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Soil alkalization has become a serious problem that limits plant growth through osmotic stress, ionic imbalance, and oxidative stress. Understanding how plants resist alkali stress has practical implications for alkaline-land utilization. In this study, we identified a small GTPase, PvARFR2 (ADP ribosylation factors related 2), that positively regulates alkali tolerance in switchgrass (Panicum virgatum) and uncovered its potential mode of action. Overexpressing PvARFR2 in switchgrass and Arabidopsis (Arabidopsis thaliana) conferred transformants tolerance to alkali stress, demonstrated by alleviated leaf wilting, less oxidative injury, and a lower Na+/K+ ratio under alkali conditions. Conversely, switchgrass PvARFR2-RNAi and its homolog mutant atgb1 in Arabidopsis displayed alkali sensitives. Transcriptome sequencing analysis showed that cytosolic ABA receptor kinase PvCARK3 transcript levels were higher in PvARFR2 overexpression lines compared to the controls and were strongly induced by alkali treatment in shoots and roots. Phenotyping analysis revealed that PvCARK3-OE×atgb1 lines were sensitive to alkali similar to the Arabidopsis atgb1 mutant, indicating that PvARFR2/AtGB1 functions in the same pathway as PvCARK3 under alkaline stress conditions. Application of ABA on PvARFR2-OE and PvCARK3-OE switchgrass transformants resulted in ABA sensitivity. Moreover, we determined that PvARFR2 physically interacts with PvCARK3 in vitro and in vivo. Our results indicate that a small GTPase, PvARFR2, positively responds to alkali stress by interacting with the cytosolic ABA receptor kinase PvCARK3, connecting the alkaline stress response to ABA signaling.
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CD4+ T-cell counts are increased and activated in patients with chronic heart failure (CHF), whereas regulatory T-cell (Treg) expansion is inhibited, probably due to aberrant T-cell receptor (TCR) signaling. TCR signaling is affected by protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in autoimmune disorders, but whether PTPN22 influences TCR signaling in CHF remains unclear. This observational case-control study included 45 patients with CHF [18 patients with ischemic heart failure versus 27 patients with nonischemic heart failure (NIHF)] and 16 non-CHF controls. We used flow cytometry to detect PTPN22 expression, tyrosine phosphorylation levels, zeta-chain-associated protein kinase, 70 kDa (ZAP-70) inhibitory residue tyrosine 292 and 319 phosphorylation levels, and CD4+ T cell and Treg proportions. We conducted lentivirus-mediated PTPN22 RNA silencing in isolated CD4+ T cells. PTPN22 expression increased in the CD4+ T cells of patients with CHF compared with that in controls. PTPN22 expression was positively correlated with left ventricular end-diastolic diameter and type B natriuretic peptide but negatively correlated with left ventricular ejection fraction in the NIHF group. ZAP-70 tyrosine 292 phosphorylation was decreased, which correlated positively with PTPN22 overexpression in patients with NIHF and promoted early TCR signaling. PTPN22 silencing induced Treg differentiation in CD4+ T cells from patients with CHF, which might account for the reduced frequency of peripheral Tregs in these patients. PTPN22 is a potent immunomodulator in CHF and might play an essential role in the development of CHF by promoting early TCR signaling and impairing Treg differentiation from CD4+ T cells.
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Insuficiência Cardíaca , Receptores de Antígenos de Linfócitos T , Humanos , Estudos de Casos e Controles , Volume Sistólico , Receptores de Antígenos de Linfócitos T/metabolismo , Função Ventricular Esquerda , Proteínas Tirosina Fosfatases , Linfócitos T Reguladores , Tirosina , Proteína Tirosina Fosfatase não Receptora Tipo 22/genéticaRESUMO
Myocardial infarction (MI) is defined as sudden ischemic death of myocardial tissue. Amphiregulin (Areg) regulates cell survival and is crucial for the healing of tissues after damage. However, the functions and mechanisms of Areg after MI remain unclear. Here, we aimed to investigate Areg's impact on myocardial remodeling. Mice model of MI was constructed and Areg-/- mice were used. Expression of Areg was analyzed using western blotting, RT-qPCR, flow cytometry, and immunofluorescence staining. Echocardiographic analysis, Masson's trichrome, and triphenyltetrazolium chloride staining were used to assess cardiac function and structure. RNA sequencing was used for unbiased analysis. Apoptosis and autophagy were determined by western blotting, TUNEL staining, electron microscopy, and mRFP-GFP-LC3 lentivirus. Lysosomal acidity was determined by Lysotracker staining. Areg was elevated in the infarct border zone after MI. It was mostly secreted by macrophages. Areg deficiency aggravated adverse ventricular remodeling, as reflected by worsening cardiac function, a lower survival rate, increased scar size, and interstitial fibrosis. RNA sequencing analyses showed that Areg related to the epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR) signaling pathways, V-ATPase and lysosome pathways. Mechanistically, Areg exerts beneficial effects via increasing lysosomal acidity to promote autophagosome clearance, and activating the EGFR/PI3K/Akt/mTOR signaling pathway, subsequently inhibiting excessive autophagosome formation and apoptosis in cardiomyocytes. This study provides a novel evidence for the role of Areg in inhibiting ventricular remodeling after MI by regulating autophagy and apoptosis and identifies Areg as a potential therapeutic target in ventricular remodeling after MI.
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Infarto do Miocárdio , Fosfatidilinositol 3-Quinases , Animais , Camundongos , Anfirregulina/genética , Apoptose , Autofagia , Receptores ErbB , Mamíferos , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Remodelação VentricularRESUMO
BACKGROUND: Human discs large-associated protein 5 (DLGAP5) is reported to play a pivotal role in regulating the cell cycle and implicate in tumorigenesis and progression of various cancers. Our current research endeavored to explore the prognostic value, immune implication, biological function and targeting strategy of DLGAP5 in LUAD through approaches including bioinformatics, network pharmacology analysis and experimental study. METHODS: Multiple databases, including TCGA, GEO, CPTAC and Human Protein Atlas, were utilized to explore the expression and clinical significance of DLGAP5 in LUAD. The genetic alterations of DLGAP5 were assessed through cBioPortal and COSMIC databases. The relationship between DLGAP5 expression and genetic abnormalities of driver genes in LUAD was analyzed through TIMER2.0 database. CancerSEA database was utilized to explore the function of DLGAP5 in 14 different states in LUAD at single-cell resolution. GDSC database was utilized to analyze the impact of DLGAP5 on IC50 of frequently-used anti-LUAD drugs. CIBERSORT method and TIMER2.0 database was utilized to explore the relationship between DLGAP5 and tumor immune infiltration. Network pharmacology was applied to screen potential DLGAP5 inhibitor. In vitro and in vivo experiments were utilized to evaluate biological function and downstream targets of DLGAP5, and the effect of screened DLGAP5 inhibitor on LUAD growth. RESULTS: High DLGAP5 expression was commonly observed in LUAD and associated with mutation of major driver genes, poor prognosis, high IC50 values of frequently-used anti-LUAD drugs, increasing immune infiltration and elevated immune checkpoint blockade-related genes in LUAD. PLK1 was revealed as a potential DLGAP5 downstream target in LUAD. DLGAP5 overexpression or knockdown significantly promoted or inhibited LUAD cell proliferation and PLK1 expression. PLK1 overexpression well rescued DLGAP5 knockdown-induced cell proliferation inhibition, or vice versa. Furthermore, by virtual screening of an investigational drug library from the DrugBank database, AT9283 was screened and identified as a novel DLGAP5 inhibitor. AT9283 effectively suppressed growth of LUAD cells both in vitro and in vivo. DLGAP5 overexpression significantly reversed AT9283-induced proliferation inhibition. Moreover, AT9283 significantly suppressed DLGAP5 and PLK1 expression, while DLGAP5 overexpression significantly reversed AT9283-induced PLK1 suppression. CONCLUSION: Our research has demonstrated that DLGAP5 is upregulated in LUAD and exhibits a strong correlation with unfavorable prognosis. Furthermore, DLGAP5 assumes a significant function in the regulation of tumor immunity and treatment outcome of immune checkpoint inhibitors. Of note, we found that DLGAP5 promotes cell proliferation of LUAD via upregulating PLK1. Targeting DLGAP5 by AT9283, our newly identified DLGAP5 inhibitor, suppresses LUAD growth. DLGAP5 may become a promising prognostic biomarker and therapeutic target for patients with LUAD.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Ureia , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Benzimidazóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas de Neoplasias , Prognóstico , Ureia/análogos & derivadosRESUMO
Background: Exploring potential biomarkers for predicting clinical outcomes and developing targeted therapies for acute myeloid leukemia (AML) is of utmost importance. This study aimed to investigate the expression pattern of the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway and its role in the prognosis of AML patients. Methods: In this study, we examined the prognostic value of TXNIP/NLRP3 pathway in AML patients using microarray data from Gene Expression Omnibus (GEO) and transcriptome data from the Cancer Genome Atlas (TCGA) to develop a prognostic model and validated the results by quantitative real-time PCR (qRT-PCR) in a validation cohort of 26 AML patients and 18 healthy individuals from Jinan University (JNU) database. Results: Analysis of the GSE13159 database revealed that TXNIP, interleukin 1 beta (IL1B) within the TXNIP/NLRP3 pathway were significantly upregulated and caspase1 (CASP1) was downregulated in AML patients (TXNIP, P = 0.031; IL1B, P = 0.042; CASP1, P = 0.038). Compared to high NLRP3 expression, AML patients with low NLRP3 expression had a longer overall survival (OS) in the GSE12417 dataset (P = 0.004). Moreover, both the training and validation results indicated that lower TXNIP, NLRP3, and IL1B expression were associated with favorable prognosis (GSE12417, P = 0.009; TCGA, P = 0.050; JNU, P = 0.026). According to the receiver operating characteristic curve analysis, this model demonstrated a sensitivity of 84% for predicting three-year survival. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TXNIP/NLRP3/IL1B genes in novel targeted therapies for AML.
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Biomarcadores Tumorais , Proteínas de Transporte , Inflamassomos , Interleucina-1beta , Leucemia Mieloide Aguda , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Feminino , Masculino , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Inflamassomos/metabolismo , Inflamassomos/genética , Transdução de Sinais/genética , Adulto , Idoso , Regulação Leucêmica da Expressão Gênica , Tiorredoxinas/genética , Tiorredoxinas/metabolismoRESUMO
BACKGROUND: Gastric cancer is the fourth leading cause of cancer-related deaths worldwide. And patient outcomes are poor due to tumor relapse and metastasis. To develop new therapeutic strategies, it is of great importance to explore the mechanism underlying the progression of gastric cancer. METHODS: Primary gastric cancer samples with lymph node metastases (LNM) and without LNM were subjected to mRNA microarray assay. The differentially expressed genes were confirmed by RT-qPCR. HRCT1 protein expression was further detected using an immunohistochemistry (IHC) assay. In vitro and in vivo assays were performed to investigate the role of HRCT1 in tumor invasion, metastasis, and proliferation. The expressions of the downstream target genes of HRCT1 were detected by microarray, RT-qPCR and Western blot assays. Dual-luciferase reporter and Western blot assays were carried out to identify miRNAs target to HRCT1. RESULTS: HRCT1 was upregulated in gastric cancer, and high expression of HRCT1 was associated with poor overall survival (OS) and disease-free survival (DFS). Moreover, HRCT1protein expression was an independent predictor for poor OS and DFS. HRCT1 could promote gastric cancer cells' migration, invasion, and proliferation in vitro as well as tumor metastasis and growth in vivo. Notably, our data showed that HRCT1 promoted gastric cancer progression by activating the ERBB2-MAPK signaling pathway. At least partially, the expression of HRCT1 could be negatively regulated by miR-124-3p. CONCLUSIONS: The upregulated expression of HRCT1 predicts poor survival for patients with gastric cancer. HRCT1 promotes tumor progression by activating the ERBB2-MAPK pathway. HRCT1, negatively regulated by miR-124-3p, may be a potential therapeutic target for patients with gastric cancer.
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MicroRNAs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Proliferação de Células/genética , Linhagem Celular Tumoral , MicroRNAs/genética , Transdução de Sinais , Metástase Linfática , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Receptor ErbB-2/metabolismoRESUMO
Cadmium (Cd) in soil inhibits plant growth and development and even harms human health through food chain transmission. Switchgrass (Panicum virgatum L.), a perennial C4 biofuel crop, is considered an ideal plant for phytoremediation due to its high efficiency in removing Cd and other heavy metals from contaminated soil. The key to understanding the mechanisms of switchgrass Cd tolerance is to identify the genes involved in Cd transport. Heavy-metal ATPases (HMAs) play pivotal roles in heavy metal transport, including Cd, in Arabidopsis thaliana and Oryza sativa, but little is known about the functions of their orthologs in switchgrass. Therefore, we identified 22 HMAs in switchgrass, which were distributed on 12 chromosomes and divided into 4 groups using a phylogenetic analysis. Then, we focused on PvHMA2.1, which is one of the orthologs of the rice Cd transporter OsHMA2. We found that PvHMA2.1 was widely expressed in roots, internodes, leaves, spikelets, and inflorescences, and was significantly induced in the shoots of switchgrass under Cd treatment. Moreover, PvHMA2.1 was found to have seven transmembrane domains and localized at the cell plasma membrane, indicating that it is a potential transporter. The ectopic expression of PvHMA2.1 alleviated the reduction in primary root length and the loss of fresh weight of Arabidopsis seedlings under Cd treatment, suggesting that PvHMA2.1 enhanced Cd tolerance in Arabidopsis. The higher levels of relative water content and chlorophyll content of the transgenic lines under Cd treatment reflected that PvHMA2.1 maintained water retention capacity and alleviated photosynthesis inhibition under Cd stress in Arabidopsis. The roots of the PvHMA2.1 ectopically expressed lines accumulated less Cd compared to the WT, while no significant differences were found in the Cd contents of the shoots between the transgenic lines and the WT under Cd treatment, suggesting that PvHMA2.1 reduced Cd absorption from the environment through the roots in Arabidopsis. Taken together, our results showed that PvHMA2.1 enhanced Cd tolerance in Arabidopsis, providing a promising target that could be engineered in switchgrass to repair Cd-contaminated soil.
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Arabidopsis , Metais Pesados , Oryza , Humanos , Cádmio/metabolismo , Arabidopsis/genética , Expressão Ectópica do Gene , Filogenia , Metais Pesados/metabolismo , Solo , Raízes de Plantas/metabolismo , Oryza/metabolismoRESUMO
Glucosamine (GlcN) is a natural amino monosaccharide in which a hydroxyl group of glucose is substituted by an amino group. It belongs to functional amino sugar compounds. In the traditional preparation process, GlcN and GlcNAc are obtained by hydrolyzing the cell wall of shrimp and crab. There are many potential problems with this method, such as geographical and seasonal restrictions on the supply of raw materials, serious environmental pollution and potential allergic reactions. Microbial fermentation has the advantages of mild conditions, low environmental pollution, high production intensity, and product safety. It can effectively solve the problem of shrimp and crab hydrolysis process, attracting many researchers to participate in the research of microbial fermentation production of GlcN. This paper mainly summarizes the research on strain construction method, metabolic pathway design and fermentation condition optimization in microbial fermentation, which has certain guiding significance for the further production, research and production of glucosamine.
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Acetilglucosamina , Glucosamina , Fermentação , Glucose , Redes e Vias MetabólicasRESUMO
Intertwining quantum order and non-trivial topology is at the frontier of condensed matter physics1-4. A charge-density-wave-like order with orbital currents has been proposed for achieving the quantum anomalous Hall effect5,6 in topological materials and for the hidden phase in cuprate high-temperature superconductors7,8. However, the experimental realization of such an order is challenging. Here we use high-resolution scanning tunnelling microscopy to discover an unconventional chiral charge order in a kagome material, KV3Sb5, with both a topological band structure and a superconducting ground state. Through both topography and spectroscopic imaging, we observe a robust 2 × 2 superlattice. Spectroscopically, an energy gap opens at the Fermi level, across which the 2 × 2 charge modulation exhibits an intensity reversal in real space, signalling charge ordering. At the impurity-pinning-free region, the strength of intrinsic charge modulations further exhibits chiral anisotropy with unusual magnetic field response. Theoretical analysis of our experiments suggests a tantalizing unconventional chiral charge density wave in the frustrated kagome lattice, which can not only lead to a large anomalous Hall effect with orbital magnetism, but also be a precursor of unconventional superconductivity.
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BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) are key players in multicellular, stromal-dependent alterations leading to HCC pathogenesis. However, the intricate crosstalk between CAFs and other components in the tumor microenvironment (TME) remains unclear. This study aimed to investigate the cellular crosstalk among CAFs, tumor cells, and tumor-associated neutrophils (TANs) during different stages of HCC pathogenesis. APPROACH AND RESULTS: In the HCC-TME, CAF-derived cardiotrophin-like cytokine factor 1 (CLCF1) increased chemokine (C-X-C motif) ligand 6 (CXCL6) and TGF-ß secretion in tumor cells, which subsequently promoted tumor cell stemness in an autocrine manner and TAN infiltration and polarization in a paracrine manner. Moreover, CXCL6 and TGF-ß secreted by HCC cells activated extracellular signal-regulated kinase (ERK) 1/2 signaling of CAFs to produce more CLCF1, thus forming a positive feedback loop to accelerate HCC progression. Inhibition of ERK1/2 or CLCF1/ciliary neurotrophic factor receptor signaling efficiently impaired CLCF1-mediated crosstalk among CAFs, tumor cells, and TANs both in vitro and in vivo. In clinical samples, up-regulation of the CLCF1-CXCL6/TGF-ß axis exhibited a marked correlation with increased cancer stem cells, "N2"-polarized TANs, tumor stage, and poor prognosis. CONCLUSIONS: This study reveals a cytokine-mediated cellular crosstalk and clinical network involving the CLCF1-CXCL6/TGF-ß axis, which regulates the positive feedback loop among CAFs, tumor stemness, and TANs, HCC progression, and patient prognosis. These results may support the CLCF1 cascade as a potential prognostic biomarker and suggest that selective blockade of CLCF1/ciliary neurotrophic factor receptor or ERK1/2 signaling could provide an effective therapeutic target for patients with HCC.
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Fibroblastos Associados a Câncer/patologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Hepatocelular/metabolismo , Quimiocina CXCL6/metabolismo , Citocinas/metabolismo , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Microambiente TumoralRESUMO
Dark hollow beams (DHBs) possess great potential for material processing, holography, and vortex beams, and thus designing a high-Q DHB cavity is significant for these applications. In this Letter, a method of designing and optimizing a high-Q DHB cavity based on a one-dimensional topological photonic crystal (TPhC) is proposed. Furthermore, how the structural parameters control the performance of the cavity is analyzed with the help of finite-element-method (FEM) simulation. According to the simulation results, the Q factor of the designed cavity can reach the order of 105 with only 19 periods of layers. It is critical to mention that, although increasing the layers can improve the average Q of the cavity, it will cause serious fluctuation of both the Q factor and the divergence angle of the output beam. The design method proposed in this Letter may not only help designers of future DHB lasers but also promote the applications of DHBs in various fields.
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A ring focus reflector is proposed for transmitting a perfect vortex (PV) beam, and the transmission characteristics of the PV beam with different topological charges in free space after passing through the reflector are studied. The reflector parameters can be determined by fitting the structural formula, and PV beams of different orders transmit with small spot sizes at the same time. The transmission trajectory calculated by the diffraction formula is consistent with the ray tracing results. The research results show that the reflector can achieve a high level of transmission efficiency of beams with different topological charges, which is conducive to the multiplexing of PV beams.
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A method of designing negative curvature anti-resonant hollow-core fibers (NC-AR-HCFs) with bending resistance is proposed, by which the fundamental mode (FM) and higher-order mode (HOM) can be adjusted. An asymmetric double-ring negative curvature hollow-core fiber (ADR-NC-HCF) is proposed to verify the method. The ADR-NC-HCF achieves the FM loss of 0.8 dB/km at 1550 nm under the bending radius of 20 mm. The coupling relation between the modes in ADR-NC-HCFs is analyzed revealing the physical principle of the design method. Based on the principle, the fiber can be directionally optimized to achieve a lower loss of the FM or higher-order mode extinction ratio.
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BACKGROUND: Distal duodenal resections are sometimes necessary for radical surgery, but how to restore duodenal continuity is still unclear. This study aimed at determining which style of anastomosis was more suitable for the duodenojejunostomy after resection of distal duodenum. PATIENTS AND METHODS: We retrospectively identified 34 patients who underwent distal duodenum resection at our center between January 2014 and December 2021. According to whether the end or the side of the proximal duodenum was involved in reconstruction, duodenojejunostomy were classified as End style (E-style) and Side style (S-style). Demographic data, clinicopathological details, and postoperative complications were analyzed between two groups. RESULTS: Thirteen patients (38.2%) received E-style duodenojejunostomy, and 21 patients (62.8%) received S-style duodenojejunostomy. Comparative analysis showed that in group of E-style, patients had a lower rate of multivisceral resection(5/13 vs 18/21; P = 0.008), delayed gastric emptying (DGE) (1/13 vs 11/21; P = 0.011) and intraperitoneal infection (2/13 vs 12/21; P = 0.03). In this study, the incidence of major complications was up to 35.3% (12/34) and no patient died of complication in perioperative period. In two group, there was no difference in the incidence of major complications (E-style vs S-style: 3/13 vs 9/21; P = 0.292). CONCLUSIONS: The E-style duodenojejunostomy for the reconstruction of distal duodenum resection is safe and feasible. The E-style anastomosis may have potential value in decreasing the occurrence of complications such as DGE and intraperitoneal infection, and the definitive advantages still need to be verified.
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Duodeno , Pancreaticoduodenectomia , Humanos , Estudos Retrospectivos , Duodeno/cirurgia , Anastomose Cirúrgica , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
Degradable polylactic acids (PLA) have been widely used in agriculture, textile, medicine and degradable plastics industry, and can completely replace petroleum-based plastics in the future. At present, polylactic acid was chemically synthesized by ring-opening polymerisation or the direct polycondensation of lactic acid, which inevitably leads to chemical and heavy metal catalyst pollution. The current research focus has gradually shifted to the development of recombinant industrial strains for the efficiently production of lactate-containing polyesters from renewable resources. This review summarizes various explorations of metabolic pathway optimization and production cost control in the industrialization of lactate-containing polyesters bio-production. In particular, the effects of key enzymes, including CoA transferase, polyhydroxyalkanoate synthase, and their mutants, culture conditions, low-cost carbon sources, and recombinant strains on the yield and composition of lactate-containing polyesters are summarized and discussed. Future prospects and challenges for the industrialization of lactate-containing polyesters are also pointed out.
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Ácido Láctico , Poliésteres , Catálise , Ácido Láctico/metabolismo , Redes e Vias Metabólicas , Plásticos , Poliésteres/metabolismoRESUMO
BACKGROUND: High probability of metastasis limited the long-term survival of patients with hepatocellular carcinoma (HCC). Our previous study revealed that Galectin-3 was closely associated with poor prognosis in HCC patients. METHODS: The effects of Galectin-3 on tumour metastasis were investigated in vitro and in vivo, and the underlying biological and molecular mechanisms involved in this process were evaluated. RESULTS: Galectin-3 showed a close correlation with vascular invasion and poor survival in a large-scale study in HCC patients from multiple sets. Galectin-3 was significantly involved in diverse metastasis-related processes in HCC cells, such as angiogenesis and epithelial-to-mesenchymal transition (EMT). Mechanistically, Galectin-3 activated the PI3K-Akt-GSK-3ß-ß-catenin signalling cascade; the ß-catenin/TCF4 transcriptional complex directly targeted IGFBP3 and vimentin to regulate angiogenesis and EMT, respectively. In animal models, Galectin-3 enhanced the tumorigenesis and metastasis of HCC cells via ß-catenin signalling. Moreover, molecular deletion of Galectin-3-ß-catenin signalling synergistically improved the antitumour effect of sorafenib. CONCLUSIONS: The Galectin-3-ß-catenin-IGFBP3/vimentin signalling cascade was determined as a central mechanism controlling HCC metastasis, providing possible biomarkers for predicating vascular metastasis and sorafenib resistance, as well as potential therapeutic targets for the treatment of HCC patients.
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Carcinoma Hepatocelular/patologia , Galectina 3/fisiologia , Neoplasias Hepáticas/patologia , beta Catenina/genética , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Neoplasias de Tecido Vascular/genética , Neoplasias de Tecido Vascular/mortalidade , Neoplasias de Tecido Vascular/secundário , Análise de Sobrevida , Análise Serial de Tecidos , Via de Sinalização Wnt/genética , beta Catenina/metabolismoRESUMO
OBJECTIVES: In China, multiple approaches to calculating EQ-5D utilities are available, including the two EQ-5D-3L (3L2014 and 3L2018) scoring functions, the EQ-5D-5L (5L) scoring function, and the crosswalk function linking the 3L utilities and 5L health states. The study compared utilities derived from them in terms of agreement and discriminative power; and assessed whether the use of different approaches may affect QALY estimation in Chinese type 2 diabetes (T2D) patients. METHODS: Cross-sectional data of 289 T2D patients who self-completed both the 5L and 3L questions were used. Agreement were examined using intraclass correlation coefficient (ICC) and Bland-Altman plots. The ability of the EQ-5D utilities in differentiating the patients with and without clinical conditions was evaluated using F-statistics. Their influence on QALY estimation was assessed adopting mean absolute difference (MAD) in utility values between the patients. RESULTS: The ICC values were 0.881 (3L2014-3L2018), 0.958 (5L-c5L2014), and 0.806 (5L-c5L2018). The two 3L utilities and the three 5L utilities had poor agreement at the lower end of utility scale according to Bland-Altman plots. The 3L2018 utilities had lower F-statistics compared to the 3L2014 utilities; the two c5L utilities had larger or similar F-statistics compared to the 5L utilities. The mean MADs were 0.138 (5L), 0.116 (3L2014), 0.115 (c5L2014), 0.055 (c5L2018), and 0.055 (3L2018). CONCLUSION: The 3L2014 utilities is more discriminative than the 3L2018 utilities; and the two c5L utilities have no worse discriminative power compared with the 5L utilities. The choice of the approach to calculating the EQ-5D utilities is likely to affect QALY estimates.
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Diabetes Mellitus Tipo 2/epidemiologia , Nível de Saúde , Qualidade de Vida/psicologia , Povo Asiático , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
A facile method was developed for synthesis of boronic acid-functionalized silica nanocomposites (SiO2 -BA) by 'thiol-ene' click reaction, where silica nanoparticles were synthesized by using tetraethoxysilane (TEOS) and γ-mercaptopropyl trimethoxysilane (γ-MPTS) as precursors. The morphology and structure properties of the resultant SiO2 -BA were characterized by transmission electronic microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and Brunner-Emmet-Teller measurements (BET). The adsorption behavior of the SiO2 -BA for glycoproteins was evaluated. Under the optimized conditions, the SiO2 -BA exhibited higher adsorption capacity towards glycoproteins (ovalbumin, OVA, 7.64 µmol/g) than non-glycoproteins (bovine serum albumin, BSA, 0.83 µmol/g). In addition, the practicality of the SiO2 -BA was further assessed by selective enrichment of glycoproteins from egg white samples.
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Ácidos Borônicos/química , Glicoproteínas/química , Nanocompostos/química , Dióxido de Silício/química , Adsorção , Clara de Ovo/química , Estrutura Molecular , Tamanho da Partícula , Dióxido de Silício/síntese química , Propriedades de SuperfícieRESUMO
BACKGROUND: Since the incidence of papillary thyroid carcinoma (PTC) combined with Hashimoto's thyroiditis (HT) has increased year by year, but the mechanism is still unknown, the goal of this study was to investigate the expression of Na+/I- symporter (NIS), vascular endothelial growth factor (VEGF)-A and thyroid autoantibodies in HT combined with PTC, and to explore the relationship between HT and PTC. METHODS: Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of VEGF-A and NIS in 38 cases of PTC and HT combined with PTC and in 20 cases of normal tissues; preoperative serum TPOAb and TgAb levels in each group were detected by ELISA. RESULTS: The expression of VEGF-A in PTC and HT combined with PTC was significantly higher than that in normal tissues (p < 0.05), and the expression of VEGF-A in HT combined with PTC was higher than that in PTC (p < 0.05). The expression of NIS mRNA in PTC and HT combined with PTC was significantly decreased compared to that in normal tissues (p < 0.05), and NIS mRNA in HT combined with PTC tissue was lower than that in PTC tissue (p < 0.05). The preoperative levels of TPOAb and TgAb in the HT combined with PTC group were higher than those in the normal group and the PTC group (p < 0.05). CONCLUSION: The presence of HT may inhibit iodine uptake and cause a decrease in NIS. Increased levels of TPOAb and TgAb in HT patients lead to a high expression of TSH and stimulate VEGF secretion. This may explain why HT could accelerate the occurrence and development of PTC.
Assuntos
Autoanticorpos/metabolismo , Doença de Hashimoto/metabolismo , Simportadores/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Feminino , Humanos , MasculinoRESUMO
Diabetic kidney disease (DKD) is a serious disease that presents a major health problem worldwide. There is a desperate need to explore novel biomarkers to further facilitate the early diagnosis and effective treatment in DKD patients, thus preventing them from developing end-stage renal disease (ESRD). However, most regulation mechanisms at the genetic level in DKD still remain unclear. In this paper, we describe our innovative methodologies that integrate biological, computational, and statistical approaches to investigate important roles performed by regulations among microRNAs (miRs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) in DKD. We conducted fully transparent, rigorously designed experiments. Our robust and reproducible results identified hsa-miR-223-3p as a candidate novel biomarker performing important roles in DKD disease process.