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1.
Bioorg Chem ; 148: 107428, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38733749

RESUMO

Five pairs of new merosesquiterpenoid enantiomers, named dauresorcinols A-E (1-5), were isolated from the leaves of Rhododendron dauricum. Their structures were elucidated by comprehensive spectroscopic data analysis, quantum chemical calculations, Rh2(OCOCF3)4-induced ECD, and single-crystal X-ray diffraction analysis. Dauresorcinols A (1) and B (2) possess two new merosesquiterpene skeletons bearing an unprecedented 2,6,7,10,14-pentamethyl-11-oxatetracyclo[8.8.0.02,7.012,17]octadecane and a caged 15-isohexyl-1,5,15-trimethyl-2,10-dioxatetracyclo[7.4.1.111,14.03,8]pentadecane motif, respectively. Plausible biosynthetic pathways of 1-5 are proposed involving key oxa-electrocyclization and Wagner-Meerwein rearrangement reactions. (+)/(-)-1 and 3-5 showed potent α-glucosidase inhibitory activity, 3 to 22 times stronger than acarbose, an antidiabetic drug targeting α-glucosidase. Docking results provide a basis to design and develop merosesquiterpenoids as potent α-glycosidase inhibitors.

2.
Front Neurosci ; 18: 1387752, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707590

RESUMO

Objectives: To summarize development processes and research hotspots of infrared imaging technology research on acupuncture and to provide new insights for researchers in future studies. Methods: Publications regarding infrared imaging technology in acupuncture from 2008 to 2023 were downloaded from the Web of Science Core Collection (WoSCC). VOSviewer 1.6.19, CiteSpace 6.2.R4, Scimago Graphica, and Microsoft Excel software were used for bibliometric analyses. The main analyses include collaboration analyses between countries, institutions, authors, and journals, as well as analyses on keywords and references. Results: A total of 346 publications were retrieved from 2008 to 2023. The quantity of yearly publications increased steadily, with some fluctuations over the past 15 years. "Evidence-Based Complementary and Alternative Medicine" and "American Journal of Chinese Medicine" were the top-cited journals in frequency and centrality. China has the largest number of publications, with the Shanghai University of Traditional Chinese Medicine being the most prolific institution. Among authors, Litscher Gerhard from Austria (currently Swiss University of Traditional Chinese Medicine, Switzerland) in Europe, was the most published and most cited author. The article published by Rojas RF was the most discussed among the cited references. Common keywords included "Acupuncture," "Near infrared spectroscopy," and "Temperature," among others. Explore the relationship between acupoints and temperature through infrared thermography technology (IRT), evaluate pain objectively by functional near-infrared spectroscopy (fNIRS), and explore acupuncture for functional connectivity between brain regions were the hotspots and frontier trends in this field. Conclusion: This study is the first to use bibliometric methods to explore the hotspots and cutting-edge issues in the application of infrared imaging technology in the field of acupuncture. It offers a fresh perspective on infrared imaging technology research on acupuncture and gives scholars useful data to determine the field's hotspots, present state of affairs, and frontier trends.

3.
Small ; : e2402057, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751062

RESUMO

Graphene nanoscroll (GNS) is an important 1D tubular form of graphene-derivative materials, which has garnered widely attention. However, conventional fabrication methods commonly suffer from complex processing and time-consuming. Herein, with graphene oxide (GO) as a precursor, the study puts forward a facile air-plasma synthesis strategy to fabricate 3D graphene nanoscroll-nanosheet aerogels (GSSA). It is demonstrated that without using any chemical additives, a highly efficient reduction-exfoliation-scrolling process can be achieved all-in-one at room temperature within 1 s. The GNSs "grew" from 2D graphene sheets and firmly cross-linked them together, and they not only provide a shortcut path for electron transport but also act as intrinsic spacers to prevent restacking of graphene sheets. When using as an electrode material for capacitive deionization (CDI), GSSA exhibits excellent merits of salt-removal performance. These findings open a new pathway to large-scale synthesis of high-quality and high-purity GNS-based materials with promising applications in CDI and beyond.

4.
Environ Sci Pollut Res Int ; 31(21): 30353-30369, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38637485

RESUMO

Chitosan stands out as the only known polysaccharide of its kind, second only to cellulose. As the second-largest biopolymer globally, chitosan and its derivatives are extensively used in diverse areas such as metal anti-corrosion prevention, food production, and medical fields. Its benefits include environmental friendliness, non-toxicity, cost-effectiveness, and biodegradability. Notably, the use of chitosan and its derivatives has gained substantial attention and has been extensively researched in the fields of metal anti-corrosion prevention and antibacterial applications. By means of chemical modification or synergistic action, the inherent limitations of chitosan can be substantially improved, thereby enhancing its biological and physicochemical properties to meet a wider range of applications and more demanding application requirements. This article offers a comprehensive review of chitosan and its modified composite materials, focusing on the enhancement of their anticorrosion and antibacterial properties, as well as the mechanisms by which they serve as anticorrosion and antibacterial agents. Additionally, it summarizes the synthesis routes of various modification methods of chitosan and their applications in different fields, aiming to contribute to the interdisciplinary development and potential applications of chitosan in various areas.


Assuntos
Quitosana , Quitosana/química , Quitosana/farmacologia , Corrosão , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química
5.
Int J Med Sci ; 21(5): 882-895, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617000

RESUMO

Purpose: Mounting evidence indicates that psychological stress adversely affects cancer progression including tumor growth and metastasis. The aim of this study was to investigate the role of chronic stress-induced microbiome perturbation in colorectal cancer (CRC) progression. Methods: Chronic restraint stress (CRS) was used to establish the chronic stress mouse model, behavioral tests were used for the CRS model evaluation. Subcutaneous xenograft model and lung metastasis model were established to investigate the growth and metastasis of CRC promoted by CRS exposure. 16S rRNA gene sequencing and liquid chromatograph-mass spectrometer (LC-MS) were applied to observe the effects of CRS exposure on the alteration of the gut microbiome and microbial metabolites. Bioinformatics analysis and correlation analyses were applied to analyse the changes in the frequency of body mass, tumor volume, inflammatory factors, neuroendocrine hormones and metabolites of the gut microbiota. Results: In this study, we identifed that CRS exposure model was appropriately constructed by achieving expected increases in disease activity index and enhanced depressive-like behaviors. CRS exposure can promote growth and metastasis of CRC. Besides, the data indicated that CRS exposure not only increased the neuro- and immune-inflammation, but also weakened the gut mucosal immunological function. The 16s rRNA gene sequencing data showed that CRS exposure increased the abundance of g_Ruminococcaceae_UCG_014. Furthermore, the LC-MS data indicated that with only 2 exceptions of carpaine and DG (15:0/20:4(5Z,8Z,11Z,14Z)/0:0), the majority of these 24 metabolites were less abundant in CRS-exposed mice. Bioinformatics analysis and correlation analyses indicated that only Ruminoscoccaceae-UCG-014 was significantly associated with inflammation (IL-6), neurotransmission (5-HT), and microbial metabolism (PS). Conclusion: CRS exposure altered diversity, composition and metabolites of the gut microbiome, with Ruminococcaceae_UCG-014 perturbation consistently correlated to inflammatory responses, suggesting a particular role of this bacterial genus in CRC growth and metastasis.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Humanos , Animais , Camundongos , RNA Ribossômico 16S/genética , Modelos Animais de Doenças , Inflamação
6.
HIV Med ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38479841

RESUMO

OBJECTIVES: The prevention of mother-to-child transmission of HIV has been a global success. But little is known about the growth parameters of infants delivered by mothers with HIV or the drug resistance of infants with HIV in China. The study aimed to assess growth parameters and drug resistance in Chinese infants exposed to HIV. METHODS: We conducted an 18-month longitudinal follow-up study of 3283 infants (3222 without HIV; 61 with HIV) born to mothers with HIV in the Guangxi Zhuang Autonomous Region between January 2015 and December 2021. The weight and length of all participants was recorded. In addition, genetic subtypes and drug resistance analysis were performed for infants with HIV. RESULTS: Compared with infants without HIV, those with HIV had significantly lower weight/length Z-scores, except at 18 months of age. The length/age Z-scores of infants with HIV was significantly reduced, except at 1 month of age. The weight/age Z-scores of infants with HIV were significantly lower at all follow-up time points. The weight/length Z-scores of male infants without HIV were significantly lower than for female infants without HIV at all follow-up time points. Male infants without HIV had lower length/age and weight/age Z-scores than female infants at the remaining follow-up points, except at 1 month of age. Of a total of 61 infants with HIV, subtype and drug-resistance data were obtained from 37 (60.66%) samples. Infants with HIV were dominated by the CRF01_AE genotype and showed a diversity of mutation sites dominated by non-nucleoside reverse transcriptase inhibitor resistance. CONCLUSION: Our study demonstrates the growth of infants exposed to HIV in southwest China and provides detailed information on subtype distribution and drug resistance of those with HIV. Nutritional support and drug-resistance surveillance for infants exposed to HIV need to be strengthened.

7.
Sci Total Environ ; 926: 171845, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38521269

RESUMO

Biochar, which including pyrochar (PBC) and hydrochar (HBC), has been tested as a soil enhancer to improve saline soils. However, the effects of PBC and HBC application on ammonia (NH3) volatilization and dissolved organic matter (DOM) in saline paddy soils are poorly understood. In this research, marsh moss-derived PBC and HBC biochar types were applied to paddy saline soils at 0.5 % (w/w) and 1.5 % (w/w) rates to assess their impact on soil NH3 volatilization and DOM using a soil column experiment. The results revealed that soil NH3 volatilization significantly increased by 56.1 % in the treatment with 1.5 % (w/w) HBC compared to the control without PBC or HBC. Conversely, PBC and the lower application rate of HBC led to decrease in NH3 volatilization ranging from 2.4 % to 12.1 %. Floodwater EC is a dominant factor in NH3 emission. Furthermore, the fluorescence intensities of the four fractions (all humic substances) were found to be significantly higher in the 1.5 % (w/w) HBC treatment applied compared to the other treatments, as indicated by parallel factor analysis modeling. This study highlights the potential for soil NH3 losses and DOM leaching in saline paddy soils due to the high application rate of HBC. These findings offer valuable insights into the effects of PBC and HBC on rice paddy saline soil ecosystems.

8.
Front Pharmacol ; 15: 1343819, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549669

RESUMO

Background: Kidney renal clear cell carcinoma (KIRC) is a common and clinically significant subtype of kidney cancer. A potential therapeutic target in KIRC is disulfidptosis, a novel mode of cell death induced by disulfide stress. The aim of this study was to develop a prognostic model to explore the clinical significance of different disulfidptosis gene typings from KIRC. Methods: A comprehensive analysis of the chromosomal localization, expression patterns, mutational landscape, copy number variations, and prognostic significance of 10 disulfide death genes was conducted. Patients were categorized into distinct subtypes using the Non-negative Matrix Factorization (NMF) typing method based on disulfidptosis gene expression patterns. Weighted Gene Co-expression Network Analysis (WGCNA) was used on the KIRC dataset to identify differentially expressed genes between subtype clusters. A risk signature was created using LASSO-Cox regression and validated by survival analysis. An interaction between risk score and immune cell infiltration, tumor microenvironment characteristics and pathway enrichment analysis were investigated. Results: Initial findings highlight the differential expression of specific DRGs in KIRC, with genomic instability and somatic mutation analysis revealing key insights into their role in cancer progression. NMF clustering differentiates KIRC patients into subgroups with distinct survival outcomes and immune profiles, and hierarchical clustering identifies gene modules associated with key biological and clinical parameters, leading to the development of a risk stratification model (LRP8, RNASE2, CLIP4, HAS2, SLC22A11, and KCTD12) validated by survival analysis and predictive of immune infiltration and drug sensitivity. Pathway enrichment analysis further delineates the differential molecular pathways between high-risk and low-risk patients, offering potential targets for personalized treatment. Lastly, differential expression analysis of model genes between normal and KIRC cells provides insights into the molecular mechanisms underlying KIRC, highlighting potential biomarkers and therapeutic targets. Conclusion: This study contributes to the understanding of KIRC and provides a potential prognostic model using disulfidptosis gene for personalized management in KIRC patients. The risk signature shows clinical applicability and sheds light on the biological mechanisms associated with disulfide-induced cell death.

9.
ACS Appl Mater Interfaces ; 16(12): 14742-14749, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38483824

RESUMO

The sluggish kinetics of the oxygen evolution reaction (OER) always results in a high overpotential at the anode of water electrolysis and an excessive electric energy consumption, which has been a major obstacle for hydrogen production through water electrolysis. In this study, we present a CoNi-LDH/Fe MOF/NF heterostructure catalyst with nanoneedle array morphology for the OER. In 1.0 M KOH solution, the heterostructure catalyst only required overpotentials of 275 and 305 mV to achieve high current densities of 500 and 1000 mA/cm2 for OER, respectively. The catalytic activities are much higher than those of the reference single-component CoNi-LDH/NF and Fe MOF/NF catalysts. The improved catalytic performance of the heterostructure catalyst can be ascribed to the synergistic effect of CoNi-LDH and Fe MOF. In particular, when the anodic OER is replaced with the urea oxidation reaction (UOR), which has a relatively lower thermodynamic equilibrium potential and is expected to reduce the cell voltage, the overpotentials required to achieve the same current densities can be reduced by 80 and 40 mV, respectively. The cell voltage required to drive overall urea splitting (OUS) is only 1.55 V at 100 mA/cm2 in the Pt/C/NF||CoNi-LDH/Fe MOF/NF two-electrode electrolytic cell. This value is 60 mV lower compared with that required for overall water splitting (OWS). Our results indicate that a reasonable construction of a heterostructure catalyst can significantly give rise to higher electrocatalytic performance, and using UOR to replace the anodic OER of the OWS can greatly reduce the electrolytic energy consumption.

10.
J Exp Clin Cancer Res ; 43(1): 46, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342894

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) poses a significant health burden in specific regions of Asia, and some of NPC patients have bone metastases at the time of initial diagnosis. Bone metastasis can cause pathologic fractures and pain, reducing patients' quality of life, and is associated with worse survival. This study aims to unravel the complex role of insulin-like growth factor 1 receptor (IGF-1R) in NPC bone metastasis, offering insights into potential therapeutic targets. METHODS: We assessed IGF-1R expression in NPC cells and explored its correlation with bone metastasis. Experiments investigated the impact of osteoclast-secreted IGF-1 on the IGF-1R/AKT/S6 pathway in promoting NPC cell proliferation within the bone marrow. Additionally, the reciprocal influence of tumor-secreted Granulocyte-macrophage colony-stimulating factor (GM-CSF) on osteoclast differentiation and bone resorption was examined. The effects of IGF-1 neutralizing antibody, IGF-1R specific inhibitor (NVP-AEW541) and mTORC inhibitor (rapamycin) on nasopharyngeal carcinoma bone metastasis were also explored in animal experiments. RESULTS: Elevated IGF-1R expression in NPC cells correlated with an increased tendency for bone metastasis. IGF-1, secreted by osteoclasts, activated the IGF-1R/AKT/S6 pathway, promoting NPC cell proliferation in the bone marrow. Tumor-secreted GM-CSF further stimulated osteoclast differentiation, exacerbating bone resorption. The IGF-1 neutralizing antibody, NVP-AEW541 and rapamycin were respectively effective in slowing down the rate of bone metastasis and reducing bone destruction. CONCLUSION: The intricate interplay among IGF-1R, IGF-1, and GM-CSF highlights potential therapeutic targets for precise control of NPC bone metastasis, providing valuable insights for developing targeted interventions.


Assuntos
Neoplasias Ósseas , Reabsorção Óssea , Neoplasias Nasofaríngeas , Animais , Humanos , Carcinoma Nasofaríngeo/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like I/uso terapêutico , Osteoclastos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Qualidade de Vida , Linhagem Celular Tumoral , Neoplasias Nasofaríngeas/patologia , Sirolimo/farmacologia , Anticorpos Neutralizantes
11.
Commun Biol ; 7(1): 114, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242964

RESUMO

The naturally occurring bisexual cone of gymnosperms has long been considered a possible intermediate stage in the origin of flowers, but the mechanisms governing bisexual cone formation remain largely elusive. Here, we employed transcriptomic and DNA methylomic analyses, together with hormone measurement, to investigate the molecular mechanisms underlying bisexual cone development in the conifer Picea crassifolia. Our study reveals a "bisexual" expression profile in bisexual cones, especially in expression patterns of B-class, C-class and LEAFY genes, supporting the out of male model. GGM7 could be essential for initiating bisexual cones. DNA methylation reconfiguration in bisexual cones affects the expression of key genes in cone development, including PcDAL12, PcDAL10, PcNEEDLY, and PcHDG5. Auxin likely plays an important role in the development of female structures of bisexual cones. This study unveils the potential mechanisms responsible for bisexual cone formation in conifers and may shed light on the evolution of bisexuality.


Assuntos
Picea , Minorias Sexuais e de Gênero , Traqueófitas , Humanos , Filogenia , Bissexualidade , Picea/genética , Picea/metabolismo , Metilação de DNA , Traqueófitas/genética
12.
Heliyon ; 10(1): e23552, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38169984

RESUMO

The high prevalence of depressive disorders in individuals with cancer and their contribution to tumour progression is a topic that is gradually gaining attention. Recent evidence has shown that there are prominent connections between immune gene variants and mood disorders. The homeostasis of the tumour immune microenvironment (TIME) and the infiltration and activation of immune cells play a very important role in the antitumour effect. In this study, we established a compound mouse model with chronic unpredictable mild stress (CUMS) and orthotopic colorectal cancer to simulate colorectal cancer (CRC) patients with depression. Using 10✕Genomics single-cell transcriptome sequencing technology, we profiled nearly 30,000 cells from tumour samples of 8 mice from the control and CUMS groups, revealed that immune cells in tumours under a chronic stress state trend toward a more immunosuppressive and exhaustive status, and described the crosstalk between the overall inflammatory environment and immunosuppressive landscape to provide mechanistic information or efficacious strategies for immune-oncology treatments in CRC with depressive disorders.

13.
Br J Cancer ; 130(5): 755-768, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228715

RESUMO

BACKGROUND: Radiotherapy is a critical treatment modality for nasopharyngeal carcinoma (NPC). However, the mechanisms underlying radiation resistance and tumour recurrence in NPC remain incompletely understood. METHODS: Oxidised lipids were assessed through targeted metabolomics. Ferroptosis levels were evaluated using cell viability, clonogenic survival, lipid peroxidation, and transmission electron microscopy. We investigated the biological functions of glutathione S-transferase mu 3 (GSTM3) in cell lines and xenograft tumours. Co-immunoprecipitation, mass spectrometry, and immunofluorescence were conducted to explore the molecular mechanisms involving GSTM3. Immunohistochemistry was performed to investigate the clinical characteristics of GSTM3. RESULTS: Ionising radiation (IR) promoted lipid peroxidation and induced ferroptosis in NPC cells. GSTM3 was upregulated following IR exposure and correlated with IR-induced ferroptosis, enhancing NPC radiosensitivity in vitro and in vivo. Mechanistically, GSTM3 stabilised ubiquitin-specific peptidase 14 (USP14), thereby inhibiting the ubiquitination and subsequent degradation of fatty acid synthase (FASN). Additionally, GSTM3 interacted with glutathione peroxidase 4 (GPX4) and suppressed GPX4 expression. Combining IR treatment with ferroptosis inducers synergistically improved NPC radiosensitivity and suppressed tumour growth. Notably, a decrease in GSTM3 abundance predicted tumour relapse and poor prognosis. CONCLUSIONS: Our findings elucidate the pivotal role of GSTM3 in IR-induced ferroptosis, offering strategies for the treatment of radiation-resistant or recurrent NPC.


Assuntos
Ferroptose , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/radioterapia , Recidiva Local de Neoplasia , Tolerância a Radiação , Ácido Graxo Sintases , Neoplasias Nasofaríngeas/patologia , Glutationa Transferase , Ubiquitina Tiolesterase , Ácido Graxo Sintase Tipo I
14.
Biotechnol Appl Biochem ; 71(2): 402-413, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38287712

RESUMO

Malonyl-CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid-derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme-engineering approach to improve the binding of acetyl-CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl-CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding-free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be -52.66 ± 0.11 kcal/mol for the wild type, -55.87 ± 0.16 kcal/mol for the S343A mutant, -60.52 ± 0.25 kcal/mol for T347W mutant, and -59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.


Assuntos
Acetil-CoA Carboxilase , Streptomyces antibioticus , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Streptomyces antibioticus/metabolismo , Acetilcoenzima A/genética , Simulação de Acoplamento Molecular , Mutação , Saccharomyces cerevisiae/metabolismo , Escherichia coli/metabolismo
15.
Chem Biol Drug Des ; 103(1): e14424, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230774

RESUMO

The acquired resistance of cancer to cisplatin (DDP) limits the efficacy of chemotherapy. The prognostic value of long noncoding RNA (lncRNA) LINC00460 has been reported in cervical cancer. However, its effect on DDP sensitivity in cervical cancer remains poorly understood. In present study, LINC00460 was screened out through bioinformatics analysis. The expression levels of mRNAs and proteins were measured by reverse transcription-quantitative PCR (RT-qPCR) or western blot analysis. The sensitivity to DDP was investigated using an CCK8 assay. Cell apoptosis was determined by flow cytometry. The differentially expressed genes that were associated with the poor prognosis of cervical cancer were screened, and their correlations with LINC00460 expression were explored using Pearson's correlation analysis. Tumor xenograft model was used to assess the effect of LINC00460 knockdown on DDP sensitivity in vivo. The interaction between miR-338-3p and LINC00460 or transforming growth factor ß-induced protein (TGFBI) was confirmed by RNA immunoprecipitation (RIP) and luciferase reporter assays. LINC00460 expression was increased in cervical cancer tissues and cells. High expression of LINC00460 was associated with dismal prognosis in cervical cancer patients. Silencing of LINC00460 increased drug sensitivity and induced apoptosis in DDP-resistant-cervical cancer cells. LINC00460 knockdown enhanced DDP sensitivity in cervical cancer cells largely by downregulating TGFBI expression. LINC00460 knockdown enhanced the sensitivity of cervical cancer to DDP in vivo, and this effect was partly mediated by the downregulation of TGFBI. LINC00460 positively regulated TGFBI expression, possibly by acting as a sponge of miR-338-3p. LINC00460 knockdown contributed to DDP sensitivity of cervical cancer by downregulating TGFBI, providing a novel mechanism underlying the acquisition of DDP sensitivity.


Assuntos
Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Neoplasias do Colo do Útero , Feminino , Humanos , Cisplatino/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/patologia , Proliferação de Células , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
16.
Fitoterapia ; 172: 105770, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056699

RESUMO

Thirteen diterpenoids (1-13), classified into four structurally diverse carbon skeletons, including 1,5-seco-kalmane (1 and 6), grayanane (2-11), kalmane (12), and rhodomollane (13), were isolated from the flowers extract of Rhododendron molle. Among them, rhodomollinols A - E (1-5) were five new diterpenoids and their structures were elucidated by extensive spectroscopic methods including HRESIMS, UV, IR, 1D and 2D NMR, as well as quantum ECD calculations. Rhodomollinol A (1) is the first representative of a 6-deoxy-1,5-seco-kalmane diterpenoid. The abnormal NMR phenomenon of the presence of only 9 carbon resonances instead of 20 carbons in the 13C NMR spectrum of 1 was observed and elucidated by the quantum NMR calculations. All diterpenoids 1-13 showed significant analgesic activities in an acetic acid-induced writhing model. It's the first time to report the analgesic activity of a rhodomollane-type diterpenoid. At a dose of 1.0 mg/kg, diterpenoids 1-3, 6, 8, 9, and 12 reduced the writhe numbers with inhibition rates over 50%, and 9 exhibited stronger analgesic activity with a writhe inhibition rate of 89.7% than that of the positive control morphine. Importantly, even at the lowest dose of 0.04 mg/kg, rhodomollinols A (1) and B (2), rhodomollein X (7), and 2-O-methylrhodojaponin VI (9) still showed more potent analgesic effects than morphine with the writhe inhibition rates of 51.8%, 48.0%, 61.7%, and 60.0%, respectively. A preliminary structure-activity relationship might provide some clues to design potential analgesics on the basis of structurally diverse Ericaceae diterpenoids.


Assuntos
Diterpenos , Rhododendron , Rhododendron/química , Estrutura Molecular , Flores/química , Analgésicos/farmacologia , Diterpenos/farmacologia , Diterpenos/química , Carbono/análise , Derivados da Morfina/análise
17.
Mar Environ Res ; 193: 106275, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992480

RESUMO

A meta-analysis was conducted to explore the effects of warming on the physiological processes of coccolithophores and diatoms by synthesizing a large number of published literatures. A total of 154 studies consisting 301 experiments were synthesized in this study. Under a projected temperature increase of 3-5 °C by IPCC AR6 at the end of this century, our results suggest that the growth and photosynthetic rate of coccolithophores were significantly enhanced by the rising temperature, while the calcification of coccolithophores was only slightly promoted. Warming also had significantly positive effects on the growth but not photosynthesis of diatoms. In comparison, the effect size of warming on the growth rate of coccolithophores was larger than that of diatoms. However, there was no significant effect of warming on either the ratio of particulate inorganic carbon to particulate organic carbon (PIC:POC) of coccolithophores or the ratio of biogenic silica to carbon (BSi:C) of diatoms. Furthermore, the results reveal latitudinal and size-specific patterns of the effect sizes of warming. For diatoms, the effects of warming on growth were more prominent in high latitudes, specifically for the Southern Hemisphere species. In addition, the effect size of warming on the small-sized diatoms was larger than that of the large-sized diatoms. For coccolithophores, the growth of the Southern Hemisphere temperate strains was significantly promoted by warming. Overall, the results based on the meta-analysis indicate that the projected warming of the end of this century will be more favor to the growth of coccolithophores than that of diatoms, thus potentially affect the competitive advantages of coccolithophores over diatoms; while the mid-to high latitude species/strains of both coccolithophores and diatoms will benefit more than their counterparts in the lower latitudes. Therefore, this study offers novel insights into predicting both the inter- and intra-group competitive advantages of diatoms and coccolithophores under the future warming climate change scenario.


Assuntos
Diatomáceas , Diatomáceas/fisiologia , Temperatura , Mudança Climática , Fotossíntese , Carbono , Fitoplâncton
18.
Bioorg Chem ; 142: 106928, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37922768

RESUMO

A systematical investigation on the chemical constituents of the flowers of Rhododendron molle (Ericaceae) led to the isolation and characterization of thirty-eight highly functionalized grayanane diterpenoids (1-38), including twelve novel analogues molleblossomins A-L (1-12). Their structures were elucidated by comprehensive methods, including 1D and 2D NMR analysis, calculated ECD, 13C NMR calculations with DP4+ probability analysis, and single crystal X-ray diffraction. Molleblossomins A (1), B (2), and E (5) are the first representatives of 2ß,3ß:9ß,10ß-diepoxygrayanane, 2,3-epoxygrayan-9(11)-ene, and 5,9-epoxygrayan-1(10),2(3)-diene diterpenoids, respectively. Molleblossomins G (7) and H (8) represent the first examples of 1,3-dioxolane-grayanane conjugates furnished with the acetaldehyde and 4-hydroxylbenzylidene acetal moieties, respectively. All grayanane diterpenoids 1-38 were screened for their analgesic activities in the acetic acid-induced writhing model, and all of them exhibited significant analgesic activities. Diterpenoids 6, 13, 14, 17, 20, and 25 showed more potent analgesic effects than morphine at a lower dose of 0.2 mg/kg, with the inhibition rates of 51.4%, 68.2%, 94.1%, 66.9%, 97.7%, and 60.0%, respectively. More importantly, even at the lowest dose of 0.04 mg/kg, rhodomollein X (14), rhodojaponin VI (20), and rhodojaponin VII (22) still significantly reduced the number of writhes in the acetic acid-induced pain model with the percentages of 61.7%, 85.8%, and 64.6%, respectively. The structure-activity relationship was summarized and might provide some hints to design novel analgesics based on the functionalized grayanane diterpenoids.


Assuntos
Diterpenos , Rhododendron , Rhododendron/química , Estrutura Molecular , Flores/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/química , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Diterpenos/química , Ácido Acético/análise
19.
BMC Med Educ ; 23(1): 936, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066596

RESUMO

BACKGROUND: The accuracy of electrocardiogram (ECG) interpretation by doctors are affected by the available clinical information. However, having a complete set of clinical details before making a diagnosis is very difficult in the clinical setting especially in the early stages of the admission process. Therefore, we developed an artificial intelligence-assisted ECG diagnostic system (AI-ECG) using natural language processing to provide screened key clinical information during ECG interpretation. METHODS: Doctors with varying levels of training were asked to make diagnoses from 50 ECGs using a common ECG diagnosis system that does not contain clinical information. After a two-week-blanking period, the same set of ECGs was reinterpreted by the same doctors with AI-ECG containing clinical information. Two cardiologists independently provided diagnostic criteria for 50 ECGs, and discrepancies were resolved by consensus or, if necessary, by a third cardiologist. The accuracy of ECG interpretation was assessed, with each response scored as correct/partially correct = 1 or incorrect = 0. RESULTS: The mean accuracy of ECG interpretation was 30.2% and 36.2% with the common ECG system and AI-ECG system, respectively. Compared to the unaided ECG system, the accuracy of interpretation was significantly improved with the AI-ECG system (P for paired t-test = 0.002). For senior doctors, no improvement was found in ECG interpretation accuracy, while an AI-ECG system was associated with 27% higher mean scores (24.3 ± 9.4% vs. 30.9 ± 10.6%, P = 0.005) for junior doctors. CONCLUSION: Intelligently screened key clinical information could improve the accuracy of ECG interpretation by doctors, especially for junior doctors.


Assuntos
Inteligência Artificial , Cardiologistas , Humanos , Estudos Transversais , Competência Clínica , Eletrocardiografia
20.
Biology (Basel) ; 12(9)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37759648

RESUMO

The ecologically important marine phytoplankton group coccolithophores have a global distribution. The impacts of ocean acidification on the cosmopolitan species Emiliania huxleyi have received much attention and have been intensively studied. However, the species-specific responses of coccolithophores and how these responses will be regulated by other environmental drivers are still largely unknown. To examine the interactive effects of irradiance and ocean acidification on the physiology of the coastal coccolithophore species Pleurochrysis carterae, we carried out a semi-continuous incubation experiment under a range of irradiances (50, 200, 500, 800 µmol photons m-2 s-1) at two CO2 concentration conditions of 400 and 800 ppm. The results suggest that the saturation irradiance for the growth rate was higher at an elevated CO2 concentration. Ocean acidification weakened the particulate organic carbon (POC) production of Pleurochrysis carterae and the inhibition rate was decreased with increasing irradiance, indicating that ocean acidification may affect the tolerating capacity of photosynthesis to higher irradiance. Our results further provide new insight into the species-specific responses of coccolithophores to the projected ocean acidification under different irradiance scenarios in the changing marine environment.

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