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Triple-negative breast cancer (TNBC) has greater infiltration of M2-like macrophages (TAMs), which enhances cancer cell invasion and leads to a poor prognosis. TNBC progression is mediated by both tumor cells and the tumor microenvironment (TME). Here we elucidate the mechanism of the interaction between TNBC cells and TAMs. In this study, we confirmed that CD44v5 is highly expressed in TNBC, which drives TNBC cell metastasis and promotes TAM polarization by co-localizing with IL4Rα and inhibiting its internalization and degradation, thereby promoting activation of the STAT3/IL6 signaling axis. At the same time, TAMs also facilitate TNBC cell metastasis by secreting IL-4, IL-6, and other cytokines, in which the IL-4/IL-4R/STAT3/IL-6 signaling axis plays the same role for TNBC cells responding to TAMs. Moreover, we found that the above progress could be suppressed when the CD44v5 domain was blocked. We demonstrated that the CD44v5/IL-4R/STAT3/IL-6 signaling pathway plays a key role in TNBC cell metastasis, and in TNBC cells inducing TAM polarization and responding to TAMs, promoting metastasis. Collectively, we suggest that the CD44v5 domain may be a promising target for regulating the TME of TNBC as well as treating TNBC.
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Receptores de Hialuranos , Factor de Transcripción STAT3 , Transducción de Señal , Neoplasias de la Mama Triple Negativas , Microambiente Tumoral , Macrófagos Asociados a Tumores , Humanos , Factor de Transcripción STAT3/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Receptores de Hialuranos/metabolismo , Femenino , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Línea Celular Tumoral , Animales , Ratones , Interleucina-6/metabolismo , Subunidad alfa del Receptor de Interleucina-4/metabolismo , Subunidad alfa del Receptor de Interleucina-4/genética , Interleucina-4/metabolismoRESUMEN
IMPORTANCE: The biogenesis and clinical application of serum HBV pgRNA have been a research hotspot in recent years. This study further characterized the heterogeneity of the 3' terminus of capsid RNA by utilizing a variety of experimental systems conditionally supporting HBV genome replication and secretion, and reveal that the 3' truncation of capsid pgRNA is catalyzed by cellular ribonuclease(s) and viral RNaseH at positions after and before 3' DR1, respectively, indicating the 3' DR1 as a boundary between the encapsidated portion of pgRNA for reverse transcription and the 3' unprotected terminus, which is independent of pgRNA length and the 3' terminal sequence. Thus, our study provides new insights into the mechanism of pgRNA encapsidation and reverse transcription, as well as the optimization of serum HBV RNA diagnostics.
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Cápside , Genoma Viral , Virus de la Hepatitis B , ARN Viral , Replicación Viral , Cápside/metabolismo , Genoma Viral/genética , Hepatitis B/diagnóstico , Hepatitis B/virología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/crecimiento & desarrollo , Virus de la Hepatitis B/metabolismo , Transcripción Reversa , Ribonucleasa H/metabolismo , ARN Viral/genética , ARN Viral/metabolismo , Replicación Viral/genéticaRESUMEN
Calreticulin (CALR) mutations are frequent, disease-initiating events in myeloproliferative neoplasms (MPNs). Although the biological mechanism by which CALR mutations cause MPNs has been elucidated, there currently are no clonally selective therapies for CALR-mutant MPNs. To identify unique genetic dependencies in CALR-mutant MPNs, we performed a whole-genome clustered regularly interspaced short palindromic repeats (CRISPR) knockout depletion screen in mutant CALR-transformed hematopoietic cells. We found that genes in the N-glycosylation pathway (among others) were differentially depleted in mutant CALR-transformed cells as compared with control cells. Using a focused pharmacological in vitro screen targeting unique vulnerabilities uncovered in the CRISPR screen, we found that chemical inhibition of N-glycosylation impaired the growth of mutant CALR-transformed cells, through a reduction in MPL cell surface expression. We treated Calr-mutant knockin mice with the N-glycosylation inhibitor 2-deoxy-glucose (2-DG) and found a preferential sensitivity of Calr-mutant cells to 2-DG as compared with wild-type cells and normalization of key MPNs disease features. To validate our findings in primary human cells, we performed megakaryocyte colony-forming unit (CFU-MK) assays. We found that N-glycosylation inhibition significantly reduced CFU-MK formation in patient-derived CALR-mutant bone marrow as compared with bone marrow derived from healthy donors. In aggregate, our findings advance the development of clonally selective treatments for CALR-mutant MPNs.
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Calreticulina , Trastornos Mieloproliferativos , Animales , Calreticulina/genética , Calreticulina/metabolismo , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Glucosa , Glicosilación , Humanos , Janus Quinasa 2/genética , Ratones , Mutación , Trastornos Mieloproliferativos/genética , Receptores de Trombopoyetina/metabolismoRESUMEN
Molecular modification strategy exhibits great potential for electrocatalytic CO2 reduction. Here, DFT calculations were applied to study the mechanism of CO2 electroreduction on glycine modified copper. The results indicate that the interaction between the modified molecule and the intermediate could change the reaction energy of CO2 electroreduction.
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Although pressure ulcers are related to substantial health burdens, they may be preventable. Since nurses play a fundamental role in pressure ulcer prevention, their knowledge and attitude are of great importance. This study aims to investigate the current situation and associated factors of nurses' knowledge and attitude on the prevention of pressure ulcers from both tertiary and secondary hospitals. A total of 11 347 nurses were recruited including 7108 nurses (62.6%) from tertiary hospitals and 4239 nurses (37.4%) from secondary hospitals. The median (interquartile range) of the pressure ulcer knowledge score was 51% (38%, 90%) for all the participants with the lowest scores on prevention of pressure ulcers (51.33%). The mean (standard deviation) of attitude towards pressure ulcer prevention was 39.64 (4.65) with the lowest scores on personal competency to prevent pressure ulcers (mean 3.09). The results of multivariate linear regression showed that hospital level, nurses' age, years of work experience, initial education level at work and time of last training significantly associated with nurses' knowledge of pressure ulcer prevention. Meanwhile, hospital level, job title, previous training, time of last training and subjective needs for further training had significant association with nurses' attitude towards pressure ulcer prevention (all p < 0.05). Results showed inadequate knowledge but relative positive attitudes in nurses indicating the importance to deliver continuing education and training regarding pressure ulcer prevention in practice to improve the quality of care.
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Enfermeras y Enfermeros , Úlcera por Presión , Humanos , Estudios Transversales , Úlcera por Presión/prevención & control , Competencia Clínica , Encuestas y Cuestionarios , Conocimientos, Actitudes y Práctica en Salud , Centros de Atención Terciaria , ChinaRESUMEN
Triggering the lattice oxygen oxidation mechanism is crucial for improving oxygen evolution reaction (OER) performance, because it could bypass the scaling relation limitation associated with the conventional adsorbate evolution mechanism through the direct formation of oxygen-oxygen bond. High-valence transition metal sites are favorable for activating the lattice oxygen, but the deep oxidation of pre-catalysts suffers from a high thermodynamic barrier. Here, taking advantage of the Jahn-Teller (J-T) distortion induced structural instability, we incorporate high-spin Mn3+ ( t 2 g 3 e g 1 ${{t}_{2g}^{3}{e}_{g}^{1}}$ ) dopant into Co4N. Mn dopants enable a surface structural transformation from Co4N to CoOOH, and finally to CoO2, as observed by various in situ spectroscopic investigations. Furthermore, the reconstructed surface on Mn-doped Co4N triggers the lattice oxygen activation, as evidenced experimentally by pH-dependent OER, tetramethylammonium cation adsorption and online electrochemical mass spectrometry measurements of 18O-labelled catalysts. In general, this work not only offers the introducing J-T effect approach to regulate the structural transition, but also provides an understanding about the influence of the catalyst's electronic configuration on determining the reaction route, which may inspire the design of more efficient catalysts with activated lattice oxygen.
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Acidic water electrolysis enables the production of hydrogen for use as a chemical and as a fuel. The acidic environment hinders water electrolysis on non-noble catalysts, a result of the sluggish kinetics associated with the adsorbate evolution mechanism, reliant as it is on four concerted proton-electron transfer steps. Enabling a faster mechanism with non-noble catalysts will help to further advance acidic water electrolysis. Here, we report evidence that doping Ba cations into a Co3O4 framework to form Co3-xBaxO4 promotes the oxide path mechanism and simultaneously improves activity in acidic electrolytes. Co3-xBaxO4 catalysts reported herein exhibit an overpotential of 278 mV at 10 mA/cm2 in 0.5 M H2SO4 electrolyte and are stable over 110 h of continuous water oxidation operation. We find that the incorporation of Ba cations shortens the Co-Co distance and promotes OH adsorption, findings we link to improved water oxidation in acidic electrolyte.
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OBJECTIVE: To understand the status of therapeutic drug monitoring (TDM) in China Mainland, and thus lay down the foundation for further improvement in TDM. METHODS: In the present study, a nationwide questionnaire survey was conducted, which was distributed and collected using a mobile-based application. Clinicians, pharmacists, and clinical laboratory physicians belonging to different levels of public hospitals were involved as subjects/objects. The contents of the survey included TDM implementation in their hospital and information regarding their opinions and suggestions on TDM work. Mann-Whitney test was used to compare the difference between top tertiary hospitals and non-top tertiary hospitals. RESULTS: A total of 475 questionnaires were collected, 383 from top tertiary hospitals (3A hospitals) and 92 from non-top tertiary hospitals (other than 3A hospitals). A total of 240 clinicians, TDM pharmacists, and clinical laboratory physicians were involved, with an effective rate of 50.5%. Top tertiary hospitals were associated with certain advantages, such as the number of TDM testing facilities, annual sample size, number of monitoring varieties, and interpretation rate of monitoring reports, compared with non-top tertiary hospitals. In particular, ß-lactamase inhibitor, olanzapine, carbamazepine, and glucocorticoids seemed to be the main projects that clinicians wanted to assess. The drugs for which TDM was commonly performed included vancomycin, valproic acid, carbamazepine, phenytoin sodium, and methotrexate. The most commonly used detection methods include high-performance liquid chromatography, immunization, 2D-LC, and LC-MS. The monitoring concentration range was found to be inconsistent for most of the drugs. Currently, no unified regulation exists for TDM charges in China, which is no more than ¥200 in general. Clinicians rely on pharmacists for professional guidance. Importantly, improvement in the interpretation of monitoring reports, proficiency testing, and cooperation with clinical departments may aid in improving the level of TDM service. CONCLUSIONS: This survey objectively reflected the current status of TDM work in hospitals in China, and provided a strong reference base for devising strategies for improvement and effective execution of TDM work.
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Monitoreo de Drogas , Fenitoína , Humanos , Monitoreo de Drogas/métodos , Fenitoína/uso terapéutico , Encuestas y Cuestionarios , Carbamazepina , China , BenzodiazepinasRESUMEN
BACKGROUND: Skin tear knowledge is an important predictor of the decreased incidence and management of skin tears, and the knowledge level among Chinese nurses is unknown so far. A validated instrument for measuring skin tear knowledge is urgent. OBJECTIVE: To culturally adapt the skin tear knowledge assessment instrument (OASES) into Chinese and verify its validity and reliability in the Chinese context. METHODS: The cultural adaptation process for OASES into Chinese was established on Beaton's translation model. Content validity was determined by the 8-expert group in wound care. A nationwide psychometric validation study was performed on a convenience sample of 3333 nurses from 113 tertiary hospitals, of whom 98 nurses finished the test-retest procedure for reliability analysis. Item validity (item difficulty and discriminating index) and construct validity (known-groups technique) were tested. RESULTS: The content validity index was 0.88-1.00. The item validity was as follows: Item difficulty ranged from 0.16 to 0.86, with an average value of 0.52; the discriminating index varied between 0.05 and 0.61. The known-group technique demonstrated excellent construct validity with a significant difference between predefined groups with theoretically expected higher knowledge scores and theoretically expected lower knowledge scores (P < 0.001). For the test-retest reliability, the Intraclass correction coefficient (ICC) during a 14-day interval for the overall tool was 0.79 (95% CI = 0.71-0.86), and Cohen's kappa value for each item varied from 0.17 to 0.62. CONCLUSIONS: The Chinese version of OASES was validated to be suitable for skin tear knowledge assessment with acceptable psychometric properties, through which the knowledge and training priorities of skin tear among Chinese nurses can be quantified.
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Proyectos de Investigación , Traducciones , Humanos , Reproducibilidad de los Resultados , Psicometría , Encuestas y CuestionariosRESUMEN
BACKGROUND: Whether serum hepatitis B virus (HBV) RNA associates with hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients has not been fully elucidated. METHODS: We enrolled 2974 patients receiving nucleos(t)ide analogues (NAs) from a prospective, observational CHB cohort to investigate the effect of serum HBV RNA, measured at study entry (baseline), on HCC development, using Cox regression analyses. RESULTS: During median follow-up of 4.4 years, 90 patients developed HCC. Patients with detectable baseline HBV RNA (nâ =â 2072) exhibited significantly higher HCC risk than those with undetectable level (5-year HCC incidence estimated by Kaplan-Meier method: 4.1% versus 1.8%, Pâ =â .009; adjusted hazard ratio [aHR]â =â 2.21, Pâ =â .005). HBV RNA levels of 609-99 999 andâ ≥100 000 copies/mL were associated with incrementally increasing HCC risk (aHRâ =â 2.15 and 3.05, respectively; P for trendâ =â .003), compared to undetectable level (<609 copies/mL). Moreover, patients with single-detectable either HBV DNA or RNA and double-detectable DNA and RNA had 1.57- and 4.02-fold higher HCC risk, respectively, than those with double-undetectable DNA and RNA (P for trendâ =â .001). CONCLUSIONS: High-level HBV RNA is associated with increased HCC risk in NAs-treated patients. Achieving undetectable HBV RNA may contribute to better clinical outcomes, indicating it could be a valuable endpoint of anti-HBV treatment.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Antivirales/farmacología , Carcinoma Hepatocelular/epidemiología , ADN Viral , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/epidemiología , Nucleósidos/farmacología , Estudios Prospectivos , ARNRESUMEN
Alterations to N-glycan expression are relevant to the progression of various diseases, particularly cancer. In many cases, specific N-glycan structural features such as sialylation, fucosylation, and branching are of specific interest. A novel MALDI imaging mass spectrometry workflow has been recently developed to analyze these features of N-glycosylation through the utilization of endoglycosidase enzymes to cleave N-glycans from associated glycoproteins. Enzymes that have previously been utilized to cleave N-glycans include peptide-N-glycosidase F (PNGase F) to target N-glycans indiscriminately and endoglycosidase F3 (Endo F3) to target core fucosylated N-glycans. In addition to these endoglycosidases, additional N-glycan cleaving enzymes could be used to target specific structural features. Sialidases, also termed neuraminidases, are a family of enzymes that remove terminal sialic acids from glycoconjugates. This work aims to utilize sialidase, in conjunction with PNGase F/Endo F3, to enzymatically remove sialic acids from N-glycans in an effort to increase sensitivity for nonsialylated N-glycan MALDI-IMS peaks. Improving detection of nonsialylated N-glycans allows for a more thorough analysis of specific structural features such as fucosylation or branching, particularly of low abundant structures. Sialidase utilization in MALDI-IMS dramatically increases sensitivity and increases on-tissue endoglycosidase efficiency, making it a very useful companion technique to specifically detect nonsialylated N-glycans.
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Neuraminidasa , Polisacáridos , Glicoproteínas/metabolismo , Glicósido Hidrolasas/metabolismo , Manosil-Glicoproteína Endo-beta-N-Acetilglucosaminidasa , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa , Polisacáridos/química , Ácidos Siálicos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
The carbon-carbon (C-C) bond formation is essential for the electroconversion of CO2 into high-energy-density C2+ products, and the precise coupling pathways remain controversial. Although recent computational investigations have proposed that the OC-COH coupling pathway is more favorable in specific reaction conditions than the well-known CO dimerization pathway, the experimental evidence is still lacking, partly due to the separated catalyst design and mechanistic/spectroscopic exploration. Here, we employ density functional theory calculations to show that on low-coordinated copper sites, the *CO bindings are strengthened, and the adsorbed *CO coupling with their hydrogenation species, *COH, receives precedence over CO dimerization. Experimentally, we construct a fragmented Cu catalyst with abundant low-coordinated sites, exhibiting a 77.8% Faradaic efficiency for C2+ products at 300 mA cm-2. With a suite of in situ spectroscopic studies, we capture an *OCCOH intermediate on the fragmented Cu surfaces, providing direct evidence to support the OC-COH coupling pathway. The mechanistic insights of this research elucidate how to design materials in favor of OC-COH coupling toward efficient C2+ production from CO2 reduction.
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The balance between T helper type 1 (Th1) and T helper type 2 (Th2) cells is critical for both innate and acquired immune reactions. However, the precise mechanisms of T helper-cell differentiation remain unclear. As an important T-cell activation molecule, CD44 participates in the differentiation of Th1 and Th2 cells. We demonstrated that CD44 variant exon v5 (CD44 v5) is highly expressed by induced human Th2 cells. To investigate the role of the CD44 v5 domain in Th2 cell differentiation, we treated human CD4+ T cells with anti-CD44v5 antibody and observed that the levels of phosphorylated STAT6 and GATA3 and the secretion of interleukin-4 (IL-4) were significantly decreased after the treatment. We also further found that the inhibition of Th2 differentiation was caused by the degradation of the alpha chain of IL-4 receptor (IL-4Rα), the CD44 v5 domain colocalized with IL-4Rα on cell surface and the degradation of IL-4Rα increased after CD44 v5 domain blocking or ablating. Our results indicated that CD44v5 antibody treatment interrupted the interaction between CD44 v5 domain and IL-4Rα, but the CD44 v5 domain blockage would not spoil the colocalization between IL-4R expression and T-cell receptor and the immunological synapse formation; similar results were also found in CD44v5-deficient CD4+ T cells. In conclusion, we revealed the function of the CD44 v5 domain in Th2 cell differentiation; blocking or ablating the CD44 v5 domain could accelerate IL-4Rα degradation and then induce the Th2 cell inhibition.
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Receptores de Hialuranos/genética , Interleucina-4 , Receptores de Interleucina-4 , Células Th2 , Animales , Diferenciación Celular , Polaridad Celular , Humanos , Interleucina-4/metabolismo , Ratones , Ratones Endogámicos BALB C , Receptores de Interleucina-4/metabolismo , Transducción de Señal , Células TH1RESUMEN
INTRODUCTION: Salvia miltiorrhiza is a frequently used herb in traditional Chinese medicine, and tanshinone IIA (Tan IIA) and salvianolic acid B (Sal Acid B) are two major extracts obtained from its dried root. The quality of herbal ingredients can be affected by environmental factors. OBJECTIVE: To evaluate the quality of wild S. miltiorrhiza and investigate the influence of soil constituents and parameters as well as climatic conditions and factors on the content of Tan IIA and Sal Acid B. METHODOLOGY: We collected samples in 12 natural locations in the Dao Di area in China, the area in which S. miltiorrhiza grows, that results in a distinctive higher quality of medicinal materials from the harvested plant. The concentrations of Tan IIA and Sal Acid B were measured by high-performance liquid chromatography (HPLC). Soil total carbon, total nitrogen, available nitrogen, available phosphorus, available potassium, and particle size distribution were determined. We also collected climate data using ArcGIS from the WorldClim database, and correlation tests, redundancy, and regression analyses were conducted to analyse the relationship and cluster the samples according to their chemical profile. RESULTS: The content of Tan IIA and Sal Acid B in most of the samples was significantly different (P < 0.05). Soil available phosphorus was considered as a key factor that influenced the quality of wild S. miltiorrhiza, and we found a significant negative association between the concentration of Tan IIA in roots and soil available phosphorus. Moreover, the accumulation of Tan IIA in S. miltiorrhiza was also significantly associated with precipitation in April, May, and October, maximum temperature in January, and standard deviation of temperature seasonality. There was no significant correlation between the content of Sal Acid B and ecological factors. In addition, samples collected from Mengshan, Hexian, and Lushi locations were rich in Tan IIA and tended to cluster together, whereas samples collected from Longquan and Huoshan locations tended to cluster and were poor in Tan IIA. CONCLUSION: The Tan IIA content in samples collected from southern Anhui was significantly lower than that in other Dao Di locations. The content of Tan IIA was related more to the soil than the temperature. Compared with Tan IIA, Sal Acid B was less influenced by soil and climate factors. The findings of this study may provide helpful references for quality control of medicinal plants that exert pharmacological effects in humans.
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Medicamentos Herbarios Chinos , Salvia miltiorrhiza , China , Cromatografía Líquida de Alta Presión , Raíces de Plantas , SueloRESUMEN
Compassionate use may play an important role in responding to major public health emergencies. The Jinyintan Hospital in Wuhan launched the III phase of clinical trials of antiviral drug-remdesivir on February 6, 2020. As an unapproved drug, remdesivir raised great concerns about compassionate use in China. Compassionate use is therapeutic use of unauthorized drugs outside of clinical trials. It is used for critically ill patients with life-threatening diseases and no effective treatment means in China. Patients voluntarily apply to their medical institutions. The Center for Drug Evaluation, National Medical Products Administration shall conduct scientific and reasonable review, approval, and supervision on patients' application for compassionate medication. By analyzing and comparing the current situation of compassionate use at home and abroad, it is expected to provide thinking for the development of compassionate use system in China.
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Ensayos de Uso Compasivo , Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Ensayos Clínicos Fase III como Asunto , HumanosRESUMEN
Specific alterations in N-linked glycans, such as core fucosylation, are associated with many cancers and other disease states. Because of the many possible anomeric linkages associated with fucosylated N-glycans, determination of specific anomeric linkages and the site of fucosylation (i.e., core vs outer arm) can be difficult to elucidate. A new MALDI mass spectrometry imaging workflow in formalin-fixed clinical tissues is described using recombinant endoglycosidase F3 (Endo F3), an enzyme with a specific preference for cleaving core-fucosylated N-glycans attached to glycoproteins. In contrast to the broader substrate enzyme peptide-N-glycosidase F (PNGaseF), Endo F3 cleaves between the two core N-acetylglucosamine residues at the protein attachment site. On tissues, this results in a mass shift of 349.137 a.m.u. for core-fucosylated N-glycans when compared to N-glycans released with standard PNGaseF. Endo F3 can be used singly and in combination with PNGaseF digestion of the same tissue sections. Initial results in liver and prostate tissues indicate core-fucosylated glycans associated to specific tissue regions while still demonstrating a diverse mix of core- and outer arm-fucosylated glycans throughout all regions of tissue. By determining these specific linkages while preserving localization, more targeted diagnostic biomarkers for disease states are possible without the need for microdissection or solubilization of the tissue.
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Acetilglucosamina , Polisacáridos , Glicosilación , Humanos , Masculino , Manosil-Glicoproteína Endo-beta-N-Acetilglucosaminidasa , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
BACKGROUND AND PURPOSE: The optimal recanalization strategy for acute ischemic stroke with large vessel occlusion continues to be an area of active interest. Network meta-analysis can provide insight when direct comparative evidence is lacking. METHODS: A systematic review of the literature using PubMed, Embase, the Cochrane Central Register of Controlled Trials, and SinoMed was performed, and a search was conducted for clinical trials on ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and StrokeCenter.org. Four independent reviewers conducted the study selection, data abstraction, and quality assessments. RESULTS: The literature review identified 17 trials including 3236 patients and 8 ongoing clinical trials. Sample sizes ranged from 7 to 656 participants. Intravenous thrombolysis (IVT) was the most common intervention, followed by IVT plus mechanical thrombectomy (MT), IVT plus intraarterial thrombolysis, intraarterial thrombolysis alone, and MT alone. In the pooled network meta-analysis, IVT+MT was associated with a higher rate of independent functioning. In contrast, IVT was ranked as the most ineffective treatment strategy with respect to neurological functions, while direct MT was ranked as the least safe intervention with respect to all-cause mortality. Also, irrespective of assessment tools, endovascular treatment plus IVT led to higher successful recanalization rate than thrombolysis alone. CONCLUSIONS: Compared with other recanalization treatments, IVT+MT seems to be the most effective strategy, without increasing detrimental effects, for thrombolysis-eligible patients with large vessel occlusion-acute ischemic stroke. To improve the current evidentiary basis for recanalization treatment, future trials and real-world studies are warranted and should use unified definitions of symptomatic intracranial hemorrhage and recanalization.
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Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Femenino , Humanos , Hemorragias Intracraneales/tratamiento farmacológico , Masculino , Trombolisis Mecánica/métodos , Persona de Mediana Edad , Trombectomía/métodos , Terapia Trombolítica/métodosRESUMEN
A new platform for N-glycoprotein analysis from serum that combines matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) workflows with antibody slide arrays is described. Antibody panel based (APB) N-glycan imaging allows for the specific capture of N-glycoproteins by antibodies on glass slides and N-glycan analysis in a protein-specific and multiplexed manner. Development of this technique has focused on characterizing two abundant and well-studied human serum glycoproteins, alpha-1-antitrypsin and immunoglobulin G. Using purified standard solutions and 1 µL samples of human serum, both glycoproteins can be immunocaptured and followed by enzymatic release of N-glycans. N-Glycans are detected with a MALDI FT-ICR mass spectrometer in a concentration-dependent manner while maintaining specificity of capture. Importantly, the N-glycans detected via slide-based antibody capture were identical to that of direct analysis of the spotted standards. As a proof of concept, this workflow was applied to patient serum samples from individuals with liver cirrhosis to accurately detect a characteristic increase in an IgG N-glycan. This novel approach to protein-specific N-glycan analysis from an antibody panel can be further expanded to include any glycoprotein for which a validated antibody exists. Additionally, this platform can be adapted for analysis of any biofluid or biological sample that can be analyzed by antibody arrays.
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Biomarcadores/metabolismo , Glicómica/métodos , Glicoproteínas/metabolismo , Cirrosis Hepática/diagnóstico , Imagen Óptica/métodos , Polisacáridos/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Estudios de Casos y Controles , Glicoproteínas/química , Glicosilación , Humanos , Cirrosis Hepática/metabolismo , Polisacáridos/químicaRESUMEN
Silver nanocones with tunable plasmon resonances and high refractive index (RI) sensitivity have attracted much attention. Herein, through systematic measuring of the RI sensitivities of silver nanocones with different geometric parameters, the size and shape effects are investigated. The results show that RI sensitivities increase as silver nanocones become longer and the widths of their heads become smaller. Through engineering of the outline symmetry, the silver nanocones exhibit RI sensitivity as high as 910 nm/RIU (RI unit) and the figure of merit arrives at 3.8.
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Geological events have been shown to be the main factors affecting the distributions and population genetic structure of species. However, the impact of the Yellow River, the second longest river in China, on the distribution and genetic structure of the endemic flora remains largely unknown. Here, we used microsatellites to evaluate the genetic structure of Tamarix austromongolica and Tamarix chinensis (343 individuals in total), two endemic tree species widely distributed along the Yellow River, as well as the role of river drainages in shaping the structure. We found that frequent gene flow resulted in low genetic differentiation among populations within species (T. austromongolica: Fst = 0.144, Nm = 1.486; T. chinensis: Fst = 0.103, Nm = 2.177); and low levels of genetic differentiation were detected between populations within species on the north and south banks. Also, high gene flow was found between populations in the upper reaches and those in the middle reaches, and middle reaches and lower reaches of the Yellow River (T. austromongolica: Fst = 0.023, Nm = 10.619; T. chinensis: Fst = 0.045, Nm = 5.306). Additionally, discriminant analysis of principal components (DAPC) and Bayesian analysis revealed a weak population structure in T. austromongolica and T. chinensis. Therefore, the Yellow River does not act as a barrier to dispersal and gene flow for Tamarix. Our findings provide support for the role of the river in shaping the spatial distribution and the genetic structure of species.