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1.
Cell ; 187(5): 1296-1311.e26, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38428397

RESUMO

Most membrane proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, shielding potentially large fractions of protein surface. High glycan conformational freedom hinders complete structural elucidation of glycoproteins. Computer simulations may be used to model glycosylated proteins but require hundreds of thousands of computing hours on supercomputers, thus limiting routine use. Here, we describe GlycoSHIELD, a reductionist method that can be implemented on personal computers to graft realistic ensembles of glycan conformers onto static protein structures in minutes. Using molecular dynamics simulation, small-angle X-ray scattering, cryoelectron microscopy, and mass spectrometry, we show that this open-access toolkit provides enhanced models of glycoprotein structures. Focusing on N-cadherin, human coronavirus spike proteins, and gamma-aminobutyric acid receptors, we show that GlycoSHIELD can shed light on the impact of glycans on the conformation and activity of complex glycoproteins.


Assuntos
Glicoproteínas , Simulação de Dinâmica Molecular , Humanos , Microscopia Crioeletrônica , Glicoproteínas/química , Glicosilação , Polissacarídeos/química
2.
J Biol Chem ; 300(1): 105553, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38072060

RESUMO

Proteins can spontaneously tie a variety of intricate topological knots through twisting and threading of the polypeptide chains. Recently developed artificial intelligence algorithms have predicted several new classes of topological knotted proteins, but the predictions remain to be authenticated experimentally. Here, we showed by X-ray crystallography and solution-state NMR spectroscopy that Q9PR55, an 89-residue protein from Ureaplasma urealyticum, possesses a novel 71 knotted topology that is accurately predicted by AlphaFold 2, except for the flexible N terminus. Q9PR55 is monomeric in solution, making it the smallest and most complex knotted protein known to date. In addition to its exceptional chemical stability against urea-induced unfolding, Q9PR55 is remarkably robust to resist the mechanical unfolding-coupled proteolysis by a bacterial proteasome, ClpXP. Our results suggest that the mechanical resistance against pulling-induced unfolding is determined by the complexity of the knotted topology rather than the size of the molecule.


Assuntos
Inteligência Artificial , Proteínas de Bactérias , Dobramento de Proteína , Ureaplasma urealyticum , Modelos Moleculares , Peptídeos , Proteínas de Bactérias/química , Estrutura Terciária de Proteína
3.
Mol Ther ; 31(11): 3322-3336, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37689971

RESUMO

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.


Assuntos
Anticorpos Monoclonais , Anticorpos Amplamente Neutralizantes , COVID-19 , Animais , Humanos , Camundongos , Enzima de Conversão de Angiotensina 2/genética , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais , COVID-19/terapia , Dependovirus/genética , RNA Viral , SARS-CoV-2/genética , Anticorpos Amplamente Neutralizantes/farmacologia , Anticorpos Amplamente Neutralizantes/uso terapêutico
4.
Neurosurg Rev ; 47(1): 331, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008189

RESUMO

To determine a rapid and accurate method for locating the keypoint and "keyhole" in the suboccipital retrosigmoid keyhole approach. (1) Twelve adult skull specimens were selected to locate the anatomical landmarks on the external surface of the skull.The line between the infraorbital margin and superior margin of the external acoustic meatus was named the baseline. A coordinate system was established using the baseline and its perpendicular line through the top point of diagastric groove.The perpendicular distance (x), and the horizontal distance (y) between the central point of the "keyhole" and the top point of the digastric groove in that coordinate system were measured. The method was applied to fresh cadaveric specimens and 53 clinical cases to evaluate its application value. (1) x and y were 14.20 ± 2.63 mm and 6.54 ± 1.83 mm, respectively (left) and 14.95 ± 2.53 mm and 6.65 ± 1.61 mm, respectively (right). There was no significant difference between the left and right sides of the skull (P > 0.05). (2) The operative area was satisfactorily exposed in the fresh cadaveric specimens, and no venous sinus injury was observed. (3) In clinical practice, drilling did not cause injury to venous sinuses, the mean diameter of the bone windows was 2.0-2.5 cm, the mean craniotomy time was 26.01 ± 3.46 min, and the transverse and sigmoid sinuses of 47 patients were well-exposed. We propose a "one point, two lines, and two distances" for "keyhole" localization theory, that is we use the baseline between the infraorbital margin and superior margin of the external acoustic meatus and the perpendicular line to the baseline through the top point of the digastric groove to establish a coordinate system. And the drilling point was 14.0 mm above and 6.5 mm behind the top point of the digastric groove in the coordinate system.


Assuntos
Cadáver , Cavidades Cranianas , Craniotomia , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Cavidades Cranianas/anatomia & histologia , Cavidades Cranianas/cirurgia , Craniotomia/métodos , Procedimentos Neurocirúrgicos/métodos , Idoso , Adulto Jovem , Seios Transversos/anatomia & histologia , Seios Transversos/cirurgia , Crânio/anatomia & histologia , Crânio/cirurgia
5.
Brief Bioinform ; 22(1): 474-484, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31885044

RESUMO

BACKGROUND: With the increasing development of biotechnology and information technology, publicly available data in chemistry and biology are undergoing explosive growth. Such wealthy information in these resources needs to be extracted and then transformed to useful knowledge by various data mining methods. However, a main computational challenge is how to effectively represent or encode molecular objects under investigation such as chemicals, proteins, DNAs and even complicated interactions when data mining methods are employed. To further explore these complicated data, an integrated toolkit to represent different types of molecular objects and support various data mining algorithms is urgently needed. RESULTS: We developed a freely available R/CRAN package, called BioMedR, for molecular representations of chemicals, proteins, DNAs and pairwise samples of their interactions. The current version of BioMedR could calculate 293 molecular descriptors and 13 kinds of molecular fingerprints for small molecules, 9920 protein descriptors based on protein sequences and six types of generalized scale-based descriptors for proteochemometric modeling, more than 6000 DNA descriptors from nucleotide sequences and six types of interaction descriptors using three different combining strategies. Moreover, this package realized five similarity calculation methods and four powerful clustering algorithms as well as several useful auxiliary tools, which aims at building an integrated analysis pipeline for data acquisition, data checking, descriptor calculation and data modeling. CONCLUSION: BioMedR provides a comprehensive and uniform R package to link up different representations of molecular objects with each other and will benefit cheminformatics/bioinformatics and other biomedical users. It is available at: https://CRAN.R-project.org/package=BioMedR and https://github.com/wind22zhu/BioMedR/.


Assuntos
Biologia Computacional/métodos , Sistemas de Gerenciamento de Base de Dados , Gerenciamento de Dados/métodos , Bases de Dados de Compostos Químicos , Bases de Dados Genéticas , Humanos
6.
Drug Dev Res ; 84(1): 36-44, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36461611

RESUMO

Prostate cancer is a male malignant tumor disease with high incidence and mortality. This study was designed to explore the effects of ulinastatin (UTI) on the malignant progression of prostate cancer and its relevant mechanism of action. Human prostate cancer cell line PC-3 was applied to investigate the anticancer activity of UTI. PC-3 cells were treated with increasing concentrations (400, 800, and 1600 U/ml) of UTI. Cell proliferation, migration, invasion, and apoptosis were determined by cell counting kit-8 (CCK-8), colony formation, wound-healing, Transwell assay, and flow cytometry analysis, respectively. The expression level of corresponding proteins was detected by western blot. In addition, PC-3 cells were pretreated with RhoA agonist CN03 (1 µg/ml) or NLRP3 agonist nigericin (10 µM) before UTI treatment, and the cellular behaviors above were detected again. It was demonstrated that UTI significantly suppressed cell proliferation, migration, and invasion but promoted apoptosis in PC-3 cells in a concentration-dependent manner. Meanwhile, UTI could block RhoA/ROCK/NLRP3 inflammasome pathway in PC-3 cells, and the activation of RhoA or NLRP3 inflammasome partly weakened the impacts of UTI on cell proliferation, migration, and apoptosis in PC-3 cells, respectively. In summary, our study demonstrated the antitumor activity of UTI against prostate cancer by regulating RhoA/NLRP3 inflammasome pathway, providing a promising candidate drug for the therapeutic treatment of prostate cancer.


Assuntos
Inflamassomos , Neoplasias da Próstata , Masculino , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Movimento Celular , Neoplasias da Próstata/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Proteína rhoA de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/farmacologia , Proteína rhoA de Ligação ao GTP/uso terapêutico
7.
Mol Cancer ; 21(1): 52, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35164788

RESUMO

Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs. Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.


Assuntos
Inteligência Artificial , Neoplasias , Adenosina/química , Descoberta de Drogas , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Prognóstico
8.
Prostate ; 82(15): 1415-1421, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35860907

RESUMO

BACKGROUND: At present, standardized parameters for quantitatively evaluating 68 Ga-PSMA-PET/CT outcomes when diagnosing lymph node metastasis in prostate cancer patients are lacking. Inflammatory hematological biomarkers offer value as robust predictors of certain cancer-related outcomes. The present study was thus developed to explore approaches to improving the utility of 68 Ga-PSMA-PET/CT for diagnosing lymph node metastasis through the combined evaluation of inflammatory hematological markers in prostate cancer patients. METHODS: Pretreatment patient details including age, initial TPSA levels, hematological findings, biopsy pathology results (Gleason score and ISUP grouping), radical pathology results, and imaging details were collected. Optimal cutoff values for each predictor then being determined based upon Youden's index, with univariate and multivariate analyses were then used to identify independent predictors of lymph node metastasis and used to construct a nomogram. RESULT: Independent predictors of lymph node metastasis in this patient cohort included SUVmax (odds ratio [OR]: 30.549, 95% confidence interval [CI]: 10.855-85.973, p < 0.001), neutrophil-lymphocyte ratio (OR:8.221, 95%CI: 1.335-50.614, p = 0.023), platelet-lymphocyte ratio (OR:8.221, 95% CI: 1.335-50.614, p = 0.023), initial TPSA (OR:2.761, 95% CI: 1.132-6.733, p = 0.026), and clinical T-stage (T3 vs. T2, OR:11.332, 95% CI:3.929-32.681, p < 0.001; T4 vs. T2, OR:9.101, 95% CI:1.962-42.213, p = 0.005), with corresponding optimal cutoff values of 2.3 (area under the curve [AUC]: 0.873, sensitivity: 0.736, specificity: 0.902), 1.72 (AUC: 0.558, sensitivity: 0.529, specificity: 0.643), 83.305 (AUC: 0.651, sensitivity: 0.299, specificity: 0.979), and 21.875 (AUC: 0.672, sensitivity: 0.736, specificity: 0.601). Subsequent nomogram construction was associated with good predictive ability, with a C-index of 0.887(95% CI: 0.793-0.981) and an AUC of 0.924 (95% CI: 0.882-0.965). CONCLUSION: SUVmax, the neutrophil-lymphocyte ratio, the platelet-lymphocyte ratio, initial TPSA, and clinical T-stage represent valuable independent predictors of lymph node metastasis in prostate cancer patients, offering an opportunity to further optimize lymph node staging for these patients.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Linfócitos/patologia , Masculino , Estadiamento de Neoplasias , Neutrófilos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos Retrospectivos
9.
Eur J Nucl Med Mol Imaging ; 49(8): 2821-2832, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34860277

RESUMO

PURPOSE: Growing evidence proved the efficacy of multi-parametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided targeted biopsy (TB) in prostate cancer (PCa) diagnosis, but there is no direct comparison between mpMRI-TB and PSMA PET/CT-TB. Gastrin-releasing peptide receptor (GRPR) is highly expressed in PCa, which can compensate for the unstable expression of PSMA in PCa. Therefore, we designed a study to compare the efficiency of mpMRI-TB, dual-tracer (GRPR and PSMA) PET/CT-TB, systematic biopsy, and combined biopsy for the diagnosis of prostate cancer. METHODS: One hundred twelve suspicious PCa patients were enrolled from September 2020 to June 2021. Patients with anyone of positive dual-tracer PET/CT or mpMRI underwent TB, and all enrolled patients underwent systematic biopsy (SB) after TB. The primary outcome was the detection rates of PCa in different biopsy strategies. Secondary outcomes were the performance of three imaging methods, omission diagnostic rates, and upgrading and downgrading of biopsy samples relative to those of prostatectomy specimens in different biopsy strategies. McNemar's tests and Bonferroni correction in multiple comparisons were used to compare the primary and secondary outcomes. RESULTS: In 112 men, clinically significant PCa (grade group[GG] ≥ 2) accounted for 34.82% (39/112), and nonclinically significant PCa (GG = 1) accounted for 4.46% (5/112). 68 Ga-PSMA PET/CT-TB achieved higher PCa detection rate (69.77%) and positive ratio of biopsy cores (0.44) compared with SB (39.29% and 0.12) and mpMRI-TB (36.14% and 0.23), respectively (P < 0.005). Dual-tracer PET/CT screen out patients for avoiding 52.67% (59/112) unnecessary biopsy, whereas dual-tracer PET/CT-TB plus SB achieved high detection rate (77.36%) without misdiagnosis of csPCa. CONCLUSION: Dual-tracer PET/CT might screen patients for avoiding unnecessary biopsy. Dual-tracer PET/CT-TB plus SB might be a more effective and promising strategy for the definite diagnosis of clinically significant PCa than mpMRI-TB.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Biópsia , Radioisótopos de Gálio , Humanos , Biópsia Guiada por Imagem , Masculino , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/patologia , Receptores da Bombesina
10.
Bioorg Med Chem Lett ; 76: 128993, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36130662

RESUMO

As a member of the nuclear receptor superfamily, the farnesoid X receptor (FXR) is a bile acid activated transcription factor. FXR is involved in many important metabolic processes and serves as a promising therapeutic target for nonalcoholic steatohepatitis (NASH). Since discovered, the first non-steroidal FXR agonist GW4064 has been widely used to explore the biological functions of FXR, however, the low pharmacokinetic limited its further clinical application. In current study, we designed a series of substituted isothiazoles as new FXR agonists. Among them, five compounds exhibited better FXR agonistic activity than GW4064. Specially, the most potent compound S5 possessed better pharmacokinetic profile and in vivo potency than lead compound.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Receptores Citoplasmáticos e Nucleares , Humanos , Ácidos e Sais Biliares/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fatores de Transcrição , Regulação da Expressão Gênica
11.
Bioorg Med Chem Lett ; 65: 128717, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35390450

RESUMO

Tumor angiogenesis is an important biological process involved in the proliferation and migration of endothelial cells, regulated by Ang/Tie-2 signaling pathways, which is essential for tumor growth and metastasis. Therefore, blocking Ang/Tie-2 signaling pathways is a promising anti-angiogenic strategy for tumor treatment. 2,5-Diketopiperazines (DKPs) are a kind of bioactive compounds derived from marine fungi and they present a wide spectrum of pharmacological properties, particularly in the field of cancer treatment. Herein, a DKP marine natural product, Cryptoechinuline D (Cry D) was applied to structural modification and twelve derivatives were synthesized. Among which, compound 5 showed significant inhibitory activity against HUVECs with an IC50 value of 12.6 µmol/L, which weakened the proliferation, migration and invasion of HUVECs by inhibiting the Ang2/Tie-2 signaling pathway. The results of these evaluations indicated that compound 5 might be a promising anti-angiogeneic agent and worth further optimization and development for cancer therapy.


Assuntos
Produtos Biológicos , Neoplasias , Inibidores da Angiogênese/farmacologia , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo
12.
J Nat Prod ; 85(2): 375-383, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35171609

RESUMO

Eight new 2,6-disubstituted piperidin-3-ol alkaloids (1-8), featuring a C10 unsaturated alkyl side chain, together with three previously reported analogues (9-11) were isolated from the leaves of medicinal plant Microcos paniculata. Their structures and absolute configurations were elucidated unambiguously by means of 1D and 2D NMR spectroscopic data analysis, modified Mosher's method, Snatzke's method, and quantum chemical electronic circular dichroism (ECD) calculations, as well as single-crystal X-ray crystallography. The isolates were evaluated for their antiangiogenic effects on human umbilical vein endothelial cells (HUVECs). Compound 2 displayed an inhibitory effect on tube formation of HUVECs in a concentration-dependent manner.


Assuntos
Alcaloides , Malvaceae , Alcaloides/química , Dicroísmo Circular , Células Endoteliais , Humanos , Estrutura Molecular , Piperidinas/química , Piperidinas/farmacologia , Folhas de Planta/química
13.
J Clin Lab Anal ; 36(4): e24287, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35170077

RESUMO

BACKGROUND: Study of the molecular biological characteristics of chronic neutrophilic leukemia complicated with plasma cell disorder (CNL-PCD) and lymphocytic proliferative disease (CNL-LPD). METHODS: The clinical data of a patient with chronic neutrophilic leukemia complicated with monoclonal gammopathy of undetermined significance (CNL-MGUS) in our hospital were reviewed, and the Chinese and/or English literature about CNL-PCD and CNL-LPD in PubMed and the Chinese database CNKI in the past 10 years was searched to analyze the molecular biological characteristics of this disease. RESULTS: A 73-year-old male had persistent leukocytosis for 18 months. The white blood cell count was 46.77 × 109/L and primarily composed of mature neutrophils; hemoglobin: 77 g/L; platelet count: 189 × 109/L. Serum immunofixation electrophoresis showed IgG-λ monoclonal M protein. A CT scan showed splenomegaly. Next-generation sequencing (NGS) showed that CSF3R T618I, ASXL1 and RUNX1 mutations were positive. It was diagnosed as CNL-MGUS. We summarized 10 cases of CNL-PCD and 1 case of CNL-LPD who underwent genetic mutation detection reported in the literature. The CSF3R mutational frequency (7/11, 63.6%) was lower than that of isolated CNL. The ASXL1 mutations were all positive (3/3), which may represent a poor prognostic factor. The SETBP1 mutation may promote the progression of CNL-PCD. We also found JAK2, RUNX1, NRAS, etc. in CNL-PCD. CONCLUSIONS: Chronic neutrophilic leukemia may be more inclined to coexist with plasma cell disorder. The CSF3R mutation in CNL-PCD is still the most common mutated gene compared with isolated CNL. Mutations in SETBP1 and ASXL1 may be poor prognostic factors for CNL-PCD.


Assuntos
Leucemia Neutrofílica Crônica , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Idoso , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Humanos , Leucemia Neutrofílica Crônica/complicações , Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/genética , Masculino , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/genética , Mutação/genética , Paraproteinemias/complicações , Paraproteinemias/genética
14.
Entropy (Basel) ; 24(1)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35052154

RESUMO

Forest fire detection from videos or images is vital to forest firefighting. Most deep learning based approaches rely on converging image loss, which ignores the content from different fire scenes. In fact, complex content of images always has higher entropy. From this perspective, we propose a novel feature entropy guided neural network for forest fire detection, which is used to balance the content complexity of different training samples. Specifically, a larger weight is given to the feature of the sample with a high entropy source when calculating the classification loss. In addition, we also propose a color attention neural network, which mainly consists of several repeated multiple-blocks of color-attention modules (MCM). Each MCM module can extract the color feature information of fire adequately. The experimental results show that the performance of our proposed method outperforms the state-of-the-art methods.

15.
BMC Genomics ; 22(1): 750, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663228

RESUMO

BACKGROUND: Chloroplast transfer RNAs (tRNAs) can participate in various vital processes. Gymnosperms have important ecological and economic value, and they are the dominant species in forest ecosystems in the Northern Hemisphere. However, the evolution and structural changes in chloroplast tRNAs in gymnosperms remain largely unclear. RESULTS: In this study, we determined the nucleotide evolution, phylogenetic relationships, and structural variations in 1779 chloroplast tRNAs in gymnosperms. The numbers and types of tRNA genes present in the chloroplast genomes of different gymnosperms did not differ greatly, where the average number of tRNAs was 33 and the frequencies of occurrence for various types of tRNAs were generally consistent. Nearly half of the anticodons were absent. Molecular sequence variation analysis identified the conserved secondary structures of tRNAs. About a quarter of the tRNA genes were found to contain precoded 3' CCA tails. A few tRNAs have undergone novel structural changes that are closely related to their minimum free energy, and these structural changes affect the stability of the tRNAs. Phylogenetic analysis showed that tRNAs have evolved from multiple common ancestors. The transition rate was higher than the transversion rate in gymnosperm chloroplast tRNAs. More loss events than duplication events have occurred in gymnosperm chloroplast tRNAs during their evolutionary process. CONCLUSIONS: These findings provide novel insights into the molecular evolution and biological characteristics of chloroplast tRNAs in gymnosperms.


Assuntos
Cycadopsida , Ecossistema , Cloroplastos/genética , Cycadopsida/genética , Filogenia , RNA de Transferência/genética
16.
J Environ Manage ; 282: 111951, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33461088

RESUMO

Algal organic matter (AOM) and natural organic matter (NOM) from a typical eutrophic lake were comprehensively investigated in terms of their physico-chemical property, components and disinfection byproduct formation potentials (DBPFPs). The relationships between specific chemical properties of AOM and NOM with their corresponding DBPFPs were further evaluated during chlorination. Results indicated that AOM had lower specific UV absorbance (SUVA) but richer organic nitrogen contents than NOM. Fluorescence excitation emission matrix spectroscopy further demonstrated that AOM were chiefly composed of aromatic protein-like and soluble microbial byproduct-like matters, while NOM were mainly contributed from humic acid-like and soluble microbial byproduct-like substances. Although the molecular weight (MW) distribution of AOM and NOM showed no significant difference, size-exclusion chromatography with organic carbon as well as organic nitrogen detection (LC-OCD-OND) revealed that AOM were concentrated with the fraction of building blocks and NOM had higher concentrations of biopolymers and humics (HS). Moreover, AOM displayed higher DBPFPs than NOM, especially for nitrogenous DBPFP (N-DBPFP). MW < 1 kDa fractions both in AOM and NOM contributed the largest proportion to the formation of carbonaceous disinfection byproducts (C-DBPs). In addition, Pearson correlation analysis showed that bulk parameter SUVA was significantly relevant to the formation potentials of trihalomethane both in AOM and NOM, but was ineffective for carbonaceous DBPFP (C-DBPFP) prediction. Dissolved organic nitrogen contents in biopolymer and HS characterized by LC-OCD-OND had strong correlations with N-DBPFPs from AOM and NOM, indicating that LC-OCD-OND quantitative analysis could improve the prediction accuracy of the DBP formation than bulk parameters during NOM and AOM chlorination.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Desinfecção , Halogenação , Nitrogênio/análise , Trialometanos/análise , Poluentes Químicos da Água/análise
17.
J Cell Mol Med ; 24(21): 12355-12367, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32961025

RESUMO

Diabetes is a disorder of glucose metabolism, and over 90% are type 2 diabetes. Diabetic cardiomyopathy (DCM) is one of the type 2 diabetes complications, usually accompanied by changes in myocardial structure and function, together with cardiomyocyte apoptosis. Our study investigated the effect of curcumin on regulating oxidative stress (OS) and apoptosis in DCM. In vivo, diabetes was induced in an experimental rat model by streptozoticin (STZ) together with high-glucose and high-fat (HG/HF) diet feeding. In vitro, H9c2 cardiomyocytes were cultured with high-glucose and saturated free fatty acid palmitate. Curcumin was orally or directly administered to rats or cells, respectively. Streptozoticin -induced diabetic rats showed metabolism abnormalities and elevated markers of OS (superoxide dismutase [SOD], malondialdehyde [MDA], gp91phox , Cyt-Cyto C), enhanced cell apoptosis (Bax/Bcl-2, Cleaved caspase-3, TUNEL-positive cells), together with reduced Akt phosphorylation and increased Foxo1 acetylation. Curcumin attenuated the myocardial dysfunction, OS and apoptosis in the heart of diabetic rats. Curcumin treatment also enhanced phosphorylation of Akt and inhibited acetylation of Foxo1. These results strongly suggest that apoptosis was increased in the heart of diabetic rats, and curcumin played a role in diabetic cardiomyopathy treatment by modulating the Sirt1-Foxo1 and PI3K-Akt pathways.


Assuntos
Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Glicemia/metabolismo , Sobrevivência Celular , Diabetes Mellitus Experimental , Masculino , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuína 1/metabolismo
18.
J Org Chem ; 85(16): 10884-10890, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32806090

RESUMO

Five novel bisindole alkaloids, hunzeylanines A-E (1-5), with an unprecedented skeleton were isolated from the roots of Hunteria zeylanica. Compounds 1-5 represent the first examples of akuammine-pleioarpamine-type bisindole alkaloids fused with a dihydropyran unit. Their structures including absolute configurations were established through comprehensive spectroscopic data analyses and computational calculation methods. The plausible biogenetic pathway of 1 was also proposed. Alkaloids 1 and 2 displayed moderate cytotoxicity toward three human cancer cell lines (MDA-MB-231, AV3, and Huh7).


Assuntos
Alcaloides , Apocynaceae , Humanos , Alcaloides Indólicos/farmacologia , Estrutura Molecular , Raízes de Plantas , Análise Espectral
19.
BMC Womens Health ; 20(1): 52, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164632

RESUMO

BACKGROUND: Acute water intoxication after hysteroscopy is a rare, life-threatening condition, often accompanied with delayed diagnosis owing to masked symptoms because of general anesthesia. CASE PRESENTATION: Herein we presented a 39-year-old female who presented with cardiac arrest after hysteroscopic myomectomy because of acute water intoxication and survived after extracorporeal membrane oxygenation, continuous venous-venous hemofiltration, and aggressive high sodium fluid resuscitation. CONCLUSION: Failure to recognize and treat this condition appropriately may lead to potentially lethal cardiopulmonary complications.


Assuntos
Oxigenação por Membrana Extracorpórea , Parada Cardíaca/etiologia , Hipocinesia/diagnóstico por imagem , Complicações Intraoperatórias , Edema Pulmonar/diagnóstico por imagem , Irrigação Terapêutica/efeitos adversos , Miomectomia Uterina/efeitos adversos , Neoplasias Uterinas/cirurgia , Intoxicação por Água/complicações , Adulto , Terapia de Substituição Renal Contínua/métodos , Ecocardiografia , Feminino , Humanos , Histeroscopia , Gravidez , Tomografia Computadorizada por Raios X , Água , Intoxicação por Água/terapia
20.
Molecules ; 25(4)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093390

RESUMO

This paper constructs planar-type graphene thin film current collectors for proton exchange membrane fuel cells (PEMFCs). The present planar-type current collector adopts FR-4 as the substrate and coats a copper thin film using thermal evaporation for the electric-conduction layer. A graphene thin film is then coated onto the current collector to prevent corrosion due to electrochemical reactions. Three different coating techniques are conducted and compared: Spin coating, RF magnetron sputtering, and screen printing. The corrosion rates and surface resistances are tested and compared for the different coating techniques. Single cell PEMFCs with the developed current collectors are assembled and tested. A PEMFC module with two cells is also designed and constructed. The cell performances are measured to investigate the device feasibility.


Assuntos
Fontes de Energia Bioelétrica , Grafite/química , Membranas Artificiais , Prótons
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