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Environmental exposure to the cadmium (Cd) has been shown to be a risk factor for colorectal cancer (CRC) progression, but the exact mechanism has not been fully elucidated. In this study, we found that chronic Cd (3⯵M) exposure promoted the proliferation, adhesion, migration, and invasion of CRC cells in vitro, as well as lung metastasis in vivo. RNA-seq and TCGA-COAD datasets revealed that decreased hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) expression may be a crucial factor in Cd-induced CRC progression. Further analysis using qRT-PCR and tissue microarrays from CRC patients showed that HADHB expression was significantly reduced in CRC tissues compared to adjacent normal tissues, and low HADHB expression was associated with adverse clinical features and poor overall survival, either directly or through TNM stage. Furthermore, HADHB was found to play an important role in the Cd-induced malignant metastatic phenotype of CRC cells and lung metastasis in mice. Mechanistically, we discovered that chronic Cd exposure resulted in hypermethylation of the HADHB promoter region via inhibition of DNA demethylase tet methylcytosine dioxygenase 2 (TET2), which then led to decreased HADHB expression and activation of the FAK signaling pathway, and ultimately contributed to CRC progression. In conclusion, this study provided a new potential insight and evaluable biomarker for Cd exposure-induced CRC progression and treatment.
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Cadmio , Neoplasias Colorrectales , Proteínas de Unión al ADN , Dioxigenasas , Progresión de la Enfermedad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inducido químicamente , Humanos , Dioxigenasas/genética , Animales , Ratones , Cadmio/toxicidad , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Línea Celular Tumoral , Masculino , Proliferación Celular/efectos de los fármacos , Femenino , Ratones Desnudos , Metilación de ADN/efectos de los fármacos , Movimiento Celular/efectos de los fármacosRESUMEN
Auxin regulates plant growth and development through the transcription factors of the AUXIN RESPONSE FACTOR (ARF) gene family. ARF7 is one of five activators that bind DNA and elicit downstream transcriptional responses. In roots, ARF7 regulates growth, gravitropism and redundantly with ARF19, lateral root organogenesis. In this study we analyzed ARF7 cis-regulation, using different non-coding sequences of the ARF7 locus to drive GFP. We show that constructs containing the first intron led to increased signal in the root tip. Although bioinformatics analyses predicted several transcription factor binding sites in the first intron, we were unable to significantly alter expression of GFP in the root by mutating these. We instead observed the intronic sequences needed to be present within the transcribed sequences to drive expression in the root meristem. These data support a mechanism by which intron-mediated enhancement regulates the tissue specific expression of ARF7 in the root meristem.
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A series of V-xCe/Ti catalysts was prepared by a step impregnation method with gradual increased Ce amount. Compared to the commercial V-W/Ti catalysts, the V-xCe/Ti catalysts exhibited considerably higher COx selectivity during the oxidation of naphthalene (Nap), and less intermediates or by-products were detected both in gas phase and on the surface of the catalysts. Through a series of characterizations, it was found that abundance of weak basic sites in the form of OH was introduced by Ce, as well as the oxygen vacancies caused by the redox cycle of V4++Ce4+âV5++Ce3+. The weak basic sites introduced by Ce could greatly enhance the Nap adsorption, and the Nap adsorbed was quickly converted to naphthol on Ce-OH. Furthermore, V existed at a high valence with the interaction of V and Ce, and the oxygen vacancies also increased the Oads and OOH. It improved the redox ability and the regeneration of Ce-OH on V-xCe/Ti catalysts. The intermediates could be further oxidized, and the Ce-OH consumed in the reaction could recover quickly. Therefore, almost 100% Nap conversion and a high COx selectivity was observed in the V-xCe/Ti catalysts system.
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Naftalenos , Oxidación-Reducción , Naftalenos/química , Catálisis , AdsorciónRESUMEN
The electrocatalytic carbon dioxide reduction reaction (ECO2RR) is a promising way to realize the transformation of waste into valuable material, which can not only meet the environmental goal of reducing carbon emissions, but also obtain clean energy and valuable industrial products simultaneously. Herein, we first introduce the complex CO2RR mechanisms based on the number of carbons in the product. Since the coupling of C-C bonds is unanimously recognized as the key mechanism step in the ECO2RR for the generation of high-value products, the structural-activity relationship of electrocatalysts is systematically reviewed. Next, we comprehensively classify the latest developments, both experimental and theoretical, in different categories of cutting-edge electrocatalysts and provide theoretical insights on various aspects. Finally, challenges are discussed from the perspectives of both materials and devices to inspire researchers to promote the industrial application of the ECO2RR at the earliest.
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For health and safety reasons, the search for green, healthy, and low-calorie sweeteners with good taste has become the demand of many consumers. Furthermore, the need for sugar substitutes of natural origin has increased dramatically. In this review, we briefly discussed the safety and health benefits of stevia sweeteners and enumerated some examples of physiological functions of steviol glycosides (SGs), such as anti-inflammatory, anti-obesity, antihypertensive, anti-diabetes, and anticaries, citing various evidence related to their application in the food industry. The latest advances in emerging technologies for extracting and purifying SGs and the process variables and operational strategies were discussed. The impact of the extraction methods and their comparison against the conventional techniques have also been demonstrated. These technologies use minimal energy solvents and simplify subsequent purification stages, making viable alternatives suitable for a possible industrial application. Furthermore, we also elucidated the potential for advancing and applying the natural sweeteners SGs.
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Diterpenos de Tipo Kaurano , Extractos Vegetales , Stevia , Edulcorantes , Stevia/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/química , Edulcorantes/aislamiento & purificación , Edulcorantes/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Humanos , Glucósidos/aislamiento & purificación , Glucósidos/química , Animales , Glicósidos/aislamiento & purificación , Glicósidos/químicaRESUMEN
Objective: To investigate the structure, composition, and functions of the gut microbiota in elderly patients with hyperlipidemia. Methods: Sixteen older patients diagnosed with hyperlipidemia (M group) and 10 healthy, age-matched normal volunteers (N group) were included. These groups were further subdivided by sex into the male normal (NM, n = 5), female normal (NF, n = 5), male hyperlipidemia (MM, n = 8), and female hyperlipidemia (MF, n = 8) subgroups. Stool samples were collected for high-throughput sequencing of 16S rRNA genes. Blood samples were collected for clinical biochemical index testing. Results: Alpha- and beta-diversity analyses revealed that the structure and composition of the gut microbiota were significantly different between the M and N groups. The relative abundances of Bacteroides, Parabacteroides, Blautia, Peptococcus, and Bifidobacterium were significantly decreased, while those of Lactobacillus, Helicobacter, and Desulfovibrio were significantly higher in the M group. There were also significant sex-related differences in microbial structure between the NM and NF groups, and between the MM and MF groups. Through functional prediction with PICRUSt 2, we observed distinct between-group variations in metabolic pathways associated with the gut microbiota and their impact on the functionality of the nervous system. Pearson's correlation coefficient was used as a distance metric to build co-abundance networks. A hypergeometric test was used to detect taxonomies with significant enrichment in specific clusters. We speculated that modules with Muribaculaceae and Lachnospiraceae as the core microbes play an important ecological role in the intestinal microbiota of the M group. The relative intestinal abundances of Agathobacter and Faecalibacterium in the M group were positively correlated with serum triglyceride and low-density lipoprotein levels, while the relative abundance of Bifidobacterium was negatively correlated with the serum lipoprotein a level.
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Bacterias , Heces , Microbioma Gastrointestinal , Hiperlipidemias , ARN Ribosómico 16S , Humanos , Microbioma Gastrointestinal/genética , Masculino , Femenino , Anciano , Hiperlipidemias/microbiología , ARN Ribosómico 16S/genética , Heces/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Persona de Mediana Edad , Anciano de 80 o más AñosRESUMEN
At present, anti-cancer drug synergy therapy is one of the most important methods to overcome drug resistance and reduce drug toxicity in cancer treatment. High-throughput screening through deep learning can effectively improve the efficiency of discovering synergistic drugs. Nowadays, most of the existing deep learning algorithms for anti-cancer drug synergy prediction use deep neural networks and can only implicitly perform feature interaction. This study proposes a deep learning algorithm, named MolCross, which combines implicit feature interaction with explicit features to improve the accuracy of prediction of the anti-cancer drug synergy score. MolCross uses a deep autoencoder to extract features from high-dimensional input, uses the drug-specific subnetworks and cross-network to perform implicit feature interaction and explicit feature interaction respectively, and finally uses a synergy prediction network to combine the two feature interaction methods to obtain the final prediction results. We adopted a five-fold cross validation and compared MolCross with other four anti-cancer drug synergy prediction models. The results show that MolCross has better prediction performance than other models. MolCross also has good performance in terms of cross-cell line and cross-tissue type. Existing studies have demonstrated that cancer molecular subtypes have different sensitivities to targeted therapy. In this study, the features of cancer molecular subtype were introduced in the model using an embedding layer in MolCross to explore the effect of cancer molecular subtype on anti-cancer drug synergy. We also found that the cancer molecular subtype is one of the main factors affecting the synergy between drugs.
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Antineoplásicos , Aprendizaje Profundo , Sinergismo Farmacológico , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Algoritmos , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI. METHODS: TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t -test. RESULTS: TSPO- KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1ß, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO -KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO -KO cells. CONCLUSION: TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.
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Lesión Pulmonar Aguda , Inflamasomas , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Receptores de GABA , Animales , Lesión Pulmonar Aguda/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Ratones , Piroptosis/fisiología , Receptores de GABA/metabolismo , Receptores de GABA/genética , Inflamasomas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Lipopolisacáridos , Ratones Endogámicos C57BL , Masculino , Macrófagos/metabolismoRESUMEN
Dried shiitake mushrooms offer rich nutritional value and unique sensory properties, prompting further investigation. The effects of different drying techniques (hot air drying (HAD), infrared hot air drying (IRHAD), pulsed vacuum drying (PVD), vacuum freeze drying (VFD), and natural drying (ND)) combined with enzymatic hydrolysis on the release of flavor compounds and nutrients from shiitake mushrooms were explored. The combination of HAD with cellulase hydrolysis yielded notably high levels of umami amino acids (5.4723 ± 0.1501 mg/g) and 5'-nucleotides (4.0536 ± 0.0062 mg/g), and superior volatile flavors. Combined with cellulase hydrolysis, IRHAD achieved the highest level of total sugars (6.57 ± 0.34 mg/mL), VFD resulted in the greatest soluble protein content (153.21 ± 0.23 µg/mL), PVD yielded the highest total phenolics content (93.20 ± 0.41 µg GAE/mL), and ND produced the maximum reducing sugar content (5.79 ± 0.13 mg/mL). This study addresses crucial gap in the post-drying processing of shiitake mushrooms, offering valuable insights for further product development of shiitake mushrooms.
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Celulasa , Desecación , Valor Nutritivo , Hongos Shiitake , Gusto , Hongos Shiitake/química , Hidrólisis , Desecación/métodos , Celulasa/química , Celulasa/metabolismo , Humanos , Aromatizantes/química , Manipulación de Alimentos , Aminoácidos/análisis , Aminoácidos/químicaRESUMEN
Although a promising method for lignin depolymerization, photocatalysis faces the challenge of low efficiency. In this study, MoS2/ZnO heterojunction catalysts, endowed with piezocatalysis and photocatalytic capabilities, were crafted through Zn ion intercalation for the depolymerization of phenoxyphenylethanol (PP-ol) and alkali lignin. Then, the synergistic interplay between ultrasonic-induced piezoelectric fields and heterojunctions was analyzed. The amalgamation of the piezoelectric field and heterojunction in MoS2/ZnO catalysts resulted in a diminished photogenerated hole/electron recombination efficiency, thereby fostering the generation of ·OH during the reaction. This pivotal role of ·OH emerged as a crucial reactive substance, converting 95.8 % of PP-ol through ß-O-4 bond breaking within a 3-h treatment. By incorporating ultrasonic, the contact probability of PP-ol with the catalyst was significantly improved, resulting in efficient conversion even with a reduced amount of acetonitrile in the solvent system (20 %). Furthermore, ultrasonic-light methods show high efficiency for depolymerizing Alkali lignin (AL), with 33.2 % of lignin undergoing depolymerization in a 4-h treatment. This treatment simultaneously reduces the molecular weight of AL and cleaves numerous chemical bonds within it. Overall, this work presents a green approach to lignin depolymerization, providing insights into the synergistic action of ultrasonic and photocatalysis.
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Lignina , Óxido de Zinc , Lignina/química , Ultrasonido , Molibdeno , Catálisis , ÁlcalisRESUMEN
Cigarette smoking substantially promotes tumorigenesis and progression of colorectal cancer; however, the underlying molecular mechanism remains unclear. Among 662 colorectal cancer patients, our investigation revealed a significant correlation between cigarette smoking and factors, such as large tumor size, poor differentiation, and high degree of invasion. Among the nicotine-derived nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) emerged as the most critical carcinogen, which significantly promoted the malignant progression of colorectal cancer both in vivo and in vitro. The results of methylated RNA immunoprecipitation and transcriptome sequencing indicated that NNK upregulated transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) via N6-adenosine methylation, which was regulated by methyltransferase-like 14 (METTL14) and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Elevated TMUB1 levels were associated with a higher risk of cancer invasion and metastasis, leading to a high mortality risk in patients with colorectal cancer. Additionally, TMUB1 promoted lysine63-linked ubiquitination of AKT by interacting with AMFR, which led to the induction of malignant proliferation and metastasis in colorectal cancer cells exposed to NNK. In summary, this study provides a new insight, indicating that targeting TMUB1 expression via METTL14/YTHDF2 mediated N6-adenosine methylation may be a potential therapeutic and prognostic target for patients with colorectal cancer who smoke.
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Adenina/análogos & derivados , Neoplasias Colorrectales , Nicotina , Humanos , Proteínas Proto-Oncogénicas c-akt , Adenosina , Proteínas de Unión al ARN , Metiltransferasas/genéticaRESUMEN
Oxygen evolution reaction (OER) is the key anode reaction of electrolytic water. To improve the slow OER kinetics, we synthesize nanoflower-like Co-Fe-Cr-Mo-Mn high-entropy spinel (HES) nanosheets on nickel foam (NF) by one-step solvothermal method, which exhibit an overpotential (η10) of only 188â mV at 10â mA cm-2, much lower than bimetallic CoFeOx/NF (233â mV), trimetallic CoFeCrOx/NF (211â mV), and tetrametallic CoFeCrMoOx/NF (200â mV). The OER overpotential decreases with the increase of the number of metals, indicating that the formation of HES has a positive effect on the improvement of electrocatalytic performance, since the synergistic effect between different metals enhances the charge transfer rate and decreases reaction barrier. In-situ Raman spectra demonstrate that the formation of γ-NiOOH on the HES surface is a crucial active species for the OER. This work demonstrates a simple and efficient synthesis method to prepare nanoflower-like high-entropy electrocatalysts for efficient OER electrocatalysis.
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The development of high activity and strong resistance to seawater corrosion oxygen evolution reaction (OER) electrocatalysts for seawater electrolysis has broad application prospects. Herein, we prepare Co-doped FeNiOOH rosette-like nanoflowers on nickel foam (NF) with different Co dosages by one-step solvothermal method. The Co0.2-FeNiOOH/NF exhibits a low overpotential (η10) of 185 mV and Tafel slope of 30 mV dec-1 in 1 M KOH. Moreover, it shows a low η10 of 244 mV in alkaline seawater electrolyte. The remarkable OER performance of Co0.2-FeNiOOH/NF is ascribed to the fact that the introduction of Co regulates the morphology and electron structure of the material, which provides abundant active sites for the reaction and promotes charge transfer. In situ Raman results demonstrate that NiOOH and γ-FeOOH are the key active species for the OER. This study provides a feasible basis for seawater electrolysis over transition metal (oxy)hydroxides.
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γδ T cells have the unique ability to detect a wide range of tumors with low mutation burdens, making them attractive candidates for CAR-T-cell therapy. Unlike αß T cells and other immune cells, γδ T cells are superior in MHC non-restriction, selective cell recruitment, and rapid activation. However, clinical trials have shown limited clinical benefits, and the adoptive transplantation of γδ T cells has often fallen short of expectations. We hypothesized that the limited effectiveness of γδ T cells in eradicating tumor cells may be attributed to the inhibitory tumor microenvironment induced by the suppressive PD-1/PD-L1 axis. Herein, we constructed novel armored γδ T cells capable of secreting humanized anti-PD-1 antibodies, referred to as "Lv-PD1-γδ T cells. Lv-PD1-γδ T cells showed improved proliferation and enhanced cytotoxicity against tumor cells, resulting in augmented therapeutic effects and survival benefits in ovarian tumor-bearing mice. These engineered cells demonstrated a prolonged in vivo survival of more than 29 days, without any potential for tumorigenicity in immunodeficient NOD/SCID/γ null mice. We also found that Lv-PD1-γδ T cells exhibited excellent tolerance and safety in humanized NOD/SCID/γ null mice. With attenuated or eliminated immunosuppression and maximized cytotoxicity efficacy by the local secretion of anti-PD1 antibodies in tumors, Lv-PD1-γδ T cells can serve as a promising "off-the-shelf" cell therapy against cancers.
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Neoplasias Ováricas , Linfocitos T , Humanos , Femenino , Ratones , Animales , Ratones SCID , Ratones Endogámicos NOD , Neoplasias Ováricas/terapia , Neoplasias Ováricas/tratamiento farmacológico , Inmunoterapia Adoptiva/métodos , Microambiente TumoralRESUMEN
High-entropy materials (HEMs) have potential application value in electrocatalytic water splitting because of their unique alloy design concept and significant mixed entropy effect. Here, we synthesize a high-entropy Ni-Fe-Cr-Mn-Co (oxy)hydroxide on nickel foam (NF) by a solvothermal method. The flower-like structure of FeNiCrMnCoOOH/NF can provide abundant active sites, thus improving the oxygen evolution reaction (OER) activity. In 1 M KOH, the FeNiCrMnCoOOH/NF shows an ultra-low overpotential (η10) of 201 mV for the OER, superior to FeNiCrMnAlOOH/NF, FeNiCrMnCuOOH/NF, FeNiCrMnMoOOH/NF, and FeNiCrMnCeOOH/NF. In addition, it exhibits a low η10 of 223 mV in 0.5 M NaCl + 1 M KOH and excellent stability. Electrochemical impedance spectroscopy measurements indicate that the synergistic effect between multiple metals accelerates charge transfer, while in situ Raman measurements reveal that NiOOH is a key active species for the OER. This work is of great significance for the construction of high-entropy (oxy)hydroxides for seawater electrolysis.
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In legumes, a common phenomenon known as nyctinastic movement is observed. This movement involves the horizontal expansion of leaves during the day and relative vertical closure at night. Nyctinastic movement is driven by the pulvinus, which consists of flexor and extensor motor cells. The turgor pressure difference between these two cell types generates a driving force for the bending and deformation of the pulvinus. This review focuses on the developmental mechanisms of the pulvinus, the factors affecting nyctinastic movement, and the biological significance of this phenomenon in legumes, thus providing a reference for further research on nyctinastic movement.
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Fabaceae , Pulvino , Hojas de la Planta/metabolismo , Pulvino/metabolismo , MovimientoRESUMEN
To improve the antimicrobial ability of MoS2-containing films, we used lignin and triple-frequency ultrasound for liquid-phase exfoliation (LPE) to obtain MoS2 nanosheets. Photoresponsive antimicrobial films with MoS2 nanosheets, lignin, polyvinyl alcohol and deep eutectic solvents were subsequently prepared. Lignin functionalized the MoS2 nanosheets by chemically linking with S in MoS2 and significantly improved the exfoliation efficiency. Tri-frequency ultrasound produces beneficial effects on the LPE process by creating a more homogeneous sound field and a stronger degree of cavitation. The concentration of MoS2 nanosheets in the exfoliating solution could reach 1.713 mg/mL under the effect of lignin-ultrasound. The antimicrobial ability of the films was analyzed, and the colony-forming units of E. coli and S. aureus could be reduced from 7 × 106 to 1 × 106 cfu/mL under the irradiation of infrared. The lignin in the film undergoes depolymerization and demethoxylation under the irradiation of infrared to have a more phenolic hydroxyl structure, which confers the growth inhibition ability of the films for bacteria that cannot be in close contact with the film. The method we used has some significance for the preparation of MoS2 nanosheets, and composite films prepared from MoS2, and lignin can be used in food packaging, wound antimicrobials, and other fields.
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Antiinfecciosos , Lignina , Lignina/farmacología , Molibdeno/farmacología , Escherichia coli , Staphylococcus aureus , Antiinfecciosos/farmacologíaRESUMEN
Objectives: Due to the severity of cancer, patients may experience feelings of helplessness and despair, resulting in demoralization among lung cancer patients. In this study, we investigated the risk factors of demoralization in middle-aged and older Chinese lung cancer patients via their relationship with patients' demographic data and disease characteristics. Methods: This study is a cross-sectional descriptive study using a structured questionnaire including assessments of demographic data and disease, the Demoralization Scale Mandarin Version (DS-MV), the Social Support Rate Scale (SSRS), the Medical Coping Modes Questionnaire (MCMQ), as well as The European Organization for Research and Treatment of Cancer (EORTC QLQ-C30). Results: Overall, 289/300 (96.3%) patients with lung cancer completed questionnaires. The mean score of DS-MV was 49.27 (SD=15.19) (range, 21-81) and the mean score of SSRS was 33.37 (SD=5.43) (range,17-48). Multiple linear regression analysis identified high demoralization was significantly related to age (p<.001), medical payment (p=.003), times of chemotherapy (p=.026), family monthly income (p=.025), avoidance dimension (p<.001), surrender dimension (p<.001), social support (p=.001), symptom score (p<.001), overall health score (p=.009) and function score (p<.001). Conclusion: This study demonstrates the factors influencing demoralization among middle-aged and older lung cancer patients. Demoralization is a prevalent psychiatric problem in Chinese lung cancer patients. Therefore, we recommend strong social support to be protective against demoralization. We suggest that medical staff establish the concept of social support for patients with lung cancer, actively seek effective resources from family, friends, and other social support organizations to help patients establish a social support system that improves patient courage and confidence in their post-cancer life.
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Desmoralización , Neoplasias Pulmonares , Persona de Mediana Edad , Humanos , Anciano , Estudios Transversales , Factores de Riesgo , ChinaRESUMEN
BACKGROUND: Growing evidence indicates that RNA methylation plays a fundamental role in epigenetic regulation, which is associated with the tumorigenesis and drug resistance. Among them, acute myeloid leukemia (AML), as the top acute leukemia for adults, is a deadly disease threatening human health. Although N7-methylguanosine (m7G) has been identified as an important regulatory modification, its distribution has still remained elusive. METHODS: The present study aimed to explore the long non-coding RNA (lncRNA) functional profile of m7G in AML and drug-resistant AML cells. The transcriptome-wide m7G methylation of lncRNA was analyzed in AML and drug-resistant AML cells. RNA MeRIP-seq was performed to identify m7G peaks on lncRNA and differences in m7G distribution between AML and drug-resistant AML cells. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to predict the possible roles and m7G-associated pathway. RESULTS: Using m7G peak sequencing, it was found that a sequence motif was necessary for m7G methylation in drug-resistant AML lncRNA. Unsupervised hierarchical cluster analysis confirmed that lncRNA m7G methylation occurred more frequently in drug-resistant AML cells than in AML cells. RNA sequencing demonstrated that more genes were upregulated by methylation in drug-resistant AML cells, while methylation downregulated more genes in AML cells. The GO and KEGG pathway enrichment analyses revealed that genes having a significant correlation with m7G sites in lncRNA were involved in drug-resistant AML signaling pathways. CONCLUSION: Significant differences in the levels and patterns of m7G methylation between drug-resistant AML cells and AML cells were revealed. Furthermore, the cellular functions potentially influenced by m7G in drug-resistant AML cells were predicted, providing evidence implicating m7G-mediated lncRNA epigenetic regulation in the progression of drug resistance in AML. These findings highlight the involvement of m7G in the development of drug resistance in AML.
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Leucemia Mieloide Aguda , ARN Largo no Codificante , Adulto , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Epigénesis Genética , Leucemia Mieloide Aguda/genética , TranscriptomaRESUMEN
Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of autoimmune diseases with various clinical manifestations, treatment responses, and prognoses. According to the clinical manifestations and presence of different myositis-specific autoantibodies (MSAs), IIM is classified into several major subgroups, including PM, DM, IBM, ASS, IMNM, and CADM. However, the pathogenic mechanisms of these subgroups remain unclear and need to be investigated. Here, we applied MALDI-TOF-MS to examine the serum metabolome of 144 patients with IIM and analyze differentially expressed metabolites among IIM subgroups or MSA groups. The results showed that the DM subgroup had lower activation of the steroid hormone biosynthesis pathway, while the non-MDA5 MSA group had higher activation of the arachidonic acid metabolism pathway. Our study may provide some insights into the heterogeneous mechanisms of IIM subgroups, potential biomarkers, and management of IIM.