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Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.g., chromothripsis) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,778 tumor whole-genome sequences, we uncovered three novel complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are "towers" of low-JCN duplications associated with early-replicating regions, superenhancers, and breast or ovarian cancers. Rigma comprise "chasms" of low-JCN deletions enriched in late-replicating fragile sites and gastrointestinal carcinomas. Tyfonas are "typhoons" of high-JCN junctions and fold-back inversions associated with expressed protein-coding fusions, breakend hypermutation, and acral, but not cutaneous, melanomas. Clustering of tumors according to genome graph-derived features identified subgroups associated with DNA repair defects and poor prognosis.
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Variación Estructural del Genoma/genética , Genómica/métodos , Neoplasias/genética , Inversión Cromosómica/genética , Cromotripsis , Variaciones en el Número de Copia de ADN/genética , Reordenamiento Génico/genética , Genoma Humano/genética , Humanos , Mutación/genética , Secuenciación Completa del Genoma/métodosRESUMEN
We report a new immunodeficiency disorder in mice caused by a viable hypomorphic mutation of Snrnp40, an essential gene encoding a subunit of the U5 small nuclear ribonucleoprotein (snRNP) complex of the spliceosome. Snrnp40 is ubiquitous but strongly expressed in lymphoid tissue. Homozygous mutant mice showed hypersusceptibility to infection by murine cytomegalovirus and multiple defects of lymphoid development, stability and function. Cell-intrinsic defects of hematopoietic stem cell differentiation also affected homozygous mutants. SNRNP40 deficiency in primary hematopoietic stem cells or T cells or the EL4 cell line increased the frequency of splicing errors, mostly intron retention, in several hundred messenger RNAs. Altered expression of proteins associated with immune cell function was also observed in Snrnp40-mutant cells. The immunological consequences of SNRNP40 deficiency presumably result from cumulative, moderate effects on processing of many different mRNA molecules and secondary reductions in the expression of critical immune proteins, yielding a syndromic immune disorder.
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Células Madre Hematopoyéticas/fisiología , Infecciones por Herpesviridae/inmunología , Síndromes de Inmunodeficiencia/inmunología , Muromegalovirus/fisiología , Ribonucleoproteína Nuclear Pequeña U5/metabolismo , Empalmosomas/metabolismo , Linfocitos T/fisiología , Alelos , Animales , Línea Celular , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Susceptibilidad a Enfermedades , Infecciones por Herpesviridae/genética , Síndromes de Inmunodeficiencia/genética , Linfopoyesis/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación/genética , Empalme del ARN , Ribonucleoproteína Nuclear Pequeña U5/genéticaRESUMEN
Oncogene amplification on extrachromosomal DNA (ecDNA) drives the evolution of tumours and their resistance to treatment, and is associated with poor outcomes for patients with cancer1-6. At present, it is unclear whether ecDNA is a later manifestation of genomic instability, or whether it can be an early event in the transition from dysplasia to cancer. Here, to better understand the development of ecDNA, we analysed whole-genome sequencing (WGS) data from patients with oesophageal adenocarcinoma (EAC) or Barrett's oesophagus. These data included 206 biopsies in Barrett's oesophagus surveillance and EAC cohorts from Cambridge University. We also analysed WGS and histology data from biopsies that were collected across multiple regions at 2 time points from 80 patients in a case-control study at the Fred Hutchinson Cancer Center. In the Cambridge cohorts, the frequency of ecDNA increased between Barrett's-oesophagus-associated early-stage (24%) and late-stage (43%) EAC, suggesting that ecDNA is formed during cancer progression. In the cohort from the Fred Hutchinson Cancer Center, 33% of patients who developed EAC had at least one oesophageal biopsy with ecDNA before or at the diagnosis of EAC. In biopsies that were collected before cancer diagnosis, higher levels of ecDNA were present in samples from patients who later developed EAC than in samples from those who did not. We found that ecDNAs contained diverse collections of oncogenes and immunomodulatory genes. Furthermore, ecDNAs showed increases in copy number and structural complexity at more advanced stages of disease. Our findings show that ecDNA can develop early in the transition from high-grade dysplasia to cancer, and that ecDNAs progressively form and evolve under positive selection.
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Adenocarcinoma , Esófago de Barrett , Carcinogénesis , ADN , Progresión de la Enfermedad , Detección Precoz del Cáncer , Neoplasias Esofágicas , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patología , Esófago de Barrett/genética , Esófago de Barrett/patología , Estudios de Casos y Controles , ADN/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinogénesis/genética , Secuenciación Completa del Genoma , Estudios de Cohortes , Biopsia , Oncogenes , Inmunomodulación , Variaciones en el Número de Copia de ADN , Amplificación de Genes , Detección Precoz del Cáncer/métodosRESUMEN
The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines, including interleukin 1ß (IL-1ß) and IL-18. We found here that activation of the NLRP3 inflammasome was restricted to interphase of the cell cycle by NEK7, a serine-threonine kinase previously linked to mitosis. Activation of the NLRP3 inflammasome required NEK7, which bound to the leucine-rich repeat domain of NLRP3 in a kinase-independent manner downstream of the induction of mitochondrial reactive oxygen species (ROS). This interaction was necessary for the formation of a complex containing NLRP3 and the adaptor ASC, oligomerization of ASC and activation of caspase-1. NEK7 promoted the NLRP3-dependent cellular inflammatory response to intraperitoneal challenge with monosodium urate and the development of experimental autoimmune encephalitis in mice. Our findings suggest that NEK7 serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division.
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Proteínas Portadoras/inmunología , Macrófagos/inmunología , Mitosis/inmunología , Proteínas Serina-Treonina Quinasas/inmunología , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis , Proteínas Adaptadoras de Señalización CARD , Proteínas Portadoras/genética , Caspasa 1 , Cromatografía en Gel , Ensayo de Unidades Formadoras de Colonias , Citocinas , Proteínas del Citoesqueleto , Células Dendríticas , Encefalomielitis Autoinmune Experimental/inmunología , Femenino , Citometría de Flujo , Células HEK293 , Humanos , Inmunoprecipitación , Técnicas In Vitro , Inflamasomas/genética , Inflamasomas/inmunología , Macrófagos Peritoneales/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/metabolismo , Monocitos , Quinasas Relacionadas con NIMA , Proteína con Dominio Pirina 3 de la Familia NLR , Proteínas Serina-Treonina Quinasas/genética , Especies Reactivas de Oxígeno , Médula Espinal/inmunologíaRESUMEN
BACKGROUND: Although network analysis studies of psychiatric syndromes have increased in recent years, most have emphasized centrality symptoms and robust edges. Broadening the focus to include bridge symptoms within a systematic review could help to elucidate symptoms having the strongest links in network models of psychiatric syndromes. We conducted this systematic review and statistical evaluation of network analyses on depressive and anxiety symptoms to identify the most central symptoms and bridge symptoms, as well as the most robust edge indices of networks. METHODS: A systematic literature search was performed in PubMed, PsycINFO, Web of Science, and EMBASE databases from their inception to May 25, 2022. To determine the most influential symptoms and connections, we analyzed centrality and bridge centrality rankings and aggregated the most robust symptom connections into a summary network. After determining the most central symptoms and bridge symptoms across network models, heterogeneity across studies was examined using linear logistic regression. RESULTS: Thirty-three studies with 78,721 participants were included in this systematic review. Seventeen studies with 23 cross-sectional networks based on the Patient Health Questionnaire (PHQ) and Generalized Anxiety Disorder (GAD-7) assessments of clinical and community samples were examined using centrality scores. Twelve cross-sectional networks based on the PHQ and GAD-7 assessments were examined using bridge centrality scores. We found substantial variability between study samples and network features. 'Sad mood', 'Uncontrollable worry', and 'Worrying too much' were the most central symptoms, while 'Sad mood', 'Restlessness', and 'Motor disturbance' were the most frequent bridge centrality symptoms. In addition, the connection between 'Sleep' and 'Fatigue' was the most frequent edge for the depressive and anxiety symptoms network model. CONCLUSION: Central symptoms, bridge symptoms and robust edges identified in this systematic review can be viewed as potential intervention targets. We also identified gaps in the literature and future directions for network analysis of comorbid depression and anxiety.
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Ansiedad , Depresión , Femenino , Humanos , Masculino , Ansiedad/complicaciones , Ansiedad/terapia , Trastornos de Ansiedad , Estudios Transversales , Depresión/complicaciones , Depresión/terapiaRESUMEN
Microbial infection as a type of environmental risk factors is considered to be associated with long-term increased risk of dementia, including Alzheimer's disease (AD). AD is characterized by two neuropathologically molecular hallmarks of hyperphosphorylated tau and amyloid-ß (Aß), the latter generated by several biochemically reactive enzymes, including γ-secretase. However, how infectious risk factors contribute to pathological development of the AD core molecules remains to be addressed. In this work, we utilized a modified herpes simplex virus type 1 (mHSV-1) and found that its hippocampal infection locally promotes Aß pathology in 5 × FAD mice, the commonly used amyloid model. Mechanistically, we identified HSV-1 membrane glycoprotein US7 (Envelope gI) that interacts with and modulates γ-secretase and consequently facilitates Aß production. Furthermore, we presented evidence that adenovirus-associated virus-mediated locally hippocampal overexpression of the US7 aggravates Aß pathology in 5 × FAD mice. Collectively, these findings identify a herpesviral factor regulating γ-secretase in the development and progression of AD and represent a causal molecular link between infectious pathogens and neurodegeneration.
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Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Péptidos beta-Amiloides , Modelos Animales de Enfermedad , Herpesvirus Humano 1 , Hipocampo , Animales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/genética , Ratones , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 1/patogenicidad , Ratones Transgénicos , Humanos , Amiloide/metabolismo , Proteínas tau/metabolismo , Ratones Endogámicos C57BLRESUMEN
Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.
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A function-impairing mutation (feeble) or genomic deletion of SLC15A4 abolishes responses of nucleic acidsensing endosomal toll-like receptors (TLRs) and significantly reduces disease in mouse models of lupus. Here, we demonstrate disease reduction in homozygous and even heterozygous Slc15a4 feeble mutant BXSB male mice with a Tlr7 gene duplication. In contrast to SLC15A4, a function-impairing mutation of SLC15A3 did not diminish type I interferon (IFN-I) production by TLR-activated plasmacytoid dendritic cells (pDCs), indicating divergence of function between these homologous SLC15 family members. Trafficking to endolysosomes and function of SLC15A4 were dependent on the Adaptor protein 3 (AP-3) complex. Importantly, SLC15A4 was required for trafficking and colocalization of nucleic acidsensing TLRs and their ligands to endolysosomes and the formation of the LAMP2+VAMP3+ hybrid compartment in which IFN-I production is initiated. Collectively, these findings define mechanistic processes by which SLC15A4 controls endosomal TLR function and suggest that pharmacologic intervention to curtail the function of this transporter may be a means to treat lupus and other endosomal TLR-dependent diseases.
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Ácidos Nucleicos , Animales , Endosomas/metabolismo , Ligandos , Lisosomas/metabolismo , Proteínas de Transporte de Membrana/genética , Ratones , Receptores Toll-Like/metabolismoRESUMEN
Null mutations of spliceosome components or cofactors are homozygous lethal in eukaryotes, but viable hypomorphic mutations provide an opportunity to understand the physiological impact of individual splicing proteins. We describe a viable missense allele (F181I) of Rnps1 encoding an essential regulator of splicing and nonsense-mediated decay (NMD), identified in a mouse genetic screen for altered immune cell development. Homozygous mice displayed a stem cellintrinsic defect in hematopoiesis of all lineages due to excessive apoptosis induced by tumor necrosis factor (TNF)dependent death signaling. Numerous transcript splice variants containing retained introns and skipped exons were detected at elevated frequencies in Rnps1F181I/F181I splenic CD8+ T cells and hematopoietic stem cells (HSCs), but NMD appeared normal. Strikingly, Tnf knockout rescued all hematopoietic cells to normal or near-normal levels in Rnps1F181I/F181I mice and dramatically reduced intron retention in Rnps1F181I/F181I CD8+ T cells and HSCs. Thus, RNPS1 is necessary for accurate splicing, without which disinhibited TNF signaling triggers hematopoietic cell death.
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Linfocitos T CD8-positivos , Ribonucleoproteínas , Animales , Linfocitos T CD8-positivos/metabolismo , Hematopoyesis/genética , Homocigoto , Mamíferos/metabolismo , Ratones , Receptores del Factor de Necrosis Tumoral/metabolismo , Ribonucleoproteínas/metabolismo , Eliminación de Secuencia , Factores de Necrosis Tumoral/metabolismoRESUMEN
Globally, 91% of plant production encounters diverse environmental stresses that adversely affect their growth, leading to severe yield losses of 50-60%. In this case, monitoring the connection between the environment and plant health can balance population demands with environmental protection and resource distribution. Fluorescent chemosensors have shown great progress in monitoring the health and environment of plants due to their high sensitivity and biocompatibility. However, to date, no comprehensive analysis and systematic summary of fluorescent chemosensors used in monitoring the correlation between plant health and their environment have been reported. Thus, herein, we summarize the current fluorescent chemosensors ranging from their design strategies to applications in monitoring plant-environment interaction processes. First, we highlight the types of fluorescent chemosensors with design strategies to resolve the bottlenecks encountered in monitoring the health and living environment of plants. In addition, the applications of fluorescent small-molecule, nano and supramolecular chemosensors in the visualization of the health and living environment of plants are discussed. Finally, the major challenges and perspectives in this field are presented. This work will provide guidance for the design of efficient fluorescent chemosensors to monitor plant health, and then promote sustainable agricultural development.
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Agricultura , Colorantes Fluorescentes , Plantas , Colorantes Fluorescentes/química , Plantas/química , Plantas/metabolismo , Imagen ÓpticaRESUMEN
BACKGROUND: Evidence remains limited about the association of maternal exposure to ambient fine particulate matter (airborne particles with an aerodynamic diameter ≤2.5 µm [PM2.5]) with fetal congenital heart defects (CHDs) in highly polluted regions, and few studies have focused on preconception exposure. METHODS: Using a nationwide surveillance-based case-control design in China, we examined the association between maternal exposure to PM2.5 during periconception (defined as 3 months before conception until 3 months into pregnancy) and risk of CHD in offspring. The study included 1 434 998 births involving 7335 CHDs from 2014 through 2017 on the basis of the National Population-Based Birth Defects Surveillance System, covering 30 provinces, municipalities, or municipal districts in China. We assigned maternal PM2.5 exposure during the periconception period to each participant using satellite-based PM2.5 concentrations at 1-km spatial resolution. Multilevel logistic regression models were used to calculate the multivariable-adjusted odds ratio and 95% CI for CHDs in offspring associated with maternal PM2.5 exposure, and the exposure-response association was investigated using restricted cubic spline analysis. Subgroup or sensitivity analyses were conducted to identify factors that may modify the association. RESULTS: The average maternal exposure to PM2.5 levels across all participants was 56.51 µg/m3 (range, 10.95 to 182.13 µg/m3). For each 10 µg/m³ increase in maternal PM2.5 exposure, the risk of CHDs in offspring was increased by 2% (odds ratio, 1.02 [95% CI, 1.00 to 1.05]), and septal defect was the most influenced subtype (odds ratio, 1.04 [95% CI, 1.01 to 1.08]). The effect of PM2.5 on CHD risk was more pronounced during the preconception period. Mothers <35 years of age, those living in northern China, and those living in low-income areas were more susceptible to PM2.5 exposure than their counterparts (all P<0.05). PM2.5 exposure showed a linear association with total CHDs or specific CHD types. CONCLUSIONS: High maternal PM2.5 exposure, especially during the preconception period, increases risk of certain types of CHD in offspring. These findings are useful for CHD prevention and highlight the public health benefits of improving air quality in China and other highly polluted regions.
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Contaminantes Atmosféricos , Contaminación del Aire , Cardiopatías Congénitas , Embarazo , Femenino , Humanos , Exposición Materna/efectos adversos , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/etiología , Material Particulado/efectos adversos , Material Particulado/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Madres , China/epidemiología , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisisRESUMEN
BACKGROUND: B-box (BBX) family is a class of zinc finger transcription factors (TFs) that play essential roles in regulating plant growth, development, as well as abiotic stress. However, no systematic analysis of BBX genes has yet been conducted in alfalfa (Medica go sativa L.), and their functions have not been elucidated up to now. RESULTS: In this study, 28 MsBBX genes were identified from the alfalfa genome, which were clustered into 4 subfamilies according to an evolutionary tree of BBX proteins. Exon-intron structure and conserved motif analysis reflected the evolutionary conservation of MsBBXs in alfalfa. Collinearity analysis showed that segmental duplication promoted the expansion of the MsBBX family. Analysis of cis-regulatory elements suggested that the MsBBX genes possessed many growth/development-, light-, phytohormone-, and abiotic stress-related elements. MsBBX genes were differentially expressed in leaves, flowers, pre-elongated stems, elongated stems, roots and nodules, and most MsBBXs were remarkably induced by drought, salt and various plant growth regulators (ABA, JA, and SA). Further functional verification demonstrated that overexpressing of the MsBBX11 gene clearly promoted salt tolerance in transgenic Arabidopsis by regulating growth and physiological processes of seedlings. CONCLUSIONS: This research provides insights into further functional research and regulatory mechanisms of MsBBX family genes under abiotic stress of alfalfa.
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Arabidopsis , Medicago sativa , Medicago sativa/genética , Evolución Biológica , Sequías , Reguladores del Crecimiento de las Plantas , Estrés Fisiológico/genéticaRESUMEN
Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is also associated with severe complications, such as aseptic meningitis and myocarditis. However, there are no antiviral drugs available to treat enteroviruses infection at present. In this study, we found that 4'-fluorouridine (4'-FlU), a nucleoside analog with low cytotoxicity, exhibited broad-spectrum activity against infections of multiple enteroviruses with EC50 values at low micromolar levels, including coxsackievirus A10 (CV-A10), CV-A16, CV-A6, CV-A7, CV-B3, enterovirus A71 (EV-A71), EV-A89, EV-D68, and echovirus 6. With further investigation, the results indicated that 4'-FlU directly interacted with the RNA-dependent RNA polymerase of enterovirus, the 3D pol, and impaired the polymerase activity of 3D pol, hence inhibiting viral RNA synthesis and significantly suppressing viral replication. Our ï¬ndings suggest that 4'-FlU could be promisingly developed as a broad-spectrum direct-acting antiviral agent for anti-enteroviruses therapy.
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Redox nanozymes have exhibited various applications in recognizing environmental pollutants but not aromatic amines (a type of typical pollutant). Herein, with Cu2+ as a node and tryptophan (Trp) as a linker, Cu-Trp as a specific ascorbic acid oxidase mimic was synthesized, which could catalyze ascorbic acid (AA) oxidation to dehydroascorbic acid (DHAA). Alternatively, with other natural amino acids as linkers to synthesize Cu-based nanozymes, such catalytic performances are also observed. The as-produced DHAA could react with o-phenylenediamine (OPD) and its derivatives (2,3-naphthalene diamine (NDA), 4-nitro-o-phenylenediamine (4-NO2-OPD), 4-fluoro-o-phenylenediamine (4-F-OPD), 4-chloro-o-phenylenediamine(4-Cl-OPD), and 4-bromo-o-phenylenediamine(4-Br-OPD)) to form a Schiff base and emit fluorescence. Based on the results, with Cu-Trp + AA and Cu-Arg (with arginine (Arg) as a linker) + AA as two sensing channels and extracted red, green, and blue (RGB) values from emitted fluorescence as read-out signals, a visual sensor array was constructed to efficiently distinguish OPD, NDA, 4-NO2-OPD, 4-F-OPD, 4-Cl-OPD, and 4-Br-OPD as low as 10 µM. Such detecting performance was further confirmed through discriminating binary, ternary, quinary, and senary mixtures with various concentration ratios, recognizing 18 unknown samples, and even quantitatively analyzing single aromatic amine. Finally, the discriminating ability was further validated in environmental waters, providing an efficient assay for large-scale scanning levels of multiple aromatic amines.
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Aminas , Ascorbato Oxidasa , Bases de Schiff , Bases de Schiff/química , Aminas/química , Aminas/análisis , Ascorbato Oxidasa/química , Ascorbato Oxidasa/metabolismo , Cobre/química , Cobre/análisis , Ácido Ascórbico/química , Ácido Ascórbico/análisis , Fenilendiaminas/química , Oxidación-ReducciónRESUMEN
Resolution control and expansibility have always been challenges to the fabrication of structural color materials. Here, a facile strategy to print cholesteric liquid crystal elastomers (CLCEs) into complex structural color patterns with variable resolution and enhanced expansibility is reported. A volatile solvent is introduced into the synthesized CLC oligomers, modifying its rheological properties and allowing direct-ink-writing (DIW) under mild conditions. The combination of printing shear flow and anisotropic deswelling of ink drives the CLC molecules into an ordered cholesteric arrangement. The authors meticulously investigate the influence of printing parameters to achieve resolution control over a wide range, allowing for the printing of multi-sized 1D or 2D patterns with constant quality. Furthermore, such solvent-cast direct-ink-writing (DIW) strategy is highly expandable and can be integrated easily into the DIW of bionic robots. Multi-responsive bionic butterfly and flower are printed with biomimetic in both locomotion and coloration. Such designs dramatically reduced the processing difficulty of precise full-color printing and expanded the capability of structural color materials to collaborate with other systems.
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OBJECTIVE: This study aimed to explore the specific pathways by which HOX transcript antisense intergenic RNA contributes to the pathogenesis of unexplained recurrent spontaneous abortion. METHODS: Real-time quantitative PCR was employed to assess the differential expression levels of HOX transcript antisense intergenic RNA in chorionic villi tissues from unexplained recurrent spontaneous abortion patients and women with voluntarily terminated pregnancies. HTR-8/SVneo served as a cellular model. Knockdown and overexpression of HOX transcript antisense intergenic RNA in the cells were achieved through siRNA transfection and pcDNA3.1 transfection, respectively. Cell viability, migration, and invasion were evaluated using cell counting kit-8, scratch, and Transwell assays, respectively. The interaction among the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 axis was predicted through bioinformatics analysis and confirmed through in vitro experiments. Furthermore, the regulatory effects of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis on cellular behaviors were validated in HTR-8/SVneo cells. RESULTS: We found that HOX transcript antisense intergenic RNA was downregulated in chorionic villi tissues from unexplained recurrent spontaneous abortion patients. Overexpression of HOX transcript antisense intergenic RNA significantly enhanced the viability, migration, and invasion of HTR-8/SVneo cells, while knockdown of HOX transcript antisense intergenic RNA had the opposite effects. We further confirmed the regulatory effect of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis in unexplained recurrent spontaneous abortion. Specifically, HOX transcript antisense intergenic RNA and fibrillin 2 were found to reduce the risk of unexplained recurrent spontaneous abortion by enhancing cell viability, migration, and invasion, whereas miR-1277-5p exerted the opposite effects. CONCLUSION: HOX transcript antisense intergenic RNA promotes unexplained recurrent spontaneous abortion development by targeting inhibition of miR-1277-5p/fibrillin 2 axis.
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Aborto Habitual , Movimiento Celular , MicroARNs , ARN Largo no Codificante , Transducción de Señal , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Femenino , Aborto Habitual/genética , Aborto Habitual/metabolismo , Aborto Habitual/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Embarazo , Fibrilina-2/genética , Fibrilina-2/metabolismo , Adulto , Proliferación Celular , Línea Celular , Trofoblastos/metabolismo , Trofoblastos/fisiología , Vellosidades Coriónicas/metabolismoRESUMEN
Plant health is intricately linked to crop quality, food security and agricultural productivity. Obtaining accurate plant health information is of paramount importance in the realm of precision agriculture. Wearable sensors offer an exceptional avenue for investigating plant health status and fundamental plant science, as they enable real-time and continuous in-situ monitoring of physiological biomarkers. However, a comprehensive overview that integrates and critically assesses wearable plant sensors across various facets, including their fundamental elements, classification, design, sensing mechanism, fabrication, characterization and application, remains elusive. In this study, we provide a meticulous description and systematic synthesis of recent research progress in wearable sensor properties, technology and their application in monitoring plant health information. This work endeavours to serve as a guiding resource for the utilization of wearable plant sensors, empowering the advancement of plant health within the precision agriculture paradigm.
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Agricultura , Dispositivos Electrónicos Vestibles , Agricultura/métodos , Productos Agrícolas , Técnicas Biosensibles/instrumentaciónRESUMEN
Emerging evidence suggests the dysregulation of long non-coding RNAs (lncRNAs) involved in pancreatic cancer (PC). However, the function of LINC00930 in PC has not been elaborated. In this study, we found that LINC00930 was significantly down-regulated in PC cell lines and tissues, and associated with tumor size, lymphatic metastasis, TNM stage and poor prognosis. According to the bioinformatics database, the downregulation of LINC00930 was a common event in PC associated with prognosis and EMT. Overexpression of LINC00930 inhibited the aggressive cancer phenotypes including proliferation, metastasis and epithelial-mesenchymal transition (EMT) of PC in vitro and in vivo. Bioinformatics and dual-luciferase reporter assay indicated that miR-6792-3p could directly bind to LINC00930. Additionally, the Zinc finger and BTB domain containing 16 (ZBTB16) was significantly declined in PC, which was predicted to be the downstream gene of miR-6792-3p. MiR-6792-3p mimic rescued the decreased proliferation, metastasis and EMT caused by ZBTB16 in PC cells. The LINC00930/miR-6792-3p/ZBTB16 axis was associated with the malignant progression and process of PC. The relative expression of LINC00930 was negatively correlated with the expression of miR-6792-3p and was closely linked with ZBTB16 levels in PC. LINC00930 might serve as a potential prognostic biomarker and therapeutic target for PC.
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Proliferación Celular , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , MicroARNs , Neoplasias Pancreáticas , ARN Largo no Codificante , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transición Epitelial-Mesenquimal/genética , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Animales , Ratones , Línea Celular Tumoral , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Movimiento Celular/genéticaRESUMEN
It has been demonstrated that hair follicle stem cells (HFSCs) can contribute to wound closure and repair. However, the specific mechanism remains unclear due to the complexity of the wound repair process. Lysine-specific demethylase 1 (LSD1), an important gene for the regulation of stem cell differentiation, has been reported to participate in wound healing regulation. Heat shock protein 90 (HSP90), a chaperone protein, is recently discovered to be a driver gene for wound healing. This study explored the molecular mechanisms by which the binding between LSD1 and HSP90 affects the role of HFSCs during skin wound healing. Following bioinformatics analysis, the key genes acting on HFSCs were identified. The expression of LSD1, HSP90, and c-MYC was found to be upregulated in differentiated HFSCs. Analysis of their binding affinity revealed that LSD1 interacted with HSP90 to enhance the stability of the transcription factor c-MYC. Lactate dehydrogenase A (LDHA) has been documented to be essential for HFSC activation. Therefore, we speculate that LDHA may induce the differentiation of HFSCs through glucose metabolism reprogramming. The results showed that c-MYC activated LDHA activity to promote glycolytic metabolism, proliferation, and differentiation of HFSCs. Finally, in vivo animal experiments further confirmed that LSD1 induced skin wound healing in mice via the HSP90/c-MYC/LDHA axis. From our data, we conclude that LSD1 interacting with HSP90 accelerates skin wound healing by inducing HFSC glycolytic metabolism, proliferation, and differentiation via c-MYC/LDHA axis.
Asunto(s)
Folículo Piloso , Células Madre , Animales , Ratones , Folículo Piloso/metabolismo , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Lactato Deshidrogenasa 5/metabolismo , Células Madre/metabolismo , Cicatrización de Heridas/fisiologíaRESUMEN
Graphdiyne (GDY) is a new two-dimensional carbon network material composed of sp2 hybrid carbon and sp hybrid carbon conjugation. It has unique physical and chemical properties, such as high porosity, good electrical conductivity, high carrier mobility, adjustable band gap, and so on. The preparation of GDY and GDY derivatives by adjusting physical and chemical methods and changing monomers has become the key material in the fields of photocatalysis, energy storage, life science, and so on. In this paper, new methods for controllable growth of GDY are reviewed, including liquid phase chemical classical total synthesis, chemical vapor deposition, the interface method, the explosion method, and the mechanically driven ball milling method. FT-IR, Raman, NMR, and XAS are the main means to characterize the structure of GDY. Finally, the representative application of GDY in the field of photocatalytic hydrogen evolution is summarized, and its future development has been explored.