RESUMEN
The advantage of 3D printing-that is, additive manufacturing (AM) of structural materials-has been severely compromised by their disappointing fatigue properties1,2. Commonly, poor fatigue properties appear to result from the presence of microvoids induced by current printing process procedures3,4. Accordingly, the question that we pose is whether the elimination of such microvoids can provide a feasible solution for marked enhancement of the fatigue resistance of void-free AM (Net-AM) alloys. Here we successfully rebuild an approximate void-free AM microstructure in Ti-6Al-4V titanium alloy by development of a Net-AM processing technique through an understanding of the asynchronism of phase transformation and grain growth. We identify the fatigue resistance of such AM microstructures and show that they lead to a high fatigue limit of around 1 GPa, exceeding the fatigue resistance of all AM and forged titanium alloys as well as that of other metallic materials. We confirm the high fatigue resistance of Net-AM microstructures and the potential advantages of AM processing in the production of structural components with maximum fatigue strength, which is beneficial for further application of AM technologies in engineering fields.
RESUMEN
Most El Niño events occur sporadically and peak in a single winter1-3, whereas La Niña tends to develop after an El Niño and last for two years or longer4-7. Relative to single-year La Niña, consecutive La Niña features meridionally broader easterly winds and hence a slower heat recharge of the equatorial Pacific6,7, enabling the cold anomalies to persist, exerting prolonged impacts on global climate, ecosystems and agriculture8-13. Future changes to multi-year-long La Niña events remain unknown. Here, using climate models under future greenhouse-gas forcings14, we find an increased frequency of consecutive La Niña ranging from 19 ± 11% in a low-emission scenario to 33 ± 13% in a high-emission scenario, supported by an inter-model consensus stronger in higher-emission scenarios. Under greenhouse warming, a mean-state warming maximum in the subtropical northeastern Pacific enhances the regional thermodynamic response to perturbations, generating anomalous easterlies that are further northward than in the twentieth century in response to El Niño warm anomalies. The sensitivity of the northward-broadened anomaly pattern is further increased by a warming maximum in the equatorial eastern Pacific. The slower heat recharge associated with the northward-broadened easterly anomalies facilitates the cold anomalies of the first-year La Niña to persist into a second-year La Niña. Thus, climate extremes as seen during historical consecutive La Niña episodes probably occur more frequently in the twenty-first century.
Asunto(s)
Modelos Climáticos , El Niño Oscilación del Sur , Calentamiento Global , Ecosistema , Estaciones del Año , Océano Pacífico , Efecto Invernadero , TermodinámicaRESUMEN
Leukemogenesis is proposed to be a multistep process by which normal hematopoietic stem and progenitor cells are transformed into full-blown leukemic cells, the details of which are not fully understood. Here, we performed serial single-cell transcriptome analyses of preleukemic and leukemic cells (PLCs) and constructed the cellular and molecular transformation trajectory in a Myc-driven acute myeloid leukemia (AML) model in mice, which represented the transformation course in patients. We found that the Myc targets were gradually up-regulated along the trajectory. Among them were splicing factors, which showed stage-specific prognosis for AML patients. Furthermore, we dissected the detailed gene network of a tipping point for hematopoietic stem and progenitor cells (HSPCs) to generate initiating PLCs, which was characterized by dramatically increased splicing factors and unusual RNA velocity. In the late stage, PLCs acquired explosive heterogeneity through RNA alternative splicing. Among them, the Hsp90aa1hi subpopulation was conserved in both human and mouse AML and associated with poor prognosis. Exon 4 skipping of Tmem134 was identified in these cells. While the exon skipping product Tmem134ß promoted the cell cycle, full-length Tmem134α delayed tumorigenesis. Our study emphasized the critical roles of RNA splicing in the full process of leukemogenesis.
Asunto(s)
Leucemia Mieloide Aguda , Análisis de Expresión Génica de una Sola Célula , Humanos , Animales , Ratones , Leucemia Mieloide Aguda/genética , Empalme del ARN/genética , ARN , Factores de Empalme de ARN/genética , Transcriptoma/genéticaRESUMEN
Solar energy conversion technologies, particularly solar-driven photothermal conversion, are both clean and manageable. Although much progress has been made in designing solar-driven photothermal materials, significant challenges remain, not least the photobleaching of organic dyes. To tackle these issues, micro-carbonized polysaccharide chains, with carbon dots (CDs) suspended from the chains, are conceived, just like grapes or tomatoes hanging from a vine. Carbonization of sodium carboxymethyl cellulose (CMC) produces just such a structure (termed CMC-g-CDs), which is used to produce an ultra-stable, robust, and efficient solar-thermal film by interfacial interactions within the CMC-g-CDs. The introduction of the CDs into the matrix of the photothermal material effectively avoided the problem of photobleaching. Manipulating the interfacial interactions (such as electrostatic interactions, van der Waals interactions, π-π stacking, and hydrogen bonding) between the CDs and the polymer chains markedly enhances the mechanical properties of the photothermal film. The CMC-g-CDs are complexed with Fe3+ to eliminate leakage of the photothermal reagent from the matrix and to solve the problem of poor water resistance. The resulting film (CMC-g-CDs-Fe) has excellent prospects for practical application as a photothermal film.
RESUMEN
BACKGROUND: Evidence from observational studies suggests an association between chronic obstructive pulmonary disease (COPD) and lung cancer. The potential interactions between the immune system and the lungs may play a causative role in COPD and lung cancer and offer therapeutic prospects. However, the causal association and the immune-mediated mechanisms between COPD and lung cancer remain to be determined. METHODS: We employed a two-sample Mendelian randomization (MR) approach to investigate the causal association between COPD and lung cancer. Additionally, we examined whether immune cell signals were causally related to lung cancer, as well as whether COPD was causally associated with immune cell signals. Furthermore, through two-step Mendelian randomization, we investigated the mediating effects of immune cell signals in the causal association between COPD and lung cancer. Leveraging publicly available genetic data, our analysis included 468,475 individuals of European ancestry with COPD, 492,803 individuals of European ancestry with lung cancer, and 731 immune cell signatures of European ancestry. Additionally, we conducted single-cell transcriptome sequencing analysis on COPD, lung cancer, and control samples to validate our findings. FINDINGS: We found a causal association between COPD and lung cancer (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.31-2.02, P-value < 0.001). We also observed a causal association between COPD and regulatory T cells (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.01-1.40, P-value < 0.05), as well as a causal association between regulatory T cells and lung cancer (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 1.002-1.045, P-value < 0.05). Furthermore, our two-step Mendelian randomization analysis demonstrated that COPD is associated with lung cancer through the mediation of regulatory T cells. These findings were further validated through single-cell sequencing analysis, confirming the mediating role of regulatory T cells in the association between COPD and lung cancer. INTERPRETATION: As far as we are aware, we are the first to combine single-celled immune cell data with two-sample Mendelian randomization. Our analysis indicates a causal association between COPD and lung cancer, with regulatory T cells playing an intermediary role.
Asunto(s)
Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Neoplasias Pulmonares/genética , Análisis de la Aleatorización Mendeliana , Análisis de Expresión Génica de una Sola Célula , Linfocitos T Reguladores , Enfermedad Pulmonar Obstructiva Crónica/genética , Estudio de Asociación del Genoma CompletoRESUMEN
Fusarium oxysporum is a widespread plant pathogen that causes fusarium wilt and fusarium root rot in many economically significant crops. Here, a novel dsRNA virus tentatively named "Fusarium oxysporum virus 1" (FoV1) was identified in F. oxysporum strain 3S-18. The genome of FoV1 is 2,944 nucleotides (nt) in length and contains two non-overlapping open reading frames (ORF1 and 2). The larger of these, ORF2, encodes an RNA-dependent RNA polymerase (RdRp) of 590 amino acids with a molecular mass of 67.52 kDa. ORF1 encodes a putative nucleocapsid protein consisting of 134 amino acids with a molecular mass of 34.25 kDa. The RdRp domain of FoV1 shares 60.00% to 84.24% sequence identity with non-segmented dsRNA viruses. Phylogenetic analysis further suggested that FoV1 is a new member of the proposed genus "Unirnavirus" accommodating unclassified monopartite dsRNA viruses.
Asunto(s)
Virus Fúngicos , Fusarium , Virus ARN , Fusarium/genética , Virus ARN Bicatenario/genética , Filogenia , Genoma Viral , Virus Fúngicos/genética , ARN Polimerasa Dependiente del ARN/genética , Sistemas de Lectura Abierta , Hongos , Aminoácidos/genética , Virus ARN/genética , ARN Bicatenario/genética , ARN Viral/genéticaRESUMEN
PURPOSE: The purpose of this study is to identify and characterize the literature on surgical smoke, visualize the data and sketch a certain trending outline. METHODS: In the Web of Science Core Collection (WoSCC), all the data were acquired from January 1st 2003 to December 31st 2022. VOSviewer and CiteSpace were employed to visualize data, based on publications, bibliographic coupling, co-citation, or co-authorship relations. Microsoft Excel 2019 was used to comb and categorize all the statistics. RESULT: A total 363 of journal papers were retrieved. The publication number was in a slow but steady growth between 2003 and 2019, followed by a sharp surge in 2020, and then the publication kept in a productive way. Surgical endoscopy and other interventional techniques was the most active journal on surgical smoke. USA played an important role among all the countries/regions. There were 1847 authors for these 363 papers, among whom 44 authors published more than three articles on surgical smoke. "Surgical smoke", "covid-19" and "surgery" were the top 3 appeared keywords, while the latest hot-spot keywords were "COVID-19", "virus", "transmission", "exposure" and "risk". There were 1105 co-cited references and 3786 links appeared in all 363 articles. Among them, 38 references are cited more than 10 times. The most co-cited article was "Detecting hepatitis B virus in surgical smoke emitted during laparoscopic surgery." Based on the titles of references and calculated by CiteSpace, the top 3 cluster trend network are "laparoscopic surgery", "COVID-19 pandemic" and "surgical smoke". CONCLUSION: According to bibliometric analysis, the research on surgical smoke has been drawing attention of more scholars in the world. Increasing number of countries or regions added in this field, and among them, USA, Italy, and China has been playing important roles, however, more wide and intense cooperation is still in expectation.
Asunto(s)
COVID-19 , Humo , Humanos , Bibliometría , COVID-19/epidemiología , China , ItaliaRESUMEN
Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infection disease in children. To date, there have been few studies on the relationship between cytological changes in bronchoalveolar lavage fluid (BALF) and clinical features. The objective of this study is to investigate the correlation between changes in the proportion of cell classifications in BALF and the clinical features in children with severe MPP (SMPP). In total, the study included 64 children with SMPP requiring bronchoalveolar lavage who were admitted to our hospital between March and September 2022 (study group) and 11 children with bronchial foreign bodies without co-infection (control group), who were admitted during the same period. The proportion of cell classifications in BALF was determined by microscopic examination after performing Wright-Giemsa staining. Patients were grouped according to different clinical characteristics, and between-group comparisons were made regarding the variations in the proportion of cell classifications in BALF. The levels of blood routine neutrophil percentage (GRA%), C-reactive protein, D-dimer and lactate dehydrogenase in the study group were higher than those in the control group (P < 0.05). There were differences in the GRA% and macrophage percentage in the BALF between the two groups (P < 0.05). The GRA% and blood lymphocyte percentage were associated with pleural effusion. Multiple indicators correlated with extrapulmonary manifestations (P < 0.05). Moreover, the percentage of lymphocytes in the BALF correlated with pleural effusion, extrapulmonary manifestations and refractory MPP (RMPP) (P < 0.05). Logistic regression showed that BALF lymphocytes were protective factors for RMPP, while serum amyloid A and extrapulmonary manifestations were risk factors (P < 0.05). CONCLUSION: The BALF of children with SMPP is predominantly neutrophilic. A lower percentage of lymphocytes is related to a higher incidence of pleural effusion, extrapulmonary manifestations and progression to RMPP, as well as a longer length of hospitalisation. WHAT IS KNOWN: ⢠Mycoplasma pneumonia in children is relatively common in clinical practice. Bronchoalveolar lavage (BAL) is a routine clinical procedure. WHAT IS NEW: However, there are relatively few studies focusing on the cytomorphological analysis of cells in BAL fluid.
RESUMEN
Platelets are terminally differentiated anucleated cells, but they still have cell-like functions and can even produce progeny platelets. However, the mechanism of platelet sprouting has not been elucidated so far. Here, we show that when platelet-rich plasma(PRP) was cultured at 37°C, platelets showed a spore phenomenon. The number of platelets increased when given a specific shear force. It is found that AMP-related signaling pathways, such as PKA and AMPK are activated in platelets in the spore state. Meanwhile, the mRNA expression levels of genes, such as CNN3, CAPZB, DBNL, KRT19, and ESPN related to PLS1 skeleton proteins also changed. Moreover, when we use the AMPK activator AICAR(AI) to treat washed platelets, cultured platelets can still appear spore phenomenon. We further demonstrate that washed platelets treated with Forskolin, an activator of PKA, not only platelet sprouting after culture but also the AMPK is activated. Taken together, these data demonstrate that AMPK plays a key role in the process of platelet budding and proliferation, suggesting a novel strategy to solve the problem of clinical platelet shortage.
What is new? In this study, we showed that when platelet-rich plasma(PRP) was cultured at 37°C, platelets showed spore phenomenon and increased.It was found that AMP-related signaling pathways, such as PKA and AMPK were activated in platelets in the spore state.In addition, we found that PKA acts as an upstream kinase of AMPK.In the process of platelet sprouting and proliferation, the mRNA expression levels of skeleton protein PLS1 and its related genes, such as CNN3, CAPZB, DBNL, KRT19, andESPN also changed.What is the impact? Our study proposes a new strategy to solve the problem of clinical platelet shortage.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Plaquetas , Humanos , Plaquetas/citología , Plaquetas/metabolismo , Diferenciación Celular , Colforsina , Técnicas de CultivoRESUMEN
Vascularization plays a significant role in promoting the expedited process of bone regeneration while also enhancing the stability and viability of artificial bone implants. Although titanium alloy scaffolds were designed to mimic the porous structure of human bone tissues to facilitate vascularization in bone repair, their biological inertness restricted their broader utilization. The unique attribute of Metal-organic framework (MOF) MIL-53(Fe), known as "breathing", can facilitate the efficient adsorption of extracellular matrix proteins and thus provide the possibility for efficient interaction between scaffolds and cell adhesion molecules, which helps improve the bioactivity of the titanium alloy scaffolds. In this study, MIL-53(Fe) was synthesized in situ on the scaffold after hydrothermal treatment. The MIL-53(Fe) endowed the scaffold with superior protein absorption ability and preferable biocompatibility. The scaffolds have been shown to possess favorable osteogenesis and angiogenesis inducibility. It was indicated that MIL-53(Fe) modulated the mechanotransduction process of endothelial cells and induced increased cell stiffness by promoting the adsorption of adhesion-mediating extracellular matrix proteins to the scaffold, such as laminin, fibronectin, and perlecan et al., which contributed to the activation of the endothelial tip cell phenotype at sprouting angiogenesis. Therefore, this study effectively leveraged the intrinsic "breathing" properties of MIL-53 (Fe) to enhance the interaction between titanium alloy scaffolds and vascular endothelial cells, thereby facilitating the vascularization inducibility of the scaffold, particularly during the sprouting angiogenesis phase. This study indicates that MIL-53(Fe) coating represents a promising strategy to facilitate accelerated and sufficient vascularization and uncovers the scaffold-vessel interaction from a biomechanical perspective.
Asunto(s)
Neovascularización Fisiológica , Andamios del Tejido , Titanio , Titanio/química , Humanos , Andamios del Tejido/química , Neovascularización Fisiológica/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Osteogénesis/efectos de los fármacos , Aleaciones/química , Células Endoteliales de la Vena Umbilical Humana , Prótesis e Implantes , Mecanotransducción Celular , Adhesión Celular/efectos de los fármacos , Ingeniería de Tejidos/métodosRESUMEN
INTRODUCTION: Mycoplasma pneumoniae pneumonia (MPP) is prevalent in paediatric patients and can progress to refractory mycoplasma pneumoniae pneumonia (RMPP). OBJECTIVE: To assess the predictive value of bronchoscopy combined with computed tomography (CT) score in identifying RMPP in children. METHODS: A retrospective analysis was conducted on 244 paediatric patients with MP, categorising them into RMPP and general mycoplasma pneumoniae pneumonia (GMPP) groups. A paired t-test compared the bronchitis score (BS) and CT score before and after treatment, supplemented by receiver operating characteristic (ROC) analysis. RESULTS: The RMPP group showed higher incidences of extrapulmonary complications and pleural effusion (58.10% and 40%, respectively) compared with the GMPP group (44.60%, p = 0.037 and 18.71%, p < 0.001, respectively). The CT scores for each lung lobe were statistically significant between the groups, except for the right upper lobe (p < 0.05). Correlation analysis between the total CT score and total BS yielded r = 0.346 and p < 0.001. The ROC for BS combined with CT score, including area under the curve, sensitivity, specificity, and cut-off values, were 0.82, 0.89, 0.64, and 0.53, respectively. CONCLUSION: The combined BS and CT score method is highly valuable in identifying RMPP in children.
Asunto(s)
Broncoscopía , Mycoplasma pneumoniae , Neumonía por Mycoplasma , Valor Predictivo de las Pruebas , Curva ROC , Tomografía Computarizada por Rayos X , Humanos , Neumonía por Mycoplasma/diagnóstico por imagen , Masculino , Femenino , Estudios Retrospectivos , Niño , Preescolar , Mycoplasma pneumoniae/aislamiento & purificación , Antibacterianos/uso terapéutico , Adolescente , Sensibilidad y Especificidad , Pulmón/diagnóstico por imagen , Bronquitis/diagnóstico por imagen , Bronquitis/microbiología , Bronquitis/diagnósticoRESUMEN
The aim of this study was to characterize the Fusarium solani species complex (FSSC) population obtained from tobacco roots with root rot symptoms by morphological characteristics, molecular tests, and assessment of pathogenicity. Cultures isolated from roots were white to cream with sparse mycelium on potato dextrose agar, with colony growth of 21.5 ± 0.5 to 29.5 ± 0.5 mm after 3 days. Sporodochia were cream on carnation leaf agar (CLA) and Spezieller Nährstoffarmer agar (SNA), and macroconidia formed in sporodochia were 3 to 6 septate and straight to slightly curved, with wide central cells, a slightly short blunt apical cell, and a straight to almost cylindrical basal cell with a distinct foot shape, ranging in size from 20.92 to 64.37 × 3.91 to 6.57 µm. Microconidia formed on CLA were reniform and fusiform, with 0 or 1 to occasionally 2 septa, that formed on long monophialidic conidiogenous cells, with a size range of 5.99 to 32.32 × 1.76 to 5.84 µm. Globose to oval chlamydospores were smooth- to rough-walled, 6.5 to 13.3 ± 0.37 µm in diameter, and terminal or intercalary and occurred singly, in pairs, or occasionally in short chains on SNA. Molecular tests consisted of sequencing and phylogenetic analysis of the translation elongation factor-1 alpha (EF-1α), RNA polymerase II largest subunit, and second largest subunit regions. All the obtained sequences revealed 98.14 to 100% identity to F. solani in both Fusarium ID and Fusarium MLST databases. Phylogenetic trees of the EF-1α gene and concatenated three-locus data showed that isolates from tobacco in Henan grouped in the proposed group 5, which is nested within FSSC clade 3 (FSSC 5). Twenty-seven of the 28 isolates caused root rot in artificially inoculated tobacco seedlings, with a disease severity index ranging from 15.00 ± 1.67 to 91.11 ± 2.22. Cross-pathogenicity tests showed that three representative isolates were virulent to six species of Solanaceae and two species of Poaceae, with disease severity indexes ranging from 6.12 ± 0.56 to 84.44 ± 0.00, indicating that these isolates have a wide host range. The results may inform the control of tobacco root rot through improved crop rotations.
RESUMEN
Sustainable carbon dots based on cellulose, particularly carboxymethyl cellulose carbon dots (CMCCDs), were confined in an inorganic network resulting in CMCCDs@SiO2. This resulted in a material exhibiting long afterglow covering a time frame of several seconds also under air. Temperature-dependent emission spectra gave information on thermally activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) while photocurrent experiments provided a deeper understanding of charge availability in the dark period, and therefore, its availability on the photocatalyst surface. The photo-ATRP initiator, ethyl α-bromophenylacetate (EBPA), quenched the emission from the millisecond to the nanosecond time frame indicating participation of the triplet state in photoinduced electron transfer (PET). Both free radical and controlled radical polymerization based on photo-ATRP protocol worked successfully. Metal-free photo-ATRP resulted in chain extendable macroinitiators based on a reductive mechanism with either MMA or in combination with styrene. Addition of 9â ppm Cu2+ resulted in Mw/Mn of 1.4 while an increase to 72â ppm improved uniformity of the polymers; that is Mw/Mn=1.03. Complementary experiments with kerria laca carbon dots confined materials, namely KCDs@SiO2, provided similar results. Deposition of Cu2+ (9â ppm) on the photocatalyst surface explains better uniformity of the polymers formed in the ATRP protocol.
RESUMEN
Sustainable carbon dots comprising surficial oxime ester groups following homolytic bond cleavage exhibit potential as photoinitiators for traditional free radical photopolymerization. Carbon dots were made following a solvothermal procedure from sustainable furfural available from lignocellulose. Surficial aldehyde moieties reacted with hydroxylamine to the respective oxime while reaction with benzoyl chloride resulted in a biobased Typeâ I photoinitiator comprising sustainable carbon dot (CD-PI). Photoinitiating ability was compared with the traditional photoinitiator (PI) ethyl (2,4,6-trimethyl benzoyl) phenyl phosphinate (TPO-L) by real-time FTIR with UV exposure at 365â nm. Photopolymer composition based on a mixture of urethane dimethacrylate (UDMA) and tripropylene glycol diacrylate (TPGDA) resulted in a similar final conversion of about 70 % using either CD-PI or TPO-L. Nevertheless, it appeared homogeneous in the case of compositions processed with CD-PI, while those made with TPO-L were heterogeneous as shown by two glass transition temperatures. Moreover, the migration rate of CD-PI in the cured samples was lower in comparison with those samples using TPO-L as PI.
RESUMEN
Carbon nanomaterials, specifically carbon dots and carbon nitrides, play a crucial role as heterogeneous photoinitiators in both radical and cationic polymerization processes. These recently introduced materials offer promising solutions to the limitations of current homogeneous systems, presenting a novel approach to photopolymerization. This review highlights the preparation and photocatalytic performance of these nanomaterials, emphasizing their application in various polymerization techniques, including photoinduced i) free radical, ii) RAFT, iii) ATRP, and iv) cationic photopolymerization. Additionally, it discusses their potential in addressing contemporary challenges and explores prospects in this field. Moreover, carbon nitrides, in particular, exhibit exceptional oxygen tolerance, underscoring their significance in radical polymerization processes and allowing their applications such as 3D printing, surface modification of coatings, and hydrogel engineering.
RESUMEN
Low-temperature stress during the germination stage is an important abiotic stress that affects the growth and development of northern spring maize and seriously restricts maize yield and quality. Although some quantitative trait locis (QTLs) related to low-temperature tolerance in maize have been detected, only a few can be commonly detected, and the QTL intervals are large, indicating that low-temperature tolerance is a complex trait that requires more in-depth research. In this study, 296 excellent inbred lines from domestic and foreign origins (America and Europe) were used as the study materials, and a low-coverage resequencing method was employed for genome sequencing. Five phenotypic traits related to low-temperature tolerance were used to assess the genetic diversity of maize through a genome-wide association study (GWAS). A total of 14 SNPs significantly associated with low-temperature tolerance were detected (-log10(P) > 4), and an SNP consistently linked to low-temperature tolerance in the field and indoors during germination was utilized as a marker. This SNP, 14,070, was located on chromosome 5 at position 2,205,723, which explained 4.84-9.68% of the phenotypic variation. The aim of this study was to enrich the genetic theory of low-temperature tolerance in maize and provide support for the innovation of low-temperature tolerance resources and the breeding of new varieties.
RESUMEN
Long noncoding RNA LINC00482 (LINC00482) is dysregulated in non-small cell lung cancer cells (NSCLC). Herein, this research examined the actions and specific mechanisms of LINC00482 in cisplatin (DDP) resistance in NSCLC. LINC00482 expression was assessed using RT-qPCR in clinical NSCLC tissues and cell lines. Knockdown and ectopic expression assays were conducted in A549 and HCC44 cells, followed by determination of cell proliferation with CCK-8 and clone formation assays, apoptosis with flow cytometry, and DDP sensitivity. The association between LINC00482, E2F1, and CLASRP was evaluated with dual-luciferase reporter, ChIP, and RIP assays. The role of LINC00482 in NSCLC was confirmed in nude mice. NSCLC tissues and cells had upregulated LINC00482 expression. LINC00482 was mainly localized in the cell nucleus, and LINC00482 recruited E2F1 to enhance CLASRP expression in NSCLC cells. LINC00482 knockdown enhanced the DDP sensitivity and apoptosis of NSCLC cells while reducing cell proliferation, which was negated by overexpressing CLASRP. LINC00482 knockdown restricted tumor growth and enhanced DDP sensitivity in NSCLC in vivo. LINC00482 silencing downregulated CLASRP through E2F1 to facilitate the sensitivity to DDP in NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , ARN Largo no Codificante , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Cisplatino/farmacología , ARN Largo no Codificante/genética , Ratones Desnudos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genéticaRESUMEN
BACKGROUND: The long noncoding RNAs' (lncRNAs) effect on cancer therapy resistance by targeting microRNA (miRNA) in the regulation of drug resistance genes has attracted more and more attention. This study attempted to explore the mechanism of "lncRNA NR2F1-AS1/miR-483-3p/IGF1â³ axis in azacitidine resistance of THP-1 cells. METHODS: THP-1 cells were treated with azacitidine to construct THP1-Aza cells. Cell number and morphological changes were observed by a microscope. CCK8, flow cytometry and transwell were used to detect cell proliferation, apoptosis, cycle, invasion and migration. The targeting relationships between NR2F1-AS1 and miR-483-3p, IGF1 and miR-483-3p were analyzed by dual-luciferase, respectively. RIP assay was applied to verify the interaction between NR2F1-AS1 and miR-483-3p. The relative mRNA expression levels of miR-483-3p, AKT1, PI3K, NR2F1-AS1 and IGF1 were detected by qRT-PCR. PI3K, p-PI3K, AKT, p-AKT and IGF1 protein expression were detected by western blot. RESULTS: Compared with THP-1 cells, NR2F1-AS1 and IGF1 were highly expressed in THP1-Aza cells, and the miR-483-3p expression was significantly decreased in THP1-Aza cells. Knockdown of NR2F1-AS1 increased apoptosis and G1 phase, and reduced cells growth, invasion and migration ability of THP1-Aza cells. Dual-luciferase demonstrated that NR2F1-AS1 could bind to miR-483-3p, and miR-483-3p could bind to IGF1. RIP assay verified the interaction between NR2F1-AS1 and miR-483-3p. Compared with the si-NR2F1-AS1 group, miR-483-3p inhibitor or oe-IGF1 treatment reduced the apoptosis and cell cycle, and increased the cell growth, invasion and migration ability of THP-1-Aza cells. CONCLUSION: LncRNA NR2F1-AS1 affects the sensitivity of THP-1 cells to azacitidine resistance by regulating the miR-483-3p/IGF1 axis, which may be a potential target for the treatment of acute monocytic leukemia.
Asunto(s)
MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células THP-1 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Movimiento Celular/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: The emergence of COVID-19 and the implementation of preventive measures and behavioral changes have led to a significant decrease in the prevalence of other respiratory viruses. However, the manner in which seasonal viruses will reemerge in the absence of COVID-19-related restrictions remains unknown. METHODS: Patients presenting with influenza-like illness in two hospitals in Beijing were subjected to testing for COVID-19, influenza A, and influenza B to determine the causative agent for viral infections. The prevalence of influenza B across China was confirmed using data from the Centers for Disease Control, China (China CDC). Clinical characteristics, laboratory findings, imaging results, and mortality data were collected for a cohort of 70 hospitalized patients with confirmed influenza B from 9 hospitals across China. RESULTS: Starting from October 2021, a substantial increase in the number of patients visiting the designated fever clinics in Beijing was observed, with this trend continuing until January 2022. COVID-19 tests conducted on these patients yielded negative results, while the positivity rate for influenza rose from approximately 8% in October 2021 to over 40% by late January 2022. The cases started to decline after this peak. Data from China CDC confirmed that influenza B is a major pathogen during the season. Sequencing of the viral strain revealed the presence of the Victoria-like lineage of the influenza B strain, with minor variations from the Florida/39/2018 strain. Analysis of the hospitalized patients' characteristics indicated that severe cases were relatively more prevalent among younger individuals, with an average age of 40.9 ± 24.1 years. Among the seven patients who succumbed to influenza, the average age was 30 ± 30.1 years. These patients exhibited secondary infections involving either bacterial or fungal pathogens and displayed elevated levels of cell death markers (such as LDH) and coagulation pathway markers (D-dimer). CONCLUSION: Influenza B represents a significant infection threat and can lead to substantial morbidity and mortality, particularly among young patients. To mitigate morbidity and mortality rates, it is imperative to implement appropriate vaccination and other preventive strategies.
Asunto(s)
COVID-19 , Gripe Humana , Humanos , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Anciano , Gripe Humana/epidemiología , COVID-19/epidemiología , Estaciones del Año , Prueba de COVID-19 , China/epidemiologíaRESUMEN
The construction of multisubstituted ß-pyrrolinones from simple starting materials remains a great challenge. Recently, a novel Cu(I)-catalyzed [2 + 2 + 1] cycloaddition reaction was developed for rapid access to fully substituted ß-pyrrolinones, which are difficult to synthesize through traditional methods as this approach may involve unusual C-nucleophilic addition of enamines and umpolung of imines. Elucidating the reaction mechanism may inspire the development of new methodologies via the unusual C-nucleophilic addition of enamines and imines. However, the reaction mechanism is still unclear because none of the intermediates was observed during the reaction process. In this work, we employed theoretical and computational chemistry to investigate the possible pathway. Finally, the calculated results indicate that ketene formed by the Wolff rearrangement of α-diazo-ß-ketoester reacts with enamine formed by the addition of alkynes and amine, affording the five-membered azaheterocycle, and this process involves the formation of a six-membered ring intermediate and sequential isomerization, and the further dehydrogenation needs to be assisted with solvent MeNO2.