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The gene encoding PTEN is one of the most frequently mutated tumor suppressor-encoding genes in human cancer. While PTEN's function in tumor suppression is well established, its relationship to anti-microbial immunity remains unknown. Here we found a pivotal role for PTEN in the induction of type I interferon, the hallmark of antiviral innate immunity, that was independent of the pathway of the kinases PI(3)K and Akt. PTEN controlled the import of IRF3, a master transcription factor responsible for IFN-ß production, into the nucleus. We further identified a PTEN-controlled negative phosphorylation site at Ser97 of IRF3 and found that release from this negative regulation via the phosphatase activity of PTEN was essential for the activation of IRF3 and its import into the nucleus. Our study identifies crosstalk between PTEN and IRF3 in tumor suppression and innate immunity.
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Inmunidad Innata/inmunología , Factor 3 Regulador del Interferón/inmunología , Interferón Tipo I/inmunología , Fosfohidrolasa PTEN/inmunología , Infecciones por Respirovirus/inmunología , Infecciones por Rhabdoviridae/inmunología , Animales , Línea Celular , Línea Celular Tumoral , Núcleo Celular , Proliferación Celular , Citocinas/inmunología , Células Dendríticas/inmunología , Electroforesis en Gel de Poliacrilamida , Técnica del Anticuerpo Fluorescente , Técnicas de Transferencia de Gen , Células HEK293 , Humanos , Immunoblotting , Inmunoprecipitación , Factor 3 Regulador del Interferón/genética , Factor 7 Regulador del Interferón/genética , Células MCF-7 , Macrófagos/inmunología , Espectrometría de Masas , Ratones , Microscopía Confocal , Mutagénesis Sitio-Dirigida , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Virus Sendai , VesiculovirusRESUMEN
Self-healing is a bioinspired strategy to repair damaged conductors under repetitive wear and tear, thereby largely extending the life span of electronic devices. The self-healing process often demands external triggering conditions as the practical challenges for the widespread applications. Here, a compliant conductor with electrically self-healing capability is introduced by combining ultrahigh sensitivity to minor damages and reliable recovery from ultrahigh tensile deformations. Conductive features are created in a scalable and low-cost fabrication process comprising a copper layer on top of liquid metal microcapsules. The efficient rupture of microcapsules is triggered by structural damages in the copper layer under stress conditions as a result of the strong interfacial interactions. The liquid metal is selectively filled into the damaged site for the instantaneous restoration of the metallic conductivity. The unique healing mechanism is responsive to various structural degradations including microcracks under bending conditions and severe fractures upon large stretching. The compliant conductor demonstrates high conductivity of â¼12,000 S/cm, ultrahigh stretchability of up to 1,200% strain, an ultralow threshold to activate the healing actions, instantaneous electrical recovery in microseconds, and exceptional electromechanical durability. Successful implementations in a light emitting diode (LED) matrix display and a multifunctional electronic patch demonstrate the practical suitability of the electrically self-healing conductor in flexible and stretchable electronics. The developments provide a promising approach to improving the self-healing capability of compliant conductors.
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Gene duplications have long been recognized as a driving force in the evolution of genes, giving rise to novel functions. The soybean (Glycine max) genome is characterized by a large number of duplicated genes. However, the extent and mechanisms of functional divergence among these duplicated genes in soybean remain poorly understood. In this study, we revealed that 4 MYB genes (GmMYBA5, GmMYBA2, GmMYBA1, and Glyma.09g235000)-presumably generated by tandem duplication specifically in the Phaseoleae lineage-exhibited a stronger purifying selection in soybean compared to common bean (Phaseolus vulgaris). To gain insights into the diverse functions of these tandemly duplicated MYB genes in anthocyanin biosynthesis, we examined the expression, transcriptional activity, induced metabolites, and evolutionary history of these 4 MYB genes. Our data revealed that Glyma.09g235000 is a pseudogene, while the remaining 3 MYB genes exhibit strong transcriptional activation activity, promoting anthocyanin biosynthesis in different soybean tissues. GmMYBA5, GmMYBA2, and GmMYBA1 induced anthocyanin accumulation by upregulating the expression of anthocyanin pathway-related genes. Notably, GmMYBA5 showed a lower capacity for gene induction compared to GmMYBA2 and GmMYBA1. Metabolomics analysis further demonstrated that GmMYBA5 induced distinct anthocyanin accumulation in Nicotiana benthamiana leaves and soybean hairy roots compared to GmMYBA2 and GmMYBA1, suggesting their functional divergence leading to the accumulation of different metabolites accumulation following gene duplication. Together, our data provide evidence of functional divergence within the MYB gene cluster following tandem duplication, which sheds light on the potential evolutionary directions of gene duplications during legume evolution.
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Genes myb , Glycine max , Glycine max/genética , Antocianinas/genética , Duplicación de Gen , Familia de Multigenes , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
A metal-organic frameworks (MOFs)-in-MOF nanovehicle (160 nm), which was constructed with newly prepared ultrasmall Cu(I)Cu(II)-BTC MOFs (UCMs, 2.95 nm) loaded with doxorubicin (DOX) and a nuclear localization signal (NLS) peptide as multicores (UCMDNs) and ZIF-8 as the shell MOF, was proposed to cross layers of biological barriers with adaptive size evolution capacity for achieving efficient nucleus-targeted drug delivery. It first enhanced tumor tissue penetration through its larger nanosize effect. Then the acidic tumor environment made the ZIF-8 shell degrade, releasing small-sized UCMDNs to enter into the cell and into the nucleus under the guidance of NLS. Furthermore, due to the distinct surface structural characteristics of UCMs, UCMDNs remained stable in the cytoplasm and collapsed in the nucleus due to the DOX-DNA interaction to deliver DOX precisely. It showed superior performance in the nucleus-directed delivery of DOX (delivery efficiency up to 56.7%) and a high tumor growth inhibition rate (96.4%), offering promising prospects in tumor chemotherapy.
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Núcleo Celular , Doxorrubicina , Estructuras Metalorgánicas , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Estructuras Metalorgánicas/química , Humanos , Núcleo Celular/metabolismo , Núcleo Celular/efectos de los fármacos , Animales , Ratones , Portadores de Fármacos/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Señales de Localización Nuclear/química , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Tamaño de la Partícula , Nanopartículas/química , Cobre/químicaRESUMEN
Stretchable electroluminescent devices represent an emerging optoelectronic technology for future wearables. However, their typical construction on sub-millimeter-thick elastomers has limited moisture permeability, leading to discomfort during long-term skin attachment. Although breathable textile displays may partially address this issue, they often have distinct visual appearances with discrete emissions from fibers or fiber junctions. This study introduces a convenient procedure to create stretchable, permeable displays with continuous luminous patterns. The design utilizes ultrathin nanocomposite devices embedded in a porous elastomeric microfoam to achieve high moisture permeability. These displays also exhibit excellent deformability, low-voltage operation, and excellent durability. Additionally, the device is decorated with fluorinated silica nanoparticles to achieve self-cleaning and washable capabilities. The practical implementation of these nanocomposite devices is demonstrated by creating an epidermal counter display that allows intimate integration with the human body. These developments provide an effective design of stretchable and breathable displays for comfortable wearing.
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Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients.
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Metanfetamina , Polimorfismo de Nucleótido Simple , Humanos , Catecol O-Metiltransferasa/genética , Dopamina , Metanfetamina/efectos adversos , Genotipo , MetilaciónRESUMEN
Pneumocystis jirovecii is a prevalent opportunistic fungal pathogen that can lead to life-threatening Pneumocystis pneumonia in immunocompromised individuals. Given that timely and accurate diagnosis is essential for initiating prompt treatment and enhancing patient outcomes, it is vital to develop a rapid, simple, and sensitive method for P. jirovecii detection. Herein, we exploited a novel detection method for P. jirovecii by combining recombinase polymerase amplification (RPA) of nucleic acids isothermal amplification and the trans cleavage activity of Cas12a. The factors influencing the efficiency of RPA and Cas12a-mediated trans cleavage reaction, such as RPA primer, crRNA, the ratio of crRNA to Cas12a and ssDNA reporter concentration, were optimized. Our RPA-Cas12a-based fluorescent assay can be completed within 30-40 min, comprising a 25-30 min RPA reaction and a 5-10 min trans cleavage reaction. It can achieve a lower detection threshold of 0.5 copies/µL of target DNA with high specificity. Moreover, our RPA-Cas12a-based fluorescent method was examined using 30 artificial samples and demonstrated high accuracy with a diagnostic accuracy of 93.33%. In conclusion, a novel, rapid, sensitive, and cost-effective RPA-Cas12a-based detection method was developed and demonstrates significant potential for on-site detection of P. jirovecii in resource-limited settings.
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Técnicas de Amplificación de Ácido Nucleico , Pneumocystis carinii , Sensibilidad y Especificidad , Pneumocystis carinii/genética , Pneumocystis carinii/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Humanos , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/microbiología , Técnicas de Diagnóstico Molecular/métodos , Endodesoxirribonucleasas/genética , Endodesoxirribonucleasas/metabolismo , Proteínas Asociadas a CRISPR/genética , ADN de Hongos/genética , Recombinasas/metabolismo , Recombinasas/genética , Proteínas BacterianasRESUMEN
BACKGROUND: Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. METHODS: Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. RESULTS: Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. CONCLUSIONS: Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Receptores Inmunológicos , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Masculino , Femenino , Pronóstico , Receptores Inmunológicos/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Quimioembolización Terapéutica/métodos , Anciano , Linfocitos T/inmunología , Linfocitos T/metabolismo , Adulto , Receptores Virales/metabolismoRESUMEN
PURPOSE: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. METHODS: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 µL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. RESULTS: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. IN CONCLUSION: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.
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Lentes de Contacto , Glaucoma , Poliésteres , Polietilenglicoles , Sulfonamidas , Tiazinas , Humanos , Timolol/farmacocinética , Timolol/uso terapéutico , Micelas , Antihipertensivos/farmacocinética , Glaucoma/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Soluciones Oftálmicas/uso terapéuticoRESUMEN
OBJECTIVE: The diagnosis of RGERD in patients typically involves 24-hour esophageal pH monitoring, but due to its invasiveness and low patient compliance, new screening methods are needed. In this study, a lactulose breath test (LBT) was conducted to detect the growth of small intestine bacteria (SIBO) and explore the potential relationship between LBT and RGERD to identify a new treatment method for RGERD. METHODS: A total of 178 patients with gastroesophageal reflux were enrolled from June 2020 to December 2022 in the Gastroenterology Department, Building 3, the First Affiliated Hospital of Kunming Medical University; these patients included 96 patients with nonrefractory GERD (NRGERD) and 82 patients with RGERD. The Gerd Q score, reflux symptom index (RSI) score, gastroscopy results, clinical symptoms, and other related indicators were collected. Statistical methods were used to analyze the gathered data. RESULTS: The incidence of acid reflux and heartburn in patients with RGERD was significantly greater than that in patients with NRGERD (67.10% vs. 42.70%, P<0.01 and 65.00% vs. 34.40%, P<0.01). The CH4 values of patients with RGERD were significantly greater than those of patients with NRGERD at each time point, and there was a correlation between the CH4 values at 60 min and RGERD (P<0.05). For patients with RGERD, the incidence of abdominal pain, acid regurgitation, and heartburn was greater in the CH4-positive group than in the CH4-negative group (61.90% vs. 57.50%, 69.05% vs. 65.00%, 69.05% vs. 57.50%, P>0.05). The incidence of nausea was also greater in the CH4-positive group than in the CH4-negative group (61.90% vs. 35.00%, P<0.05). CONCLUSION: Increased CH4 levels are correlated with RGERD. In addition, patients with RGERD may develop SIBO after long-term use of PPIs, and interventions involving SIBO could provide new ideas for the treatment of RGERD.
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The mechanism and kinetics of reactive oxygen species (ROS) formation when atmospheric secondary organic aerosol (SOA) is exposed to solar radiation are poorly understood. In this study, we combined an in situ UV-vis irradiation system with electron paramagnetic resonance (EPR) spectroscopy to characterize the photolytic formation of ROS in aqueous extracts of SOA formed by the oxidation of isoprene, α-pinene, α-terpineol, and toluene. We observed substantial formation of free radicals, including â¢OH, superoxide (HO2â¢), and organic radicals (Râ¢/ROâ¢) upon irradiation. Compared to dark conditions, the radical yield was enhanced by a factor of â¼30 for â¢OH and by a factor of 2-10 for superoxide radicals, and we observed the emergence of organic radicals. Total peroxide measurements showed substantial decreases of peroxide contents after photoirradiation, indicating that organic peroxides can be an important source of the observed radicals. A liquid chromatography interfaced with high-resolution mass spectrometry was used to detect a number of organic radicals in the form of adducts with a spin trap, BMPO. The types of detected radicals and aqueous photolysis of model compounds indicated that photolysis of carbonyls by Norrish type I mechanisms plays an important role in the organic radical formation. The photolytic ROS formation serves as the driving force for cloud and fog processing of SOA.
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Contaminantes Atmosféricos , Peróxidos , Peróxidos/química , Especies Reactivas de Oxígeno , Fotólisis , Superóxidos , AerosolesRESUMEN
Environmentally persistent free radicals (EPFRs) play an important role in aerosol effects on air quality and public health, but their atmospheric abundance and sources are poorly understood. We measured EPFRs contained in PM2.5 collected in Fairbanks, Alaska, in winter 2022. We find that EPFR concentrations were enhanced during surface-based inversion and correlate strongly with incomplete combustion markers, including carbon monoxide and elemental carbon (R2 > 0.75). EPFRs exhibit moderately good correlations with PAHs, biomass burning organic aerosols, and potassium (R2 > 0.4). We also observe strong correlations of EPFRs with hydrocarbon-like organic aerosols, Fe and Ti (R2 > 0.6), and single-particle mass spectrometry measurements reveal internal mixing of PAHs, with potassium and iron. These results suggest that residential wood burning and vehicle tailpipes are major sources of EPFRs and nontailpipe emissions, such as brake wear and road dust, may contribute to the stabilization of EPFRs. Exposure to the observed EPFR concentrations (18 ± 12 pmol m-3) would be equivalent to smoking â¼0.4-1 cigarette daily. Very strong correlations (R2 > 0.8) of EPFR with hydroxyl radical formation in surrogate lung fluid indicate that exposure to EPFRs may induce oxidative stress in the human respiratory tract.
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Contaminantes Atmosféricos , Emisiones de Vehículos , Madera , Madera/química , Alaska , Radicales Libres , Material Particulado , Monitoreo del Ambiente , Aerosoles , Hidrocarburos Policíclicos Aromáticos/análisisRESUMEN
OBJECTIVE: To understand the status of spiritual well-being in patients with esophageal cancer and analyze its influencing factors. METHODS: A total of 187 patients with esophageal cancer (EC) from two grade A hospitals in Chengdu were selected and investigated by general data questionnaire, chronic disease function evaluation-spirituality scale 12 (FACIT-SP-12), general well-being scale (GWB), and Anderson symptom assessment scale gastrointestinal tract (MDASI-GI). RESULTS: The spiritual well-being score of patients with esophageal cancer was (25.13 ± 9.63). Spiritual well-being was positively correlated with general well-being and negatively correlated with symptom burden (P < 0.01). The results of multiple stepwise linear regression analysis showed that hobbies, disease stage, general well-being, and symptom burden were the main influencing factors for the spiritual well-being of esophageal cancer patients (P < 0.05), explaining 49.0% of the total variation. CONCLUSIONS: The spiritual well-being of patients with esophageal cancer is lower than the middle level, In addition, whether there is a hobby in life, disease stage, subjective well-being, and symptom burden are the main factors affecting the spiritual well-being of patients with EC. It is suggested that medical staff should take targeted care measures according to the influencing factors, so as to improve the spiritual well-being level of patients and improve the quality of life of patients.
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Neoplasias Esofágicas , Espiritualidad , Humanos , Masculino , Estudios Transversales , Femenino , Neoplasias Esofágicas/psicología , Persona de Mediana Edad , Anciano , Encuestas y Cuestionarios , Calidad de Vida , Adulto , Modelos Lineales , China , Anciano de 80 o más AñosRESUMEN
Strain FF17T, a Gram-negative, obligate aerobic, motile, pink-pigmented, and methylotrophic bacterium, was selected for a polyphasic taxonomic investigation due to its capacity for aggregation, or floc formation. The predominant respiratory quinone observed was Q-10, accounting for 83.36% of the total, while the major fatty acids were summed feature 8 (18:1 w6c and/or 18:1 w7c). The major polar lipids included Diphosphatidylglycerol (DPG), phosphatidylglycerol, phosphatidylethanolamine (PE), phosphatidylinositol (PI), and one unknown polar lipid. Phylogenetic analysis showed that strain FF17T was hithermost related to Methylobacterium goesingense iEII3T (99.86%), M. gossipiicola Gh-105 T (99.22%), M. adhaesivum AR27T (98.92%), and M. iners 5317S-33 T (97.27%) based on 16S rRNA gene sequence similarity. A 5,735,273-bp chromosome and six plasmids make up the genome, making it larger than the genomes of the other four Methylobacterium species described above. The digital DNA-DNA hybridization and average nucleotide identity values between strain FF17T and the reference strains were 21.90-28.70 and 77.39-85.04%, respectively. Strain FF17T had a genome DNA G + C content of 68.5 mol%. The analysis of genomes indicated that cellulose apparently plays an important character in the aggregation of Methylobacterium species. Genome annotation revealed the presence of genes involved in assimilatory/dissimilatory nitrate reduction and ammonia assimilation. In conclusion, Strain FF17T is identified as a new species in the Methylobacterium genus, based on analyses of genomics, phylogeny, biochemistry, and fatty acids, and the name Methylobacterium flocculans sp. nov. is proposed. The type strain is FF17T (= MCCC 1K08738T = KCTC 8320 T).
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Composición de Base , ADN Bacteriano , Ácidos Grasos , Methylobacterium , Filogenia , Estanques , ARN Ribosómico 16S , ARN Ribosómico 16S/genética , Methylobacterium/clasificación , Methylobacterium/genética , Methylobacterium/aislamiento & purificación , Estanques/microbiología , Ácidos Grasos/análisis , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Genoma Bacteriano , Hibridación de Ácido Nucleico , Análisis de Secuencia de ADN , Fosfolípidos/análisisRESUMEN
Seven new monoterpene alkaloids (1 - 7), along with 16 known analogues, were isolated from an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). Their structures were determined by spectroscopic data analysis, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are stereoisomers belonging to a novel type of pseudoindoxyl monoterpene alkaloids, 3 is the first monoterpene furoindole alkaloid from nature, and 4 - 7 are derivatives of the known monoterpene alkaloids featuring different structures.
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Alcaloides , Uncaria , Alcaloides Indólicos/química , Uncaria/química , MonoterpenosRESUMEN
Stretchable conductive nanocomposites are essential for deformable electronic devices. These conductors currently face significant limitations, such as insufficient deformability, significant resistance changes upon stretching, and drifted properties during cyclic deformations. To tackle these challenges, we present an electrically self-healing and ultrastretchable conductor in the form of bilayer silver nanowire/liquid metal microcapsule nanocomposites. These nanocomposites utilize silver nanowires to establish their initial excellent conductivity. When the silver nanowire networks crack during stretching, the microcapsules are ruptured to release the encased liquid metal for recovering the electrical properties. This self-healing capability allows the nanocomposite to achieve ultrahigh stretchability for both uniaxial and biaxial strains, minor changes in resistance during stretching, and stable resistance after repetitive deformations. The conductors have been used to create skin-attachable electronic patches and stretchable light-emitting diode arrays with enhanced robustness. These developments provide a bioinspired strategy to enhance the performance and durability of conductive nanocomposites.
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The CRISPR (clustered regularly interspaced short palindromic repeat) system is an RNA-guided immune system that protects prokaryotes from invading genetic elements. This system represents an inheritable and adaptable immune system that is mediated by multisubunit effector complexes. In the Type III-B system, the Cmr effector complex has been found to cleave ssRNA in vitro. However, in vivo, it has been implicated in transcription-dependent DNA targeting. We show here that the Cmr complex from Thermotoga maritima can cleave an ssRNA target that is complementary to the CRISPR RNA. We also show that binding of a complementary ssRNA target activates an ssDNA-specific nuclease activity in the histidine-aspartate (HD) domain of the Cmr2 subunit of the complex. These data suggest a mechanism for transcription-coupled DNA targeting by the Cmr complex and provide a unifying mechanism for all Type III systems.
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Sistemas CRISPR-Cas/fisiología , División del ADN , Thermotoga maritima/genética , Thermotoga maritima/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Desoxirribonucleasas/metabolismo , Activación Enzimática , Unión Proteica , Estructura Terciaria de Proteína , ARN Bacteriano/metabolismoRESUMEN
Through a mixed-methods approach (randomized controlled trial and thematic analysis of pre and post-service-learning reflections), this study evaluated the impact of a student death doula service-learning experience on nursing students' palliative competencies and learning experiences. The intervention group underwent a 2-day student death doula training workshop followed by a 6-month service-learning experience, while the control group received standard palliative care education. Attitudes toward the care of the dying significantly improved for the intervention group but not for compassion competence and palliative care knowledge. Six themes were developed: (1) Motivations for being a student death doula, (2) Improved perceptions of palliative care patients, (3) Perceptions of a good death, (4) Confidence in caring for palliative care patients, (5) Understanding the multifaceted nature of palliative care, and (6) Joys and challenges during service-learning. Service-learning helped students to understand palliative care patients and acquire confidence in engaging with them.
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BACKGROUND: Alberta stroke program early CT score (ASPECTS) is a semi-quantitative evaluation method used to evaluate early ischemic changes in patients with acute ischemic stroke, which can guide physicians in treatment decisions and prognostic judgments. OBJECTIVE: We propose a method combining deep learning and radiomics to alleviate the problem of large inter-observer variance in ASPECTS faced by physicians and assist them to improve the accuracy and comprehensiveness of the ASPECTS. METHODS: Our study used a brain region segmentation method based on an improved encoding-decoding network. Through the deep convolutional neural network, 10 regions defined for ASPECTS will be obtained. Then, we used Pyradiomics to extract features associated with cerebral infarction and select those significantly associated with stroke to train machine learning classifiers to determine the presence of cerebral infarction in each scored brain region. RESULTS: The experimental results show that the Dice coefficient for brain region segmentation reaches 0.79. Three radioactive features are selected to identify cerebral infarction in brain regions, and the 5-fold cross-validation experiment proves that these 3 features are reliable. The classifier trained based on 3 features reaches prediction performance of AUCâ=â0.95. Moreover, the intraclass correlation coefficient of ASPECTS between those obtained by the automated ASPECTS method and physicians is 0.86 (95% confidence interval, 0.56-0.96). CONCLUSIONS: This study demonstrates advantages of using a deep learning network to replace the traditional template registration for brain region segmentation, which can determine the shape and location of each brain region more precisely. In addition, a new brain region classifier based on radiomics features has potential to assist physicians in clinical stroke detection and improve the consistency of ASPECTS.
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Isquemia Encefálica , Aprendizaje Profundo , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/diagnóstico por imagen , Alberta , Radiómica , Tomografía Computarizada por Rayos X/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Infarto Cerebral/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Background and Objectives: Our study compared the visual and anatomical outcomes of polypoidal choroidal vasculopathy (PCV) patients receiving intravitreal aflibercept (IVA) with or without photodynamic therapy (PDT) over 12 months. Materials and Methods: This retrospective study was performed for 60 eyes from 60 patients with treatment-naïve PCV. Thirty eyes were treated using IVA monotherapy (IVA group), and thirty eyes were treated using a combination of IVA with PDT (IVA/PDT group). The baseline characteristics, treatment outcomes, and retreatment rates were compared between the two groups over a one-year follow-up period. Results: The best-corrected visual acuity (BCVA) was found to have improved significantly in the IVA/PDT group at every 3-month visit. However, no significant BCVA improvement was observed in the IVA group. A significantly lower retreatment rate and higher dry macula rate were found in the IVA/PDT group than that in the IVA group. In the entire population of the study, a better baseline vision and younger age were associated with better final visual outcomes. Retreatment was associated with poor baseline BCVA and IVA monotherapy. Conclusions: The combination of IVA and PDT may offer superior visual improvement and a higher dry macula rate compared to IVA monotherapy in the treatment of PCV patients while requiring fewer retreatments over 12 months.