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Plant height is an important agronomic trait with a significant impact on grain yield, as demonstrated by the positive effect of the REDUCED HEIGHT (RHT) dwarfing alleles (Rht1b) on lodging and harvest index in the "Green Revolution" wheat varieties. However, these gibberellic acid (GA)-insensitive alleles also reduce coleoptile length, biomass production, and yield potential in some environments, triggering the search for alternative GA-sensitive dwarfing genes. Here we report the identification, validation, and characterization of the gene underlying the GA-sensitive dwarfing locus RHT25 in wheat. This gene, designated as PLATZ-A1 (TraesCS6A02G156600), is expressed mainly in the elongating stem and developing spike and encodes a plant-specific AT-rich sequence- and zinc-binding protein (PLATZ). Natural and induced loss-of-function mutations in PLATZ-A1 reduce plant height and its overexpression increases plant height, demonstrating that PLATZ-A1 is the causative gene of RHT25. PLATZ-A1 and RHT1 show a significant genetic interaction on plant height, and their encoded proteins interact with each other in yeast and wheat protoplasts. These results suggest that PLATZ1 can modulate the effect of DELLA on wheat plant height. We identified four natural truncation mutations and one promoter insertion in PLATZ-A1 that are more frequent in modern varieties than in landraces, suggesting positive selection during wheat breeding. These mutations can be used to fine-tune wheat plant height and, in combination with other GA-sensitive dwarfing genes, to replace the GA-insensitive Rht1b alleles and search for grain yield improvements beyond those of the Green Revolution varieties.
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Melhoramento Vegetal , Triticum , Triticum/genética , Fatores de Transcrição/metabolismo , Giberelinas/metabolismo , Proteínas de Plantas/genéticaRESUMO
Polypeptides encoded by long noncoding RNAs (lncRNAs) are a novel class of functional molecules. However, whether these hidden polypeptides participate in the TP53 pathway and play a significant biological role is still unclear. Here, we discover that TP53-regulated lncRNAs can encode peptides, two of which are functional in various human cell lines. Using ribosome profiling and RNA-seq approaches in HepG2 cells, we systematically identified more than 300 novel TP53-regulated lncRNAs and further confirmed that 15 of these TP53-regulated lncRNAs encode peptides. Furthermore, several peptides were validated by mass spectrometry. Ten of the novel translational lncRNAs are directly inducible by TP53 in response to DNA damage. We show that the TP53-inducible peptides TP53LC02 and TP53LC04, but not their lncRNAs, can suppress cell proliferation. TP53LC04 peptide also has a function associated with cell proliferation by regulating the cell cycle in response to DNA damage. This study shows that TP53-regulated lncRNAs can encode new functional peptides, leading to the expansion of the TP53 tumor-suppressor network and providing novel potential targets for cancer therapy.
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RNA Longo não Codificante , Proliferação de Células/genética , Humanos , Peptídeos/metabolismo , Peptídeos/farmacologia , RNA Longo não Codificante/metabolismo , Ribossomos/metabolismo , Proteína Supressora de Tumor p53/genéticaRESUMO
Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2â¢-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2â¢-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.
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Aterosclerose , Cicloexilaminas , Ferroptose , Fenilenodiaminas , Animais , Camundongos , Humanos , Fosfolipídeos , Fosforilcolina , Éteres Fosfolipídicos/metabolismo , Éteres Fosfolipídicos/farmacologia , Camundongos Endogâmicos C57BL , Células Endoteliais da Veia Umbilical Humana/metabolismo , Endotélio/metabolismo , Glutationa/metabolismo , Ferro/metabolismo , Proteína 3 Ligante de Ácido GraxoRESUMO
Flowering cherry is a very popular species around the world. High-quality genome resources for different elite cultivars are needed, and the understanding of their origins and the regulation of key ornamental traits are limited for this tree. Here, a high-quality chromosome-scale genome of Prunus campanulata 'Plena' (PCP), which is a native and elite flowering cherry cultivar in China, was generated. The contig N50 of the genome was 18.31 Mb, and 99.98% of its contigs were anchored to eight chromosomes. Furthermore, a total of 306 accessions of flowering cherry germplasm and six lines of outgroups were collected. Resequencing of these 312 lines was performed, and 761â 267 high-quality genomic variants were obtained. The origins of flowering cherry were predicted, and these 306 accessions could be classified into three clades, A, B and C. According to phylogenetic analysis, we predicted two origins of flowering cherry. Flowering cherry in clade A originated in southern China, such as in the Himalayan Mountains, while clades B and C originated in northeastern China. Finally, a genome-wide association study of flower colour was performed for all 312 accessions of flowering cherry germplasm. A total of seven quantitative trait loci (QTLs) were identified. One gene encoding glycosylate transferase was predicted as the candidate gene for one QTL. Taken together, our results provide a valuable genomic resource and novel insights into the origin, evolution and flower colour variations of flowering cherry.
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Estudo de Associação Genômica Ampla , Prunus avium , Filogenia , Cor , Prunus avium/genética , Flores/genéticaRESUMO
Ammonium vanadates, featuring an NâH···O hydrogen bond network structure between NH4 + and VâO layers, have become popular cathode materials for aqueous zinc-ion batteries (AZIBs). Their appeal lies in their multi-electron transfer, high specific capacity, and facile synthesis. However, a major drawback arises as Zn2+ ions tend to form bonds with electronegative oxygen atoms between VâO layers during cycling, leading to irreversible structural collapse. Herein, Li+ pre-insertion into the intermediate layer of NH4V4O10 is proposed to enhance the electrochemical activity of ammonium vanadate cathodes for AZIBs, which extends the interlayer distance of NH4V4O10 to 9.8 Å and offers large interlaminar channels for Zn2+ (de)intercalation. Moreover, Li+ intercalation weakens the crystallinity, transforms the micromorphology from non-nanostructured strips to ultrathin nanosheets, and increases the level of oxygen defects, thus exposing more active sites for ion and electron transport, facilitating electrolyte penetration, and improving electrochemical kinetics of electrode. In addition, the introduction of Li+ significantly reduces the bandgap by 0.18 eV, enhancing electron transfer in redox reactions. Leveraging these unique advantages, the Li+ pre-intercalated NH4V4O10 cathode exhibits a high reversible capacity of 486.1 mAh g-1 at 0.5 A g-1 and an impressive capacity retention rate of 72% after 5,000 cycles at 5 A g-1.
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A synthetic biopolymer derived from furandicarboxylic acid monomer and hydroxyethyl-terminated poly(ether sulfone) is presented. The synthesis involves 4,4'-dichlorodiphenyl sulfone and 4,4-dihydroxydiphenyl sulfone, resulting in poly(butylene furandicarboxylate)-poly(ether sulfone) copolyesters (PBFES) through melt polycondensation with titanium-catalyzed polymerization. This facile method yields segmented polyesters incorporating polysulfone, creating a versatile group of high-temperature thermoplastics with adjustable thermomechanical properties. The PBFES copolyesters demonstrate an impressive tensile modulus of 2830 MPa and a tensile strength of 84 MPa for PBFES55. Additionally, the poly(ether sulfone) unit imparts a relatively high glass transition temperature (Tg), ranging from 36.6 °C for poly(butylene 2,5-furandicarboxylate) to 112.3 °C for PBFES62. Moreover, the complete amorphous film of PBFES exhibits excellent transparency and solvent resistance, making it suitable for applications, such as food packaging materials.
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Alcenos , Materiais Biocompatíveis , Poliésteres , Polímeros , Sulfonas , ÉteresRESUMO
KEY MESSAGE: PnNAC2 positively regulates saponin biosynthesis by binding the promoters of key biosynthetic genes, including PnSS, PnSE, and PnDS. PnNAC2 accelerates flowering through directly associating with the promoters of FT genes. NAC transcription factors play an important regulatory role in both terpenoid biosynthesis and flowering. Saponins with multiple pharmacological activities are recognized as the major active components of Panax notoginseng. The P. notoginseng flower is crucial for growth and used for medicinal and food purposes. However, the precise function of the P. notoginseng NAC transcription factor in the regulation of saponin biosynthesis and flowering remains largely unknown. Here, we conducted a comprehensive characterization of a specific NAC transcription factor, designated as PnNAC2, from P. notoginseng. PnNAC2 was identified as a nuclear-localized protein with transcription activator activity. The expression profile of PnNAC2 across various tissues mirrored the accumulation pattern of total saponins. Knockdown experiments of PnNAC2 in P. notoginseng calli revealed a significant reduction in saponin content and the expression level of pivotal saponin biosynthetic genes, including PnSS, PnSE, and PnDS. Subsequently, Y1H assays, dual-LUC assays, and electrophoretic mobility shift assays (EMSAs) demonstrated that PnNAC2 exhibits binding affinity to the promoters of PnSS, PnSE and PnDS, thereby activating their transcription. Additionally, an overexpression assay of PnNAC2 in Arabidopsis thaliana witnessed the acceleration of flowering and the induction of the FLOWERING LOCUS T (FT) gene expression. Furthermore, PnNAC2 demonstrated the ability to bind to the promoters of AtFT and PnFT genes, further activating their transcription. In summary, these results revealed that PnNAC2 acts as a multifunctional regulator, intricately involved in the modulation of triterpenoid saponin biosynthesis and flowering processes.
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Panax notoginseng , Saponinas , Triterpenos , Panax notoginseng/genética , Panax notoginseng/química , Panax notoginseng/metabolismo , Triterpenos/metabolismo , Flores/genética , Flores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Harmine (HM), a ß-carboline alkaloid extracted from plants, is a crucial component of traditional Chinese medicine (TCM) known for its diverse pharmacological activities. Thrombocytopenia, a common and challenging hematological disorder, often coexists with serious illnesses. Previous research has shown a correlation between HM and thrombocytopenia, but the mechanism needs further elucidation. The aim of this study was to clarify the mechanisms underlying the effects of HM on thrombocytopenia and to develop new therapeutic strategies. Flow cytometry, Giemsa staining, and Phalloidin staining were used to assess HM's impact on Meg-01 and HEL cell differentiation and maturation in vitro. A radiation-induced thrombocytopenic mouse model was employed to evaluate HM's effect on platelet production in vivo. Network pharmacology, molecular docking, and protein blotting were utilized to investigate HM's targets and mechanisms. The results demonstrated that HM dose-dependently promoted Meg-01 and HEL cell differentiation and maturation in vitro and restored platelet levels in irradiated mice in vivo. Subsequently, HM was found to be involved in the biological process of platelet production by upregulating the expressions of Rac1, Cdc42, JNK, and 5-HTR2A. Furthermore, the targeting of HM to 5-HTR2A and its correlation with downstream Rac1/Cdc42/JNK were also confirmed. In conclusion, HM regulates megakaryocyte differentiation and thrombopoiesis through the 5-HTR2A and Rac1/Cdc42/JNK pathways, providing a potential treatment strategy for thrombocytopenia.
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AIM: To construct key quality indicators for aged care facilities in China. BACKGROUND: Evaluating the care quality in aged care facilities is problematic. Evaluation of nursing care quality is important for improving nursing and self-supervision in aged care facilities. However, a few regulations and studies regarding care quality evaluation have been implemented in China. DESIGN AND METHOD: This two-tier Delphi study aimed to achieve consensus on key quality indicators for aged care facilities in China. The entry pool was determined by literature review and research team discussion, followed by a discussion by a panel of experts to establish the items of the Delphi study. Finally, key care quality indicators were established through a two-round Delphi study. This study followed the SQUIRE 2.0 guidelines. RESULTS: The initial 16 quality indicators of the entry pool was developed based on a literature review and a group discussion. Sixteen quality indicators were reduced to eight after the expert discussion. After two rounds of expert consultation, the eight quality indicators became nine, which were then evaluated for importance, formula rationality, and operability using Kendall's harmony coefficients (first round: 0.150, 0.143 and 0.169, respectively; second round: 0.209, 0.159 and 0.173, respectively). CONCLUSIONS: Key quality indicators provide quantifiable evidence for evaluating the care quality in aged care facilities, but their applicability needs continuous improvement. RELEVANCE TO CLINICAL PRACTICE: Nine key quality indicators were selected from numerous indicators for measuring the care quality in aged care facilities, supporting the evaluation of the care quality and self-supervision for aged care facilities. ELDERLY OR PUBLIC CONTRIBUTION: No elderly or public contribution.
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Indicadores de Qualidade em Assistência à Saúde , Idoso , Humanos , Técnica Delphi , China , ConsensoRESUMO
Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances in understanding the molecular pathogenesis and biology of this tumor in the past decade, the prognosis for GBM patients remains poor. GBM is characterized by aggressive biological behavior and high degrees of inter-tumor and intra-tumor heterogeneity. Increased understanding of the molecular and cellular heterogeneity of GBM may not only help more accurately define specific subgroups for precise diagnosis but also lay the groundwork for the successful implementation of targeted therapy. Herein, we systematically review the key achievements in the understanding of GBM molecular pathogenesis, mechanisms, and biomarkers in the past decade. We discuss the advances in the molecular pathology of GBM, including genetics, epigenetics, transcriptomics, and signaling pathways. We also review the molecular biomarkers that have potential clinical roles. Finally, new strategies, current challenges, and future directions for discovering new biomarkers and therapeutic targets for GBM will be discussed.
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Biomarcadores Tumorais , Neoplasias Encefálicas , Glioblastoma , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/genética , Glioblastoma/diagnóstico , Humanos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , PrognósticoRESUMO
Anemarrhena asphodeloides is a common medicinal material used in clinical prescriptions and Chinese patent medicine. In this study, the Illumina platform was used to obtain the chloroplast genome sequences of seven kinds of A. asphodeloides from different areas. The specific DNA barcodes were screened by comparative genomics analysis, and the DNA barcodes were used to identify the germplasm resources and analyze the genetic diversity of A. asphodeloides samples from different areas in China. All the seven chloroplast genomes had a ring structure. The total length was 156 801-156 930 bp, and 113 genes were annotated, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The comparative genomics analysis showed that rps16, trnG-GCC, atpF, rpoB, ycf3, rpl16, ndhF, trnS-GCU_trnG-GCC, petN-psbM, and ndhF-rpl32 were potential candidates for specific DNA barcodes of A. asphodeloides. In this study, the second intron of ycf3 and atpF intron sequences with a sequence length of 700-800 bp and easy amplification were selected for polymerase chain reaction(PCR) amplification and sequencing of 594 samples from 26 areas. The sequence analysis showed that six and eight haplotypes of ycf3 and atpF sequences could be identified, respectively, and 17 haplotypes could be identified by combined analysis of the two sequences, which were named Hap1-Hap17. The haplotype diversity(H_d), nucleotide diversity(P_i), and genetic distance of A. asphodeloides in 26 populations were 0.68, 0.93×10~(-3), and 0-0.003 1, respectively, indicating that the genetic diversity within the species of A. asphodeloides is rich. The intermediary adjacent network analysis showed that Hap5 was the oldest haplotype, which was mainly distributed in Yixian county of Baoding, Hebei province, Hequ county of Xinzhou, Shanxi province, and Xiangfen county of Linfen, Shanxi province. This study has important guiding significance for the identification of A. asphodeloides species, the protection and development of germplasm resources, and the identification of production areas, and it provides a research basis for further revealing the genetic evolution law of A. asphodeloides.
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Anemarrhena , Anemarrhena/química , Código de Barras de DNA Taxonômico , Variação Genética , China , FilogeniaRESUMO
S-acylation is a widespread lipidation form in eukaryotes in which various fatty acids can be covalently attached to specific cysteine residues. However, due to the low reactivity of the lipid moieties and lack of specific antibodies, purification of intact S-acylated peptides remains challenging. Here, we developed a pretreatment method for direct separation and global analysis of endogenously intact S-acylated peptides by nanographite fluoride-based solid-phase extraction (nGF-SPE), together with the investigation and optimization of the enrichment procedure as well as the LC-MS/MS analysis process. Consequently, we performed the first global profiling of endogenously intact S-acylated peptides, with 701 S-palmitoylated peptides from HeLa cell lysates in a restricted search. Furthermore, coupling the nGF-SPE method with open search mode, altogether 1119 intact S-acylated peptides were identified with the attached palmitate, palmitoleate, myristate, and octanoate chain, respectively, providing a global insight into the endogenously heterogeneous modification state. Notably, we found and validated that S-palmitoleoylation (C16:1) provided less affinity toward lipid rafts compared with S-palmitoylation (C16:0). This study developed the first straightforward way to characterize endogenously intact S-acylated peptides on a proteome-wide scale, providing the modified residues together with their attached lipid moieties simultaneously, which paves the way for further understanding of protein S-acylation.
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Fluoretos , Espectrometria de Massas em Tandem , Animais , Humanos , Cromatografia Líquida , Células HeLa , Acilação , Diferenciação Celular , MamíferosRESUMO
Sodium superionic conductor (NASICON)-type Na3 V2 (PO4 )3 has attracted considerable interest owing to its stable three-dimensional framework and high operating voltage; however, it suffers from a low-energy density due to the poor intrinsic electronic conductivity and limited redox couples. Herein, the partial substitution of Mn3+ for V3+ in Na3 V2 (PO4 )3 is proposed to activate V4+ /V5+ redox couple for boosting energy density of the cathodes (Na3 V2- x Mnx (PO4 )3 ). With the introduction of Mn3+ into Na3 V2 (PO4 )3 , the band gap is significantly reduced by 1.406 eV and thus the electronic conductivity is greatly enhanced. The successive conversions of four stable oxidation states (V2+ /V3+ , V3+ /V4+ , and V4+ /V5+ ) are also successfully achieved in the voltage window of 1.4-4.0 V, corresponding to three electrons involved in the reversible reaction. Consequently, the cathode with x = 0.5 exhibits a high reversible discharge capacity of 170.9 mAh g-1 at 0.5 C with an ultrahigh energy density of 577 Wh kg-1 . Ex-situ x-ray diffraction (XRD) analysis reveals that the sodium-storage mechanism for Mn-doped Na3 V2 (PO4 )3 consists of single-phase and bi-phase reactions. This work deepens the understanding of the activation of reversible three-electron reaction in NASICON-structured polyanionic phosphates and provides a feasible strategy to develop high-energy-density cathodes for sodium-ion batteries.
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Aqueous zinc-ion batteries (AZIBs) have attracted considerable attention due to their low cost and environmental friendliness. However, the rampant dendrite growth and severe side reactions during plating/stripping on the surface of zinc (Zn) anode hinder the practicability of AZIBs. Herein, an effective and non-toxic cationic electrolyte additive of Rb2 SO4 is proposed to address the issues. The large cation of Rb+ is preferentially adsorbed on the surface of Zn metal to induce a strong shielding effect for realizing the lateral deposition of Zn2+ ions along the Zn surface and isolating water from Zn metal to effectively inhibit side reactions. Consequently, the Zn||Zn symmetric cell with the addition of 1.5 mm Rb2 SO4 can cycle more than 6000 h at 0.5 mA cm-2 /0.25 mAh cm-2 , which is 20 times longer than that without Rb2 SO4 . Besides, the Zn||Cu asymmetric cell with Rb2 SO4 achieves a very high average Coulombic efficiency of 99.16% up to 500 cycles. Moreover, the electrolyte with Rb2 SO4 well matches with the VO2 cathode, achieving high initial capacity of 412.7 mAh g-1 at 5 A g-1 and excellent cycling stability with a capacity retention of 71.6% at 5 A g-1 after 500 cycles for the Zn//VO2 full cell.
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Rubella virus infection can cause vertical transmission to the fetus during pregnancy. In China's Henan province, rubella surveillance needs to be well-established. In this research, a total of 1933 neonates and 2502 pregnant women were enrolled, and their sera for IgG and IgM antibodies against rubella were tested by chemiluminescence assay. Of 1933 neonates' sera tested, the seropositive of rubella IgG was 68.7%. The seroprevalence of rubella IgM in neonates was 0.4%. 30.9% of neonates had negative results for IgG and IgM antibodies. Two thousand five hundred and two pregnant women participated in the serosurvey, and 79.3% were rubella IgG positive. Rubella IgG seropositivity in pregnant women differed by age and number of births. 0.8% of the pregnant women had positive results for IgM against the rubella virus. The seronegative of rubella IgG and IgM antibodies in pregnant women was 19.8%. Due to the negative rubella-specific IgG antibody, many neonates remain at risk of rubella virus infection. Rubella virus continues to spread since some neonates and pregnant women with rubella-specific IgM antibody positive have been detected. Rubella vaccination may be introduced for childbearing-age women to increase immunity levels against rubella with periodic sero-surveillance.
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Complicações Infecciosas na Gravidez , Rubéola (Sarampo Alemão) , Recém-Nascido , Gravidez , Feminino , Humanos , Gestantes , Vírus da Rubéola , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Soroepidemiológicos , Imunoglobulina G , Rubéola (Sarampo Alemão)/epidemiologia , Hospitais , Anticorpos Antivirais , Imunoglobulina M , China/epidemiologiaRESUMO
Lysine-specific histone demethylase 1 (LSD1) as the first identified histone/lysine demethylase regulates gene expression and protein functions in diverse diseases. In this study, we show that the expression of LSD1 is increased in mouse kidneys with unilateral ureteral obstruction (UUO) and in cultured NRK-52E cells undergoing TGF-ß1-induced epithelial-mesenchymal transition (EMT). Inhibition of LSD1 with its specific inhibitor ORY1001 attenuated renal EMT and fibrosis, which was associated with decreased the deposition of extracellular matrix proteins and the expression of fibrotic markers, including α-smooth muscle actin (α-SMA) and fibronectin, and the recovery of E-cadherin expression and decrease of N-cadherin expression in UUO kidneys and in NRK-52E cells induced with TGF-ß1. Targeting LSD1 also decreased the expression of Snail family transcriptional repressor 1 (Snail-1) and its interaction with LSD1 in UUO kidneys and in NRK-52E cells treated with TGF-ß1. In addition, we identified a novel LSD1-14-3-3ζ-PKCα axis in the regulation of the activation of AKT and Stat3 and then the activation of fibroblasts. This study suggests that LSD1 plays a critical role in regulation of renal EMT and fibrosis through activation of diverse signaling pathways and places an emphasis that LSD1 has potential as a therapeutic target for the treatment of renal fibrosis.
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Sistemas de Liberação de Medicamentos , Inibidores Enzimáticos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Histona Desmetilases , Rim/enzimologia , Animais , Linhagem Celular , Transição Epitelial-Mesenquimal/genética , Fibrose , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/enzimologia , Nefropatias/genética , Masculino , Camundongos , RatosRESUMO
Lysyl oxidase (LOX) is a copper-dependent monoamine oxidase whose primary function is the covalent cross-linking of collagen in the extracellular matrix (ECM). Evidence has shown that LOX is associated with cancer and some fibrotic conditions. We recently found that serum LOX is a potential diagnostic biomarker for renal fibrosis, but the mechanism by which LOX is regulated and contributes to renal fibrosis remains unknown. The current study demonstrates the following: (1) LOX expression was increased in fibrotic kidneys including ischemia-reperfusion injury-(IRI-), unilateral ureteral obstruction-(UUO-), and folic acid- (FA-) induced fibrotic kidneys as well as in the paraffin-embedded sections of human kidneys from the patients with renal fibrosis. (2) The increasing deposition and cross-linking of collagen induced by LOX was observed in IRI-, UUO- and FA-kidneys. (3) LOX was regulated by the ß-arrestin-ERK-STAT3 pathway in renal fibrosis. STAT3 was the downstream of AT1R-ß-arrestin-ERK, ERK entered the nucleus and activated STAT3-pY705 but not STAT3-pS727. (4) STAT3 nuclear subtranslocation and binding to the LOX promoter may be responsible for the upregulation of LOX expression. (5) Pharmacologic inhibition of LOX with BAPN in vivo inhibited the upregulation of LOX, decreased collagen over cross-linking and ameliorated renal fibrosis after ischemic injury. Collectively, these observations suggest that LOX plays an essential role in the development of renal fibrosis by catalyzing collagen over cross-linking. Thus, strategies targeting LOX could be a new avenue in developing therapeutics against renal fibrosis.
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Nefropatias , Proteína-Lisina 6-Oxidase , Colágeno , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibrose , Humanos , Fator de Transcrição STAT3 , beta-Arrestina 1 , beta-ArrestinasRESUMO
The demand for sustainable development has led to increasing attention in biobased polyesters due to their adjustable thermal and mechanical properties and biodegradability. In this study, we used a novel bioderived aromatic diacid, 2,5-thiophenedicarboxylic acid (TDCA) to synthesize a list of novel aromatic-aliphatic poly(alkylene adipate-co-thiophenedicarboxylate) (PAATh) copolyesters through a facile melt polycondensation method. PAAThs are random copolyesters with weight-average molecular weights of 58400 to 84200 g·mol-1 and intrinsic viscosities of 0.80 to 1.27 dL·g-1. All PAAThs exhibit sufficiently high thermal stability as well as the highest tensile strength of 6.2 MPa and the best gas barrier performances against CO2 and O2, 4.3- and 3.3-fold better than those of poly(butylene adipate-co-terephthalate) (PBAT). The biodegradability of PAAThs was fully evaluated through a degradation experiment and various experimental parameters, including residue weights, surface morphology, and molecular compositions. The state-of-the-art molecular dynamics (MD) simulations were applied to elucidate the different enzymatic degradation behaviors of PAAThs due to the effect of diols with different chain structures. The sterically hindered carbonyl carbon of the PHATh-enzyme complex was more susceptible to nucleophilic attack and exhibited a higher tendency to enter a prereaction state. This study has introduced a group of novel biobased copolyesters with their structure-property relationships investigated thoroughly, and the effect of diol components on the enzymatic degradation was revealed by computational analysis. These findings may lay the foundation for the development of promising substitutes for commercial biodegradable polyesters and shed light on their complicated degradation mechanisms.
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Adipatos , Poliésteres , Poliésteres/químicaRESUMO
BACKGROUND/AIMS: Gastro-oesophageal reflux disease (GORD) is a chronic high-morbidity disease with a bidirectional relationship with sleep disturbance (SD) that may occur via the transient receptor potential vanilloid type 1 receptor (TRPV1) in the oesophageal mucosa. Yet the related mechanism was still unclear, the aim of this study is to investigate whether TRPV1 is associated with the presence of SD in GORD patients. METHODS: A case-control study was performed. After the screening, A total of 88 subjects were assigned to GORD without sleep disturbance (GORD + NOSD, n = 28), GORD comorbid sleep disturbance (GORD + SD, n = 30) and matched healthy controls (n = 30). Mucosal tissue was obtained from the participants by digestive endoscopy, the levels of TRPV1 expressed in the oesophageal mucosa were detected via RT-qPCR and western blot in different groups, and the correlation between GORD and SD were also analysed. RESULTS: In this study, we found that the Gastroesophageal Reflux Disease Diagnostic Questionnaire (GerdQ) scores was positively correlated with Pittsburgh Sleep Quality Index (PSQI) scores but negatively correlated with total sleep time (TST). We also found that the level of TRPV1 expressed in the oesophageal mucosa of GORD + SD was significantly higher than GORD + NOSD patients, and they were all higher than healthy controls. CONCLUSION: The current study suggested a closer link exists between GORD and sleep disturbance, and TRPV1 in oesophageal mucosa may be a crucial factor affecting sleep in GORD patients.
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Refluxo Gastroesofágico , Transtornos do Sono-Vigília , Canais de Cátion TRPV , Humanos , Estudos de Casos e Controles , Doença Crônica , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/genética , Fatores de Risco , Transtornos do Sono-Vigília/genética , Inquéritos e Questionários , Canais de Cátion TRPV/genéticaRESUMO
OBJECTIVE: Both patients and physicians may be hesitant toward vaccination in patients with asthma, which may result in lower vaccine uptake. The aim of this work was to investigate the vaccination rate, the adverse reactions, as well as the factors associated with vaccine acceptance and hesitancy toward COVID-19 vaccination among asthmatic patients in Beijing. METHODS: A multi-center, cross-sectional face-to-face survey was conducted in patients with asthma consecutively recruited from December 2021 to April 2022. The survey included asthma status, COVID-19 vaccine uptake and adverse reactions, and knowledge of and attitude toward COVID-19 vaccination. RESULTS: A total of 261 patients were enrolled. The rate of COVID-19 vaccination during the study period was 73.6%, as compared to 87.64% in the general population in China. Patients who were currently working, had received other vaccines in the past, and had had no adverse reactions to other vaccines, showed a higher rate of COVID-19 vaccination. Patients believing that the vaccination of family members and colleagues had a positive impact on their decision to get vaccinated, were more likely to get the COVID-19 vaccines. The COVID-19 vaccination rate was lower in those with poorly monitored asthma and those using biologic therapies. The adverse effects of COVID-19 vaccines in asthmatic patients were similar to those in the general population. CONCLUSION: The COVID-19 vaccination rate in asthmatic patients was lower than the general population in China. Active measures should be taken to control asthma and increase vaccination rates in these patients.