RESUMO
Due to their immobility and possession of underground parts, plants have evolved various mechanisms to endure and adapt to abiotic stresses such as extreme temperatures, drought, and salinity. However, the contribution of long noncoding RNAs (lncRNAs) to different abiotic stresses and distinct rice seedling parts remains largely uncharacterized beyond the protein-coding gene (PCG) layer. Using transcriptomics and bioinformatics methods, we systematically identified lncRNAs and characterized their expression patterns in the roots and shoots of wild type (WT) and ososca1.1 (reduced hyperosmolality-induced [Ca2+]i increase in rice) seedlings under hyperosmolarity and salt stresses. Here, 2937 candidate lncRNAs were identified in rice seedlings, with intergenic lncRNAs representing the largest category. Although the detectable sequence conservation of lncRNAs was low, we observed that lncRNAs had more orthologs within the Oryza. By comparing WT and ososca1.1, the transcription level of OsOSCA1.1-related lncRNAs in roots was greatly enhanced in the face of hyperosmolality stress. Regarding regulation mode, the co-expression network revealed connections between trans-regulated lncRNAs and their target PCGs related to OsOSCA1.1 and its mediation of hyperosmolality stress sensing. Interestingly, compared to PCGs, the expression of lncRNAs in roots was more sensitive to hyperosmolarity stress than to salt stress. Furthermore, OsOSCA1.1-related hyperosmolarity stress-responsive lncRNAs were enriched in roots, and their potential cis-regulated genes were associated with transcriptional regulation and signaling transduction. Not to be ignored, we identified a motif-conserved and hyperosmolarity stress-activated lncRNA gene (OSlncRNA), speculating on its origin and evolutionary history in Oryza. In summary, we provide a global perspective and a lncRNA resource to understand hyperosmolality stress sensing in rice roots, which helps to decode the complex molecular networks involved in plant sensing and adaptation to stressful environments.
Assuntos
Regulação da Expressão Gênica de Plantas , Oryza , Raízes de Plantas , RNA Longo não Codificante , Estresse Salino , Oryza/genética , Oryza/metabolismo , RNA Longo não Codificante/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Estresse Salino/genética , Pressão Osmótica , Estresse Fisiológico/genética , Perfilação da Expressão Gênica , RNA de Plantas/genética , Plântula/genética , TranscriptomaRESUMO
Long noncoding RNAs (lncRNAs) are RNA molecules longer than 200 nt, which lack the ability to encode proteins and are involved in multifarious growth, development, and regulatory processes in plants and mammals. However, the environmental-regulated expression profiles of lncRNAs in Orinus that may associated with their adaptation on the Qinghai-Xizang (Tibet) Plateau (QTP) have never been characterized. Here, we utilized transcriptomic sequencing data of two Orinus species (O. thoroldii and O. kokonoricus) to identify 1624 lncRNAs, including 1119 intergenic lncRNAs, 200 antisense lncRNAs, five intronic lncRNAs, and 300 sense lncRNAs. In addition, the evolutionary relationships of Orinus lncRNAs showed limited sequence conservation among 39 species, which implied that Orinus-specific lncRNAs contribute to speciation adaptation evolution. Furthermore, considering the cis-regulation mechanism, from 286 differentially expressed lncRNAs (DElncRNAs) and their nearby protein coding genes (PCGs) between O. thoroldii and O. kokonoricus, 128 lncRNA-PCG pairs were obtained in O. thoroldii, whereas 92 lncRNA-PCG pairs were obtained in O. kokonoricus. In addition, a total of 19 lncRNA-PCG pairs in O. thoroldii and 14 lncRNA-PCG pairs in O. kokonoricus were found to participate in different biological processes, indicating that the different expression profiles of DElncRNAs between O. thoroldii and O. kokonoricus were associated with their adaptation at different elevations on the QTP. We also found several pairs of DElncRNA nearby transcription factors (TFs), indicating that these DElncRNAs regulate the expression of TFs to aid O. thoroldii in adapting to the environment. Therefore, this work systematically identified a series of lncRNAs in Orinus, laying the groundwork for further exploration into the biological function of Orinus in environmental adaptation.
RESUMO
Diabetic wounds are characterized by chronic trauma, with long-term non-healing attributed to persistent inflammation and recurrent bacterial infections. Exacerbation of the inflammatory response is largely due to increased levels of reactive oxygen species (ROS). In this study, catalase (CAT) was used as a biological template to synthesize nanozyme-supported natural enzymes (CAT-Mn(SH)x) using a biomimetic mineralization method. Subsequently, polymyxin B (CAT-Mn(SH)x@PMB) was immobilized on its surface through electrostatic assembly. CAT-Mn(SH)x@PMB demonstrates the ability for slow and sustained release of hydrogen sulfide (H2S). Finally, CAT-Mn(SH)x@PMB loaded microneedles (MNs) substrate were synthesized using polyvinyl alcohol (PVA) and hydroxyethyl methacrylate (HEMA), and named CAT-(MnSH)x@PMB-MNs. It exhibited enhanced enzyme and antioxidant activities, along with effective antibacterial properties. Validation findings indicate that it can up-regulate the level of M2 macrophages and reduce the level of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Additionally, it promotes angiogenesis and rapid nerve regeneration, thereby facilitating wound healing through its dual anti-inflammatory and antibacterial effects. Hence,this study introduces a time-space tissue-penetrating and soluble microneedle patch with dual anti-inflammatory and antibacterial effects for the treatment of diabetic wounds.
Assuntos
Antibacterianos , Catalase , Agulhas , Polimixina B , Cicatrização , Polimixina B/farmacologia , Polimixina B/química , Polimixina B/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Animais , Catalase/metabolismo , Catalase/química , Cicatrização/efeitos dos fármacos , Camundongos , Escherichia coli/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Ratos , Células RAW 264.7 , Testes de Sensibilidade Microbiana , Tamanho da PartículaRESUMO
Ubiquitination, a highly adaptable post-translational modification, plays a pivotal role in maintaining cellular protein homeostasis, encompassing cancer chemoresistance-associated proteins. Recent findings have indicated a potential correlation between perturbations in the ubiquitination process and the emergence of drug resistance in CRC cancer. Consequently, numerous studies have spurred the advancement of compounds specifically designed to target ubiquitinates, offering promising prospects for cancer therapy. In this review, we highlight the role of ubiquitination enzymes associated with chemoresistance to chemotherapy via the Wnt/ß-catenin signaling pathway, epithelial-mesenchymal transition (EMT), and cell cycle perturbation. In addition, we summarize the application and role of small compounds that target ubiquitination enzymes for CRC treatment, along with the significance of targeting ubiquitination enzymes as potential cancer therapies.
Assuntos
Neoplasias Colorretais , Humanos , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , beta Catenina/metabolismo , Ubiquitinação , Via de Sinalização Wnt , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Proliferação de CélulasRESUMO
BACKGROUND: The development and progression of hepatocellular carcinoma (HCC) have been reported to be associated with immune-related genes and the tumor microenvironment. Nevertheless, there are not enough prognostic biomarkers and models available for clinical use. Based on seven prognostic genes, this study calculated overall survival in patients with HCC using a prognostic survival model and revealed the immune status of the tumor microenvironment (TME). AIM: To develop a novel immune cell-related prognostic model of HCC and depict the basic profile of the immune response in HCC. METHODS: We obtained clinical information and gene expression data of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. TCGA and ICGC datasets were used for screening prognostic genes along with developing and validating a seven-gene prognostic survival model by weighted gene coexpression network analysis and least absolute shrinkage and selection operator regression with Cox regression. The relative analysis of tumor mutation burden (TMB), TME cell infiltration, immune checkpoints, immune therapy, and functional pathways was also performed based on prognostic genes. RESULTS: Seven prognostic genes were identified for signature construction. Survival receiver operating characteristic curve analysis showed the good performance of survival prediction. TMB could be regarded as an independent factor in HCC survival prediction. There was a significant difference in stromal score, immune score, and estimate score between the high-risk and low-risk groups stratified based on the risk score derived from the seven-gene prognostic model. Several immune checkpoints, including VTCN1 and TNFSF9, were found to be associated with the seven prognostic genes and risk score. Different combinations of checkpoint blockade targeting inhibitory CTLA4 and PD1 receptors and potential chemotherapy drugs hold great promise for specific HCC therapies. Potential pathways, such as cell cycle regulation and metabolism of some amino acids, were also identified and analyzed. CONCLUSION: The novel seven-gene (CYTH3, ENG, HTRA3, PDZD4, SAMD14, PGF, and PLN) prognostic model showed high predictive efficiency. The TMB analysis based on the seven genes could depict the basic profile of the immune response in HCC, which might be worthy of clinical application.
RESUMO
BACKGROUND: Hereditary hearing loss is a highly heterogeneous disorder. This study aimed to identify the genetic cause of a Chinese family with autosomal recessive non-syndromic sensorineural hearing loss (ARNSHL). METHODS: Clinical information and peripheral blood samples were collected from the proband and its parents. Two-step high-throughput next-generation sequencing on the Ion Torrent platform was applied to detect variants as follows. First, long-range PCR was performed to amplify all the regions of the GJB2, GJB3, SLC26A4, and MT-RNR1 genes, followed by next-generation sequencing. If no candidate pathogenetic variants were found, the targeted exon sequencing with AmpliSeq technology was employed to examine another 64 deafness-associated genes. Sanger sequencing was used to identify variants and the lineage co-segregation. The splicing of the MYO15A gene was assessed by in silico bioinformatics prediction and minigene assays. RESULTS: Two candidate MYO15A gene (OMIM, #602,666) heterozygous splicing variants, NG_011634.2 (NM_016239.3): c.6177 + 1G > T and c.9690 + 1G > A, were identified in the proband, and these two variants were both annotated as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Further bioinformatic analysis predicted that the c.6177 + 1G > T variant might cause exon skipping and that the c.9690 + 1G > A variant might activate a cryptic splicing donor site in the downstream intronic region. An in vitro minigene assay confirmed the above predictions. CONCLUSIONS: We identified a compound heterozygous splicing variant in the MYO15A gene in a Han Chinese family with ARNSHL. Our results broaden the spectrum of MYO15A variants, potentially benefiting the early diagnosis, prevention, and treatment of the disease.
Assuntos
Surdez , Perda Auditiva Neurossensorial , Humanos , Miosinas/genética , Surdez/genética , Perda Auditiva Neurossensorial/genética , Genes Recessivos , Linhagem , MutaçãoRESUMO
Rheumatoid arthritis (RA) is a self-immune inflammatory disease characterized by joint damage. A series of cytokines are involved in the development of RA. Oncostatin M (OSM) is a pleiotropic cytokine that primarily activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and other physiological processes such as cell proliferation, inflammatory response, immune response, and hematopoiesis through its receptor complex. In this review, we first describe the characteristics of OSM and its receptor, and the biological functions of OSM signaling. Subsequently, we discuss the possible roles of OSM in the development of RA from clinical and basic research perspectives. Finally, we summarize the progress of clinical studies targeting OSM for the treatment of RA. This review provides researchers with a systematic understanding of the role of OSM signaling in RA, which can guide the development of drugs targeting OSM for the treatment of RA.
Assuntos
Artrite Reumatoide , Transdução de Sinais , Humanos , Oncostatina M , Transdução de Sinais/fisiologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Janus Quinases/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismoRESUMO
We have theoretically investigated the size-dependent optoelectronic properties of InGaP/AlGaInP-based red micro-LEDs through an electro-optical-thermal coupling model. The model considers thermal effects due to current crowding near the electrodes, non-thermal efficiency droop due to electron leakage, and etch defects on the LED sidewall. Sidewall defects reduce the carrier concentration at the light-emitting surface's edge and exacerbate the current crowding effect. In addition, p-side electron leakage at high current densities is the leading cause of the efficiency droop of AlGaInP LEDs. In contrast, the effect of temperature on the overall efficiency degradation of LEDs is even more significant.
RESUMO
Nasopharyngeal carcinoma (NPC) is one of the most common squamous cell carcinomas of the head and neck, and Epstein-Barr virus (EBV) infection is one of the pathogenic factors involved in the oncogenetic development and progression of NPC. E3 ligases, which are key members of the ubiquitin proteasome system (UPS), specifically recognize various oncogenic factors and tumor suppressors and contribute to determining their fate through ubiquitination. Several studies have demonstrated that E3 ligases are aberrantly expressed and mutated in NPC and that these changes are closely associated with the occurrence and progression of NPC. Herein, we aim to thoroughly review the specific action mechanisms by which E3 ligases participate in NPC signaling pathways and discuss their functional relationship with EBV. Moreover, we describe the current progress in and limitations for targeted therapies against E3 ligases in NPC. KEY MESSAGES: ⢠E3 ubiquitin ligases, as members of the UPS system, determine the fate of their substrates and may act either as oncogenic or anti-tumorigenic factors in NPC. ⢠Mutations or dysregulated expression of E3 ubiquitin ligases is closely related to the occurrence, development, and therapeutic sensitivity of NPC, as they play important roles in several signaling pathways affected by EBV infection. ⢠As promising therapeutic targets, E3 ligases may open new avenues for treatment and for improving the prognosis of NPC patients.
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Ubiquitina-Proteína Ligases/genética , Neoplasias Nasofaríngeas/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Carcinogênese/genética , UbiquitinaRESUMO
Bladder cancer was one of the most common carcinomas around the world. However, the mechanism of the disease still remained to be investigated. We expected to establish a prognostic survival model with 9 prognostic genes to predict overall survival (OS) in patients of bladder cancer. The gene expression data of bladder cancer were obtained from TCGA and GEO datasets. TCGA and GEO datasets were used for screening prognostic genes along with developing and validating a 9-gene prognostic survival model by method of weighted gene co-expression network analysis (WGCNA) and LASSO with Cox regression. The relative analysis of evaluate tumor burden mutation (TBM), GO, KEGG, chemotherapy drug and functional pathway were also performed based on CAF-related mRNAs. 151 Overlapping CAF-related genes were distinguished after intersecting differentially expressed genes from 945 genes in TCGA and 491 genes in GEO dataset. 9 Prognostic genes (MSRB2, AGMAT, KLF6, DDAH2, GADD45B, SERPINE2, STMN3, TEAD2, and COMP) were used for construction of prognostic model after LASSO with Cox regression. Receiver operating characteristic (ROC) curves showed a good survival prediction by this model. Functional analysis indicated chemokine, cytokine, ECM interaction, oxidative stress and apoptosis were highly appeared. Potential drugs targeted different CAF-related genes like vemurafenib, irofulven, ghiotepa, and idarubicin were found as well. We constructed a novel 9 CAF-related mRNAs prognostic model and explored the gene expression and potential functional information of related genes, which might be worthy of clinical application. In addition, potential chemotherapy drugs could provide useful insights into the potential clinical treatment of bladder cancer.
RESUMO
Many plants have the capability to accumulate anthocyanins for coloration, and anthocyanins are advantageous to human health. In the case of hulless barley (Hordeum vulgare L. var. nudum), investigation into the mechanism of anthocyanin formation is limited to the level of protein-coding genes (PCGs). Here, we conducted a comprehensive bioinformatics analysis to identify a total of 9414 long noncoding RNAs (lncRNAs) in the seed coats of purple and white hulless barley along a developmental gradient. Transcriptome-wide profiles of lncRNAs documented several properties, including GC content fluctuation, uneven length, a diverse range of exon numbers, and a wide variety of transcript classifications. We found that certain lncRNAs in hulless barley possess detectable sequence conservation with Hordeum vulgare and other monocots. Furthermore, both differentially expressed lncRNAs (DElncRNAs) and PCGs (DEPCGs) were concentrated in the later seed development stages. On the one hand, DElncRNAs could potentially cis-regulate DEPCGs associated with multiple metabolic pathways, including flavonoid and anthocyanin biosynthesis in the late milk and soft dough stages. On the other hand, there was an opportunity for trans-regulated lncRNAs in the color-forming module to affect seed coat color by upregulating PCGs in the anthocyanin pathway. In addition, the interweaving of hulless barley lncRNAs and diverse TFs may function in seed coat coloration. Notably, we depicted a dynamic portrait of the anthocyanin synthesis pathway containing hulless barley lncRNAs. Therefore, this work provides valuable gene resources and more insights into the molecular mechanisms underlying anthocyanin accumulation in hulless barley from the perspective of lncRNAs, which facilitate the development of molecular design breeding in crops.
Assuntos
Hordeum , RNA Longo não Codificante , Antocianinas/genética , Antocianinas/metabolismo , Hordeum/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sementes/genética , Tibet , TranscriptomaRESUMO
This paper presents an easy and intact process based on microfluidics static droplet array (SDA) technology to fabricate quantum dot (QD) arrays for full-color micro-LED displays. A minimal sub-pixel size of 20 µm was achieved, and the fluorescence-converted red and green arrays provide good light uniformity of 98.58% and 98.72%, respectively.
RESUMO
Background: Malnutrition is particularly common in patients undergoing radiotherapy for head and neck cancers (HNC) and esophageal cancers (EC). Proper nutritional management plays an important role in improving the nutritional status and reducing complications in patients undergoing radiotherapy for malignancy. With most nutrition studies limited to the nutritional management of patients during hospitalization or after discharge, there is a lack of research evidence on the nutritional management of patients in combination with out-of-hospital. The aim of this study was to evaluate the effect of the hospital-community-family (HCF) nutritional management model on nutritional status and radiotherapy complications in EC and HNC radiotherapy patients. Methods: Between October 2019 and October 2021, a total of 116 EC and HNC radiotherapy patients were randomized into control group (conventional nutritional support) and experimental group (HCF-model nutritional management), and assessed weekly for 3 months. The primary endpoint was the patient's Nutrition Risk Screening 2002 (NRS2002) score, Scored Patient-Generated Subjective Global Assessment (PG-SGA), weight change, and Eastern Cooperative Oncology Group (ECOG) score from baseline level to 3 months after the end of treatment. The secondary endpoints were the incidence of albumin, hemoglobin, hematological parameters, and radiotherapy complications. Results: A total of 95 patients (47 in the control group and 48 in the experimental group) completed the study. At 3 months after treatment, NRS2002 (P=0.028) and PG-SGA (P=0.022) decreased, and albumin was higher (P=0.001) than at the beginning of treatment in HCF group. Weight decreased (P<0.001) and PG-SGA was higher after 3 months of treatment (P=0.012) in the control group. PG-SGA (P<0.001), NRS2002 (P<0.001), and ECOG (P=0.006) in the HCF group at the end of the 3-month treatment period were lower in the conventional group (P<0.05). The incidence of radiation mucositis (P=0.018)and radiation dermatitis (P=0.028) in the HCF nutrition management group was significantly reduced (P<0.05). Conclusions: HCF-model nutritional management significantly improved the nutritional status and reduced the incidence and severity of radiation mucositis and dermatitis for EC and HNC radiotherapy patients. These findings suggest that HCF-model nutritional management is a promising nutritional management model. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2300068399.
RESUMO
Endometrial cancer (EC) is the third leading gynecological malignancy, and its treatment remains challenging. B cell-specific Moloney murine leukemia virus integration site-1 (BMI1) is one of the core members of the polycomb group (PcG) family, which plays a promoting role in the occurrence and development of various tumors. Notably, BMI1 has been found to be frequently upregulated in endometrial cancer (EC) and promote the occurrence of EC through promoting epithelial-mesenchymal transition (EMT) and AKT/PI3K pathways. This review summarizes the structure and upstream regulatory mechanisms of BMI1 and its role in EC. In addition, we focused on the role of BMI1 in chemoradiotherapy resistance and summarized the current drugs that target BMI1.
Assuntos
Neoplasias do Endométrio , Fosfatidilinositol 3-Quinases , Feminino , Animais , Camundongos , Humanos , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas do Grupo Polycomb , Neoplasias do Endométrio/genética , Transformação Celular Neoplásica/metabolismo , Transição Epitelial-Mesenquimal , Proteínas Proto-Oncogênicas/genéticaRESUMO
Long noncoding RNAs (lncRNAs) are distributed in various species and play critical roles in plant growth, development, and defence against stimuli. However, the lncRNA response to methyl jasmonate (MeJA) treatment has not been well characterized in Nicotiana tabacum Bright Yellow-2 (BY-2) cells, and their roles in plant defence remain elusive. Here, 7848 reliably expressed lncRNAs were identified in BY-2 cells, of which 629 differentially expressed (DE) lncRNAs were characterized as MeJA-responsive lncRNAs. The lncRNAs in BY-2 cells had a strong genus specificity in Nicotiana. The combined analysis of the cis-regulated lncRNAs and their target genes revealed the potential up- and downregulated target genes that are responsible for different biological functions and metabolic patterns. In addition, some lncRNAs for response-associated target genes might be involved in plant defence and stress resistance via their MeJA- and defence-related cis-regulatory elements. Moreover, some MeJA-responsive lncRNA target genes were related to quinolinate phosphoribosyltransferase, lipoxygenases, and endopeptidase inhibitors, which may contribute to nicotine synthesis and disease and insect resistance, indicating that MeJA-responsive lncRNAs regulate nicotine biosynthesis and disease resistance by regulating their potential target genes in BY-2 cells. Therefore, our results provide more targets for genetically engineering the nicotine content and plant defence in tobacco plants.
Assuntos
Nicotiana , RNA Longo não Codificante , Nicotiana/genética , Nicotiana/metabolismo , Nicotina/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that results in impaired enzyme activity. The G6PD/6PGD ratio assay was routinely used for G6PD deficiency screening in China, but there is an apparent defect of missed diagnosis in heterozygous females. The study aims to explore the means to improve its accuracy. METHODS: A total of 4161 Chinese females of childbearing age were collected in this retrospective study. All samples were first subjected to G6PD/6PGD ratio assay and then screened by amplification refractory mutation system PCR (ARMS-PCR) for six hotspot mutants in Chinese population (c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.392G>T, and c.871G>A). For the samples with G6PD/6PGD ratio <1.0 and no mutations were found by ARMS-PCR, next-generation sequencing (NGS) was performed. Sanger sequencing was finally used to verify all the variants. RESULTS: The prevalence of G6PD deficiency in Shenzhen females of childbearing age was 7.31%. The proportion of the six hotspot mutations accounted for 98.03% of all 304 G6PD variants carriers. Taking the ARMS-PCR/NGS results as a reference, the missed diagnosis rate of the G6PD/6PGD ratio assay was 33.88%. Using ARMS-PCR to retest the samples with a G6PD/6PGD ratio between 1.00~1.10 or 1.00~1.15 could reduce the missed diagnosis rate from the original 33.88% to 18.09% or 12.05% separately. CONCLUSION: ARMS-PCR is an appropriate supplementary method for discovering most carriers missed by the G6PD/6PGD ratio assay.
RESUMO
The expression of ULK1, a core protein of autophagy, is closely related to autophagic activity. Numerous studies have shown that pathological abnormal expression of ULK1 is associated with various human diseases such as neurological disorders, infections, cardiovascular diseases, liver diseases and cancers. In addition, new advances in the regulation of ULK1 have been identified. Furthermore, targeting ULK1 as a therapeutic strategy for diseases is gaining attention as new corresponding activators or inhibitors are being developed. In this review, we describe the structure and regulation of ULK1 as well as the current targeted activators and inhibitors. Moreover, we highlight the pathological disorders of ULK1 expression and its critical role in human diseases.
Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Autofagia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias , Autofagia/fisiologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/química , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias/genéticaRESUMO
Subtilisin-like proteases (SUBs), which are extensively distributed in three life domains, affect all aspects of the plant life cycle, from embryogenesis and organogenesis to senescence. To explore the role of SUBs in rice caryopsis development, we recharacterized the OsSUB gene family in rice (Oryza sativa ssp. japonica). In addition, investigation of the SUBs was conducted across cultivated and wild rice in seven other Oryza diploid species (O. brachyantha, O. glaberrima, O. meridionalis, O. nivara, O. punctata, O. rufipogon, and O. sativa ssp. indica). Sixty-two OsSUBs were identified in the latest O. sativa ssp. japonica genome, which was higher than that observed in wild species. The SUB gene family was classified into six evolutionary branches, and SUB1 and SUB3 possessed all tandem duplication (TD) genes. All paralogous SUBs in eight Oryza plants underwent significant purifying selection. The expansion of SUBs in cultivated rice was primarily associated with the occurrence of tandem duplication events and purifying selection and may be the result of rice domestication. Combining the expression patterns of OsSUBs in different rice tissues and qRT-PCR verification, four OsSUBs were expressed in rice caryopses. Moreover, OsSUBs expressed in rice caryopses possessed an earlier origin in Oryza, and the gene cluster formed by OsSUBs together with the surrounding gene blocks may be responsible for the specific expression of OsSUBs in caryopses. All the above insights were inseparable from the continuous evolution and domestication of Oryza. Together, our findings not only contribute to the understanding of the evolution of SUBs in cultivated and wild rice but also lay the molecular foundation of caryopsis development and engineering improvement of crop yield.
RESUMO
BACKGROUND: A meta-analysis was performed by summarizing relevant researches to evaluate the relationship between miRNA-146a gene polymorphism rs2910164 and Behcet's disease (BD). METHODS: A systematic search of published studies was conducted in PubMed and Embase. Five eligible studies involving 1167 BD cases and 1662 controls were included in the current meta-analysis. RESULTS: The results suggested that the polymorphism rs2910164 was correlated with BD susceptibility in all genetic models. In subgroup analysis according to ethnicity, the relationship between this polymorphism and BD was more significant in Caucasians (allele model: OR = 0.49, 95% CI 0.39-0.61; heterozygote model: OR = 0.35, 95% CI 0.26-0.47; homozygote model: OR = 0.29, 95% CI 0.16-0.53; dominant model: OR = 0.34, 95% CI 0.25-0.45; recessive model: OR = 0.56, 95% CI 0.50-0.72) than that in Asians. CONCLUSION: In conclusion, this meta-analysis indicates that miRNA-146a gene polymorphism rs2910164 G allele confers BD susceptibility, especially in Caucasians.
Assuntos
Síndrome de Behçet , MicroRNAs , Humanos , Síndrome de Behçet/genética , Polimorfismo Genético , MicroRNAs/genéticaRESUMO
Nanoglass (NG) as a new structure-tunable material has been investigated using both experiments and computational modeling. Experimentally, inert gas condensation (IGC) is commonly employed to prepare metallic glass (MG) nanoparticles that are consolidated using cold compression to generate an NG. In computational modeling, various methods have been used to generate NGs. However, due to the high computational cost involved, heretofore modeling investigations have not followed the experimental synthesis route. In this work, we use molecular dynamics simulations to generate an NG model by consolidating IGC-prepared Cu64Zr36 nanoparticles following a workflow similar to that of experiments. The resulting structure is compared with those of NGs produced following two alternative procedures previously used: direct generation employing Voronoi tessellation and consolidation of spherical nanoparticles carved from an MG sample. We focus on the characterization of the excess free volume and the Voronoi polyhedral statistics in order to identify and quantify contrasting features of the glass-glass interfaces in the three NG samples prepared using distinct methods. Results indicate that glass-glass interfaces in IGC-based NGs are thicker and display higher structural contrast with their parent MG structure. Nanoparticle-based methods display excess free volume exceeding 4%, in agreement with experiments. IGC-prepared nanoparticles, which display Cu segregation to their surfaces, generate the highest glass-glass interface excess free volume levels and the largest relative interface volume with excess free volume higher than 3%. Voronoi polyhedral analysis indicates a sharp drop in the full icosahedral motif fraction in the glass-glass interfaces in nanoparticle-based NG as compared to their parent MG.