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1.
Neuroendocrinology ; : 1-16, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710164

RESUMEN

INTRODUCTION: Well-calibrated models for personalized prognostication of patients with gastrointestinal neuroendocrine neoplasms (GINENs) are limited. This study aimed to develop and validate a machine-learning model to predict the survival of patients with GINENs. METHODS: Oblique random survival forest (ORSF) model, Cox proportional hazard risk model, Cox model with least absolute shrinkage and selection operator penalization, CoxBoost, Survival Gradient Boosting Machine, Extreme Gradient Boosting survival regression, DeepHit, DeepSurv, DNNSurv, logistic-hazard model, and PC-hazard model were compared. We further tuned hyperparameters and selected variables for the best-performing ORSF. Then, the final ORSF model was validated. RESULTS: A total of 43,444 patients with GINENs were included. The median (interquartile range) survival time was 53 (19-102) months. The ORSF model performed best, in which age, histology, M stage, tumor size, primary tumor site, sex, tumor number, surgery, lymph nodes removed, N stage, race, and grade were ranked as important variables. However, chemotherapy and radiotherapy were not necessary for the ORSF model. The ORSF model had an overall C index of 0.86 (95% confidence interval, 0.85-0.87). The area under the receiver operation curves at 1, 3, 5, and 10 years were 0.91, 0.89, 0.87, and 0.80, respectively. The decision curve analysis showed superior clinical usefulness of the ORSF model than the American Joint Committee on Cancer Stage. A nomogram and an online tool were given. CONCLUSION: The machine learning ORSF model could precisely predict the survival of patients with GINENs, with the ability to identify patients at high risk for death and probably guide clinical practice.

2.
Ecotoxicol Environ Saf ; 273: 116106, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38377782

RESUMEN

Silica nanoparticle (SiNP) exposure induces severe pulmonary inflammation and fibrosis, but the pathogenesis remains unclear, and effective therapies are currently lacking. To explore the mechanism underlying SiNPs-induced pulmonary fibrosis, we constructed in vivo silica exposure animal models and in vitro models of silica-induced macrophage pyroptosis and fibroblast transdifferentiation. We found that SiNP exposure elicits upregulation of pulmonary proteins associated with pyroptosis, including NLRP3, ASC, IL-1ß, and GSDMD, while the immunofluorescence staining co-localized NLRP3 and GSDMD with macrophage-specific biomarker F4/80 in silica-exposed lung tissues. However, the NLRP3 inhibitor MCC950 and classical anti-fibrosis drug pirfenidone (PFD) were found to be able to alleviate silica-induced collagen deposition in the lungs. In in vitro studies, we exposed the fibroblast to a conditioned medium from silica-induced pyroptotic macrophages and found enhanced expression of α-SMA, suggesting increased transdifferentiation of fibroblast to myofibroblast. In line with in vivo studies, the combined treatment of MCC950 and PFD was demonstrated to inhibit the expression of α-SMA and attenuate fibroblast transdifferentiation. Mechanistically, we adopted high throughput RNA sequencing on fibroblast with different treatments and found activated signaling of relaxin and osteoclast differentiation pathways, where the expression of the dysregulated genes in these two pathways was examined and found to be consistently altered both in vitro and in vivo. Collectively, our study demonstrates that SiNP exposure induces macrophage pyroptosis, which subsequently causes fibroblast transdifferentiation to myofibroblasts, in which the relaxin and osteoclast differentiation signaling pathways play crucial roles. These findings may provide valuable references for developing new therapies for pulmonary fibrosis.


Asunto(s)
Fibrosis Pulmonar , Relaxina , Animales , Fibrosis Pulmonar/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Dióxido de Silicio/toxicidad , Relaxina/metabolismo , Relaxina/farmacología , Piroptosis/fisiología , Osteoclastos/metabolismo , Osteoclastos/patología , Fibroblastos , Fibrosis , Macrófagos
3.
Angew Chem Int Ed Engl ; 63(18): e202402369, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38446496

RESUMEN

Solar-energy-driven photoreduction of CO2 is promising in alleviating environment burden, but suffers from low efficiency and over-reliance on sacrificial agents. Herein, rhenium (Re) is atomically dispersed in In2O3 to fabricate a 2Re-In2O3 photocatalyst. In sacrificial-agent-free photoreduction of CO2 with H2O, 2Re-In2O3 shows a long-term stable efficiency which is enhanced by 3.5 times than that of pure In2O3 and is also higher than those on Au-In2O3, Ag-In2O3, Cu-In2O3, Ir-In2O3, Ru-In2O3, Rh-In2O3 and Pt-In2O3 photocatalysts. Moreover, carbon-based product of the photoreduction overturns from CO on pure In2O3 to CH3OH on 2Re-In2O3. Re promotes charge separation, H2O dissociation and CO2 activation, thus enhancing photoreduction efficiency of CO2 on 2Re-In2O3. During the photoreduction, CO is a key intermediate. CO prefers to desorption rather than hydrogenation on pure In2O3, as CO binds to pure In2O3 very weakly. Re strengthens the interaction of CO with 2Re-In2O3 by 5.0 times, thus limiting CO desorption but enhancing CO hydrogenation to CH3OH. This could be the origin for photoreduction product overturn from CO on pure In2O3 to CH3OH on 2Re-In2O3. The present work opens a new way to boost sacrificial-agent-free photoreduction of CO2.

4.
J Virol ; 96(23): e0087922, 2022 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-36377874

RESUMEN

The glycan loop of Zika virus (ZIKV) envelope protein (E) contains the glycosylation site and has been well documented to be important for viral pathogenesis and transmission. In the present study, we report that deletions in the E glycan loop, which were recorded in African ZIKV strains previously, have re-emerged in their contemporary Asian lineages. Here, we generated recombinant ZIKV containing specific deletions in the E glycan loop by reverse genetics. Extensive in vitro and in vivo characterization of these deletion mutants demonstrated an attenuated phenotype in an adult A129 mouse model and reduced oral infections in mosquitoes. Surprisingly, these glycan loop deletion mutants exhibited an enhanced neurovirulence phenotype, and resulted in a more severe microcephalic brain in neonatal mouse models. Crystal structures of the ZIKV E protein and a deletion mutant at 2.5 and 2.6 Å, respectively, revealed that deletion of the glycan loop induces encephalitic flavivirus-like conformational alterations, including the appearance of perforations on the surface and a clear change in the topology of the loops. Overall, our results demonstrate that the E glycan loop deletions represent neonatal mouse neurovirulence markers of ZIKV. IMPORTANCE Zika virus (ZIKV) has been identified as a cause of microcephaly and acquired evolutionary mutations since its discovery. Previously deletions in the E glycan loop were recorded in African ZIKV strains, which have re-emerged in the contemporary Asian lineages recently. The glycan loop deletion mutants are not glycosylated, which are attenuated in adult A129 mouse model and reduced oral infections in mosquitoes. More importantly, the glycan loop deletion mutants induce an encephalitic flavivirus-like conformational alteration in the E homodimer, resulting in a significant enhancement of neonatal mouse neurovirulence. This study underscores the critical role of glycan loop deletion mutants in ZIKV pathogenesis, highlighting a need for global virological surveillance for such ZIKV variants.


Asunto(s)
Proteínas del Envoltorio Viral , Infección por el Virus Zika , Virus Zika , Animales , Ratones , Modelos Animales de Enfermedad , Polisacáridos/química , Proteínas del Envoltorio Viral/genética , Virulencia , Replicación Viral/genética , Virus Zika/genética , Virus Zika/patogenicidad , Infección por el Virus Zika/virología
5.
Fish Shellfish Immunol ; 142: 109113, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37788751

RESUMEN

Circular RNA (circRNA), one of the important non-coding RNA molecules with a closed-loop structure, plays a key regulatory role in cell processing. In this study, circRNAs of Epinephelus coioides, an important marine cultured fish in China, were isolated and characterized, and the network of circRNAs and mRNA was explored during Singapore grouper iridovirus (SGIV) infection, one of the most important double stranded DNA virus pathogens of marine fish. 10 g of raw data was obtained by high-throughput sequencing, and 2599 circRNAs were classified. During SGIV infection, 123 and 37 circRNAs occurred differential expression in spleen and spleen cells, indicating that circRNAs would be involved in the viral infection. GO annotation and KEGG demonstrated that circRNAs could target E. coioides genes to regulate cell activity and the activation of immune factors. The results provide some insights into the circRNAs mediated immune regulatory network during bony fish virus infection.


Asunto(s)
Lubina , Infecciones por Virus ADN , Enfermedades de los Peces , Iridovirus , Perciformes , Ranavirus , Animales , Lubina/genética , Lubina/metabolismo , ARN Circular/genética , ARN Mensajero/genética , Singapur , Proteínas de Peces/genética , Proteínas de Peces/metabolismo
6.
J Environ Manage ; 335: 117472, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36827800

RESUMEN

In this study, we aimed to investigate the long-term spatiotemporal changes in hydrodynamics, antibiotics, nine typical subtypes of antibiotic resistance genes (ARGs), class 1 integron gene (intI1), and microbial communities in the sediments of a semi-enclosed estuary during ecological restoration with four treatment stages (influent (#1), effluent of the biological treatment area (#2), oxic area (#3), and plant treatment area (#4)). Ecological restoration of the estuary reduced common pollutants (nitrogen and phosphorus) in the water, whereas variations in ARGs showed noticeable seasonal and spatial features. The absolute abundance of ARGs at sampling site #2 considerably increased in autumn and winter, while it significantly increased at sampling site #3 in spring and summer. The strong intervention of biological treatment (from #1 to #2) and aerators (from #2 to #3) in the estuary substantially affected the distribution of ARGs and dominant antibiotic-resistant bacteria (ARB). The dominant ARB (Thiobacillus) in estuarine sediments may have low abundance but important dissemination roles. Meanwhile, redundancy and network analysis revealed that the microbial communities and intl1 were key factors related to ARG dissemination, which was affected by spatial and seasonal ecological restoration. A positive correlation between low flow velocity and certain ARGs (tetM, tetW, tetA, sul2, and ermC) was observed, implying that flow optimization should also be considered in future ecological restoration to remediate ARGs. Furthermore, the absolute abundance of ARGs can be utilized as an index to evaluate the removal capacity of ARGs by estuarine restoration.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Genes Bacterianos , Antibacterianos , Inhibidores de la Enzima Convertidora de Angiotensina , Farmacorresistencia Microbiana/genética , China
7.
World J Microbiol Biotechnol ; 39(12): 340, 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37821760

RESUMEN

Fusarium graminearum, a devastating fungal pathogen, is the main pathogen of Fusarium head blight (FHB) in wheat globally; it results in significant yield loss and mycotoxin contamination that severely threatens global wheat production and food safety. However, despite ongoing efforts, controlling this pathogen still remains a major challenge. Surfactin, primarily synthesized by Bacillus sp. via non-ribosomal peptide synthetases, exhibits potent surfactant and antibacterial properties, but its antifungal mechanism has yet to be fully elucidated. We found that the EC50 of surfactin against hyphal growth of F. graminearum was 102.1 µg/mL, and control efficacy against wheat FHB under field conditions achieved 86.38% in wheat cultivar Huaimai 40 and 81.60% in wheat cultivar Zhoumai 36, indicating that surfactin has potential antifungal activity against F. graminearum. Accumulated intracellular ROS, decreased mitochondrial membrane potential (MMP), activated metacaspase activity and condensed chromatin, were induced by surfactin in F. graminearum hyphae, suggesting that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Furthermore, accumulated intracellular ROS was evidenced to act as a key mediator of surfactin-induced apoptosis. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that surfactin induces caspase-independent apoptosis in F. graminearum. Collectively, this study provides evidence that surfactin induces a ROS-mediated mitochondrial apoptosis in F. graminearum hyphae, and may exert its antifungal activity against F. graminearum by activating apoptosis. This study demonstrates the potential of surfactin as an antifungal agent for FHB biocontrol, provides a new perspective on the antifungal mechanism of surfactin against filamentous fungi, and contributes to the application of surfactin-producing microbes in the biocontrol of plant diseases.


Asunto(s)
Antifúngicos , Fusarium , Antifúngicos/farmacología , Antifúngicos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Caspasas , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiología
8.
Zhongguo Zhong Yao Za Zhi ; 48(11): 2919-2924, 2023 Jun.
Artículo en Zh | MEDLINE | ID: mdl-37381951

RESUMEN

Zearalenone(ZEN) is a toxic metabolite produced by Fusarium culmorum, F. graminearum, F. tricinctum, and other fungi, with estrogenic characteristics. Exposure to or ingestion of ZEN during pregnancy can cause reproductive dysfunction, miscarriage, stillbirth, and malformation, and seriously endanger human life and health. The detection methods for ZEN in the Chinese Pharmacopoeia(2020 edition) are liquid chromatography(LC) and liquid chromatography-mass spectrometry(LC-MS), and it is stipulated that ZEN should not exceed 500 µg in 1 000 g of Coicis Semen. Although these detection methods by instruments can achieve the qualitative and quantitative analysis of ZEN in Coicis Semen, their high detection cost and long periods hinder the rapid screening of a large number of samples in the field. In this study, the synthesized ZEN hapten was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) to obtain the complete ZEN antigen. By virtue of antibody preparation techniques, ZEN monoclonal antibody 4F6 was prepared, which showed 177.5%, 137.1%, and 109.7% cross-reactivity with ZEN structural analogs zearalanol, zearalenone, and α-zearalenol, respectively, and no cross-reactivity with other fungal toxins such as aflatoxin. Direct competitive enzyme-linked immunosorbent assay(dcELISA) based on ZEN monoclonal antibody 4F6 was developed for the determination of ZEN in Coicis Semen with an IC_(50) of 1.3 µg·L~(-1) and a detection range of 0.22-21.92 µg·L~(-1). The recoveries were 83.91%-105.3% and the RSD was 4.4%-8.0%. The established dcELISA method was used to determine the ZEN residuals in nine batches of Coicis Semen samples, and the results were validated by LC-MS. The correlation between the two detection methods was found to be 0.993 9, indicating that the established dcELISA could be used for the rapid qualitative and quantitative detection of ZEN residuals in Coicis Semen.


Asunto(s)
Coix , Micotoxinas , Zearalenona , Humanos , Femenino , Embarazo , Ensayo de Inmunoadsorción Enzimática , Anticuerpos Monoclonales
9.
Angew Chem Int Ed Engl ; 62(38): e202309443, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37523150

RESUMEN

By supporting platinum (Pt) and cadmium sulfide (CdS) nanoparticles on indium oxide (In2 O3 ), we fabricated a CdS/Pt/In2 O3 photocatalyst. Selective photoreduction of carbon dioxide (CO2 ) to methane (CH4 ) was achieved on CdS/Pt/In2 O3 with electronic Pt-In2 O3 interactions, with CH4 selectivity reaching to 100 %, which is higher than that on CdS/Pt/In2 O3 without electronic Pt-In2 O3 interactions (71.7 %). Moreover, the enhancement effect of electronic Pt-(metal-oxide) interactions on selective photoreduction of CO2 to CH4 also occurs by using other common metal oxides, such as photocatalyst supports, including titanium oxide, gallium oxide, zinc oxide, and tungsten oxide. The electronic Pt-(metal-oxide) interactions separate photogenerated electron-hole pairs and convert CO2 into CO2 δ- , which can be easily hydrogenated into CH4 via a CO2 δ- →HCOO*→HCO*→CH*→CH4 path, thus boosting selective photoreduction of CO2 to CH4 . This offers a new way to achieve selective photoreduction of CO2 .

10.
Angew Chem Int Ed Engl ; 62(32): e202307490, 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37318956

RESUMEN

Photocatalytic hydrogen (H2 ) production is significant to overcome challenges like fossil fuel depletion and carbon dioxide emission, but its efficiency is still far below that which is needed for commercialization. Herein, we achieve long-term stable H2 bubbling production from water (H2 O) and lactic acid via visible-light-driven photocatalysis in a porous microreactor (PP12); the catalytic system benefits from photocatalyst dispersion, charge separation, mass transfer, and dissociation of O-H bonds associated with H2 O. With the widely used platinum/cadmium-sulfide (Pt/CdS) photocatalyst, PP12 leads to a H2 bubbling production rate of 602.5 mmol h-1 m-2 , which is 1000 times higher than that in a traditional reactor. Even when amplifying PP12 into a flat-plate reactor with an area as large as 1 m2 and extending the reaction time to 100 h, the H2 bubbling production rate still remains at around 600.0 mmol h-1 m-2 , offering great potential for commercialization.

11.
Langmuir ; 38(40): 12179-12188, 2022 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-36170049

RESUMEN

Lead ion (Pb2+) is one of the most common water pollutants. Herein, with bamboo as the raw material, we fabricate a thin-walled hollow ellipsoidal carbon-based adsorbent (CPCs900) containing abundant O-containing groups and carbon defects and having a specific surface area as large as 730.87 m2 g-1. CPCs900 shows a capacity of 37.26 mg g-1 for adsorbing Pb2+ in water and an efficiency of 98.13% for removing Pb2+ from water. This is much better than the activated carbon commonly used for removing Pb2+ from water (12.19 mg g-1, 30.48%). The bond interaction of Pb2+ with the O-containing groups on CPCs900 and the electrostatic interaction of Pb2+ with the electron-rich carbon defects on CPCs900 could be the main forces to drive Pb2+ adsorption on CPCs900. The outstanding adsorption performance of CPCs900 could be due to the abundant O-containing groups and carbon defects as well as the large specific surface area of CPCs900. Bamboo has a large reserve and a low price. The present work successfully converts bamboo into adsorbents with outstanding performances in removing Pb2+ from water. This is of great significance for meeting the huge industrial demand on highly efficient adsorbents for removing toxic metal ions from water.


Asunto(s)
Contaminantes Químicos del Agua , Contaminantes del Agua , Adsorción , Carbón Orgánico/química , Concentración de Iones de Hidrógeno , Iones , Cinética , Plomo , Agua , Contaminantes Químicos del Agua/análisis
12.
Support Care Cancer ; 30(3): 2445-2453, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34775535

RESUMEN

PURPOSE: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. For better understanding the application of olanzapine in antiemetic strategies for breast cancer patients who suffered anthracycline plus cyclophosphamide-induced nausea and vomiting, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled-analyzed the results to confirm the efficacy and safety of olanzapine in breast cancer. METHODS: PubMed, Web of Science, EMBASE, and Cochrane CENTRAL databases were searched from inception through Sep 15, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate, and the secondary outcome was treatment-related adverse events. RESULTS: Four studies with 466 breast cancer patients were identified in the pooled analysis. In the acute period (0-24 h), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group, while in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. CONCLUSION: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.


Asunto(s)
Antieméticos , Antineoplásicos , Neoplasias de la Mama , Antraciclinas/efectos adversos , Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/efectos adversos , Dexametasona/uso terapéutico , Femenino , Humanos , Olanzapina/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico
13.
Proc Natl Acad Sci U S A ; 116(6): 2220-2225, 2019 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-30659143

RESUMEN

Homoharringtonine (HHT), a known protein synthesis inhibitor, has an anti-myeloid leukemia effect and potentiates the therapeutic efficacy of anthracycline/cytarabine induction regimens for acute myelogenous leukemia (AML) with favorable and intermediate prognoses, especially in the t(8;21) subtype. Here we provide evidence showing that HHT inhibits the activity of leukemia-initiating cells (Lin-/Sca-1-/c-kit+; LICs) in a t(8;21) murine leukemia model and exerts a down-regulating effect on MYC pathway genes in human t(8;21) leukemia cells (Kasumi-1). We discovered that NF-κB repressing factor (NKRF) is bound directly by HHT via the second double-strand RNA-binding motif (DSRM2) domain, which is the nuclear localization signal of NKRF. A series of deletion and mutagenesis experiments mapped HHT direct binding sites to K479 and C480 amino acids in the DSRM2 domain. HHT treatment shifts NKRF from the nucleus (including nucleoli) to the cytoplasm by occupying the DSRM2 domain, strengthens the p65-NKRF interaction, and interferes with p65-p50 complex formation, thereby attenuating the transactivation activity of p65 on the MYC gene. Moreover, HHT significantly decreases the expression of KIT, a frequently mutated and/or highly expressed gene in t(8;21) AML, in concert with MYC down-regulation. Our work thus identifies a mechanism of action of HHT that is different from, but acts in concert with, the known mode of action of this compound. These results justify further clinical testing of HHT in AML.


Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Genes myc , Homoharringtonina/farmacología , Proteínas Represoras/metabolismo , Animales , Sitios de Unión , Biomarcadores de Tumor , Línea Celular Tumoral , Cromosomas Humanos Par 21 , Cromosomas Humanos Par 8 , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Homoharringtonina/química , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Ratones , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteínas Represoras/química , Factor de Transcripción ReIA/metabolismo , Transcripción Genética , Translocación Genética , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Int J Mol Sci ; 23(15)2022 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-35955649

RESUMEN

Type III CRISPR-Cas systems show the target (tg)RNA-activated indiscriminate DNA cleavage and synthesis of oligoadenylates (cOA) and a secondary signal that activates downstream nuclease effectors to exert indiscriminate RNA/DNA cleavage, and both activities are regulated in a spatiotemporal fashion. In III-B Cmr systems, cognate tgRNAs activate the two Cmr2-based activities, which are then inactivated via tgRNA cleavage by Cmr4, but how Cmr4 nuclease regulates the Cmr immunization remains to be experimentally characterized. Here, we conducted mutagenesis of Cmr4 conserved amino acids in Saccharolobus islandicus, and this revealed that Cmr4α RNase-dead (dCmr4α) mutation yields cell dormancy/death. We also found that plasmid-borne expression of dCmr4α in the wild-type strain strongly reduced plasmid transformation efficiency, and deletion of CRISPR arrays in the host genome reversed the dCmr4α inhibition. Expression of dCmr4α also strongly inhibited plasmid transformation with Cmr2αHD and Cmr2αPalm mutants, but the inhibition was diminished in Cmr2αHD,Palm. Since dCmr4α-containing effectors lack spatiotemporal regulation, this allows an everlasting interaction between crRNA and cellular RNAs to occur. As a result, some cellular RNAs, which are not effective in mediating immunity due to the presence of spatiotemporal regulation, trigger autoimmunity of the Cmr-α system in the S. islandicus cells expressing dCmr4α. Together, these results pinpoint the crucial importance of tgRNA cleavage in autoimmunity avoidance and in the regulation of immunization of type III systems.


Asunto(s)
Proteínas Asociadas a CRISPR , Sulfolobus , Autoinmunidad/genética , Proteínas Asociadas a CRISPR/genética , Sistemas CRISPR-Cas/genética , ARN/genética , División del ARN , Sulfolobus/genética
15.
Molecules ; 27(21)2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36364407

RESUMEN

A series of novel anti-corrosive coatings were synthesized successfully. Water-borne polyurethane (WPU) was synthesized using polyethylene glycol and modified by grafting benzotriazole (BTA) as a pendant group (WPU-g-BTA) and N-alkylated amines (ethylene diamine (A), diethylene triamine (B), triethylene tetramine (C)) as side-chain extenders. Fourier-transform infrared spectroscopy, thermogravimetry, and dynamic mechanical analyses were used to characterize the structural and thermomechanical properties of the samples. A gas permeability analyzer (GPA) was used to evaluate molecular barrier properties. The corrosion inhibition performance of WPU-g-BTA-A, WPU-g-BTA-B, and WPU-g-BTA-C coatings in 3.5 wt% NaCl solution was determined by electrochemical measurements. WPU-g-BTA-C coating synthesized with a high cross-linking density showed superior anticorrosive performance. The as-prepared coatings exhibited a very low icorr value of 0.02 µA.cm-2, a high Ecorr value of -0.02 V, as well as excellent inhibition efficiency (99.972%) and impedance (6.33 Ω) after 30 min of exposure.


Asunto(s)
Poliuretanos , Triazoles , Poliuretanos/química , Corrosión , Agua
16.
Nurs Ethics ; 29(1): 104-113, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34296649

RESUMEN

BACKGROUND: High ethical sensitivity positively affects the quality of nursing care; nevertheless, Chinese nurses' ethical sensitivity and the factors influencing it have not been described. RESEARCH OBJECTIVES: The purpose of this study was to describe ethical sensitivity and to explore factors influencing it among Chinese-registered nurses, to help nursing administrators improve nurses' ethical sensitivity, build harmony between nurses and patients, and promote the patients' health. RESEARCH DESIGN: This was a descriptive, cross-sectional study. PARTICIPANTS AND RESEARCH CONTEXT: We recruited 500 nurses from several departments in three tertiary hospitals. The Chinese Moral Sensitivity Questionnaire-Revised version and the Jefferson Scale of Empathy-Health Professionals were used to assess the nurses' ethical sensitivity and empathy ability, respectively. Fifteen sociodemographic variables were included in the questionnaires. ETHICAL CONSIDERATIONS: Informed consent was obtained from the participants regarding participation and data storage and handling. This program has been examined and supported by the research center of medical ethics and professional ethics of Guilin Medical University. The Approval No. was 2016RWYB04. The whole research process is conducted strictly according to ethical requirements. RESULTS: The valid response rate was 84.40% (n = 422). The total score of Chinese Moral Sensitivity Questionnaire-Revised was 35.82 ± 8.17. The subscale scores of moral responsibility and strength and sense of moral burden were 21.50 ± 4.91 and 14.33 ± 3.98, respectively. Significant differences were found among age groups, gender, years of working, category of profession, and quality of family communication regarding nurses' ethical sensitivity (p < 0.05). Regression analysis showed that the main factors influencing nurses' ethical sensitivity were gender, years of working, quality of family communication, career satisfaction, and empathic ability. DISCUSSION: Our findings suggest that Chinese nurses' ethical sensitivity in tertiary hospitals in Guilin is at a medium level. CONCLUSION: The director of nursing schools and hospitals in China should pay attention to nurses' ethical sensitivity and should intensify education and training to improve nurses' ethical sensitivity. Further studies should focus on interventions aimed at improving Chinese nurses' ethical sensitivity.


Asunto(s)
Ética en Enfermería , Enfermeras y Enfermeros , Estudios Transversales , Humanos , Principios Morales , Encuestas y Cuestionarios , Centros de Atención Terciaria
17.
Zhongguo Zhong Yao Za Zhi ; 47(24): 6581-6586, 2022 Dec.
Artículo en Zh | MEDLINE | ID: mdl-36604906

RESUMEN

Coicis Semen is a common bulk medicinal material used for both medicine and food, which has the effect of promoting diuresis, draining dampness, invigorating the spleen and checking diarrhea. It is derived from Coix lacryma-jobi var. ma-yuen of the family Poaceae, and is easily contaminated by fungi such as Fusarium graminearum and F. flavum due to climate reasons to produce vomitoxin. The guiding principles for determination of vomitoxin in Chinese medicinal materials in Chinese Pharmacopoeia are mainly HPLC and LC-MS, which have long detection period and are time-consuming and laborious, and thus cannot meet the requirements of on-site quality inspection of drugs. The complete antigen of vomitoxin-protein was obtained by chemical derivatization of vomitoxin. The monoclonal antibody against vomitoxin was prepared by classic monoclonal antibody preparation technology, and enzyme-linked immunosorbent assay(ELISA) method for detection of vomitoxin in Coicis Semen was established through methodological investigation. The IC_(50) based on the ELISA for vomitoxin in Coicis Semen was 3.88 µg·L~(-1), and the average recoveries and the RSD were 77.32%-93.73% and 4.6%-9.7%, respectively. With the established ELISA method, the vomitoxin residue in 14 batches of Coicis Semen samples were determined and validated by LC-MS, and the correlation between the two assays was found to be 0.997 8, indicating that the established ELISA method could be used for quantitative determination of vomitoxin residue in Coicis Semen and could achieve the rapid quantitative determination of the vomitoxin residue.


Asunto(s)
Coix , Tricotecenos , Anticuerpos Monoclonales , Ensayo de Inmunoadsorción Enzimática
18.
Anal Chem ; 93(4): 2244-2253, 2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33399443

RESUMEN

As a kind of bioactive sulfur species, biothiols (Cys, Hcy, and GSH) play an irreplaceable role in regulating the redox balance of life processes. Because of their similar chemical structures and properties, a sulfydryl group, and an amino group, it is an important challenge to distinguish two or more of them at the same time. Herein, a fluorescent sensor (NTPC) based on the coumarin structure was developed to discriminate Cys/Hcy and GSH simultaneously. The sensor has no fluorescence due to the d-PET effect but displays strong fluorescence after its reaction with biothiols. There are two potential reaction sites (nitrophenyl sulfide group and aldehyde group) in the structure of NTPC, resulting in different fluorescent signal changes after reacting with biothiols (green for Cys and Hcy and red for GSH). Under double-wavelength excitation, the sensor shows low background fluorescence, high selectivity, and low detection limits toward biothiols. Moreover, the sensor can be used to discriminate different biothiols (Cys/Hcy and GSH) in cells and zebra fish by different fluorescence signals with low toxicity and might provide a promising tool for studying the roles of different biothiols in various physiological and pathological processes.


Asunto(s)
Cisteína , Colorantes Fluorescentes , Glutatión/química , Homocisteína/química , Animales , Estructura Molecular , Pez Cebra
19.
Org Biomol Chem ; 19(31): 6812-6816, 2021 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-34297020

RESUMEN

A facile synthesis of 2-phosphorylated 2H-chromenes has been accomplished herein via a Y(OTf)3-catalyzed dehydrative coupling of 2H-chromene hemiacetals with P(O)-H compounds. This protocol features low catalyst loading, mild reaction conditions, broad substrate scope and easy elaboration of the products.

20.
Genes Chromosomes Cancer ; 59(7): 417-421, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32167630

RESUMEN

Chromosomal translocations and generating fusion genes are closely associated with disease initiation and progression in acute myeloid leukemia (AML). In this study, we identified a novel t(X;17)(q28;q21) chromosomal rearrangement in a patient with acute monocytic leukemia. Using RNA-sequencing, we identified a KANSL1-MTCP1 and a KANSL1-CMC4 fusion gene. 5'-UTR sequences of the KANSL1 gene were found to become fused upstream of the coding sequence region of the MTCP1 and CMC4 genes, respectively, resulting in an aberrantly high expression of these genes. Functional studies revealed that overexpression of the MTCP1 gene induced an increased cell proliferation and partial blockage of cell differentiation, suggesting that the aberrant expression of MTCP1 is of critical importance in leukemogenesis.


Asunto(s)
Leucemia Mieloide Aguda/genética , Proteínas Nucleares/genética , Fusión de Oncogenes , Translocación Genética , Regiones no Traducidas 5' , Adulto , Animales , Línea Celular Tumoral , Proliferación Celular , Células Cultivadas , Femenino , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Ratones , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo
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