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1.
BMC Cardiovasc Disord ; 24(1): 147, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448835

RESUMO

OBJECTIVE: Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period. METHODS: The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine. CONCLUSION: Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.


Assuntos
Anestésicos , Delírio do Despertar , Hipnóticos e Sedativos , Humanos , Anestésicos/uso terapêutico , Bradicardia , Dexmedetomidina , Delírio do Despertar/prevenção & controle , Hipnóticos e Sedativos/uso terapêutico , Midazolam , Propofol , Solução Salina , Sevoflurano , Metanálise em Rede
2.
Gerontology ; 70(2): 165-172, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37995668

RESUMO

INTRODUCTION: The relationship among physiologic reserve, intrinsic capacity, and physical resilience has not been examined, and a conceptual model that includes these key determinants of healthy ageing is needed. This study aimed to test a conceptual model using real-world data to determine the relationships among physiologic reserve, intrinsic capacity, physical resilience, and clinical outcomes. METHODS: This longitudinal study was conducted at a 1,343-bed tertiary-care medical centre. Patients were eligible for inclusion if they were 65 years of age or older and able to communicate independently. Demographic factors, cumulative illness rating scale for geriatrics [CIRS-G] (assessing physiologic reserve), intrinsic capacity, physical resilience instrument for older adults [PRIFOR] (assessing physical resilience), and clinical frailty scale [CFS] were collected at admission. The CFS and EuroQoL 5-dimension 3-level questionnaire [EQ5D] were administered at discharge. RESULTS: The mean age of the 413 patients was 76.34 ± 6.72 (52.5% female). Two conceptual models were identified and supported. Specifically, the path coefficients in the two models showed that the CIRS-G had diverse associations with each intrinsic capacity domain, and that all intrinsic capacity domains (except vitality) were significantly associated with PRIFOR. Moreover, PRIFOR was significantly associated with follow-up CFS, baseline control, and EQ5D scores. CONCLUSION: Physiologic reserve positively correlated with the cognitive and locomotive domains of intrinsic capacity. Moreover, older patients with better intrinsic capacity may have improved physical resilience, which may lead to better clinical outcomes. Efforts to improve the intrinsic capacity and physical resilience of older patients are necessary to promote healthy ageing.


Assuntos
Resiliência Psicológica , Humanos , Feminino , Idoso , Masculino , Estudos Longitudinais , Análise de Classes Latentes
3.
Skin Res Technol ; 30(1): e13548, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38174788

RESUMO

BACKGROUND: Excessive inflammation may cause tissue damage and disrupt the function of the skin barrier. Hyaluronic acid (HA), an endogenous component, was found to regulate multiple inflammatory factors for skin health. This work aims to further enhance its efficacy by grafting amino acid onto its molecule. METHODS: Glutamic acid (Glu) was selected as the ligand to react with low-molecular-weight HA. Fibroblast tests and a 3D skin model were used to investigate the anti-inflammation efficacy of HA-Glu. RESULTS: For IL-1α, IL-6 and TNF-α, the grafted compound presents stronger inhibition ability versus native HA. Moreover, HA-Glu could promote the repair of damaged skin by improving the compactness of the stratum corneum and increasing the thickness of the living cell layer. CONCLUSION: The application of HA-Glu compound in skin care formulas would be effective to alleviate inflammation-induced skin symptoms and skin aging.


Assuntos
Ácido Glutâmico , Ácido Hialurônico , Humanos , Ácido Hialurônico/farmacologia , Ácido Hialurônico/uso terapêutico , Ácido Hialurônico/química , Ácido Glutâmico/metabolismo , Pele/metabolismo , Inflamação/tratamento farmacológico , Fibroblastos/metabolismo
4.
Angew Chem Int Ed Engl ; 63(27): e202401669, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38651244

RESUMO

cis-Prenyltransferases (cis-PTs) catalyze the sequential head-to-tail condensation of isopentenyl diphosphate (IPP) to allylic diphosphates, producing mixed E-Z prenyl diphosphates of varying lengths; however, the specific enzymes synthesizing cis-C25 prenyl diphosphates have not been identified. Herein, we present the discovery and characterization of a cis-geranylfarnesyl diphosphate synthase (ScGFPPS) from Streptomyces clavuligerus. This enzyme demonstrates high catalytic proficiency in generating six distinct cis-polyisoprenoids, including three C25 and three C20 variants. We determined the crystal structure of ScGFPPS. Additionally, we unveil the crystal structure of nerylneryl diphosphate synthase (NNPS), known for synthesizing an all-cis-C20 polyisoprenoid. Comparative structural analysis of ScGFPPS and NNPS has identified key differences that influence product specificity. Through site-directed mutagenesis, we have identified eight single mutations that significantly refine the selectivity of ScGFPPS for cis-polyisoprenoids. Our findings not only expand the functional spectrum of cis-PTs but also provide a structural comparison strategy in cis-PTs engineering.


Assuntos
Streptomyces , Streptomyces/enzimologia , Streptomyces/genética , Engenharia de Proteínas , Cristalografia por Raios X , Alquil e Aril Transferases/metabolismo , Alquil e Aril Transferases/química , Alquil e Aril Transferases/genética , Modelos Moleculares
5.
Beilstein J Org Chem ; 20: 815-822, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655553

RESUMO

Drimane-type sesquiterpenoids (DMTs) are characterized by a distinctive 6/6 bicyclic skeleton comprising the A and B rings. While DMTs are commonly found in fungi and plants, their presence in bacteria has not been reported. Moreover, the biosynthetic pathways for DMTs have been primarily elucidated in fungi, with identified P450s only acting on the B ring. In this study, we isolated and characterized three bacterial DMTs, namely 3ß-hydroxydrimenol (2), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4), from Streptomyces clavuligerus. Through genome mining and heterologous expression, we identified a cav biosynthetic gene cluster responsible for the biosynthesis of DMTs 2-4, along with a P450, CavA, responsible for introducing the C-2 and C-3 hydroxy groups. Furthermore, the substrate scope of CavA revealed its ability to hydroxylate drimenol analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria.

6.
Anal Chem ; 95(33): 12321-12328, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37527540

RESUMO

Photoinduced electron-transfer (PET) immunoassay based on a fluorescence site-specifically labeled nanobody, also called mini Quenchbody (Q-body), exhibits extraordinary sensitivity and saves much time in the homogeneous noncompetitive mode and is therefore regarded as a valuable method. However, limited by the efficiency of both quenching and dequenching of the fluorescence signal before and after antigen binding associated with the PET principle, not all original nanobodies can be used as candidates for mini Q-bodies. Herein, with the anti-quinalphos nanobody 11A (Nb-11A) as the model, we, for the first time, adopt a strategy by combining X-ray structural analysis with site-directed mutagenesis to design and produce a mutant Nb-R29W, and then successfully generate a mini Q-body by labeling with ATTO520 fluorescein. Based on this, a novel PET immunoassay is established, which exhibits a limit of detection of 0.007 µg/mL with a detection time of only 15 min, 25-fold improved sensitivity, and faster by 5-fold compared to the competitive immunoassay. Meanwhile, the recovery test of vegetable samples and validation by the standard ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) both demonstrated that the established PET immunoassay is a novel, sensitive, and accurate detection method for quinalphos. Ultimately, the findings of this work will provide valuable insights into the development of triggered PET fluorescence probes by using existing antibody resources.


Assuntos
Corantes Fluorescentes , Espectrometria de Massas em Tandem , Cromatografia Líquida , Corantes Fluorescentes/química , Imunoensaio/métodos , Antígenos , Tomografia por Emissão de Pósitrons
7.
Anal Chem ; 95(30): 11306-11315, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37428097

RESUMO

Nanobodies (Nbs) have great potential in immunoassays due to their exceptional physicochemical properties. With the immortal nature of Nbs and the ability to manipulate their structures using protein engineering, it will become increasingly valuable to understand what structural features of Nbs drive high stability, affinity, and selectivity. Here, we employed an anti-quinalphos Nb as a model to illustrate the structural basis of Nbs' distinctive physicochemical properties and the recognition mechanism. The results indicated that the Nb-11A-ligand complexes exhibit a "tunnel" binding mode formed by CDR1, CDR2, and FR3. The orientation and hydrophobicity of small ligands are the primary determinants of their diverse affinities to Nb-11A. In addition, the primary factors contributing to Nb-11A's limited stability at high temperatures and in organic solvents are the rearrangement of the hydrogen bonding network and the enlargement of the binding cavity. Importantly, Ala 97 and Ala 34 at the active cavity's bottom and Arg 29 and Leu 73 at its entrance play vital roles in hapten recognition, which were further confirmed by mutant Nb-F3. Thus, our findings contribute to a deeper understanding of the recognition and stability mechanisms of anti-hapten Nbs and shed new light on the rational design of novel haptens and directed evolution to produce high-performance antibodies.


Assuntos
Anticorpos de Domínio Único , Haptenos
8.
Histopathology ; 83(5): 798-809, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37565303

RESUMO

AIMS: Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions resulting from an intrachromosomal inversion of chromosome 11. Immunohistochemistry with an antibody directed against the C-terminus of YAP1 has shown loss of expression in YAP1-rearranged vascular neoplasms, poromas, and porocarcinomas. This study aimed to validate an anti-YAP1 C-terminal antibody as an ancillary immunohistochemical marker for the diagnosis of metaplastic thymoma. MATERIALS AND METHODS: Ten metaplastic thymomas were selected for the current study. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed to detect YAP1::MAML2 fusions. We then performed immunohistochemistry to detect YAP1 C-terminus expression in 10 metaplastic thymomas, 50 conventional thymomas (10 each of type A thymoma, type AB thymoma, type B1 thymoma, type B2 thymoma, and type B3 thymoma) and seven thymic carcinomas. RESULTS: All 10 cases showed narrow split signals with a distance of nearly two signal diameters and sometimes had false-negative results in YAP1 and MAML2 break-apart FISH (BA-FISH). Abnormal colocalized signals of the YAP1::MAML2 fusion were observed in all 10 cases using fusion FISH (F-FISH) assays. Eight of 10 cases with adequate nucleic acids were successfully sequenced and all showed YAP1::MAML2 fusions; in two cases the fusions were detected by both DNA and RNA sequencing and in six cases by RNA sequencing only. YAP1::MAML2 fusion transcripts were identified in four cases by RT-PCR. Metaplastic thymoma showed loss of YAP1 C-terminus expression in all 10 (100%) cases. All other thymic neoplasms showed retained YAP1 C-terminus expression. CONCLUSION: YAP1 C-terminus immunohistochemistry is a highly sensitive and specific ancillary marker that distinguishes metaplastic thymoma from its mimics. BA-FISH assays could not effectively detect YAP1::MAML2 fusions due to the proximity of the two genes. Loss of YAP1 C-terminus expression is a reliable surrogate for the detection of YAP1::MAML2 fusions in metaplastic thymoma.


Assuntos
Timoma , Neoplasias do Timo , Humanos , Timoma/diagnóstico , Timoma/genética , Timoma/metabolismo , Hibridização in Situ Fluorescente , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/genética , Neoplasias do Timo/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Rearranjo Gênico , Transativadores/genética
9.
Virol J ; 20(1): 10, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650505

RESUMO

BACKGROUND: To investigate the mechanism of RNA silencing suppression, the genetic transformation of viral suppressors of RNA silencing (VSRs) in Arabidopsis integrates ectopic VSR expression at steady state, which overcomes the VSR variations caused by different virus infections or limitations of host range. Moreover, identifying the insertion of the transgenic VSR gene is necessary to establish a model transgenic plant for the functional study of VSR. METHODS: Developing an endogenous AGO1-based in vitro RNA-inducing silencing complex (RISC) assay prompts further investigation into VSR-mediated suppression. Three P1/HC-Pro plants from turnip mosaic virus (TuMV) (P1/HC-ProTu), zucchini yellow mosaic virus (ZYMV) (P1/HC-ProZy), and tobacco etch virus (TEV) (P1/HC-ProTe) were identified by T-DNA Finder and used as materials for investigations of the RISC cleavage efficiency. RESULTS: Our results indicated that the P1/HC-ProTu plant has slightly lower RISC activity than P1/HC-ProZy plants. In addition, the phenomena are consistent with those observed in TuMV-infected Arabidopsis plants, which implies that HC-ProTu could directly interfere with RISC activity. CONCLUSIONS: In this study, we demonstrated the application of various plant materials in an in vitro RISC assay of VSR-mediated RNA silencing suppression.


Assuntos
Arabidopsis , Potyvirus , Interferência de RNA , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Potyvirus/genética , Nicotiana , Doenças das Plantas
10.
Hu Li Za Zhi ; 70(2): 34-45, 2023 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38532673

RESUMO

BACKGROUND: The increasing complexity of the healthcare environment in recent years highlights the importance of cultivating in head nurses the leadership and management competencies necessary to effectively handle complicated administrative tasks and lead nurses in facing various challenges. Identifying the core administrative management competencies required of head nurses and evaluating competency level using behavioral indicators are fundamental to evaluating related training outcomes. PURPOSE: This study was designed to identify the core administrative management competencies required of head nurses as well as the associated job responsibilities, tasks, behavioral evaluation indicators, work outputs, and requisite knowledge and skills. METHODS: This study was conducted in two phases using a qualitative method. The first phase identified the core administrative management competencies and their behavioral definitions. The second phase established competency-related job responsibilities, tasks, behavioral evaluation indicators, work outputs, and requisite knowledge and skills. Each phase consisted of (1) a qualitative interview (first stage) or focus group discussion (second stage) to establish the prototype content; (2) a head nurse workshop to obtain multiple perspectives to modify the prototype content; and (3) a focus group discussion to achieve consensus regarding the content. RESULTS: Nine core competencies related to head nurse administration were identified, including: strategic planning, care supervision, quality improvement, communication, crisis management, responsible leadership, evidence-based practice, digital technology application, and presentation persuasion. Corresponding to these competencies, four responsibilities and associated work tasks were identified. Finally, the related behavioral evaluation indicators, work outputs, and requisite knowledge and skills were confirmed. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results of this study may be used as the basis for head nurse administrative management training programs, while the identified behavioral evaluation indicators may be used to evaluate head nurse work performance and training outcomes. We recommend other institutions apply the results of this study and develop their own administrative core competencies and evaluation indicators for head nurses.


Assuntos
Enfermeiras e Enfermeiros , Supervisão de Enfermagem , Humanos , Competência Clínica , Consenso , Liderança , Comunicação
11.
J Am Chem Soc ; 144(48): 22067-22074, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36416740

RESUMO

Terpene cyclases (TCs), extraordinary enzymes that create the structural diversity seen in terpene natural products, are traditionally divided into two classes, class I and class II. Although the structural and mechanistic features of class I TCs are well-known, the corresponding details in class II counterparts have not been fully characterized. Here, we report the genome mining discovery and structural characterization of two class II sesquiterpene cyclases (STCs) from Streptomyces. These drimenyl diphosphate synthases (DMSs) are the first STCs shown to possess ß,γ-didomain architecture. High-resolution X-ray crystal structures of DMS from Streptomyces showdoensis (SsDMS) in complex with both a farnesyl diphosphate and Mg2+ unveiled an induced-fit mechanism, with an unprecedented Mg2+ binding mode, finally solving one of the lingering questions in class II TC enzymology. This study supports continued genome mining for novel bacterial TCs and provides new mechanistic insights into canonical class II TCs that will lead to advances in TC engineering and synthetic biology.


Assuntos
Biologia Sintética
12.
BMC Geriatr ; 22(1): 229, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313802

RESUMO

BACKGROUND: Physical resilience is known to minimize the adverse outcomes of health stressors for older people. However, validated instruments that assess physical resilience in older adults are rare. Therefore, we aimed to validate the Physical Resilience Instrument for Older Adults (PRIFOR) to fill the literature gap. METHODS: Content analysis with content validity was first carried out to generate relevant items assessing physical resilience for older adults, and 19 items were developed. Psychometric evaluation of the 19 items was then tested on 200 older adults (mean [SD] age = 76.4 [6.6] years; 51.0% women) for item properties, factor structure, item fit, internal consistency, criterion-related validity, and known-group validity. RESULTS: All 19 items had satisfactory item properties, as they were normally distributed (skewness = -1.03 to 0.38; kurtosis = -1.05 to 0.32). However, two items were removed due to substantial ceiling effects. The retained 17 items were embedded in three factors as suggested by the exploratory factor analysis (EFA) results. All items except one had satisfactory item fit statistics in Rasch model; thus, the unidimensionality was supported for the three factors on 16 items. The retained 16 items showed promising properties in known-group validity, criterion-related validity, and internal consistency (α = 0.94). CONCLUSIONS: The 16-item PRIFOR exhibits good psychometric properties. Using this instrument to measure physical resilience would be beneficial to identify factors that could protect older people from negative health consequence. With the use of the PRIFOR, intervention effects could also be evaluated. It is helpful to strengthen resilience and thereby facilitate successful aging.


Assuntos
Exame Físico , Idoso , Análise Fatorial , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
13.
Molecules ; 27(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35566196

RESUMO

The profound pharmacological properties of macrocyclic compounds have led to their development as drugs. In conformationally pre-organized ring structures, the multiple functions and stereochemical complexity provided by the macrocycle result in high affinity and selectivity of protein targets while maintaining sufficient bioavailability to reach intracellular locations. Therefore, the construction of macrocycles is an ideal choice to solve the problem of "undruggable" targets. Inspection of 68 macrocyclic drugs on the market showed that 10 of them were used to treat cancer, but this structural class still has been poorly explored within drug discovery. This perspective considers the macrocyclic compounds used for anti-tumor with different targets, their advantages and disadvantages, and the various synthetic methods of them.


Assuntos
Química Farmacêutica , Compostos Macrocíclicos , Disponibilidade Biológica , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia
14.
Hu Li Za Zhi ; 69(2): 67-79, 2022 Apr.
Artigo em Zh | MEDLINE | ID: mdl-35318634

RESUMO

BACKGROUND: In response to the promotion of long-term care policies, nurses in hospitals must not only have professional knowledge related to disease care but also be equipped with care competencies related to long-term care. PURPOSE: The purpose of this study was to explore the self-perceived competencies of nurses working in acute care facilities with regard to long-term-care and related factors. METHODS: A cross-sectional research design with quota sampling was used. The participants were recruited from registered nurses employed at a medical center in southern Taiwan, and data from 159 valid, returned questionnaires were used in the analysis. The research instruments used included the long-term care competency scale and long-term care-related knowledge, and care intention. T test, Chi-square, ANOVA, and Pearson correlation coefficient were used to examine the relationship between the targeted variables and long-term care competency. Regression analysis was used to determine the important determinants of long-term care competency. RESULTS: The average age of the participants was 30.86 years (± 3.38). Most currently worked in the internal medicine department, 93.1% were educated to the university level, 44% had worked for fewer than 5 years, and 32.7% were N3 level nurses. Long-term care competency was found to be significantly and positively correlated with gender (t = 2.06, p = .041), seniority at the facility (F = 2.49, p = .046), job satisfaction (r = .28, p < .001), and long-term care service practices (r = .227, p < .001). After the regression analysis, self-perceived long-term care competency was found to be positively related to job satisfaction and long-term care service practices. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results of this study suggest that a long-term care training should be incorporated into the regular in-service education program to improve the knowledge and attitudes of nurses with regard to older and disabled patients and to develop their professional role in long-term care. Furthermore, the results may be referenced by nursing supervisors in acute care facilities when making arrangements for nurses to participation in the Clinical Nursing Ladder Program and when arranging nursing staff training and setting the direction of long-term care-related education and training in healthcare facilities.


Assuntos
Assistência de Longa Duração , Recursos Humanos de Enfermagem , Adulto , Estudos Transversais , Humanos , Satisfação no Emprego , Inquéritos e Questionários
15.
Hu Li Za Zhi ; 69(2): 13-18, 2022 Apr.
Artigo em Zh | MEDLINE | ID: mdl-35318628

RESUMO

Health problems in older adults are often concomitant with multiple comorbidities and geriatric syndromes that involve the psychological and social domains. Traditional models of disease care address the health problems of older adults inadequately. Therefore, we applied a case management framework (assess, plan, act, coordinate, evaluate and interact) to discuss how to implement an elderly-centered approach to integrated care that integrates comprehensive, multidisciplinary, and continuous care. The Geriatrics Formulated by Outcome Related Care & Empowerment (Geri-FORCE) was developed by the Formosan Association of Care and Education for the Seniors to help establish a geriatric case management system grounded in precision health care. We propose developing an informatics technology system for older adults that integrates the Geri-FORCE model with case management. This system should accurately identify the main health problems in older adults and provide a care plan that is patient-tailored, integrated, and continuous. We expect that the developed Geri-FORCE case management system will improve quality of care and promote health while reducing care burdens and costs.


Assuntos
Administração de Caso , Geriatria , Idoso , Comorbidade , Promoção da Saúde , Humanos , Medicina de Precisão
16.
Beilstein J Org Chem ; 18: 881-888, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957755

RESUMO

The clerodane and ent-kaurane diterpenoids are two typical categories of diterpenoid natural products with complicated polycyclic carbon skeletons and significant pharmacological activities. Despite exciting advances in organic chemistry, access to these skeletons is still highly challenging. Using synthetic biology to engineer microbes provides an innovative alternative to bypass synthetic challenges. In this study, we constructed two truncated artificial pathways to efficiently produce terpentetriene and ent-kaurene, two representative clerodane and ent-kaurane diterpenes, in Escherichia coli. Both pathways depend on the exogenous addition of isoprenoid alcohol to reinforce the supply of IPP and DMAPP via two sequential phosphorylation reactions. Optimization of these constructs provided terpentetriene and ent-kaurene titers of 66 ± 4 mg/L and 113 ± 7 mg/L, respectively, in shake-flask fermentation. The truncated pathways to overproduce clerodane and ent-kaurane skeletons outlined here may provide an attractive route to prepare other privileged diterpene scaffolds.

17.
J Pathol ; 251(4): 365-377, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32418203

RESUMO

The classification of the distinct group of mesenchymal neoplasms, first described as 'Xp11 translocation perivascular epithelioid cell tumor (PEComa)' and for which the term 'melanotic Xp11 neoplasm' or 'Xp11 neoplasm with melanocytic differentiation' has recently been proposed, remains challenging and controversial. We collected 27 melanotic Xp11 neoplasms, the largest series to date, for a comprehensive evaluation. Fourteen of the cases, together with eight alveolar soft part sarcomas (ASPS), nine conventional PEComas and a control group of seven normal tissues were submitted to RNA sequencing. Follow-up available in 22 patients showed 5-year overall survival and 5-year disease-free survival of 47.6 and 35.7%, respectively, which were similar to ASPS and significantly worse than conventional PEComa. Univariate analysis of location (occurring in the kidney versus not kidney), infiltrative growth pattern, nuclear pleomorphism, mitotic activity ≥2/50 high-power fields (HPF), necrosis and lymphovascular invasion were found to be associated with overall survival and/or disease-free survival. Multivariate analysis identified that location was the only factor found to independently correlate with disease-free survival. More importantly, RNA sequencing-based clustering analysis segregated melanotic Xp11 neoplasm and ASPS from other tumors, including conventional PEComa and Xp11 translocation renal cell carcinoma, and formed a compact cluster representative of the largely similar expression signature. Here we clearly define the true biologic nature of melanotic Xp11 neoplasms which are distinctive malignant mesenchymal tumors, rather than simply PEComa variants with occasionally unpredictable behavior. Meanwhile, melanotic Xp11 neoplasm and ASPS more likely represent phenotypic variants of the same entity, which is distinct from conventional PEComa and Xp11 translocation renal cell carcinoma. Based on these important findings, melanotic Xp11 neoplasm might be reclassified into a distinctive entity together with ASPS, independent from PEComa, in future revisions of the current WHO categories of tumors of soft tissue and bone for the improved reclassification. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Carcinoma de Células Renais/classificação , Neoplasias Renais/classificação , Neoplasias de Células Epitelioides Perivasculares/classificação , Sarcoma Alveolar de Partes Moles/classificação , Translocação Genética , Adolescente , Adulto , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Criança , Pré-Escolar , Análise por Conglomerados , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patologia , Sarcoma Alveolar de Partes Moles/genética , Sarcoma Alveolar de Partes Moles/patologia , Análise de Sequência de RNA , Análise de Sobrevida , Adulto Jovem
18.
Genomics ; 112(6): 3978-3990, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32650096

RESUMO

Thorea hispida exclusively inhabits freshwater environments and is characterized by a triphasic life history. In this study, the organelle genomes and transcriptomes of different life history stages of T. hispida were examined using next generation sequencing. The chloroplast and mitochondrial genomes of the chantransia stage were 175,747 and 25,411 bp in length, respectively. The chantransia stage was highly similar to the gametophyte stage based on comparisons of organelle genomes and phylogenetic reconstruction. Transcriptomic comparisons of two stages found that ribosome-related genes were the most up-regulated in the gametophyte stage of T. hispida. Seven meiosis-specific genes, including SPO11 initiator of meiotic double-stranded breaks(spo11), meiotic nuclear divisions 1(mnd1), RAD51 recombinase(rad51), mutS homolog 4(msh4), mutS homolog 5(msh5), REC8 meiotic recombination protein(rec8), and DNA helicase Mer3(mer3), were differentially regulated between the two life history stages. The organelle genomes and transcriptomes from T. hispida provided in this study will be valuable for future studies of freshwater red algae.


Assuntos
Água Doce , Rodófitas/fisiologia , Transcriptoma , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Rodófitas/genética
19.
J Tissue Viability ; 30(4): 544-551, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34535352

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors. According to the authors, concerns with the experimental conduct presented in the paper have been identified, in addition to the grounds that that ethical approval was not sought or confirmed for the research undertaken. After a review, the Editor has confirmed approval that this paper should be retracted as it presents a violation of the Journal's publishing policies and publishing ethics standards.


Assuntos
MicroRNAs , Apoptose , Proliferação de Células , Humanos , Queratinócitos , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(4): 533-539, 2020 Jul.
Artigo em Zh | MEDLINE | ID: mdl-32691563

RESUMO

OBJECTIVE: A retrospective study was designed to explore the relationship between the satittal spinopelvic alignment in patients with lumbar disc extrusion and spontaneous resorption. METHODS: From May 2010 to March 2019, referring to NASS evidence-based clinical guidelines, patients with lumbar disc extrusion were enrolled in this retrospective study, according to the degree of herniation size during the follow-up, the patients were divided into two groups: resorption (group R: the herniated disc completely disappeared or the herniation size was grade 1 according to Michgan State University (MSU) classification) and nonresorption (group N: the herniated disc remain unchanged or the herniation size overpass grade 1), spinopelvic parameters (including the pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL)) were determined on standing profile radiographs of the lumbar spine and pelvis, and mean values were compared using the multi-factor analysis of variance. RESULTS: This study included 67 patients with lumbar disc extrusion. There were 37 in group R (the average age was 42.6 years), 21 males and 16 females, 13 cases at L 4-5 level and 24 cases at L 5-S 1 level, follow-up 22 months, and 30 in group N (the average age was 40.8 years), 19 males and 11 females, 12 cases at L 4-5 level and 18 cases at L 5-S 1 level, follow-up 21 months, at the follow up time, there symptoms were all satisfactorily relieved. There were no signifcant differences in age, gender, smoking history, chronic medical history, prominent segmnet, MSU classification, follow up time and other baseline conditions between two groups ( P>0.05). At the follow-up, in group R, all 30 cases of sagittal displaced disc disappeared, the herniated disc changed from the initial MSU classification of grade 2 in 19 cases and grade 3 in 18 cases to the post-absorption residual disc, which were limited to grade 1; in group N, 20 cases of sagittal displaced disc reduced to 14 cases, the herniated disc changed from the initial MSU classification of grade 2 in 21 cases and grade 3 in 9 cases to grade 2 in 27 cases and grade 3 in 3 cases. There was no significant difference in spinopelvic parameters between the two groups before the treatment ( P>0.05). At the follow-up, there was no significant difference in PI between the two groups ( P>0.05); the SS and LL in group R were bigger than those in group N, the PT in group R was smaller than that in group N, and the difference was statistically significant ( P<0.05). Compared within the same group, before treatment and follow-up, there were no significant differences in PI, SS and PT in group R, but a bigger LL ( P<0.05); no significant differences in all the parameters in group N were found. CONCLUSION: Resorption may result in pinopelvic parameter changes, which suggest that the lumbar spine is better at cushioning against load, reducing the disc pressure, and leading to resorption of the herniated disc.


Assuntos
Deslocamento do Disco Intervertebral , Vértebras Lombares , Adulto , Feminino , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Lordose , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/metabolismo , Vértebras Lombares/patologia , Masculino , Pelve/diagnóstico por imagem , Estudos Retrospectivos
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