL-C levels showed no linear relationship among HHV-8 seropositive individuals (ρ = -0.080, p = 0.058). HHV-8 serum antibody titers were also not significantly correlated with BMI (ρ = -0.015, p = 0.381). Low HDL-C levels may be an independent risk factor for HHV-8 infection, but there is no significant correlation between HDL-C levels and HHV-8 antibody titers.


Asunto(s)
Infecciones por Herpesviridae , Herpesvirus Humano 8 , Lípidos , Humanos , Herpesvirus Humano 8/inmunología , China/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/sangre , Infecciones por Herpesviridae/virología , Adulto , Estudios Seroepidemiológicos , Anciano , Lípidos/sangre , Adulto Joven , Adolescente , Anticuerpos Antivirales/sangre , Factores de Riesgo , Anciano de 80 o más Años , Índice de Masa Corporal
7.
Neural Netw ; 179: 106480, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38986184

RESUMEN

Sequential recommender systems (SRSs) aim to suggest next item for a user based on her historical interaction sequences. Recently, many research efforts have been devoted to attenuate the influence of noisy items in sequences by either assigning them with lower attention weights or discarding them directly. The major limitation of these methods is that the former would still prone to overfit noisy items while the latter may overlook informative items. To the end, in this paper, we propose a novel model named Multi-level Sequence Denoising with Cross-signal Contrastive Learning (MSDCCL) for sequential recommendation. To be specific, we first introduce a target-aware user interest extractor to simultaneously capture users' long and short term interest with the guidance of target items. Then, we develop a multi-level sequence denoising module to alleviate the impact of noisy items by employing both soft and hard signal denoising strategies. Additionally, we extend existing curriculum learning by simulating the learning pattern of human beings. It is worth noting that our proposed model can be seamlessly integrated with a majority of existing recommendation models and significantly boost their effectiveness. Experimental studies on five public datasets are conducted and the results demonstrate that the proposed MSDCCL is superior to the state-of-the-art baselines. The source code is publicly available at https://github.com/lalunex/MSDCCL/tree/main.


Asunto(s)
Algoritmos , Humanos , Redes Neurales de la Computación , Aprendizaje Automático , Relación Señal-Ruido
8.
Nat Med ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39079993

RESUMEN

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

9.
Int J Biol Macromol ; 277(Pt 1): 134157, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39059522

RESUMEN

Ketoreductases play an indispensable role in the asymmetric synthesis of chiral drug intermediates, and an in-depth understanding of their substrate selectivity can improve the efficiency of enzyme engineering. In this endeavor, a new short-chain dehydrogenase/reductase (SDR) SsSDR1 identified from Sphingobacterium siyangense SY1 by gene mining method was successfully cloned and functionally expressed in Escherichia coli. Its activity against halogenated acetophenones has been tested and the results illustrated that SsSDR1-WT exhibits high activity for 3,5-bis(trifluoromethyl)acetophenone (1f), an important precursor in the synthesis of aprepitant. In addition, SsSDR1-WT showed obvious substrate preference for acetophenones without α-halogen substitution compared to their α-halogen analogs. To explore the structural basis of substrate selectivity, the X-ray crystal structures of SsSDR1-WT in its apo form and the complex structure with NAD were resolved. Taking 2-chloro-1-(3, 4-difluorophenyl) ethanone (1i) as the representative α-haloacetophenone, the key sites affecting substrate selectivity of SsSDR1-WT were identified and through the rational remodeling of the cavities C1 and C2 of SsSDR1, an excellent mutant I144A/S153L with significantly improved activity against α-halogenated acetophenones was obtained. The asymmetric catalysis of 1f and 1i was performed at the scale of 50 mL, and the space-time yields (STY) of the two were 1200 and 6000 g/L∙d, respectively. This study not only provides valuable biocatalysts for halogenated acetophenones, but also yields insights into the relationship between the substrate-binding pocket and substrate selectivity.


Asunto(s)
Acetofenonas , Sphingobacterium , Acetofenonas/química , Acetofenonas/metabolismo , Especificidad por Sustrato , Sphingobacterium/enzimología , Sphingobacterium/genética , Modelos Moleculares , Cristalografía por Rayos X , Relación Estructura-Actividad , Cinética , Dominio Catalítico
10.
Front Neurorobot ; 18: 1423738, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015151

RESUMEN

Introduction: Road cracks significantly shorten the service life of roads. Manual detection methods are inefficient and costly. The YOLOv5 model has made some progress in road crack detection. However, issues arise when deployed on edge computing devices. The main problem is that edge computing devices are directly connected to sensors. This results in the collection of noisy, poor-quality data. This problem adds computational burden to the model, potentially impacting its accuracy. To address these issues, this paper proposes a novel road crack detection algorithm named EMG-YOLO. Methods: First, an Efficient Decoupled Header is introduced in YOLOv5 to optimize the head structure. This approach separates the classification task from the localization task. Each task can then focus on learning its most relevant features. This significantly reduces the model's computational resources and time. It also achieves faster convergence rates. Second, the IOU loss function in the model is upgraded to the MPDIOU loss function. This function works by minimizing the top-left and bottom-right point distances between the predicted bounding box and the actual labeled bounding box. The MPDIOU loss function addresses the complex computation and high computational burden of the current YOLOv5 model. Finally, the GCC3 module replaces the traditional convolution. It performs global context modeling with the input feature map to obtain global context information. This enhances the model's detection capabilities on edge computing devices. Results: Experimental results show that the improved model has better performance in all parameter indicators compared to current mainstream algorithms. The EMG-YOLO model improves the accuracy of the YOLOv5 model by 2.7%. The mAP (0.5) and mAP (0.9) are improved by 2.9% and 0.9%, respectively. The new algorithm also outperforms the YOLOv5 model in complex environments on edge computing devices. Discussion: The EMG-YOLO algorithm proposed in this paper effectively addresses the issues of poor data quality and high computational burden on edge computing devices. This is achieved through optimizing the model head structure, upgrading the loss function, and introducing global context modeling. Experimental results demonstrate significant improvements in both accuracy and efficiency, especially in complex environments. Future research can further optimize this algorithm and explore more lightweight and efficient object detection models for edge computing devices.

11.
Sci Rep ; 14(1): 15056, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38956075

RESUMEN

Celiac Disease (CD) is a primary malabsorption syndrome resulting from the interplay of genetic, immune, and dietary factors. CD negatively impacts daily activities and may lead to conditions such as osteoporosis, malignancies in the small intestine, ulcerative jejunitis, and enteritis, ultimately causing severe malnutrition. Therefore, an effective and rapid differentiation between healthy individuals and those with celiac disease is crucial for early diagnosis and treatment. This study utilizes Raman spectroscopy combined with deep learning models to achieve a non-invasive, rapid, and accurate diagnostic method for celiac disease and healthy controls. A total of 59 plasma samples, comprising 29 celiac disease cases and 30 healthy controls, were collected for experimental purposes. Convolutional Neural Network (CNN), Multi-Scale Convolutional Neural Network (MCNN), Residual Network (ResNet), and Deep Residual Shrinkage Network (DRSN) classification models were employed. The accuracy rates for these models were found to be 86.67%, 90.76%, 86.67% and 95.00%, respectively. Comparative validation results revealed that the DRSN model exhibited the best performance, with an AUC value and accuracy of 97.60% and 95%, respectively. This confirms the superiority of Raman spectroscopy combined with deep learning in the diagnosis of celiac disease.


Asunto(s)
Enfermedad Celíaca , Aprendizaje Profundo , Espectrometría Raman , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/sangre , Humanos , Espectrometría Raman/métodos , Femenino , Masculino , Adulto , Redes Neurales de la Computación , Estudios de Casos y Controles , Persona de Mediana Edad
12.
Molecules ; 29(14)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39064872

RESUMEN

Applying chemical enhanced oil recovery (EOR) to shale and tight formations is expected to accelerate China's Shale Revolution as it did in conventional reservoirs. However, its screening and modeling are more complex. EOR operations are faced with choices of chemicals including traditional surfactant solutions, surfactant solutions in the form of micro-emulsions (nano-emulsions), and nano-fluids, which have similar effects to surfactant solutions. This study presents a systematic comparative analysis composed of laboratory screening and numerical modeling. It was conducted on three scales: tests of chemical morphology and properties, analysis of micro-oil-displacing performance, and simulation of macro-oil-increasing effect. The results showed that although all surfactant solutions had the effects of reducing interfacial tension, altering wettability, and enhancing imbibition, the nano-emulsion with the lowest hydrodynamic radius is the optimal selection. This is attributed to the fact that the properties of the nano-emulsion match well with the characteristics of these shale and tight reservoirs. The nano-emulsion is capable of integrating into the tight matrix, interacting with the oil and rock, and supplying the energy for oil to flow out. This study provides a comprehensive understanding of the role that surfactant solutions could play in the EOR of unconventional reservoirs.

13.
Sci Rep ; 14(1): 16640, 2024 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-39025873

RESUMEN

The Internet of Things (IoT) is an extensive system of interrelated devices equipped with sensors to monitor and track real world objects, spanning several verticals, covering many different industries. The IoT's promise is capturing interest as its value in healthcare continues to grow, as it can overlay on top of challenges dealing with the rising burden of chronic disease management and an aging population. To address difficulties associated with IoT-enabled healthcare, we propose a secure routing protocol that combines a fuzzy logic system and the Whale Optimization Algorithm (WOA) hierarchically. The suggested method consists of two primary approaches: the fuzzy trust strategy and the WOA-inspired clustering methodology. The first methodology plays a critical role in determining the trustworthiness of connected IoT equipment. Furthermore, a WOA-based clustering framework is implemented. A fitness function assesses the likelihood of IoT devices acting as cluster heads. This formula considers factors such as centrality, range of communication, hop count, remaining energy, and trustworthiness. Compared with other algorithms, the proposed method outperformed them in terms of network lifespan, energy usage, and packet delivery ratio by 47%, 58%, and 17.7%, respectively.


Asunto(s)
Algoritmos , Lógica Difusa , Internet de las Cosas , Atención a la Salud , Humanos , Análisis por Conglomerados , Redes de Comunicación de Computadores
15.
Biotechnol Bioeng ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39082641

RESUMEN

d-Lactic acid holds significant industrial importance due to its versatility and serves as a crucial component in the synthesis of environmentally friendly and biodegradable thermal-resistant poly-lactic acid. This polymer exhibits promising potential as a substitute for nonbiodegradable, petroleum-based plastics. The production of d-lactic acid from lignocellulosic biomass, a type of biorenewable and nonfood resources, can lower costs and improve product competitiveness. Glucose and xylose are the most abundant sugar monomers in lignocellulosic biomass materials. Despite Escherichia coli possessing native xylose catabolic pathways and transport, their ability to effectively utilize xylose is often hindered in the presence of glucose. Here, the E. coli strain Rec1.0, previously engineered to overcome carbon catabolite repression, was selected as the initial strain for reengineering to produce d-lactic acid. An adaptive evolution approach was employed to achieve highly efficient fermentation of glucose-xylose mixtures. The resulting strain, QJL010, could produce d-lactic acid of 87.5 g/L with a carbon yield of 0.99 mol/mol. Notably, the consumption rates of glucose and xylose reached 0.75 and 0.82 g/gDCW/h, respectively. Further analysis revealed that increased Glk activity, resulting from glk mutations (A142V and R188H), along with their upregulated expression, contributed to an elevated glucose consumption rate. Additionally, a CRP G141D mutation, cAMP-independent, stimulated the expression of the xylR, xylE, and galABC* genes, resulting in an accelerated xylose consumption rate. These findings provide valuable support for the utilization of E. coli platform strains in the production of value-added chemicals from lignocellulosic biomass.

16.
J Zhejiang Univ Sci B ; 25(7): 541-556, 2024 Jul 15.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39011675

RESUMEN

The protein kinase B (Akt) pathway can regulate the growth, proliferation, and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes, thus affecting the development and treatment of a range of diseases. Thioesterase superfamily member 4 (THEM4), a member of the thioesterase superfamily, is one of the Akt kinase-binding proteins. Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation. Initially, THEM4 was considered an endogenous inhibitor of Akt, which can inhibit the phosphorylation of Akt in diseases such as lung cancer, pancreatic cancer, and liver cancer, but subsequently, THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma, which contradicts previous findings. Considering these two distinct views, this review summarizes the important roles of THEM4 in the Akt pathway, focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases, especially cancer. This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.


Asunto(s)
Neoplasias , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosforilación , Neoplasias/metabolismo , Proliferación Celular , Animales , Neoplasias de la Mama/metabolismo , Femenino , Proteínas Adaptadoras Transductoras de Señales
17.
RSC Adv ; 14(32): 23322-23331, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39049885

RESUMEN

Nanofluid application in enhanced oil recovery (EOR) recently emerged and garnered significant attention within the field. Nanofluids possess unique properties of reducing oil-water interfacial tension, stabilizing emulsions, altering rock surface wettability, and enhancing disjoining pressure between crude oil and rock surfaces, therefore have potential for the oil recovery process. This review provides an in-depth exploration of various aspects related to nanofluids in EOR. Different types of nanofluids are presented with their preparation methods and representative properties. More importantly, the disjoining pressure, a key physical concept in nanofluid-assisted EOR, is introduced and discussed in terms of the mechanism of oil displacement and measurement methods. Further understanding the role of disjoining pressure in nanofluid-assisted oil displacement is necessary for the development and application of effective nanofluids for EOR.

18.
ACS Omega ; 9(22): 23903-23916, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38854575

RESUMEN

Microemulsions are one of the most promising directions in enhanced oil recovery, but conventional screening methods are time-consuming and labor-intensive and lack the means to analyze them at the microscopic level. In this paper, we used the Clint model to predict the changes in the synergistic effect of the mixed system of anionic surfactant sodium dodecyl benzenesulfonate and nonionic surfactant polyethoxylated fatty alcohols (C12E6), generated microemulsions using surfactant systems with different mole fractions, and used particle size to analyze the performance and stability of microemulsions, analyze the properties and stability of microemulsions using particle size, and analyze the interfacial behaviors and changes of microemulsions when different systems constitute microemulsions from the point of view of mesoscopic microemulsion self-assembly behaviors by combining with dissipative particle dynamics. It has been shown that microemulsion systems generated from anionic and nonanionic surfactants with a synergistic effect, based on the Clint model, exhibit excellent performance and stability at the microscopic level. The method proposed in this paper can dramatically improve the screening efficiency of microemulsions of anionic and nonanionic surfactants and accurately analyze the properties of microemulsions, so as to provide a theoretical basis for the subsequent research on microemulsions.

19.
BMC Anesthesiol ; 24(1): 197, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834948

RESUMEN

BACKGROUND: Ciprofol is a promising sedative. This study aims to explore the median effective dose (ED50) of ciprofol in inhibiting responses to fiberoptic bronchoscopy in patients with pulmonary tuberculosis (PTB) of different genders and ages when combined with 0.15 µg/kg sufentanil, and to evaluate its efficacy and safety, providing a reference for the rational use of ciprofol in clinical practice. METHODS: PTB patients who underwent bronchoscopy examination and treatment at The Third People's Hospital of Changzhou between May 2023 and June 2023 were selected and divided into four groups using a stratified random method. All patients received intravenous injection of 0.15 µg/kg sufentanil followed by injection of the test dose of ciprofol according to Dixon's up-and-down method. The initial dose of ciprofol in all four groups was 0.4 mg/kg, with an adjacent ratio of 1:1.1. The next patient received a 10% increase in the dose of ciprofol if the previous patient in the same group experienced positive reactions such as choking cough, frowning, and body movements during the endoscopy. Otherwise, it was judged as a negative reaction, and the next patient received a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study of the group was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points in all groups. The Probit regression analysis method was used to calculate the ED50 of ciprofol in the four groups and compare between the groups. RESULTS: The ED50 of ciprofol combined with 0.15 µg/kg sufentanil for bronchoscopy in the four groups were 0.465 mg/kg, 0.433 mg/kg, 0.420 mg/kg and 0.396 mg/kg, respectively. CONCLUSION: The ED50 of ciprofol used for fiberoptic bronchoscopy varied among PTB patients of different genders and ages. TRIAL REGISTRATION: The Chinese Clinical Trial Registry, ChiCTR2300071508, Registered on 17 May 2023.


Asunto(s)
Broncoscopía , Tecnología de Fibra Óptica , Sufentanilo , Tuberculosis Pulmonar , Humanos , Masculino , Broncoscopía/métodos , Femenino , Persona de Mediana Edad , Sufentanilo/administración & dosificación , Adulto , Tuberculosis Pulmonar/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Anciano , Hipnóticos y Sedantes/administración & dosificación , Adulto Joven , Quimioterapia Combinada
20.
Polymers (Basel) ; 16(11)2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38891451

RESUMEN

This work aimed to investigate the effects of aging on the microstructures and rheological properties of modified asphalt with a GO/SBS composite, since the styrene-butadiene-styrene block copolymer is potentially compatible with graphene oxide (GO). The GO/SBS composites, which were used as a kind of modifier, were prepared via the solution-blending method. GO/SBS composites with varying GO contents were employed to prepare the GO/SBS-compound-modified asphalt (GO/SBS-MA). Then, the GO/SBS-MA underwent PAV (pressure aging vessel) or UV (ultraviolet) aging tests to simulate different aging circumstances. The microstructures of the asphalt binders were studied using FTIR (Fourier-transform infrared spectroscopy) and AFM (atomic force microscope) tests. Moreover, DSR (dynamic shear rheometer) and BBR (bending beam rheometer) experiments were carried out to investigate the rheological properties of the GO/SBS-MA. The results showed that the addition of GO improved the high-temperature stability of the asphalt binder while slightly impairing its performance at low temperatures. GO restrained the formation of carbonyl and sulfoxide groups as well as the breakdown of C=C bonds in the polybutadiene (PB) segment, promoting the anti-aging performance of GO/SBS-MA. Furthermore, the interactions between the GO/SBS and the asphalt binder resulted in the formation of needle-like aggregates, enhancing the stability of the asphalt binder. The asphalt binders with a higher content of graphene oxide (GO) exhibited not only a better high-temperature performance, but also a better aging resistance. It was concluded that the macroscopic properties and microstructures were significantly affected by GO, and a moderate increase in the amount of GO could contribute to a better aging resistance for GO/SBS-MA.

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