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1.
Biotechnol Lett ; 45(8): 939-953, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37243777

RESUMEN

White rot fungi is a kind of filamentous fungi which can degrade lignin, hemicellulose and cellulose effectively. In this study, a wild white rot fungi collected from Pingba Town, Bijie City of China was identified as Coprinellus disseminatus (fruiting body) based on morphological and molecular identification. The mycelium of C. disseminatus cultured in the medium supplemented xylan as carbon showed the higher xylanase (XLE) and cellulase (CLE) activity. Further, the activities of tissue degradation-related enzymes including XLE, CLE, acetyl xylanesterase (AXE) and α-L-arabinofuran glycosidase (α-L-AF) were determined after fermenting Eucommia ulmoides leaves by inoculating C. disseminatus mycelium. The results showed that the activities of XLE, CLE, AXE and α-L-AF of mycelium cultured in xylan-contained medium reached the maximum at 5 d after inoculation, which were 777.606 ± 4.248 U mL-1, 9.594 ± 0.008 U mL-1, 4.567 ± 0.026 U mL-1 and 3.497 ± 0.10 U mL-1 respectively. Also, the activities of AXE and α-L-AF both reached the maximum in C. disseminatus mycelium cultured in glucose-contained medium. By comparing the yield of E. ulmoides gum under different fermentation treatments, the extraction yield of E. ulmoides gum were 2.156 ± 0.031% and 2.142 ± 0.044% at 7 d and 14 d after fermentation with mycelium supplemented xylan as carbon source, which were significantly higher than other groups. This study provides a theoretical reference for the preparation of E. ulmoides gum by large-scale fermentation of E. ulmoides leaves with C. disseminatus.


Asunto(s)
Ascomicetos , Basidiomycota , Eucommiaceae , Eucommiaceae/metabolismo , Xilanos/metabolismo , Hojas de la Planta/metabolismo , Carbono/metabolismo
2.
BMC Biotechnol ; 22(1): 18, 2022 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-35787694

RESUMEN

BACKGROUND: Tetramethylpyrazine (TTMP) is a flavoring additive that significantly contributes to the formation of flavor compounds in soybean-based fermented foods. Over recent years, the application of TTMP in the food industry and medicine has been widely investigated. In addition, several methods for the industrial-scale production of TTMP, including chemical and biological synthesis, have been proposed. However, there have been few reports on the synthesis of TTMP through amino acid metabolic flux. In this study, we investigated genetic alterations of arginine metabolic flux in solid-state fermentation (SSF) of soybeans with Bacillus subtilis (B.subtilis) BJ3-2 to enhance the TTMP yield. RESULTS: SSF of soybeans with BJ3-2 exhibited a strong Chi-flavour (a special flavour of ammonia-containing smelly distinct from natto) at 37 °C and a prominent soy sauce-like aroma at 45 °C. Transcriptome sequencing and RT-qPCR verification showed that the rocF gene was highly expressed at 45 °C but not at 37 °C. Moreover, the fermented soybeans with BJ3-2ΔrocF (a rocF knockout strain in B. subtilis BJ3-2 were obtained by homologous recombination) at 45 °C for 72 h displayed a lighter color and a slightly decreased pH, while exhibiting a higher arginine content (increased by 14%) than that of BJ3-2. However, the ammonia content of fermented soybeans with BJ3-2ΔrocF was 43% lower than that of BJ3-2. Inversely, the NH4+ content in fermented soybeans with BJ3-2ΔrocF was increased by 28% (0.410 mg/kg). Notably, the TTMP content in fermented soybeans with BJ3-2ΔrocF and BJ3-2ΔrocF + Arg (treated with 0.05% arginine) were significantly increased by 8.6% (0.4617 mg/g) and 18.58% (0.504 mg/g) respectively than that of the BJ3-2. CONCLUSION: The present study provides valuable information for understanding the underlying mechanism during the TTMP formation process through arginine metabolic flux.


Asunto(s)
Glycine max , Alimentos de Soja , Amoníaco/metabolismo , Arginina/metabolismo , Bacillus subtilis/genética , Pirazinas , Glycine max/genética , Glycine max/metabolismo
3.
BMC Cancer ; 22(1): 650, 2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35698100

RESUMEN

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .


Asunto(s)
Neoplasias Esofágicas , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Neoplasias Esofágicas/patología , Humanos , Estudios Multicéntricos como Asunto , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
4.
Mol Cell Biochem ; 428(1-2): 1-8, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27995415

RESUMEN

This study is to investigate the role of adenovirus 36 (Ad36) in regulating expression of peroxisome proliferator-activated receptor γ (PPARγ) and cell death-inducing DFFA-like effector c (CIDEC) in Ad36-induced adipocyte differentiation. Human adipose-derived mesenchymal stem cells (hAMSCs) were isolated and cultured, and then infected with Ad36. Ad36-induced adipocytes were identified using quantitative real-time PCR and Oil red O staining. The expression levels of PPARγ and CIDEC in Ad36-induced adipocytes were determined by quantitative real-time PCR and Western blot analysis. Glucose uptake and intracellular triglyceride content were also determined in these induced cells. Our results from the Oil red O staining showed that Ad36 induced the differentiation of hAMSCs into human adipocytes in vitro. Moreover, the medium glucose concentration was significantly decreased, while the intracellular triglyceride content was significantly increased, in the Ad36-induced adipocytes, compared with the control group. Furthermore, our results showed that, the mRNA and protein expression levels of PPARγ and CIDEC were significantly upregulated in Ad36-induced adipocytes, in a time-dependent manner. On the other hand, compared with the control group, the CIDEC expression was downregulated when the Ad36-induced adipocytes were treated with the PPARγ inhibitor, GW9662. Ad36 could upregulate the expression level of CIDEC through increasing PPARγ expression during the adipocyte differentiation process.


Asunto(s)
Adenoviridae/fisiología , Adipocitos/citología , Células Madre Mesenquimatosas/virología , PPAR gamma/genética , Proteínas/genética , Adipocitos/metabolismo , Adipocitos/virología , Anilidas/farmacología , Proteínas Reguladoras de la Apoptosis , Diferenciación Celular , Células Cultivadas , Glucosa/metabolismo , Humanos , Células Madre Mesenquimatosas/citología , PPAR gamma/metabolismo , Proteínas/metabolismo , Factores de Tiempo , Triglicéridos/metabolismo , Regulación hacia Arriba/efectos de los fármacos
5.
Biol Pharm Bull ; 40(3): 249-255, 2017 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-27990002

RESUMEN

To determine the combined effect of type 2 diabetes (T2D) and chronic cerebral hypoperfusion (CCH) on learning and spatial memory, we developed a rat model of CCH by permanent occlusion of bilateral common carotid arteries (2-vessel occlusion (2VO)) in high-fat diet (HFD)-fed rats injected with low-dose streptozotocin (STZ). Furthermore, we examined the effect of cinepazide maleate (CM) on cognitive deficits and brain damage in this rat model. Rats were maintained on HFD for 6 weeks and then injected with 35 mg/kg STZ to induce T2D. Sham or 2VO surgery was performed in non-diabetic or diabetic (DM) rats to obtain four groups: blank, DM, CCH, and DM-CCH groups. Cognitive function was tested by the Morris water maze (MWM) test. To determine the effects of the vasodilator cinepazide maleate (CM) on cognitive deficits and brain damage, DM-CCH rats were administered with 10 mg/kg CM or saline daily for 14 d. Neuronal damage in DM-CCH rats was associated with increased expression of glial fibrillary acidic protein (GFAP) and ß-secretase 1 (BACE1), but decreased expression of choline acetyltransferase (ChAT). Moreover, the levels of all these proteins were significantly alleviated by CM treatment. These results suggest that T2D exacerbated CCH-induced brain damage and cognitive impairment, and CM ameliorated these effects.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Trastornos del Conocimiento/tratamiento farmacológico , Cognición/efectos de los fármacos , Diabetes Mellitus Tipo 2/complicaciones , Aprendizaje/efectos de los fármacos , Piperazinas/uso terapéutico , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Ácido Aspártico Endopeptidasas/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/metabolismo , Colina O-Acetiltransferasa/metabolismo , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta Alta en Grasa , Proteína Ácida Fibrilar de la Glía/metabolismo , Hipocampo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Neuronas , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Piperazinas/farmacología , Ratas Sprague-Dawley , Memoria Espacial/efectos de los fármacos , Vasodilatadores/farmacología , Vasodilatadores/uso terapéutico
6.
Nano Lett ; 16(12): 7650-7654, 2016 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-27960444

RESUMEN

We demonstrate for the first time that a single-crystalline epitaxial MgxCa1-xO film can be deposited on gallium nitride (GaN) by atomic layer deposition (ALD). By adjusting the ratio between the amounts of Mg and Ca in the film, a lattice matched MgxCa1-xO/GaN(0001) interface can be achieved with low interfacial defect density. High-resolution X-ray diffraction (XRD) shows that the lattice parameter of this ternary oxide nearly obeys Vegard's law. An atomically sharp interface from cross-sectional transmission electron microscopy (TEM) confirmed the high quality of the epitaxy. High-temperature capacitance-voltage characterization showed that the film with composition Mg0.25Ca0.75O has the lowest interfacial defect density. With this optimal oxide composition, a Mg0.25Ca0.75O/AlGaN/GaN metal-oxide-semiconductor high-electron-mobility (MOS-HEMT) device was fabricated. An ultrahigh on/off ratio of 1012 and a near ideal SS of 62 mV/dec were achieved with this device.

7.
Yi Chuan ; 38(6): 543-559, 2016 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-27655316

RESUMEN

Over the last decade, a larger number of type 2 diabetes mellitus (T2DM) susceptible candidate genes have been reported by numerous genome-wide association studies (GWAS). Understanding the genetic diversity of these candidate genes among worldwide populations not only facilitates to elucidating the genetic mechanism of T2DM, but also provides guidance to further studies of pathogenesis of T2DM in any certain population. In this study, we identified 170 genes or genomic regions associated with T2DM by searching the GWAS databases and related literatures. We next analyzed the genetic diversity of these genes (or genomic regions) among present-day human populations by curetting the 1000 Genomes Projects phase1 dataset covering 14 worldwide populations. We further compared the characteristics of T2DM genes in different populations. No significant differences of genetic diversity were observed among the 14 worldwide populations between the T2DM candidate genes and the non-T2DM genes in terms of overall pattern. However, we observed some genes, such as IL20RA, RNMTL1-NXN, NOTCH2, ADRA2A-BTBD7P2, TBC1D4, RBM38-HMGB1P1, UBE2E2, and PPARD, show considerable differentiation between populations. In particular, IL20RA (FST=0.1521) displays the greatest population difference which is mainly contributed by that between Africans and non-Africans. Moreover, we revealed genetic differences between East Asians and Europeans on some candidate genes such as DGKB-AGMO (FST=0.173) and JAZF1 (FST=0.182). Our results indicate that some T2DM susceptible candidate genes harbor highly-differentiated variants between populations. These analyses, despite preliminary, should advance our understanding of the population difference of susceptibility to T2DM and provide insightful reference that future studies can relay on.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , África , Pueblo Asiatico/genética , Europa (Continente) , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos
8.
Biol Pharm Bull ; 38(6): 827-35, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25787895

RESUMEN

Dendritic cell (DC)-based vaccines are a promising therapeutic modality for cancer. Results from recent trials and approval of the first DC vaccine by the U.S. Food and Drugs Administration for prostate cancer have paved the way for DC-based vaccines. A total of 21 hormone refractory prostate cancer (HRPC) patients with a life expectancy >3 months were randomised into two groups. DC loaded with recombinant Prostate Specific Membrane Antigen (rPSMA) and recombinant Survivin (rSurvivin) peptides was administered as an subcutaneous (s.c.) injection (5×10(6) cells). Docetaxel (75 mg/m(2) intravenous (i.v.)) and prednisone (5 mg, bis in die (b.i.d.)) served as control. Clinical and immunological responses were evaluated. Primary endpoints were safety and feasibility; secondary endpoint was overall survival. Responses were evaluated on day 15, day 30, day 60, and day 90. DC vaccination was well tolerated with no signs of grade 2 toxicity. DC vaccination induced delayed-type hypersensitivity reactivity and an immune response in all patients. Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumours (RECIST) was 72.7% (8/11) versus 45.4 (5/11) in the docetaxel arm and immune related response criteria (irRC) was 54.5% (6/11) compared with 27.2% (3/11) in the control arm. The DC arm showed stable disease (SD) in 6 patients, progressive disease (PD) in 3 patients, and partial remission (PR) in two patients compared to SD in 5 patients, PD in 6 patients, and PR in none in the docetaxel arm. There was a cellular response, disease stabilization, no adverse events, and partial remission with the rPSMA and rSurvivin primed DC vaccine.


Asunto(s)
Antineoplásicos/uso terapéutico , Vacunas contra el Cáncer , Células Dendríticas , Proteínas Inhibidoras de la Apoptosis/uso terapéutico , Antígeno Prostático Específico/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Vacunación , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias , Antineoplásicos/farmacología , Docetaxel , Humanos , Hipersensibilidad Tardía/inmunología , Proteínas Inhibidoras de la Apoptosis/farmacología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias , Antígeno Prostático Específico/farmacología , Neoplasias de la Próstata/inmunología , Survivin , Taxoides/farmacología , Taxoides/uso terapéutico
9.
Cancers (Basel) ; 16(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38275900

RESUMEN

Once considered "undruggable" due to the strong affinity of RAS proteins for GTP and the structural lack of a hydrophobic "pocket" for drug binding, the development of proprietary therapies for KRAS-mutant tumors has long been a challenging area of research. CRISPR technology, the most successful gene-editing tool to date, is increasingly being utilized in cancer research. Here, we provide a comprehensive review of the application of the CRISPR system in basic and translational research in KRAS-mutant cancer, summarizing recent advances in the mechanistic understanding of KRAS biology and the underlying principles of drug resistance, anti-tumor immunity, epigenetic regulatory networks, and synthetic lethality co-opted by mutant KRAS.

10.
Mar Pollut Bull ; 201: 116197, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38422827

RESUMEN

Phytoplankton's death contributes to marine settleable particulate organic matter (POM). In this study, we used laboratory cultivation of different algal species to identify a positive correlation between the cumulative number of dead algal cells and POC>75 (carbon content of the settleable POM). The contribution coefficient of cell death to POC>75 varied among different algal species. Additionally, the field survey and incubation experiment were conducted in the East China Sea (ECS) to explore the spatial-temporal correlation between phytoplankton death and POC>75. The results concluded that phytoplankton death was the main factor controlling POC>75. In the ECS, the relationship between the surface cumulative mass of POC>75 and the cumulative number of dead cells followed: Cumulative mass of POC>75(mg) = 0.487 × Cumulative number of dead cells (/104) + 0.069. This study provided a methodology to quantitatively explain the relationship between phytoplankton death and settleable POM.


Asunto(s)
Carbono , Fitoplancton , Carbono/análisis , Fitoplancton/fisiología , Material Particulado/análisis , Polvo , Muerte Celular , China
11.
Biomolecules ; 14(2)2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38397465

RESUMEN

Mitophagy, a conserved cellular mechanism, is crucial for cellular homeostasis through the selective clearance of impaired mitochondria. Its emerging role in cancer development has sparked interest, particularly in lung adenocarcinoma (LUAD). Our study aimed to construct a risk model based on mitophagy-related genes (MRGs) to predict survival outcomes, immune response, and chemotherapy sensitivity in LUAD patients. We mined the GeneCards database to identify MRGs and applied LASSO/Cox regression to formulate a prognostic model. Validation was performed using two independent Gene Expression Omnibus (GEO) cohorts. Patients were divided into high- and low-risk categories according to the median risk score. The high-risk group demonstrated significantly reduced survival. Multivariate Cox analysis confirmed the risk score as an independent predictor of prognosis, and a corresponding nomogram was developed to facilitate clinical assessments. Intriguingly, the risk score correlated with immune infiltration levels, oncogenic expression profiles, and sensitivity to anticancer agents. Enrichment analyses linked the risk score with key oncological pathways and biological processes. Within the model, MTERF3 emerged as a critical regulator of lung cancer progression. Functional studies indicated that the MTERF3 knockdown suppressed the lung cancer cell proliferation and migration, enhanced mitophagy, and increased the mitochondrial superoxide production. Our novel prognostic model, grounded in MRGs, promises to refine therapeutic strategies and prognostication in lung cancer management.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Pronóstico , Mitofagia/genética , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Biología
12.
Front Immunol ; 15: 1371831, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38840910

RESUMEN

Introduction: Lung cancer, with the highest global mortality rate among cancers, presents a grim prognosis, often diagnosed at an advanced stage in nearly 70% of cases. Recent research has unveiled a novel mechanism of cell death termed disulfidptosis, which is facilitated by glucose scarcity and the protein SLC7A11. Methods: Utilizing the least absolute shrinkage and selection operator (LASSO) regression analysis combined with Cox regression analysis, we constructed a prognostic model focusing on disulfidptosis-related genes. Nomograms, correlation analyses, and enrichment analyses were employed to assess the significance of this model. Among the genes incorporated into the model, CHRNA5 was selected for further investigation regarding its role in LUAD cells. Biological functions of CHRNA5 were assessed using EdU, transwell, and CCK-8 assays. Results: The efficacy of the model was validated through internal testing and an external validation set, with further evaluation of its robustness and clinical applicability using a nomogram. Subsequent correlation analyses revealed associations between the risk score and infiltration of various cancer types, as well as oncogene expression. Enrichment analysis also identified associations between the risk score and pivotal biological processes and KEGG pathways. Our findings underscore the significant impact of CHRNA5 on LUAD cell proliferation, migration, and disulfidptosis. Conclusion: This study successfully developed and validated a robust prognostic model centered on disulfidptosis-related genes, providing a foundation for predicting prognosis in LUAD patients.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Nomogramas , Receptores Nicotínicos , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Pronóstico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/patología , Receptores Nicotínicos/genética , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Proteínas del Tejido Nervioso/genética , Línea Celular Tumoral , Masculino , Proliferación Celular/genética , Femenino
13.
Artículo en Inglés | MEDLINE | ID: mdl-38936342

RESUMEN

OBJECTIVES: Thoracoscopic segmentectomy is the recommended treatment option for small peripheral pulmonary nodules. To assess the ability of preoperative 3D reconstruction CT to shorten the operative time and improve perioperative outcomes in thoracoscopic segmentectomy compared with standard chest CT, we conducted this randomized controlled trial. METHODS: The DRIVATS study was a multicentre, randomized controlled trial conducted in three hospitals between July 2019 and November 2023. Patients with small peripheral pulmonary nodules not reaching segments borders were randomized in a 1:1 ratio to receive either 3D reconstruction CT or standard chest CT before thoracoscopic segmentectomy. The primary end-point was operative time. The secondary end-points included incidence of postoperative complications, intraoperative blood loss and operative accident event. RESULTS: A total of 191 patients were enrolled in this study: 95 in the 3D reconstruction CT group and 96 in the standard chest CT group. All patients underwent thoracoscopic segmentectomy except for one patient in the standard chest CT group who received a wedge resection. There is no significant difference in operative time between the 3D reconstruction CT group (median, 100 min [IQR, 85-120]) and the standard chest CT group (median, 100 min [IQR, 81-140]) (P = 0.82). Only one intraoperative complication occurred in the standard chest CT group. No significant difference was observed in the incidence of postoperative complications between the two groups (P = 0.52). Other perioperative outcomes were also similar. CONCLUSIONS: In patients with small peripheral pulmonary nodules not reaching segments borders, the use of 3D reconstruction CT in thoracoscopic segmentectomy was feasible, but it did not result in significant differences in operative time or perioperative outcomes compared to standard chest CT.

14.
Nat Nanotechnol ; 19(3): 319-329, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38135719

RESUMEN

Electronic devices for recording neural activity in the nervous system need to be scalable across large spatial and temporal scales while also providing millisecond and single-cell spatiotemporal resolution. However, existing high-resolution neural recording devices cannot achieve simultaneous scalability on both spatial and temporal levels due to a trade-off between sensor density and mechanical flexibility. Here we introduce a three-dimensional (3D) stacking implantable electronic platform, based on perfluorinated dielectric elastomers and tissue-level soft multilayer electrodes, that enables spatiotemporally scalable single-cell neural electrophysiology in the nervous system. Our elastomers exhibit stable dielectric performance for over a year in physiological solutions and are 10,000 times softer than conventional plastic dielectrics. By leveraging these unique characteristics we develop the packaging of lithographed nanometre-thick electrode arrays in a 3D configuration with a cross-sectional density of 7.6 electrodes per 100 µm2. The resulting 3D integrated multilayer soft electrode array retains tissue-level flexibility, reducing chronic immune responses in mouse neural tissues, and demonstrates the ability to reliably track electrical activity in the mouse brain or spinal cord over months without disrupting animal behaviour.


Asunto(s)
Encéfalo , Elastómeros , Ratones , Animales , Estudios Transversales , Electrodos , Encéfalo/fisiología , Neuronas/fisiología
15.
Adv Sci (Weinh) ; : e2309307, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38923329

RESUMEN

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

16.
Eur J Drug Metab Pharmacokinet ; 38(4): 245-53, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23355373

RESUMEN

Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel superoxide dismutase mimic. It exhibits strong free-radical scavenging activities in vitro and in vivo. The aim of the present study was to investigate the pharmacokinetics, tissue distribution and excretion of HSJ-0017 in Wistar rats following a single intravenous administration. Wistar rats were given different doses of HSJ-0017 by single intravenous injection. Biological samples of rats were collected and were assayed by the HPLC method. The pharmacokinetics, tissue distribution and excretion of HSJ-0017 were investigated. The pharmacokinetic data of HSJ-0017 in rats following intravenous injection was best-fit by a two-compartment model. T max of HSJ-0017 in plasma following intravenous injection was 0.083 h. AUC and plasma drug concentration were found to increase in a dose-related fashion. The highest concentrations of HSJ-0017 were detected in the liver (82.25 ± 13.99 µg/g) of rats, followed by the kidney, small intestine, lung, plasma, heart, spleen, and stomach within 2 h postdose. No HSJ-0017 was detected in the uterus, parorchis or brain of rats during the 24-h period of examination. The total cumulative excretion of HSJ-0017 in rat bile and urine were found to be 78.85 and 67.58 %, respectively. Our study has led to the view that the HSJ-0017 can be rapidly distributed to tissues after intravenous administration, but cannot diffuse through the blood-brain barrier. The faecal and biliary excretion of unchanged HSJ-0017 are the major routes of HSJ-0017 elimination.


Asunto(s)
Depuradores de Radicales Libres/farmacocinética , Metaloporfirinas/farmacocinética , Superóxido Dismutasa/metabolismo , Animales , Bilis/metabolismo , Calibración , Cromatografía Líquida de Alta Presión , Heces/química , Femenino , Depuradores de Radicales Libres/orina , Inyecciones Intravenosas , Masculino , Metaloporfirinas/orina , Ratas , Ratas Wistar , Distribución Tisular
17.
Zhonghua Yan Ke Za Zhi ; 49(8): 700-5, 2013 Aug.
Artículo en Zh | MEDLINE | ID: mdl-24246808

RESUMEN

OBJECTIVE: To compare the results of secondary in-the-bag intraocular lens (IOL) implantation with secondary sulcus IOL implantation in the eyes which received cataract extraction during early infancy. METHODS: A case control study. We selected 60 eyes of 44 patients with pediatric aphakia that meet the inclusion criterion in Affiliated Eye Hospital of Wenzhou Medical College from September 2005 to August, 2011. Thirty eyes received in-the-bag secondary IOL implantation and were compared with 30 eyes that received secondary sulcus IOL implantation. Data were collected for the ages at cataract extraction and at secondary IOL implantation, the preoperative axial length, the length of follow-up, postoperative complications, postoperative best-corrected visual acuity (BCVA) and refraction. When sufficient capsular opening was possible or capsular support deemed adequate, an IOL was placed within the capsular bag, otherwise the IOL was implanted in the sulcus. The χ(2) test or Fisher exact test was used to compare complications between the in-the-bag and sulcus groups. The independent-samples t test or Wilcoxon rank sum test was used to compare demographic, preoperative and postoperative refractive relevant data between the in-the-bag and sulcus groups. RESULTS: The median of 1-week-postoperative spherical equivalent clustered 1.00 D (range, -2.13 to 3.38 D) for in-the-bag group and 0.69 D (range, -2.25 to 2.38 D) for the sulcus group (Z = -1.01, P = 0.31). The median of 1-year-postoperative spherical equivalent clustered 0.00 D (range, -3.50 to 3.00 D) for in-the-bag and -0.50 D (range, -3.25 to 2.50 D) for the sulcus (Z = -0.53, P = 0.60). The last follow-up BCVA was available in 23 of 30 eyes in the in-the-bag group and 22 of 30 eyes in the sulcus group. The median of visual outcome clustered around 0.20 D (range, 0.05 to 0.70 D) for in-the-bag and 0.20 D (range, 0.05 to 0.60 D) for the sulcus (Z = -1.06, P = 0.29). The rate of nystagmus was significantly greater in the sulcus group (63.3%) than in the in-the-bag group (33.3%) (χ(2) = 5.41, P = 0.02). The incidence of strabismus, glaucoma and corneal calcific band keratopathy in the in-the-bag group were 36.7% (11/30), 3.0% (1/30) and 10.0% (3/30); 23.3% (7/30), 3.0% (1/30) and 13.3% (4/30) in the sulcus group, respectively. There were no significant differences between the two groups (Strabismus: χ(2) = 1.27, P = 0.26; Glaucoma: χ(2) = 0.16, P = 0.69; corneal calcific band keratopathy: P = 1.00). CONCLUSIONS: For children who have been aphakic due to receiving cataract extraction during their early infancy, there was no significant difference in both postoperative complications and visual acuity between the secondary in-the-bag IOL implantation and secondary sulcus IOL implantation during 1 year to 6 years follow-up time after the implantation surgery.


Asunto(s)
Afaquia Poscatarata/cirugía , Catarata/congénito , Implantación de Lentes Intraoculares/métodos , Femenino , Humanos , Lactante , Masculino , Resultado del Tratamiento
18.
Org Lett ; 25(28): 5262-5267, 2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37417807

RESUMEN

The developed methodology describes an efficient Rh(III)-catalyzed oxidative C-H/C-H cross-coupling between acyclic enamides and heteroarenes. This cross dehydrogenative coupling (CDC) reaction offers advantages, including excellent regioselectivity and stereoselectivity, good functional group compatibility, and a broad substrate scope. Mechanistically, Rh(III)-catalyzed ß-C(sp2)-H activation of acyclic enamides is proposed to be the critical step.

19.
Sci Rep ; 13(1): 17200, 2023 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-37848462

RESUMEN

Startup companies solve many of today's most challenging problems, such as the decarbonisation of the economy or the development of novel life-saving vaccines. Startups are a vital source of innovation, yet the most innovative are also the least likely to survive. The probability of success of startups has been shown to relate to several firm-level factors such as industry, location and the economy of the day. Still, attention has increasingly considered internal factors relating to the firm's founding team, including their previous experiences and failures, their centrality in a global network of other founders and investors, as well as the team's size. The effects of founders' personalities on the success of new ventures are, however, mainly unknown. Here, we show that founder personality traits are a significant feature of a firm's ultimate success. We draw upon detailed data about the success of a large-scale global sample of startups (n = 21,187). We find that the Big Five personality traits of startup founders across 30 dimensions significantly differ from that of the population at large. Key personality facets that distinguish successful entrepreneurs include a preference for variety, novelty and starting new things (openness to adventure), like being the centre of attention (lower levels of modesty) and being exuberant (higher activity levels). We do not find one 'Founder-type' personality; instead, six different personality types appear. Our results also demonstrate the benefits of larger, personality-diverse teams in startups, which show an increased likelihood of success. The findings emphasise the role of the diversity of personality types as a novel dimension of team diversity that influences performance and success.


Asunto(s)
Industrias , Personalidad , Humanos , Trastornos de la Personalidad , Logro
20.
Environ Pollut ; 316(Pt 2): 120604, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36347414

RESUMEN

The association between oxidative protein damage in early pregnant women and ambient fine particulate matter (PM2.5) is unknown. We estimated the effect of PM2.5 exposures within seven days before blood collection on serum 3-nitrotyrosine (3-NT) and advanced oxidation protein products (AOPP) in 100 women with normal early pregnancy (NEP) and 100 women with clinically recognized early pregnancy loss (CREPL). Temporally-adjusted land use regression model was applied for estimation of maternal daily PM2.5 exposure. Daily nitrogen dioxide (NO2) exposure of each participant was estimated using city-level concentrations of NO2. Single-day lag effect of PM2.5 was analyzed using multivariable linear regression model. Net cumulative effect and distributed lag effect of PM2.5 and NO2 within seven days were analyzed using distributed lag non-linear model. In all 200 subjects, the serum 3-NT were significantly increased with the single-day lag effects (4.72%-8.04% increased at lag 0-2), distributed lag effects (2.32%-3.49% increased at lag 0-2), and cumulative effect within seven days (16.91% increased). The single-day lag effects (7.41%-10.48% increased at lag 0-1), distributed lag effects (3.42%-5.52% increased at lag 0-2), and cumulative effect within seven days (24.51% increased) of PM2.5 significantly increased serum 3-NT in CREPL group but not in NEP group. The distributed lag effects (2.62%-4.54% increased at lag 0-2) and cumulative effect within seven days (20.25% increased) of PM2.5 significantly increased serum AOPP in early pregnant women before the coronavirus disease (COVID-19) pandemic but not after that, similarly to the effects of NO2 exposures. In conclusion, PM2.5 exposures were associated with oxidative stress to protein in pregnant women in the first trimester, especially in CREPL women. Analysis of NO2 exposures suggested that combustion PM2.5 was the crucial PM2.5 component. Wearing masks may be potentially preventive in PM2.5 exposure and its related oxidative protein damage.


Asunto(s)
Productos Avanzados de Oxidación de Proteínas , Contaminantes Atmosféricos , Contaminación del Aire , Material Particulado , Femenino , Humanos , Embarazo , Productos Avanzados de Oxidación de Proteínas/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Estrés Oxidativo , Material Particulado/efectos adversos , Material Particulado/análisis , Mujeres Embarazadas
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