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Genetic load refers to the accumulated and potentially life-threatening deleterious mutations in populations. Understanding the mechanisms underlying genetic load variation of transposable element (TE) insertion, a major large-effect mutation, during range expansion is an intriguing question in biology. Here, we used 1,115 global natural accessions of Arabidopsis (Arabidopsis thaliana) to study the driving forces of TE load variation during its range expansion. TE load increased with range expansion, especially in the recently established Yangtze River basin population. Effective population size, which explains 62.0% of the variance in TE load, high transposition rate, and selective sweeps contributed to TE accumulation in the expanded populations. We genetically mapped and identified multiple candidate causal genes and TEs, and revealed the genetic architecture of TE load variation. Overall, this study reveals the variation in TE genetic load during Arabidopsis expansion and highlights the causes of TE load variation from the perspectives of both population genetics and quantitative genetics.
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Arabidopsis , Elementos Transponibles de ADN , Elementos Transponibles de ADN/genética , Arabidopsis/genética , Genética de Población , Evolución MolecularRESUMEN
In our quest to leverage the capabilities of the emerging single-atom catalysts (SACs) for wastewater purification, we confronted fundamental challenges related to electron scarcity and instability. Through meticulous theoretical calculations, we identified optimal placements for nitrogen vacancies (Nv) and iron (Fe) single-atom sites, uncovering a dual-site approach that significantly amplified visible-light absorption and charge transfer dynamics. Informed by these computational insights, we cleverly integrated Nv into the catalyst design to boost electron density around iron atoms, yielding a potent and flexible photoactivator for benign peracetic acid. This exceptional catalyst exhibited remarkable stability and effectively degraded various organic contaminants over 20 cycles with self-cleaning properties. Specifically, the Nv sites captured electrons, enabling their swift transfer to adjacent Fe sites under visible light irradiation. This mechanism accelerated the reduction of the formed "peracetic acid-catalyst" intermediate. Theoretical calculations were used to elucidate the synergistic interplay of dual mechanisms, illuminating increased adsorption and activation of reactive molecules. Furthermore, electron reduction pathways on the conduction band were elaborately explored, unveiling the production of reactive species that enhanced photocatalytic processes. A six-flux model and associated parameters were also applied to precisely optimize the photocatalytic process, providing invaluable insights for future photocatalyst design. Overall, this study offers a molecule-level insight into the rational design of robust SACs in a photo-Fenton-like system, with promising implications for wastewater treatment and other high-value applications.
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Viruses pose a great threat to animal and plant health worldwide, with many being dependent on insect vectors for transmission between hosts. While the virus-host arms race has been well established, how viruses and insect vectors adapt to each other remains poorly understood. Begomoviruses comprise the largest genus of plant-infecting DNA viruses and are exclusively transmitted by the whitefly Bemisia tabaci. Here, we show that the vector Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway plays an important role in mediating the adaptation between the begomovirus tomato yellow leaf curl virus (TYLCV) and whiteflies. We found that the JAK/STAT pathway in B. tabaci functions as an antiviral mechanism against TYLCV infection in whiteflies as evidenced by the increase in viral DNA and coat protein (CP) levels after inhibiting JAK/STAT signaling. Two STAT-activated effector genes, BtCD109-2 and BtCD109-3, mediate this anti-TYLCV activity. To counteract this vector immunity, TYLCV has evolved strategies that impair the whitefly JAK/STAT pathway. Infection of TYLCV is associated with a reduction of JAK/STAT pathway activity in whiteflies. Moreover, TYLCV CP binds to STAT and blocks its nuclear translocation, thus, abrogating the STAT-dependent transactivation of target genes. We further show that inhibition of the whitefly JAK/STAT pathway facilitates TYLCV transmission but reduces whitefly survival and fecundity, indicating that this JAK/STAT-dependent TYLCV-whitefly interaction plays an important role in keeping a balance between whitefly fitness and TYLCV transmission. This study reveals a mechanism of plant virus-insect vector coadaptation in relation to vector survival and virus transmission.
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Begomovirus , Hemípteros , Virus de Plantas , Solanum lycopersicum , Animales , Antivirales , Begomovirus/genética , ADN Viral , Hemípteros/fisiología , Quinasas Janus/genética , Solanum lycopersicum/genética , Enfermedades de las Plantas , Virus de Plantas/genética , Factores de Transcripción STAT/genética , Transducción de SeñalRESUMEN
Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.
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Cancer is associated with the highest mortality rate globally. While life-saving screening and treatments exist, better awareness is needed. RNF187, an E3 ligase regulating biological processes, belongs to the RING domain-containing E3 ligase family. RNF187 may serve as an oncogene due to abnormal expression in tumors. However, its association with immune infiltration and prognosis across various cancers remains unclear. We searched several databases including TCGA, GTE x, CCLE, TIMER, and GSEA. R software was used to evaluate RNF187 differential expression, survival, pathology stage, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), gene co-expression analysis, mismatch repairs (MMRs), tumor microenvironment (TME), and immune cell infiltration. Clinicopathological data were collected, and immunohistochemistry was used to verify RNF187 expression in tumor tissues. RNF187 expression was up-regulated in various cancers compared to that in normal tissues and associated with poor patient outcomes. Dysregulation of RNF187 expression in multiple cancer types was strongly correlated with DNA methylation, MMR, MSI, and TMB. RNF187 could interact with different immune cells in cancers. Biomarkers associated with RNF187 may be helpful for prognosis and immunology in treating pan-cancer patients.
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Biomarcadores de Tumor , Neoplasias , Humanos , Biomarcadores de Tumor/genética , Pronóstico , Neoplasias/diagnóstico , Neoplasias/genética , Programas Informáticos , Ubiquitina-Proteína Ligasas/genética , Microambiente Tumoral/genética , TransactivadoresRESUMEN
MOTIVATION: The registration of serial section electron microscope images is a critical step in reconstructing biological tissue volumes, and it aims to eliminate complex nonlinear deformations from sectioning and replicate the correct neurite structure. However, due to the inherent properties of biological structures and the challenges posed by section preparation of biological tissues, achieving an accurate registration of serial sections remains a significant challenge. Conventional nonlinear registration techniques, which are effective in eliminating nonlinear deformation, can also eliminate the natural morphological variation of neurites across sections. Additionally, accumulation of registration errors alters the neurite structure. RESULTS: This article proposes a novel method for serial section registration that utilizes an unsupervised optical flow network to measure feature similarity rather than pixel similarity to eliminate nonlinear deformation and achieve pairwise registration between sections. The optical flow network is then employed to estimate and compensate for cumulative registration error, thereby allowing for the reconstruction of the structure of biological tissues. Based on the novel serial section registration method, a serial split technique is proposed for long-serial sections. Experimental results demonstrate that the state-of-the-art method proposed here effectively improves the spatial continuity of serial sections, leading to more accurate registration and improved reconstruction of the structure of biological tissues. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/TongXin-CASIA/EFSR.
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Flujo Optico , Microscopía/métodos , Programas Informáticos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
The aquaculture sector, vital to global food security, grapples with bacterial pathogens compromising fish health and industry sustainability. This investigation probes mucosal immune responses and gut microbiota dynamics in snakehead (Channa argus) post-Aeromonas infection, a prevalent aquaculture challenge. Employing infection models, we delineated the integral role of immunoglobulin T (IgT) in mucosal immunity and its interaction with gut microbiota. Fish from a local farm, maintained under controlled conditions, were infected with Aeromonas veronii TH0426 and Aeromonas hydrophila TPS. Post-infection, daily monitoring and sample collection at specified intervals were conducted for comprehensive analysis. Histopathology, quantitative PCR, immunofluorescence, and microbiota profiling revealed significant immune and microbial changes, particularly at day 7. Intestinal IgT, IgM, and pIgR gene expression surged, indicative of a robust response. Immunofluorescence microscopy confirmed increased IgT+ and pIgR+ cell infiltration in the epithelium. Post-infection dysbiosis, with altered bacterial composition, was partially offset by elevated IgT levels. These insights underscore IgT's crucial function in mucosal defense and suggest potential for probiotic and vaccine strategies to enhance aquaculture disease resilience.
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Ameson portunus (Microsporidia) has caused serious economic losses to the aquaculture industry of swimming crab, Portunus trituberculatus. The hemolymph and hepatopancreas are the main immune organs of P. trituberculatus, and the main sites of A. portunus infection. Elucidating the response characteristics of hemolymph and hepatopancreas to microsporidian infection facilitates the development of microsporidiosis prevention and control strategy. This study performed comparative transcriptomic analysis of hemolymph (PTX/PTXA) and hepatopancreas (PTG/PTGA) of P. trituberculatus uninfected and infected with A. portunus. The results showed that there were 223 and 1309 differentially expressed genes (DEGs) in PTX/PTXA and PTG/PTGA, respectively. The lysosome pathway was significantly enriched after the invasion of the hemolymph by A. portunus. Also, immune-related genes were all significantly up-regulated in the hemolymph and hepatopancreas, suggesting that the invasion by A. portunus may activate host immune responses. Unlike hemolymph, antioxidant and detoxification-related genes were also significantly up-regulated in the hepatopancreas. Moreover, metabolism-related genes were significantly down-regulated in the hepatopancreas, suggesting that energy synthesis, resistance to pathogens, and regulation of oxidative stress were suppressed in the hepatopancreas. Hemolymph and hepatopancreas have similarity and tissue specificity to microsporidian infection. The differential genes and pathways identified in this study can provide references for the prevention and control of microsporidiosis.
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Braquiuros , Microsporidios , Microsporidiosis , Animales , Braquiuros/genética , Hemolinfa , Hepatopáncreas/metabolismo , Microsporidios/genética , Microsporidiosis/metabolismo , TranscriptomaRESUMEN
Bisphenol A (BPA) is a common component in the manufacture of daily plastic consumer goods. Recent studies have suggested that prenatal exposure to BPA can increase the susceptibility of offspring to mental illness, although the underlying mechanisms remain unclear. In this study, we performed transcriptomic and epigenomic profiling in the adult mouse brain following prenatal exposure to low-dose BPA. We observed a sex-specific transcriptional dysregulation in the cortex, with more significant differentially expressed genes was observed in adult cortex from male offspring. Moreover, the upregulated genes primarily influenced neuronal functions, while the downregulated genes were significantly associated with energy metabolism pathways. More evidence supporting impaired mitochondrial function included a decreased ATP level and a reduced number of mitochondria in the cortical neuron of the BPA group. We further investigated the higher-order chromatin regulatory patterns of DEGs by incorporating published Hi-C data. Interestingly, we found that upregulated genes exhibited more distal interactions with multiple enhancers, while downregulated genes displayed relatively short-range interactions among adjacent genes. Our data further revealed decreased H3K9me3 signal on the distal enhancers of upregulated genes, whereas increased DNA methylation and H3K27me3 signals on the promoters of downregulated genes. In summary, our study provides compelling evidence for the potential health risks associated with prenatal exposure to BPA, and uncovers sex-specific transcriptional changes with a complex interplay of multiple epigenetic mechanisms.
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Compuestos de Bencidrilo , Encéfalo , Metilación de ADN , Epigénesis Genética , Fenoles , Efectos Tardíos de la Exposición Prenatal , Animales , Compuestos de Bencidrilo/toxicidad , Fenoles/toxicidad , Femenino , Embarazo , Efectos Tardíos de la Exposición Prenatal/genética , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/metabolismo , Epigénesis Genética/efectos de los fármacos , Masculino , Ratones , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Transcriptoma/genética , Ratones Endogámicos C57BLRESUMEN
AIM: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. METHODS: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. RESULTS: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. CONCLUSIONS: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.
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The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.
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Antineoplásicos , Proliferación Celular , Neoplasias Colorrectales , Depsipéptidos , Compuestos Macrocíclicos , Proteínas Proto-Oncogénicas c-akt , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Depsipéptidos/farmacología , Depsipéptidos/uso terapéutico , Depsipéptidos/química , Depsipéptidos/síntesis química , Descubrimiento de Drogas , Ensayos de Selección de Medicamentos Antitumorales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Ameson portunus, the recently discovered causative agent of "toothpaste disease" of pond-cultured swimming crabs in China has caused enormous economic losses in aquaculture. Understanding the process of spore germination is helpful to elucidate the molecular mechanism of its invasion of host cells. Here, we obtained mature and germinating spores by isolation and purification and in vitro stimulation, respectively. Then, non-germinated and germinated spores were subjected to the comparative transcriptomic analysis to disclose differential molecular responses of these two stages. The highest germination rate, i.e., 71.45 %, was achieved in 0.01 mol/L KOH germination solution. There were 9,609 significantly differentially expressed genes (DEGs), with 685 up-regulated and 8,924 down-regulated DEGs. The up-regulated genes were significantly enriched in ribosome pathway, and the down-regulated genes were significantly enriched in various metabolic pathways, including carbohydrate metabolism, amino acid metabolism and other metabolism. The results suggested that spores require various carbohydrates and amino acids as energy to support their life activities during germination and synthesize large amounts of ribosomal proteins to provide sites for DNA replication, transcription, translation and protein synthesis of the spores of A. portunus within the host cells. Functional genes related to spore germination, such as protein phosphatase CheZ and aquaporin, were also analyzed. The analysis of transcriptome data and identification of functional genes will help to understand the process of spore germination and invasion.
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Microsporidios , Transcriptoma , Animales , Esporas , Microsporidios/genética , Perfilación de la Expresión Génica , Esporas Bacterianas/genéticaRESUMEN
This review provides an overview of the treatment options available for gastric varices (GV) with a focus on endoscopic methods. Various minimally invasive techniques, including endoscopic band ligation, endoscopic cyanoacrylate injection, and transjugular intrahepatic portosystemic shunt, can be applied to the treatment of GV. Endoscopic cyanoacrylate injection is now recognized as a first-line treatment for GV. Endoscopic ultrasound-guided cyanoacrylate injection combined with coils has shown good security and effectiveness. Thrombin injection therapy is a promising treatment, with a similar hemostasis rate to cyanoacrylate injection but with fewer serious complications. With the deepening understanding of the hemodynamics of the GV system, various treatment methods and their combination are gradually evaluated to provide patients with safer and more effective treatment options.
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Várices Esofágicas y Gástricas , Hemostasis Endoscópica , Humanos , Várices Esofágicas y Gástricas/terapia , Hemostasis Endoscópica/métodos , Ligadura/métodos , Derivación Portosistémica Intrahepática Transyugular/métodos , Cianoacrilatos/administración & dosificación , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/etiología , Masculino , Resultado del Tratamiento , Femenino , EndosonografíaRESUMEN
When it comes to mass spectrometry data analysis for identification of peptide pairs linked by N-hydroxysuccinimide (NHS) ester cross-linkers, search engines bifurcate in their setting of cross-linkable sites. Some restrict NHS ester cross-linkable sites to lysine (K) and protein N-terminus, referred to as K only for short, whereas others additionally include serine (S), threonine (T), and tyrosine (Y) by default. Here, by setting amino acids with chemically inert side chains such as glycine (G), valine (V), and leucine (L) as cross-linkable sites, which serves as a negative control, we show that software-identified STY-cross-links are only as reliable as GVL-cross-links. This is true across different NHS ester cross-linkers including DSS, DSSO, and DSBU, and across different search engines including MeroX, xiSearch, and pLink. Using a published data set originated from synthetic peptides, we demonstrate that STY-cross-links indeed have a high false discovery rate. Further analysis revealed that depending on the data and the search engine used to analyze the data, up to 65% of the STY-cross-links identified are actually K-K cross-links of the same peptide pairs, up to 61% are actually K-mono-links, and the rest tend to contain short peptides at high risk of false identification.
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Ésteres , Proteínas , Reactivos de Enlaces Cruzados/química , Espectrometría de Masas/métodos , Péptidos/química , Proteínas/metabolismoRESUMEN
The rich genetic diversity in Citrullus lanatus and the other six species in the Citrullus genus provides important sources in watermelon breeding. Here, we present the Citrullus genus pan-genome based on the 400 Citrullus genus resequencing data, showing that 477 Mb contigs and 6249 protein-coding genes were absent in the Citrullus lanatus reference genome. In the Citrullus genus pan-genome, there are a total of 8795 (30.5%) genes that exhibit presence/absence variations (PAVs). Presence/absence variation (PAV) analysis showed that a lot of gene PAV were selected during the domestication and improvement, such as 53 favorable genes and 40 unfavorable genes were identified during the C. mucosospermus to C. lanatus landrace domestication. We also identified 661 resistance gene analogs (RGAs) in the Citrullus genus pan-genome, which contains 90 RGAs (89 variable and 1 core gene) located on the pangenome additional contigs. By gene PAV-based GWAS, 8 gene presence/absence variations were found associated with flesh color. Finally, based on the results of gene PAV selection analysis between watermelon populations with different fruit colors, we identified four non-reference candidate genes associated with carotenoid accumulation, which had a significantly higher frequency in the white flesh. These results will provide an important source for watermelon breeding.
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Citrullus , Citrullus/genética , Domesticación , Fitomejoramiento , Genoma de Planta , Análisis de Secuencia de ADNRESUMEN
In recent years, bone loss related diseases have attracted more and more attention, such as osteoporosis and osteonecrosis of the femoral head exhibited symptoms of osteopenia or insufficient bone mass in a certain stage. Mesenchymal stem cells (MSCs), which can be induced to differentiate into osteoblasts under certain conditions can provide a new solution bone disease. Herein, we deciphered the possible mechanism by which BMP2 drives the transduction of MSCs to the osteoblast lineage through ACKR3/p38/MAPK signaling. The levels of ACKR3 in femoral tissues of samples from humans with different ages and sexes were measured firstly and found that ACKR3 protein levels increase with age. In vitro cellular assays showed that ACKR3 inhibits BMP2-induced osteo-differentiation and promotes adipo-differentiation of MSCs, whereas siACKR3 exhibited the opposite effects. In vitro embryo femur culture experiment showed that inhibition of ACKR3 enhanced BMP2-induced trabecular bone formation in C57BL6/J mouse. In terms of molecular mechanisms, we found that p38/MAPK signaling might play the key role. ACKR3 agonist TC14012 suppressed the phosphorylation of p38 and STAT3 in BMP2 induced MSCs differentiation. Our findings suggested that ACKR3 might be a novel therapeutic target for the treatment of bone-associated diseases and bone-tissue engineering.
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Células Madre Mesenquimatosas , Osteogénesis , Animales , Ratones , Humanos , Diferenciación Celular , Huesos/metabolismo , Osteoblastos/metabolismo , Proteína Morfogenética Ósea 2/metabolismo , Células CultivadasRESUMEN
Decades of spaceflight studies have provided abundant evidence that individual cells in vitro are capable of sensing space microgravity and responding with cellular changes both structurally and functionally. However, how microgravity is perceived, transmitted, and converted to biochemical signals by single cells remains unrevealed. Here in this review, over 40 cellular biology studies of real space fights were summarized. Studies on cells of the musculoskeletal system, cardiovascular system, and immune system were covered. Among all the reported cellular changes in response to space microgravity, cytoskeleton (CSK) reorganization emerges as a key indicator. Based on the evidence of CSK reorganization from space flight research, a possible mechanism from the standpoint of "cellular mechanical equilibrium" is proposed for the explanation of cellular response to space microgravity. Cytoskeletal equilibrium is broken by the gravitational change from ground to space and is followed by cellular morphological changes, cell mechanical properties changes, extracellular matrix reorganization, as well as signaling pathway activation/inactivation, all of which ultimately lead to the cell functional changes in space microgravity.
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Citoesqueleto/fisiología , Humanos , Sistema Inmunológico/fisiología , Transducción de Señal/fisiología , Vuelo Espacial/métodos , IngravidezRESUMEN
2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO) is the essential precursor keto acid for the asymmetric biosynthesis of herbicide l-phosphinothricin (l-PPT). Developing a biocatalytic cascade for PPO production with high efficiency and low cost is highly desired. Herein, a d-amino acid aminotransferase from Bacillus sp. YM-1 (Ym DAAT) with high activity (48.95 U/mg) and affinity (Km = 27.49 mM) toward d-PPT was evaluated. To circumvent the inhibition of by-product d-glutamate (d-Glu), an amino acceptor (α-ketoglutarate) regeneration cascade was constructed as a recombinant Escherichia coli (E. coli D), by coupling Ym d-AAT, d-aspartate oxidase from Thermomyces dupontii (TdDDO) and catalase from Geobacillus sp. CHB1. Moreover, the regulation of the ribosome binding site was employed to overcome the limiting step of expression toxic protein TdDDO in E. coli BL21(DE3). The aminotransferase-driven whole-cell biocatalytic cascade (E. coli D) showed superior catalytic efficiency for the synthesis of PPO from d,l-phosphinothricin (d,l-PPT). It revealed the production of PPO exhibited high space-time yield (2.59 g L-1 h-1 ) with complete conversion of d-PPT to PPO at high substrate concentration (600 mM d,l-PPT) in 1.5 L reaction system. This study first provides the synthesis of PPO from d,l-PPT employing an aminotransferase-driven biocatalytic cascade.
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Escherichia coli , Transaminasas , Transaminasas/genética , Transaminasas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Aminobutiratos/metabolismo , Aminoácidos/metabolismoRESUMEN
The MYC oncogenic family is dysregulated in diverse tumors which is generally linked to the poor prognosis of tumors. The members in MYC family are transcription factors which are responsible for the regulation of various genes expression. Among them, c-MYC is closely related to the progression of tumors. Furthermore, c-MYC aberrations is tightly associated with the prevalence of breast cancer. Tumor microenvironment (TME) is composed of many different types of cellular and non-cellular factors, mainly including cancer-associated fibroblasts, tumor-associated macrophages, vascular endothelial cells, myeloid-derived suppressor cells and immune cells, all of which can affect the diagnosis, prognosis, and therapeutic efficacy of breast cancer. Importantly, the biological processes occurred in TME, such as angiogenesis, immune evasion, invasion, migration, and the recruition of stromal and tumor-infiltrating cells are under the modulation of c-MYC. These findings indicated that c-MYC serves as a critical regulator of TME. Here, we aimed to summarize and review the relevant research, thus to clarify c-MYC is a key mediator between breast cancer cells and TME. Video Abstract.
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Neoplasias de la Mama , Genes myc , Microambiente Tumoral , Fibroblastos Asociados al Cáncer , Células Endoteliales , Expresión Génica , Evasión InmuneRESUMEN
In the realm of wastewater treatment, the power of ferrate (Fe(VI)) and peracetic acid (PAA) as oxidants stands out. But their combined might is where the enhancement truly lies. Their collaborative effect intensifies, but the underlying mechanics, especially across varying pH levels and pollutant types, still lurks in obscurity. Our study delved into the sophisticated oxidation interplay among Fe(VI)-PAA, Fe(VI)-H2O2, and standalone Fe(VI) systems. Notably, at a pH of 9.0, boasting a kinetic constant of â¼0.127 M-1·s-1, the Fe(VI)-PAA system annihilated the pollutant sulfamethoxazole, outpacing its counterparts by a staggering 48.73-fold when compared to the Fe(VI)-H2O2 system and 105.58-fold when using Fe(VI) individually. The behavior of active speciesâsuch as the dynamic â¢OH radicals and high-valent iron species (Fe(IV)/Fe(V))âshifted with pH variations, leading to distinct degradation pathways. Our detailed exploration pinpoints the behaviors of certain species across pH levels from 3.0 to 9.0. In more acidic environments, the â¢OH species proved indispensable for the system's reactivity. Conversely, as the pH inclined, degradation was increasingly steered by high-valent iron species. This intensive probe demystifies Fe(VI) interactions, deepening our understanding of the capabilities of the Fe(VI)-centered system and guiding us toward cleaner water solutions. Importantly, pH value, often underappreciated, holds the reins in organic wastewater decontamination. Embracing this key player is vital as we strategize for more expansive systems in upcoming ventures.