RESUMEN
JOURNAL/nrgr/04.03/01300535-202503000-00027/figure1/v/2024-06-17T092413Z/r/image-tiff Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/ß-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury-induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.
RESUMEN
Long terminal repeat retroelements (LTR-REs) have profound effects on DNA methylation and gene regulation. Despite the vast abundance of LTR-REs in the genome of Moso bamboo (Phyllostachys edulis), an industrial crop in underdeveloped countries, their precise implication of the LTR-RE mobility in stress response and development remains unknown. We investigated the RNA and DNA products of LTR-REs in Moso bamboo under various developmental stages and stressful conditions. Surprisingly, our analyses identified thousands of active LTR-REs, particularly those located near genes involved in stress response and developmental regulation. These genes adjacent to active LTR-REs exhibited an increased expression under stress and are associated with reduced DNA methylation that is likely affected by the induced LTR-REs. Moreover, the analyses of simultaneous mapping of insertions and DNA methylation showed that the LTR-REs effectively alter the epigenetic status of the genomic regions where they inserted, and concomitantly their transcriptional competence which might impact the stress resilience and growth of the host. Our work unveils the unusually strong LTR-RE mobility in Moso bamboo and its close association with (epi)genetic changes, which supports the co-evolution of the parasitic DNAs and host genome in attaining stress tolerance and developmental robustness.
RESUMEN
N6-methyladenosine (m6A) is the most abundant post-transcriptional dynamic RNA modification process in eukaryotes, extensively implicated in cellular growth, embryonic development and immune homeostasis. One of the most profound biological functions of m6A is to regulate RNA metabolism, thereby determining the fate of RNA. Notably, the regulation of m6A-mediated organized RNA metabolism critically relies on the assembly of membraneless organelles (MLOs) in both the nucleus and cytoplasm, such as nuclear speckles, stress granules and processing bodies. In addition, m6A-associated MLOs exert a pivotal role in governing diverse RNA metabolic processes encompassing transcription, splicing, transport, decay and translation. However, emerging evidence suggests that dysregulated m6A levels contribute to the formation of pathological condensates in a range of human diseases, including tumorigenesis, reproductive diseases, neurological diseases and respiratory diseases. To date, the molecular mechanism by which m6A regulates the aggregation of biomolecular condensates associated with RNA metabolism is unclear. In this review, we comprehensively summarize the updated biochemical processes of m6A-associated MLOs, particularly focusing on their impact on RNA metabolism and their pivotal role in disease development and related biological mechanisms. Furthermore, we propose that m6A-associated MLOs could serve as predictive markers for disease progression and potential drug targets in the future.
Asunto(s)
Adenosina , ARN , Humanos , Adenosina/metabolismo , Adenosina/análogos & derivados , ARN/metabolismo , Orgánulos/metabolismo , Animales , Procesamiento Postranscripcional del ARN , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patología , Núcleo Celular/metabolismo , Citoplasma/metabolismoRESUMEN
BACKGROUND: Scutellaria, a sub-cosmopolitan genus, stands as one of the Lamiaceae family's largest genera, encompassing approximately 500 species found in both temperate and tropical montane regions. Recognized for its significant medicinal properties, this genus has garnered attention as a research focus, showcasing anti-cancer, anti-inflammatory, antioxidant, and hepatoprotective qualities. Additionally, it finds application in agriculture and horticulture. Comprehending Scutellaria's taxonomy is pivotal for its effective utilization and conservation. However, the current taxonomic frameworks, primarily based on morphological characteristics, are inadequate. Despite several phylogenetic studies, the species relationships and delimitations remain ambiguous, leaving the genus without a stable and reliable classification system. RESULTS: This study analyzed 234 complete chloroplast genomes, comprising 220 new and 14 previously published sequences across 206 species, subspecies, and varieties worldwide. Phylogenetic analysis was conducted using six data matrices through Maximum Likelihood and Bayesian Inference, resulting in a robustly supported phylogenetic framework for Scutellaria. We propose three subgenera, recommending the elevation of Section Anaspis to subgeneric rank and the merging of Sections Lupulinaria and Apeltanthus. The circumscription of Subgenus Apeltanthus and Section Perilomia needs to be reconsidered. Comparative analysis of chloroplast genomes highlighted the IR/SC boundary feature as a significant taxonomic indicator. We identified a total of 758 SSRs, 558 longer repetitive sequences, and ten highly variable regions, including trnK-rps16, trnC-petN, petN-psbM, accD-psaI, petA-psbJ, rpl32-trnL, ccsA-ndhD, rps15-ycf1, ndhF, and ycf1. These findings serve as valuable references for future research on species identification, phylogeny, and population genetics. CONCLUSIONS: The phylogeny of Scutellaria, based on the most comprehensive sample collection to date and complete chloroplast genome analysis, has significantly enhanced our understanding of its infrageneric relationships. The extensive examination of chloroplast genome characteristics establishes a solid foundation for the future development and utilization of Scutellaria, an important medicinal plant globally.
Asunto(s)
Genoma del Cloroplasto , Filogenia , Scutellaria , Scutellaria/genéticaRESUMEN
Introduction: Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in EGFR-mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce. Methods: We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing. Results: Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the EGFR mutation, including four patients with EGFR exon 19 deletion and three patients with EGFR exon 21 L858R mutation. Another patient harbored ERBB2 insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that TP53 and RB1 mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0-17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2-29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0-5.9 mo). Conclusions: SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.
RESUMEN
The pathogen Agrobacterium tumefaciens is known for causing crown gall tumours in plants. However, it has also been harnessed as a valuable tool for plant genetic transformation. Apart from the T-DNA, Agrobacterium also delivers at least five virulence proteins into the host plant cells, which are required for an efficient infection. One of these virulence proteins is VirD5. F-box proteins, encoded in the host plant genome or the Ti plasmid, and the ubiquitin/26S proteasome system (UPS) also play an important role in facilitating Agrobacterium infection. Our study identified two Arabidopsis F-box proteins, D5BF1 and D5BF2, that bind VirD5 and facilitate its degradation via the UPS. Additionally, we found that Agrobacterium partially suppresses the expression of D5BF1 and D5BF2. Lastly, stable transformation and tumorigenesis efficiency assays revealed that D5BF1 and D5BF2 negatively regulate the Agrobacterium infection process, showing that the plant F-box proteins and UPS play a role in defending against Agrobacterium infection.
Asunto(s)
Agrobacterium tumefaciens , Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Transformación Genética , Arabidopsis/microbiología , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Agrobacterium tumefaciens/genética , Agrobacterium tumefaciens/patogenicidad , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Carcinogénesis/genética , Tumores de Planta/microbiología , Complejo de la Endopetidasa Proteasomal/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
INTRODUCTION: The purpose of this study was to analyse the correlation between zinc finger antisense 1 (ZFAS1) and obesity and the diagnostic value of obesity complicated with metabolic syndrome (obesity-MS). MATERIAL AND METHODS: Serum levels of ZFAS1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in healthy children, children with simple obesity, and children with obesity-MS. The diagnostic accuracy of ZFAS1 was evaluated using the receiver operator characteristic (ROC) curve. Pearson's method was used to study the correlation between ZFAS1 and other indicators. Logistic regression was used to analyse the significance of ZFAS1 in the progression of obesity to obesity-MS. StarBase V2.0 was used to predict the target gene of ZFAS1 (miR-193a-3p). Bioinformatics methods were used to identify the molecular functions and possible enrichment signalling pathways of downstream target genes of miR-193a-3p. RESULTS: The expression of ZFAS1 in patients with obesity and obesity-MS showed a gradual upward trend, while the expression of miR-193a-3p was the opposite. ZFAS1 could identify obesity-MS children from children with obesity (area under the curve [AUC] = 0.880). ZFAS1 was significantly correlated with body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), and other indicators, while ZFAS1 was an independent influencing factor for the development of obesity into obesity-MS. Furthermore, a total of 104 downstream target genes of miR-193a-3p were identified, which participated in many biological processes such as protein phosphatase regulation, activation of transcription factor activity, and enrichment in MAPK signalling pathway. CONCLUSION: ZFAS1 is dysregulated in obesity and obesity-MS. Abnormal expression of ZFAS1 has high diagnostic value for obesity-MS, and it has the potential to become a clinical diagnostic biomarker for obesity-MS.
Asunto(s)
Síndrome Metabólico , Obesidad Infantil , ARN Largo no Codificante , Humanos , Síndrome Metabólico/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/sangre , Niño , Masculino , Femenino , Obesidad Infantil/genética , Valor Predictivo de las Pruebas , AdolescenteRESUMEN
BACKGROUND: Value analysis of a small-molecule fluorescent probe for methylation detection in different cervical lesions. MATERIALS AND METHODS: (1) The grayscale values of distinct lesion tissues were remarkably distinct among the four groups (p < 0.05). The comparison of the grayscale value between the two groups showed that the CA group noticeably exceeded the LSIL and cervicitis groups, and the HSIL group was apparently higher than the LSIL and cervicitis groups (p < 0.05); (2) The mean grayscale values of the enrolled subjects were calculated with 55.21 as the midline, with >55.21 as positive and ≤55.21 as negative. RESULTS: The results showed that the positive rate of the cervicitis group was 0.00%, the LSIL group 67.74%, the HSIL group 83.33%, and the CA group 100.00%. The results among the four groups were notably distinct (p < 0.05); (3) The comparison among DAPI, probe, bright, and merged images of cervicitis, LSIL, HSIL, and CA indicated that different cervical lesions were with quite various stains. CONCLUSION: The grayscale value, positive rate, and stained picture of distinct cervical lesions were remarkably different. The small-molecule fluorescent probe has a good value in differentiating cervical lesions and can be considered for popularization and application.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasa 1 , Metilación de ADN , Colorantes Fluorescentes , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/genética , Adulto , Persona de Mediana Edad , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , Anciano , Sensibilidad y Especificidad , Cervicitis Uterina/metabolismo , Displasia del Cuello del Útero/diagnósticoRESUMEN
The Guangdong-Hong Kong-Macao Greater Bay Area has attracted attention for its extraordinary pace of economic development and is considered to be leading the way in China's transformation from a manufacturing to an innovation cluster. However, due to rapid economic expansion and rapid urbanization, the Great Bay Area still struggles with low energy efficiency and environmental degradation, which has slowed down the pace of development. Therefore, in order to alleviate energy pressure, promote the country's sustainable development and gain a competitive advantage in the global market, researching energy efficiency and improving energy utilization efficiency is crucial. In this study, macro-level energy efficiency indicators are constructed using energy consumption data from various cities in the Greater Bay Area for the period from 2000 to 2020, and the spatio-temporal evolution of energy efficiency is analysed. The results show that all cities in the Greater Bay Area experienced an increasing trend in energy efficiency from 2000 to 2019, with significant variation in growth rates and magnitudes between cities. Compared to the nine cities in Guangdong province, Hong Kong and Macao exhibited significantly superior energy efficiency, with Foshan recording the highest growth rate of 14%. In 2020, most cities experienced a decline in energy efficiency due to the COVID-19 pandemic, with Macao experiencing the greatest decrease at 57%. Hong Kong and Macao are both in the "low consumption and high efficiency" target region, while Guangzhou, Shenzhen and Zhuhai are consistently in the "both high" region. Changes in the industrial upgrading index correspond significantly with changes in energy efficiency trajectories, with the transition from primary to secondary and tertiary industries playing a more substantial role. There is no significant association found between the strength of environmental regulation and changes in energy efficiency. The study's findings indicate that the most effective way to achieve economic transformation in the majority of China's regions is to combine adequate environmental legislation with industrial structural adjustment.
Asunto(s)
Desarrollo Económico , China , Hong Kong , Humanos , COVID-19/epidemiología , Bahías , Urbanización , Ciudades , Macao , Fuentes Generadoras de Energía , Análisis Espacio-TemporalRESUMEN
Intraluminal epithelial abnormalities, potential precursors to significant conditions like cancer, necessitate early detection for improved prognosis. We present a motor-free telerobotic optical coherence tomography (OCT) endoscope that offers high-resolution intraluminal imaging and overcomes the limitations of traditional systems in navigating curved lumens. This system incorporates a compact magnetic rotor with a rotatable diametrically magnetized cylinder permanent magnet (RDPM) and a reflector, effectively mitigating thermal and electrical risks by utilizing an external magnetic field to maintain temperature increases below 0.5 °C and generated voltage under 0.02 mV. Additionally, a learning-based method corrects imaging distortions resulting from nonuniform rotational speeds. Demonstrating superior maneuverability, the device achieves steerable angles up to 110° and operates effectively in vivo, providing distortion-free 3D programmable imaging in mouse colons. This advancement represents a significant step towards guidewire-independent endomicroscopy, enhancing both safety and potential patient outcomes.
Asunto(s)
Tomografía de Coherencia Óptica , Animales , Tomografía de Coherencia Óptica/métodos , Tomografía de Coherencia Óptica/instrumentación , Ratones , Imagenología Tridimensional/métodos , Imagenología Tridimensional/instrumentación , Endoscopios , Humanos , Diseño de Equipo , Microscopía/métodos , Microscopía/instrumentación , Endoscopía/métodos , Endoscopía/instrumentaciónRESUMEN
To detect damage in mechanical structures, acoustic emission (AE) inspection is considered as a powerful tool. Generally, the classical acoustic emission detection method uses a sparse sensor array to identify damage and its location. It often depends on a pre-defined wave velocity and it is difficult to yield a high localization accuracy for complicated structures using this method. In this paper, the passive guided wave phased array method, a dense sensor array method, is studied, aiming to obtain better AE localization accuracy in aluminum thin plates. Specifically, the proposed method uses a cross-shaped phased array enhanced with four additional far-end sensors for AE source localization. The proposed two-step method first calculates the real-time velocity and the polar angle of the AE source using the phased array algorithm, and then solves the location of the AE source with the additional far-end sensor. Both numerical and physical experiments on an aluminum flat panel are carried out to validate the proposed method. It is found that using the cross-shaped guided wave phased array method with enhanced far-end sensors can localize the coordinates of the AE source accurately without knowing the wave velocity in advance. The proposed method is also extended to a stiffened thin-walled structure with high localization accuracy, which validates its AE source localization ability for complicated structures. Finally, the influences of cross-shaped phased array element number and the time window length on the proposed method are discussed in detail.
RESUMEN
The all-atomic full-dimensional-level simulations of nonadiabatic molecular dynamics (NAMD) in large realistic systems has received high research interest in recent years. However, such NAMD simulations normally generate an enormous amount of time-dependent high-dimensional data, leading to a significant challenge in result analyses. Based on unsupervised machine learning (ML) methods, considerable efforts were devoted to developing novel and easy-to-use analysis tools for the identification of photoinduced reaction channels and the comprehensive understanding of complicated molecular motions in NAMD simulations. Here, we tried to survey recent advances in this field, particularly to focus on how to use unsupervised ML methods to analyze the trajectory-based NAMD simulation results. Our purpose is to offer a comprehensive discussion on several essential components of this analysis protocol, including the selection of ML methods, the construction of molecular descriptors, the establishment of analytical frameworks, their advantages and limitations, and persistent challenges.
RESUMEN
Medulloblastoma (MB) is the most common malignant brain tumor in children. Within MB, tumors driven by the Sonic Hedgehog (SHH) pathway represent the most heterogeneous subtype, known as SHH subtype medulloblastoma (SHH-MB). Tenovin-6, a recognized p53 activator, has been demonstrated to inhibit autophagy and modulate sirtuin activity, underscoring its potential as a novel therapeutic agent across various malignancies. However, its efficacy in treating SHH-MB remains unexplored. This study aims to investigate the inhibitory effects of tenovin-6 on SHH-MB and elucidate its underlying signaling pathways. We assessed the impact of tenovin-6 on cell proliferation through the CCK-8 and colony formation assays. The scratch and transwell invasion assays were utilized to evaluate the drug's effects on metastasis. Apoptosis and reactive oxygen species (ROS) levels were measured using flow cytometry. Potential signaling pathways were identified via transcriptomics and quantitative PCR (qPCR). Our in vivo studies involved a mouse xenograft model to explore tenovin-6's anticancer efficacy against SHH-MB. The findings indicate that tenovin-6 not only inhibits cell proliferation and metastasis in SHH-MB cell lines but also promotes apoptosis, which is closely linked to its proliferation-inhibiting properties. Additionally, animal experiments confirmed that tenovin-6 suppresses MB growth in vivo. We discovered that tenovin-6 reduces intracellular ROS levels and inhibits autophagy in SHH-MB by disrupting the fusion of autophagosomes with lysosomes, likely through inducing autophagosome formation.
RESUMEN
The study of topological band insulators has revealed fascinating phases characterized by band topology indices and anomalous boundary modes protected by global symmetries. In strongly correlated systems, where the traditional notion of electronic bands becomes obsolete, it has been established that topological insulator phases persist as stable phases, separate from the trivial insulators. However, due to the inability to express the ground states of such systems as Slater determinants, the formulation of generic variational wave functions for numerical simulations is highly desirable. In this paper, we tackle this challenge for two-dimensional topological insulators by developing a comprehensive framework for fermionic tensor network states. Starting from simple assumptions, we obtain possible sets of tensor equations for any given symmetry group, capturing consistent relations governing symmetry transformation rules on tensor legs. We then examine the connection between these tensor equations andnon-chiraltopological insulators by constructing edge theories and extracting quantum anomaly data from each set of tensor equations. By exhaustively exploring all possible sets of equations, we achieve a systematic classification of non-chiral topological insulator phases. Imposing the solutions of a given set of equations onto local tensors, we obtain generic variational wavefunctions for the corresponding topological insulator phases. Our methodology provides an important step toward simulating topological insulators in strongly correlated systems. We discuss the limitations and potential generalizations of our results, paving the way for further advancements in this field.
RESUMEN
Toxoplasma gondii (T. gondii) is widely spread around the world, which can cause serious harm to immunosuppressed patients. Currently, the commercial test kits are poor at assessing T. gondii infection and vaccine effectiveness, making an urgent need to exploit effective enzyme-linked immunosorbent assay with great performance to compensate for this deficiency. Here, the TgIMP1 recombinant protein was expressed in E. coli BL(21) cells. The TgIMP1 was purified with affinity chromatography and the reactivity was retained with anti-TgIMP1 antibodies. The TgIMP1 was then used to develop an indirect ELISA (IMP1-iELISA) and the reaction conditions of IMP1-iELISA were optimized. As a result, the cut-off value was determined to be 0.2833 by analyzing the OD450nm values of forty T. gondii-negative sera. The coefficient of variation of 6 T. gondii-positive sera within and between runs were both less than 10%. The IMP1-iELISA was non-cross-reactive with the sera of cytomegalovirus, herpes virus, rubella virus, Cryptosporidium spp., Theileria spp., Neospora spp. and Plasmodium spp.. Furthermore, the sensitivity and specificity of IMP1-iELISA were 98.9% and 96.7%, respectively, based on testing 150 serum samples. The results suggest that this IMP1-iELISA is specific, sensitive, repeatable and can be applied to the detection of T. gondii infections in the medical and health industries.
Asunto(s)
Anticuerpos Antiprotozoarios , Ensayo de Inmunoadsorción Enzimática , Toxoplasma , Toxoplasmosis , Animales , Humanos , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Escherichia coli/genética , Inmunoglobulina G/sangre , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Sensibilidad y Especificidad , Toxoplasma/inmunología , Toxoplasma/genética , Toxoplasmosis/diagnóstico , Toxoplasmosis/inmunología , Toxoplasmosis/parasitologíaRESUMEN
Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.
Asunto(s)
Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Neoplasias Pulmonares , Macrófagos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Acrilamidas/farmacología , Acrilamidas/uso terapéutico , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Animales , Ratones , Línea Celular Tumoral , Femenino , Carcinomatosis Meníngea/tratamiento farmacológico , Carcinomatosis Meníngea/patología , Carcinomatosis Meníngea/secundario , Metabolismo de los Lípidos/efectos de los fármacos , Antígeno CD47/metabolismo , Antígeno CD47/genética , Masculino , Fagocitosis/efectos de los fármacos , Receptores ErbB/metabolismo , Receptores ErbB/genética , Indoles , PirimidinasRESUMEN
In situ growth of intertwined trinuclear copper complexes (nCu3) on a cellulose-derived carbon support (CMC) produced a high-performance electrocatalyst (CMC-nCu3) for the oxygen reduction reaction (ORR), which demonstrated superior performance in zinc-air batteries compared to a commercial Pt/C catalyst. This work highlights the importance of copper-based molecular catalysts with rich and intertwined tricopper structures for boosting both ORR activity and stability.
RESUMEN
The processes of forming lineages undergoing widespread radiations remain a knowledge gap that is fundamental to our understanding of the geographic distributions of species. Although early studies emphasized the importance of dispersal ability and historical migration events, key innovations that promote rapid diversification and/or adaptation to new habitats may also strongly influence distribution ranges. Juniperus is the second largest genus of conifers and is widely distributed throughout the Northern Hemisphere. Here, we used phylogenetic, phenotypic, and climatic data to investigate the contributions of these processes to the wide distribution and rapid diversification of Juniperus. Combining a time-scaled phylogeny and macroevolutionary theory, we show that the key innovations of berry-like seed cones and dioecy promoted the rapid diversification of Juniperus and that increased dispersal ability promoted allopatric speciation. Ecological niches had significant divergence among different clades of Juniperus. Biogeographic results supported multiple long-distance dispersal events and niche variation that contributed to the modern range of Juniperus, while both phenotypic adaptation and ecological opportunity probably drove its distribution range. Our findings suggest that the current widespread distribution is likely the result of significant divergence driven by niche variation in which ecological opportunities from key innovation and phenotypic divergence.
Asunto(s)
Ecosistema , Juniperus , Filogenia , Juniperus/genética , Evolución Biológica , Fenotipo , Filogeografía , BiodiversidadRESUMEN
OBJECTIVES: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified. Hence, we conducted this study tofind correlations between the tumor immune microenvironment of EGFR ex20ins and the efficacy of ICI-combined regimen. METHODS: We performed single-cell transcriptome sequencing and multiplex immunofluorescence staining (mIF) to investigate the immune microenvironment of NSCLC patients with EGFR ex20ins, L858R, and EGFR wild-type. We analyzed 15 treatment-naïve NSCLC samples utilizing single-cell RNA sequencing (scRNA-seq). Another 30 cases of EGFR L858R and 4 cases of wild-type were recruited to compare the immune microenvironment with that of EGFR ex20ins (28 cases) by mIF. RESULTS: We observed that cell components, function and interactions varied between EGFR ex20ins, L858R, and wild-type NSCLC.We discovered similar T cell and CD8+ T cell distributions among groups but found noninferior or even better T cell activation in ex20ins patients. Infiltrating CD8+ FOXP3- T cells were significantly lower in the tumor region of EGFR ex20ins compared to wild-type. T cells from the ex20ins group had a greater tendency to promote cancer cell inflammation and epithelial-mesenchymal transition (EMT) compared to wild-type group. For macrophages, there were more M2-like macrophages in ex20ins patients. M1-like macrophages in ex20ins group produced fewer antitumor cytokines than in other groups. CONCLUSIONS: The immune microenvironment of EGFR ex20ins is more suppressive than that of L858R and wild-type, suggesting that ICI monotherapy may not be sufficient for these patients. ICI-combined regimen might be a treatment option for EGFR ex20ins due to tumor-promoting inflammation and noninferior T cell functions in the immune microenvironment.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Exones , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Exones/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mutagénesis Insercional , PronósticoRESUMEN
Episyrphus balteatus can provide dual ecosystem services including pest control and pollination, which the larvae are excellent predators of aphid pest whereas adults are efficient pollinator. In this study, we assembled a high-quality genome of E. balteatus from northern China geographical population at the chromosome level by using Illumina, PacBio long reads, and Hi-C technologies. The 467.42 Mb genome was obtained from 723 contigs, with a contig N50 of 9.16 Mb and Scaffold N50 of 118.85 Mb, and 90.25% (431.75 Mb) of the assembly was anchored to 4 pseudo-autosomes and one pseudo-heterosome. In total, 14,848 protein-coding genes were annotated, and 95.14% of genes were fully represented in NR, GO, KEGG databases. Besides, we also obtained the mitochondrial genome of E. balteatus of 16, 837 bp in length with 37 typical mitochondrial genes. Overall, this high-quality genome is valuable for evolutionary and genetic studies of E. balteatus and other Syrphidae hoverfly species.