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The design and synthesis of high-performance sensors are very important but remain great challenges. In this work, a new aggregation-induced-emission (AIE) molecule 4,4'-(((9H-fluoren-9-ylidene)methylene)bis(4,1-phenylene))dipyridine (L) was successfully synthesized and first developed as a functional ligand to construct two isomorphic metal-organic frameworks (MOFs) [M(L)(OBBA)]n [M2+ = Cd2+ (1), Co2+ (2); H2OBBA = 4,4'-oxybisbenzoic acid]. They adopt [M2(COO)4] flywheel clusters, OBBA2- bridges, and terminal L ligands as building units to form isomorphic 2-D networks with Lewis base active cites (uncoordinated pyridyl N). Both 1 and 2 exhibit excellent water, pH, and thermal stabilities and extremely efficient Fe3+ sensing abilities in the water environment. The quenching constants and detection limits reach the best levels reported so far. The sensing mechanism of 1 and 2 toward Fe3+ is studied in depth, and the difference in their sensing performance is also explained.
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BACKGROUND: Pseudomonas aeruginosa is a major Gram-negative pathogen that can exacerbate lung infections in the patients with cystic fibrosis, which can ultimately lead to death. METHODS: From 2016 to 2021, 103 strains of P. aeruginosa were isolated from hospitals and 20 antibiotics were used for antimicrobial susceptibility determination. Using next-generation genome sequencing technology, these strains were sequenced and analyzed in terms of serotypes, ST types, and resistance genes for epidemiological investigation. RESULTS: The age distribution of patients ranged from 10 days to 94 years with a median age of 69 years old. The strains were mainly isolated from sputum (72 strains, 69.9%) and blood (14 strains, 13.6%). The size of these genomes ranged from 6.2 Mb to 7.4 Mb, with a mean value of 6.5 Mb. In addition to eight antibiotics that show inherent resistance to P. aeruginosa, the sensitivity rates for colistin, amikacin, gentamicin, ceftazidime, piperacillin, piperacillin-tazobactam, ciprofloxacin, meropenem, aztreonam, imipenem, cefepime and levofloxacin were 100%, 95.15%, 86.41%, 72.82%, 71.84%, 69.90%, 55.34%, 52.43%, 50.49%, 50.49%, 49.51% and 47.57% respectively, and the carriage rate of MDR strains was 30.69% (31/101). Whole-genome analysis showed that a total of 50 ST types were identified, with ST244 (5/103) and ST1076 (4/103) having a more pronounced distribution advantage. Serotype predictions showed that O6 accounted for 29.13% (30/103), O11 for 23.30% (24/103), O2 for 18.45% (19/103), and O1 for 11.65% (12/103) of the highest proportions. Notably, we found a significantly higher proportion of ExoU in P. aeruginosa strains of serotype O11 than in other cytotoxic exoenzyme positive strains. In addition to this, a total of 47 crpP genes that mediate resistance to fluoroquinolones antibiotics were found distributed on 43 P. aeruginosa strains, and 10 new variants of CrpP were identified, named 1.33, 1.34, 1.35, 1.36, 1.37, 1.38, 1.39, 1.40, 1.41 and 7.1. CONCLUSIONS: We investigated the antibiotic susceptibility of clinical isolates of P. aeruginosa and genomically enriched the diversity of P. aeruginosa for its prophylactic and therapeutic value.
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Infecção Hospitalar , Infecções por Pseudomonas , Humanos , Idoso , Recém-Nascido , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa/genética , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/tratamento farmacológico , Piperacilina/farmacologia , HospitaisRESUMO
A millimeter-wave noise generation scheme is proposed in this paper. The scheme is based on a monolithically integrated dual-mode chaotic laser, which consists of a distributed Bragg feedback (DFB) section, a phase section, and an optical amplification section. The output spectrum state of the dual-mode laser can be controlled by adjusting the injection current in the three regions. The monolithically integrated dual-mode chaotic laser has stable chaotic output and can be used as a light source for integrated millimeter-wave noise source. As a feasibility demonstration, a dual-mode chaotic laser with a mode interval of 2.05â nm was generated in the experiment, the optical mixing on a photodetector produced millimeter-wave noise with a center frequency of 259â GHz and a bandwidth of 44â GHz (237-281â GHz), achieving a typical value of excess noise ratio of 47â dB. It has the advantages of high noise source utilization, small noise source volume, and high integration.
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Sixteen new quinolizidine alkaloids (QAs), named ormosianines A-P (1-16), and 18 known congeners (17-34) were isolated from the stems and leaves of Ormosia yunnanensis. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Structurally, ormosianines A (1) and B (2) are the first examples of cytisine and Ormosia-type alkaloids with the cleavage of the piperidine ring. Results of the acetylcholinesterase (AChE) inhibitory assay revealed that the pentacycline Ormosia-type QAs, including 1, 16, 24, and 27-29, are good AChE inhibitors. Ormosianine A (1) exhibited more potent AChE inhibitory activity with an IC50 value of 1.55 µM. Molecular docking revealed that 1 might bind to the protein 1DX4, forming two hydrogen bonds with residues SER-238 and HIS-480.
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Alcaloides , Fabaceae , Acetilcolinesterase/metabolismo , Alcaloides Quinolizidínicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Alcaloides/química , Dicroísmo Circular , Fabaceae/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/químicaRESUMO
Infectious serositis of ducks, caused by Riemerella anatipestifer, is one of the main infectious diseases that harm commercial ducks. Whole-strain-based vaccines with no or few cross-protection were observed between different serotypes of R. anatipestifer, and so far, control of infection is hampered by a lack of effective vaccines, especially subunit vaccines with cross-protection. Since the concept of reverse vaccinology was introduced, it has been widely used to screen for protective antigens in important pathogens. In this study, pan-genome binding reverse vaccinology, an emerging approach to vaccine candidate screening, was used to screen for cross-protective antigens against R. anatipestifer. Thirty proteins were identified from the core-genome as potential cross-protective antigens. Three of these proteins were recombinantly expressed, and their immunoreactivity with five antisera (anti-serotypes 1, 2, 6, 10, and 11) was demonstrated by Western blotting. Our study established a method for high-throughput screening of cross-protective antigens against R. anatipestifer in silico, which will lay the foundation for the development of a cross-protective subunit vaccine controlling R. anatipestifer infection. KEY POINTS: ⢠Pan-genome binding reverse vaccine approach was first established in R. anatipestifer to screen for subunit vaccine candidates. ⢠Thirty potential cross-protective antigens against R. anatipestifer were identified by this method. ⢠The reliability of the method was verified preliminarily by the results of Western blotting of three of these potential antigens.
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Infecções por Flavobacteriaceae , Doenças das Aves Domésticas , Riemerella , Animais , Doenças das Aves Domésticas/prevenção & controle , Reprodutibilidade dos Testes , Riemerella/genética , Vacinas de Subunidades Antigênicas , Patos , Infecções por Flavobacteriaceae/prevenção & controle , Infecções por Flavobacteriaceae/veterináriaRESUMO
Fine dust generated by particulate matter (PM) pollution is a serious ecological issue in industrialized countries and causes disorders of the respiratory system and skin in humans. In the previous study, Sargassum fusiforme was treated with citric acid to remove heavy metals. In this study, the transfer of PM-mediated inflammatory responses through the skin to macrophages was evaluated. Moreover, the anti-adhesive effects of calcium alginate isolated from S. fusiforme (SFCA) against PM-induced inflammation were investigated. The structures of processing and unprocessing SFCA were then analyzed by Fourier-transform infrared spectroscopy (FT-IR), revealing minimal change after acid-processing. SFCA had protective effects both in PM-stimulated HaCaT keratinocytes and RAW 264.7 macrophages. In cellular environments, it was found that SFCA attenuated signal protein expressions such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E2 (PGE2), and pro-inflammatory cytokines. Furthermore, macrophages were added to the culture medium of PM-stimulated keratinocytes to induce inflammation. SFCA was observed to significantly inhibit inflammatory responses; additionally, SFCA showed an in vivo anti-adhesive effect in zebrafish embryos.
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With the development of superframe high-dynamic-range infrared imaging technology that extends the dynamic range of thermal imaging systems, a key issue that has arisen is how to choose different integration times to obtain an HDR fusion image that contains more information. This paper proposes a multi-integration time adaptive method, in order to address the lack of objective evaluation methods for the selection of superframe infrared images, consisting of the following steps: image evaluation indicators are used to obtain the best global exposure image (the optimal integration time); images are segmented by region-growing point to obtain the ambient/high-temperature regions, selecting the local optimum images with grayscale closest to the medium grayscale of the IR imaging system for the two respective regions (lowest and highest integration time); finally, the three images above are fused and enhanced to achieve HDR infrared imaging. By comparing this method with some existing integration time selection methods and applying the proposed method to some typical fusion methods, via subjective and objective evaluation, the proposed method is shown to have obvious advantages over existing algorithms, and it can optimally select the images from different integration time series images to form the best combination that contains full image information, expanding the dynamic range of the IR imaging system.
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Algoritmos , Interpretação de Imagem Assistida por Computador , Interpretação de Imagem Assistida por Computador/métodosRESUMO
Isoquercitrin (IQ) widely exists in natural products, with a variety of pharmacological activities. In this study, the anti-apoptotic and antioxidative activities of IQ were evaluated. IQ showed protective activity against 2, 2'-azobis [2-methylpropionamidine] dihydrochloride (AAPH)-induced cell damage, as well as a marked reduction in reactive oxygen species (ROS). The evidence of IQ regulating Keap1-Nrf2-ARE and the mitochondrial-mediated Caspase 3 pathway were found in the MC3T3 osteoblastic cell line. Furthermore, IQ significantly decreased ROS production, apoptosis, and lipid peroxidation in AAPH-treated 72 h post-fertilization (hpf) zebrafish, as observed via DCFH-DA, acridine orange (AO), and a 1,3-bis(diphenylphosphino) propane (DPPP) probe, respectively. In AAPH-treated 9 day post-fertilization (dpf) zebrafish, IQ strongly promoted osteogenic development, with increased concentrations by calcein staining, compared with the untreated group. In a molecular docking assay, among all signal proteins, Keap1 showed the strongest affinity with IQ at -8.6 kcal/mol, which might be the reason why IQ regulated the Keap1-Nrf2-ARE pathway in vitro and in vivo. These results indicated that IQ promotes bone development and repairs bone injury, which is valuable for the prevention and treatment of bone diseases.
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Fator 2 Relacionado a NF-E2 , Peixe-Zebra , Animais , Apoptose , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Quercetina/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Peixe-Zebra/metabolismoRESUMO
Basic leucine zipper (bZIP) is a conserved transcription factor (TF) widely present in eukaryotes, and it plays an important role in regulating plant growth and stress responses. To better understand the white pear bZIP gene family, comprehensive bioinformatics analysis of the pear genome was performed. A total of 84 PbbZIP genes were identified, which were divided into 13 subfamilies by phylogenetic analysis. The 84 PbbZIP genes were all located in the nucleus, and 77 of those genes were unevenly distributed across the 17 chromosomes of white pear. The other 7 PbbZIP genes were located on the scaffold. Subsequent expression profile analysis showed that PbbZIP genes in exocarp were significantly upregulated or downregulated in 'Huangguan' pear with brown spot (BS) compared with healthy pear and in response to hormonal treatment with gibberellin A3 (GA3). These results provide helpful insights into the characteristics of PbbZIP genes and their responses to BS in 'Huangguan' pear.
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BACKGROUND: The content of stone cells in pears has a great influence on taste. Stone cells are formed by the accumulation of lignin. The treatment of exogenous calcium can affect the lignin synthesis, but this Ca-mediated mechanism is still unclear. In this study, the author performed a comparative transcriptomic analysis of callus of pears (Pyrus x bretschneideri) treated with calcium nitrate Ca (NO3)2 to investigate the role of calcium in lignin synthesis. RESULTS: There were 2889 differentially expressed genes (DEGs) detected between the Control and Ca (NO3)2 treatment in total. Among these 2889 DEGs, not only a large number of genes related to Ca single were found, but also many genes were enriched in secondary metabolic pathway, especially in lignin synthesis. Most of them were up-regulated during the development of callus after Ca (NO3)2 treatment. In order to further explore how calcium nitrate treatment affects lignin synthesis, the author screened genes associated with transduction of calcium signal in DEGs, and finally found CAM, CML, CDPK, CBL and CIPK. Then the author identified the PbCML3 in pears and conducted relevant experiments finding the overexpression of PbCML3 would increase the content of pear stone cells, providing potential insights into how Ca treatment enhances the stone cell in pears. CONCLUSIONS: Our deep analysis reveals the effects of exogenous calcium on calcium signal and lignin biosynthesis pathway. The function of PbCML3 on stone cells formation was verified in pear.
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Pyrus , Cálcio , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Pyrus/genética , TranscriptomaRESUMO
Cyclin D1 (CCND1) has been identified as a metastatic promoter in various tumors including lung adenocarcinoma (LUAD), a subtype of non small cell lung cancer (NSCLC). The previous observation revealed that CCND1 was upregulated in NSCLC and predicted poor prognosis of LUAD patients. In this study, we examined a chaperonin containing TCP1 subunit 5 (CCT5) protein interacts with CCND1 in LUAD. Immunofluorescence demonstrated the co-localization of CCT5 and CCND1 protein in LUAD cells. CCT5 expression was detected with both immunohistochemistry (IHC) and bioinformatics analyses. Similar with the expression pattern of CCND1, CCT5 displayed a high level in LUAD tissues compared to non cancerous lung specimens. Patients with high CCT5 expression showed a significant shorter overall survival relative to those with low expression level. Furthermore, upregulated CCT5 exhibited significant positive correlation with TNM stage of LUAD patients in both IHC analyses and bioinformatics. Knocking down CCT5 remarkably inhibited LUAD cell migration and invasion in vitro by inactivating PI3K/AKT and its downstream EMT signals, which could abrogated the accelerated migration and invasion caused by CCND1 overexpression. In summary, our study discovered a highly expressed protein CCT5 in LUAD which interacted with CCND1 and promoted migration and invasion of LUAD cells by positively moderating PI3K/AKT-induced EMT pathway.
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Adenocarcinoma de Pulmão/metabolismo , Chaperonina com TCP-1/metabolismo , Ciclina D1/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular , Humanos , Neoplasias Pulmonares/patologia , Invasividade Neoplásica/patologia , Mapas de Interação de ProteínasRESUMO
RATIONALE: Ginsenoside Rg3 and glimepiride have been applied to treat type 2 diabetes (T2DM) because of their good hypoglycemic effects. In this study, the effects of ginsenoside Rg3 acting synergistically with glimepiride were investigated in liver microsomes from rats with type 2 diabetes. METHODS: An in vitro incubation system with normal rat liver microsomes (RLM) and type 2 diabetic rat liver microsomes (TRLM) was developed. The system also included two experimental groups consisting of RLM and TRLM pretreated with ginsenoside Rg3 and glimepiride (named the RLMR and TRLMR groups, respectively). The metabolism in the different groups was analyzed by ultra-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry (UPLC/Q-Orbitrap MS). RESULTS: The results showed that the concentration of glimepiride increased in RLM and TRLM after treatment with ginsenoside Rg3. Five metabolites (M1-M5) of glimepiride were found, and they were named 3N-hydroxyglimepiride, hydroxyglimepiride, 1,2-epoxy ether-3-hydroxyglimepiride, 1N-hydroxyglimepiride and 1N,2C,S,O,O-epoxy ether-3-hydroxyglimepiride. The metabolite of ginsenoside Rg3 was ginsenoside Rh2. CONCLUSIONS: An in vitro incubation system with RLM and TRLM was developed. The system revealed pathways that produce glimepiride metabolites. Ginsenoside Rg3 may inhibit the activity of cytochrome P450 enzymes in vitro. The present study showed that ginsenoside Rg3 and glimepiride may be combined for the treatment of T2DM.
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Cromatografia Líquida/métodos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ginsenosídeos/farmacocinética , Hipoglicemiantes/farmacocinética , Microssomos Hepáticos/enzimologia , Espectrometria de Massas por Ionização por Electrospray/métodos , Compostos de Sulfonilureia/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Inibidores das Enzimas do Citocromo P-450/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica , Sinergismo Farmacológico , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Estreptozocina , Compostos de Sulfonilureia/análise , Compostos de Sulfonilureia/uso terapêuticoRESUMO
Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury.
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Encéfalo , Células Endoteliais , Células Progenitoras Endoteliais , Exossomos , Lipopolissacarídeos , MicroRNAs , Exossomos/metabolismo , Animais , Células Progenitoras Endoteliais/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Lipopolissacarídeos/toxicidade , Camundongos , Encéfalo/metabolismo , Encéfalo/patologia , Células Endoteliais/metabolismo , Apoptose , Proliferação de Células , Microvasos/metabolismo , Masculino , Sepse/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Sepsis is a multisystem disease characterized by dysregulation of the host immune response to infection. Immune response kinetics play a crucial role in the pathogenesis and progression of sepsis. Macrophages, which are known for their heterogeneity and plasticity, actively participate in the immune response during sepsis. These cells are influenced by the ever-changing immune microenvironment and exhibit two-sided immune regulation. Recently, the immunomodulatory function of mesenchymal stem cells (MSCs) in sepsis has garnered significant attention. The immune microenvironment can profoundly impact MSCs, prompting them to exhibit dual immunomodulatory functions akin to a double-edged sword. This discovery holds great importance for understanding sepsis progression and devising effective treatment strategies. Importantly, there is a close interrelationship between macrophages and MSCs, characterized by the fact that during sepsis, these two cell types interact and cooperate to regulate inflammatory processes. This review summarizes the plasticity of macrophages and MSCs within the immune microenvironment during sepsis, as well as the intricate crosstalk between them. This remains an important concern for the future use of these cells for immunomodulatory treatments in the clinic.
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Células-Tronco Mesenquimais , Sepse , Humanos , Macrófagos , Imunomodulação , Imunidade , Células-Tronco Mesenquimais/metabolismo , Sepse/metabolismoRESUMO
Tumor-derived extracellular vesicles (tEVs) hold immense promise as potential biomarkers for the precise diagnosis of hepatocellular carcinoma (HCC). However, their clinical translation is hampered by their inherent characteristics, such as small size and high heterogeneity and complex environment, including non-EV particles and normal cell-derived EVs, which prolong separation procedures and compromise detection accuracy. In this study, we devised a DNA cascade reaction-triggered individual EV nanoencapsulation (DCR-IEVN) strategy to achieve the ultrasensitive and specific detection of tEV subpopulations via routine flow cytometry in a one-pot, one-step fashion. DCR-IEVN enables the direct and selective packaging of multiple tEV subpopulations in clinical serum samples into flower-like particles exceeding 600 nm. This approach bypasses the need for EV isolation, effectively reducing interference from non-EV particles and nontumor EVs. Compared with conventional analytical technologies, DCR-IEVN exhibits superior efficacy in diagnosing HCC owing to its high selectivity for tEVs. Integration of machine learning algorithms with DCR-IEVN resulted in differential diagnosis accuracy of 96.7% for the training cohort (n = 120) and 93.3% for the validation cohort (n = 30), effectively distinguishing HCC, cirrhosis, and healthy donors. This strategy offers a streamlined workflow and rapid assay completion and requires only small-volume serum samples and routine clinical devices, facilitating the clinical translation of tEV-based tumor diagnosis.
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Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/sangue , Humanos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Diagnóstico Diferencial , DNA/química , Biomarcadores Tumorais/sangue , Aprendizado de MáquinaRESUMO
BACKGROUND: In this study, the relationship between C-reactive protein-albumin-lymphocyte (CALLY) index, a novel composite indicator based on inflammation and nutrition, and major adverse cardiovascular events (MACEs) was investigated in patients with ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS: This retrospective study included 438 patients with STEMI who were treated at a single center between January 2017 and December 2020. The CALLY index was calculated for each patient on admission. The predictive value of the CALLY index for short- and long-term MACEs was evaluated using the area under the curve (AUC) analysis, and the corresponding AUC values were calculated. Clinical characteristics were analyzed after categorizing the population based on the optimal cut-off value of the CALLY index. Multivariate Cox regression analysis was used to determine factors independently associated with MACEs, while logistic regression analysis was used to identify factors independently associated with the severity of coronary artery lesions. Kaplan-Meier estimation and log-rank test were used to assess event-free survival rates among different CALLY index groups. Additionally, Spearman's correlation test was used to determine the association between the CALLY index and the Gensini score. RESULTS: The AUC for predicting short-term MACEs in STEMI patients using the CALLY index was 0.758, while the AUC for predicting long-term MACEs was 0.740. Similarly, the AUC values were 0.815 and 0.819, respectively, when evaluating the short- and long-term mortality rates using the CALLY index. Multivariable Cox regression analysis revealed that a high CALLY index (threshold of 1.50) independently reduced the risk of short-term MACEs in patients with STEMI (hazard ratio [HR] = 0.274, 95 % confidence interval [CI] = 0.121-0.621, P=0.002). Multivariable Cox regression also demonstrated that a high CALLY index (threshold > 0.91) independently reduced the occurrence of long-term MACEs during follow-up in STEMI patients (HR=0.439, 95 % CI=0.292-0.659, P<0.001). Furthermore, multivariate logistic regression analysis revealed that a high CALLY index (threshold > 1.13) independently reduced the risk of severe coronary artery lesions in patients with STEMI (odds ratio = 0.299 [95 % CI=184-0.485], P<0.001). A positive correlation was observed between the CALLY index and the Gensini score (P<0.001). CONCLUSION: The CALLY index is a novel, convenient, and valuable prognostic indicator exhibiting a protective effect against both short- and long-term MACEs in patients with STEMI, emphasizing the significance of inflammation/nutrition in this patient population.
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OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.
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Metabolismo dos Carboidratos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Humanos , Prognóstico , Metabolismo dos Carboidratos/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Perfilação da Expressão GênicaRESUMO
Towards the difficulties of traditional processing technology in loading high-concentration functional fillers to realize the target electromagnetic interference shielding (EMI SE) performance, and constructing the arbitrary-designated architectures for serving advanced electronics, this work innovatively formulated a functional multi-walled carbon nanotubes@cellulose nanofibers (MWCNT@OCNF) ink for direct ink writing (DIW) 3D printing, which not only possessed high freedom on the proportion of functional particles, but also imparted to the ideal rheological performance for 3D printing. Based on the pre-programmed printing trajectories, a series of porous scaffolds featuring exceptional functionalities were architected. Particularly for the electromagnetic waves (EMWs) shielding behaviors, the optimized one with "full-mismatched" architecture posed the ultralight structure (0.11 g/cm3) and superior SE performance (43.5 dB) in the X-band frequency region. More encouragingly, the 3D-printed scaffold with hierarchical pores possessed the ideal electromagnetic compatibility on EMWs signal, where the radiation intensity generated by EMWs signal fluctuated in a step pattern in 0 and 1500 µT/cm2 as loading and unloading scaffolds. Overall, this study paved a novel path for the formulation of functional inks to print lightweight, multi-structure, and high-efficiency EMI SE scaffolds for the next-generation shielding elements.
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Worldwide, fruit is an indispensable treasure house of nutrition for human beings, occupying a vital position of human diet. Postharvest fruit storage requires efficient antifungal agents to control Botrytis cinerea, which is a vital postharvest disease affecting fruit and leading to enormous losses. However, with the enormous abuse of existing antifungal drugs, the problem of drug-resistant fungi is imminent, making the controlling diseases caused by pathogenic fungi even more challenging. Drug repurposing is an efficient alternative method, we evaluated a well-known antifungal chemical, terbinafine, against the agricultural pathogen, B. cinerea in vitro, as a result, terbinafine showed strong antifungal activity. Furthermore, the in vivo antifungal activity of terbinafine was evaluated, the results showed that terbinafine could reduce the decay area on grapes. Terbinafine could disrupt the cell membrane integrity, increase cell membrane permeability, and eventual cell death of B. cinerea. In addition, terbinafine reduced decay incidence, and weight loss and maintained the soluble solids, titratable acidity, ascorbic acid, total phenolic, and malondialdehyde content during the storage period of grapes. Overall, terbinafine could be an antifungal preservative for postharvest table grapes fresh-keeping.
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BACKGROUND: LINC00173 had been reported as a cisplatin (cis-diamminedichloroplatinum, DDP) chemotherapy-resistant inducer in small-cell lung cancer (SCLC) and lung squamous cell carcinoma (LUSC). This study aimed to display reverse data for LINC00173 as a DDP chemosensitivity-inducing factor in lung adenocarcinoma (LUAD). METHODS: LINC00173 was screened from the Gene Expression Omnibus database (GSE43493). The expression level of LINC00173 in LUAD tissues and cell lines was detected using in situ hybridization and quantitative reverse transcription-polymerase chain reaction. Colony formation, cell viability, half-maximal inhibitory concentration, flow cytometry, and xenograft mouse model were used to evaluate the role of LINC00173 in the chemosensitivity of LUAD to DDP. The mechanism of LINC00173 in DDP resistance by mediating miR-1275/PROCA1/ZFP36L2 axis to impair BCL2 mRNA stability was applied, and co-immunoprecipitation, chromatin immunoprecipitation, RNA antisense purification, RNA immunoprecipitation, and luciferase reporter assays were performed. RESULTS: LINC00173 downregulation in patients with DDP-resistant LUAD was correlated with poor prognosis. Further, LINC00173 expression was significantly reduced in DDP-resistant LUAD cells and DDP-treated human LUAD tissues. Suppressed LINC00173 expression in LUAD cells enhanced DDP chemoresistance in vivo and in vitro, while restored LINC00173 expression in DDP-resistant LUAD cells markedly regained chemosensitivity to DDP. Mechanistically, DDP-resistant LUAD cells activated PI3K/AKT signal and further elevated the c-Myc expression. The c-Myc, as an oncogenic transcriptional factor, bound to the promoter of LINC00173 and suppressed its expression. The reduced LINC00173 expression attenuated the adsorption of oncogenic miR-1275, downregulating the expression of miR-1275 target gene PROCA1. PROCA1 played a potential tumor-suppressive role inducing cell apoptosis and DDP chemosensitivity via recruiting ZFP36L2 to bind to the 3' untranslated region of BCL2, reducing the stability of BCL2 mRNA and thus activating the apoptotic signal. CONCLUSIONS: This study demonstrated a novel and critical role of LINC00173. It was transcriptionally repressed by DDP-activated PI3K/AKT/c-Myc signal in LUAD, promoting DDP-acquired chemotherapeutic resistance by regulating miR-1275 to suppress PROCA1/ZFP36L2-induced BCL2 degradation, which led to apoptotic signal reduction. These data were not consistent with the previously described role of LINC00173 in SCLC or LUSC, which suggested that LINC00173 could play fine-tuned DDP resistance roles in different pathological subtypes of lung cancer. This study demonstrated that the diminished expression of LINC00173 might serve as an indicator of DDP-acquired resistance in LUAD.