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Plant transporters regulating the distribution of secondary metabolites play critical roles in defending against pathogens, insects, and interacting with beneficial microbes. The phosphorylation of these transporters can alter their activity, stability, and intracellular protein trafficking. However, the regulatory mechanism underlying this modification remains elusive. In this study, we discovered two orthologs of mammalian PKA, PKG, and PKC (AGC) kinases, oxidative signal-inducible 1 (OXI1) and its closest homologue, AGC subclass 2 member 2 (AGC2-2; 75% amino acid sequence identity with OXI1), associated with the extracellular secretion of camalexin and Arabidopsis (Arabidopsis thaliana) resistance to Pseudomonas syringae, and Botrytis cinerea. These kinases can undergo in vitro kinase reactions with three pleiotropic drug resistance (PDR) transporters: PDR6, PDR8, and PDR12. Moreover, our investigation confirmed PDR6 interaction with OXI1 and AGC2-2. By performing LC-MS/MS and parallel reaction monitoring, we identified the phosphorylation sites on PDR6 targeted by these kinases. Notably, chitin-induced PDR6 phosphorylation at specific residues, namely S31, S33, S827, and T832. Additional insights emerged by expressing dephosphorylated PDR6 variants in a pdr6 mutant background, revealing that the target residues S31, S33, and S827 promote PDR6 efflux activity, while T832 potentially contributes to PDR6 stability within the plasma membrane. The findings of this study elucidate partial mechanisms involved in the activity regulation of PDR-type transporters, providing valuable insights for their potential application in future plant breeding endeavors.
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Proteínas de Arabidopsis , Arabidopsis , Botrytis , Resistencia a la Enfermedad , Enfermedades de las Plantas , Pseudomonas syringae , Tiazoles , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Botrytis/fisiología , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas , Indoles/metabolismo , Fosforilación , Fitoalexinas , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/inmunología , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Pseudomonas syringae/patogenicidad , Pseudomonas syringae/fisiología , Tiazoles/metabolismoRESUMEN
In this work, a trimetallic (Ni/Co/Zn) organic framework (tMOF), synthesized by a solvothermal method, was calcinated at 400 and 600 °C and the final products were used as a support for lipase immobilization. The material annealed at 400 °C (Ni-Co-Zn@400) had an improved surface area (66.01 m2/g) and pore volume (0.194 cm3/g), which showed the highest enzyme loading capacity (301 mg/g) with a specific activity of 0.196 U/mg, and could protect the enzyme against thermal denaturation at 65 °C. The optimal pH and temperature for the lipase were 8.0 and 45 °C but could tolerate pH levels 7.0-8.0 and temperatures 40-60 °C. Moreover, the immobilized enzyme (Ni-Co-Zn@Lipase, Ni-Co-Zn@400@Lipase, or Ni-Co-Zn@600@Lipase) could be recovered and reused for over seven cycles maintaining 80, 90, and 11% of its original activity and maintained a residual activity >90% after 40 storage days. The remarkable thermostability and storage stability of the immobilized lipase suggest that the rigid structure of the support acted as a protective shield against denaturation, while the improved pH tolerance toward the alkaline range indicates a shift in the ionization state attributed to unequal partitioning of hydroxyl and hydrogen ions within the microenvironment of the active site, suggesting that acidic residues may have been involved in forming an enzyme-support bond. The high enzyme loading capacity, specific activity, encouraging stability, and high recoverability of the tMOF@Lipase indicate that a multimetallic MOF could be a better platform for efficient enzyme immobilization.
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Enzimas Inmovilizadas , Lipasa , Nanocompuestos , Zinc , Lipasa/química , Lipasa/metabolismo , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Nanocompuestos/química , Concentración de Iones de Hidrógeno , Zinc/química , Estabilidad de Enzimas , Temperatura , Cobalto/química , Níquel/química , Aleaciones/química , Estructuras Metalorgánicas/químicaRESUMEN
In this study, we proposed a method for fabricating Janus sheets using biological "microflowers" as a sacrificial template. The microflower-templated Janus sheets (MF-JNSs) were employed as a foam stabilizer in foam separation of the whey soybean protein (WSP). The MF-JNSs took inorganic hybrid microflowers (BSA@Cu3 (PO4)2-MF) as template, followed by the sequential attachment of protamine and silica to the surface of the BSA@Cu3(PO4)2-MF. Subsequently, the template was removed using ethylenediaminetetraacetic acid after the silicon dioxide was modified by 3-(methacryloyloxy) propyl trimethoxysilane. Upon template dissolution, the modified silica layer, lacking support from the core, fractured to form the MF-JNSs. This method omitted the step of treating the hollow ball by external force and obtained Janus sheets in one step, indicating that it was simple and feasible. The morphology, structure, and composition of the MF-JNSs were analyzed by SEM, TEM, AFM, XRD, and FT-IR. The MF-JNSs were found to delay the breakage time of the Pickering emulsion, demonstrating their emulsion stabilizing capability. Importantly, they significantly enhanced the foam half-life and foam height of soybean whey wastewater (SWW). Moreover, the recovery percentage and enrichment ratio of WSP, separated from SWW by foam separation, were improved to 81 ± 0.28 and 1.20 ± 0.05%, respectively.
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The current study presents a scalable approach for the preparation of temperature-responsive PEG/SiO2/PNIPAM-PEA Janus particles and, for the first time, investigates their potential applications in stabilizing foam and defoaming by adjusting the temperature. The method utilizes a (W1 + O)/W2 emulsion system, which incorporates appropriate surfactants to stabilize the emulsion and prevent rapid dissolution of the hydrophilic triblock polymer PEG-b-PTEPM-b-PNIPAM in water. The PEG/SiO2/PNIPAM-PEA Janus particles with temperature-responsive characteristics were synthesized in a single step that combined the sol-gel reaction and photoinduced free radical polymerization. The contact angle of the hydrophilic PEG/SiO2/PNIPAM surface was measured to be 54.7 ± 0.1°, while the contact angle of the hydrophobic PEA surface was found to be 122.4 ± 0.1°. By incorporating PEG/SiO2/PNIPAM-PEA Janus particles at a temperature of 25 °C, the foam's half-life is significantly prolonged from 42 s to nearly 30 min. However, with an increase in temperature to 50 °C, the foam's half-life rapidly diminished to only 44 s. This innovative application effectively enhances foam stabilization at low temperatures and facilitates the rapid dissipation of foam at high temperatures.
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Human superoxide dismutase (hSOD1) plays an important role in the aerobic metabolism and free radical eliminating process in the body. However, the production of existing SOD faces problems such as complex purification methods, high costs, and poor product stability. This experiment achieved low-cost, rapid, and simple purification of hSOD1 through ammonium sulfate precipitation method and heat resistance of recombinant protein. We constructed a recombinant protein hSOD1-LR containing a resilin-like polypeptide tag and expressed it. The interest protein was purified by ammonium sulfate precipitation method, and the results showed that the purification effect of 1.5 M (NH4)2SO4 was the best, with an enzyme activity recovery rate of 80 % after purification. Then, based on its thermal stability, further purification of the interest protein at 60 °C revealed a purification fold of up to 24 folds, and the purification effect was similar to that of hSOD1-6xHis purified by nickel column affinity chromatography. The stability of hSOD1-LR showed that the recombinant protein hSOD1-LR has better stability than hSOD-6xHis. hSOD1-LR can maintain 76.57 % activity even after 150 min of reaction at 70 °C. At same time, hSOD1-LR had activity close to 80 % at pH < 5, indicating good acid resistance. In addition, after 28 days of storage at 4 °C and 40 °C, hSOD1-LR retained 92 % and 87 % activity, respectively. Therefore, the method of purifying hSOD1-LR through salt precipitation may have positive implications for the study of SOD purification.
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Proteínas Recombinantes de Fusión , Humanos , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/metabolismo , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/química , Superóxido Dismutasa-1/aislamiento & purificación , Superóxido Dismutasa-1/metabolismo , Estabilidad de Enzimas , Superóxido Dismutasa/aislamiento & purificación , Superóxido Dismutasa/química , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Escherichia coli/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Clonación Molecular , Proteínas de InsectosRESUMEN
Metal-organic frameworks (MOFs) are limited by small pores and buried active sites, and their enzyme-like catalytic activity is still very low. Herein, laccase was employed as the organic component to construct laccase@Cu3(BTC)2 nanofractal microspheres. During the preparation process, laccase adsorbed Cu2+ by electrostatic attractive interaction, then combined with Cu2+ by coordination interaction, and finally induced the in situ growth of H3BTC2 in multiple directions by electrostatic repulsion. Interestingly, electrostatic repulsion was tuned efficiently by adjusting the Cu2+ concentration to obtain laccase@Cu3(BTC)2 nanofractal microspheres (nanosheet microspheres, nanorod microspheres, and nanoneedle microspheres). Laccase@Cu3(BTC)2 nanorod microspheres exhibited the highest catalytic efficiency, which was 14-fold higher than that of smooth microspheres. The mechanism of the improvement of catalytic activity in the degradation of BPA was proposed for the first time. The enhanced catalytic activity depended on the adsorption effect of the nanorod framework and dual cycle synergistic catalysis of Cu+/Cu2+ active sites, which accelerated substrate diffusion and electron transfer. The catalytic mechanism of enzyme@MOF nanofractal microspheres not only deepens our understanding of enzyme and MOF synergistic catalysis but also provides new insights into the design of catalysts.
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Excited-state intramolecular double proton transfer (ESIDPT) has received much attention because of its widespread existence in the life reactions of living organisms, and materials with this property are significant for their special luminescent properties. In this work, the complete active space self-consistent field (CASSCF) and OM2/multireference configuration interaction (OM2/MRCI) methods have been employed to study the static electronic structure calculations of the photochemistry and the possibility of ESIDPT process of hydroxyquinoline benzimidazole (HQB) molecule, along with the nonadiabatic dynamics simulations. The computational results show that the HQB molecule is relaxed to the S1-ENOL minimum after being excited to the Franck-Condon point in the S1 state. Subsequently, during the nonadiabatic deactivation process, the OH···N proton transfer and the twisting of benzimidazole occur before arriving at the single proton transfer conical intersection S1S0-KETO. Finally, the system can either return to the initial ground-state structure S0-ENOL or to the single proton transfer ground-state structure S0-KETO, both of which have almost the same probability. The dynamics simulations also show that no double proton transfer occurs. The excited-state lifetime of HQB is fitted to 1.1 ps, and only 64% of the dynamic trajectories return to the ground state within the 2.0 ps simulation time. We hope the detailed reaction mechanism of the HQB molecule will provide new insights into similar systems.
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Food waste has emerged as a critical global concern, with households identified as major contributors to this pressing issue. As the world grapples with sustainability challenges, addressing food waste in the context of rural labor migration is crucial for achieving broader sustainable development goals. However, there is still limited research regarding the relationship between labor migration and food waste. We utilized propensity score matching to analyze cross-sectional data collected from 1270 rural households in China. Labor migration led to significant increases of 37% in overall food waste and 35% in plant-based food waste, respectively. Furthermore, households with labor migration exhibited 29%, 31%, and 30 % higher energy, protein, and carbohydrate waste, respectively, compared to non-migration households. Regarding micronutrients, migration led to a 39% increase in iron waste, a 42% increase in zinc waste, and a 47% increase in selenium waste. The results of the categorical analysis indicate variations in the impact of labor migration on food wastage within rural households. Food wastage in rural households with chronic illness patients responds differently to labor migration. Moreover, labor migration predominantly affects households without courier services in villages, where dietary diversity plays a significant role. Understanding these variations is essential for crafting targeted interventions and policies to address food waste in different rural contexts. The policy implications of our study are crucial for addressing food waste and advancing sustainable development in rural China, where labor migration plays a significant role.
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Alimento Perdido y Desperdiciado , Eliminación de Residuos , Humanos , Puntaje de Propensión , Alimentos , Estudios Transversales , Emigración e Inmigración , Población Rural , ChinaRESUMEN
This paper reports an innovative study that aims to address key issues in the efficient recycling of wastepaper cellulose. The research team utilized the temperature-responsive upper critical solution temperature (UCST) polymer P(NAGA-b-DMA) in combination with the LytA label's affinity for choline analogs. This innovative approach enabled them to successfully develop a novel soluble immobilized enzyme, P(NAGA-b-DMA)-cellulase. This new enzyme has proven highly effective, significantly enhancing the degradation of wastepaper cellulose while demonstrating exceptional stability. Compared with the traditional insoluble immobilized cellulase, the enzyme showed a significant improvement in the pH, temperature stability, recycling ability, and storage stability. A kinetic parameter calculation showed that the enzymatic effectiveness of the soluble immobilized enzyme was much better than that of the traditional insoluble immobilized cellulase. After the immobilization reaction, the Michaelis constant of the immobilized enzyme was only increased by 11.5%. In the actual wastepaper degradation experiment, the immobilized enzyme was effectively used, and it was found that the degradation efficiency of wastepaper cellulose reached 80% of that observed in laboratory conditions. This novel, thermosensitive soluble immobilized cellulase can efficiently catalyze the conversion of wastepaper cellulose into glucose under suitable conditions, so as to further ferment into environmentally friendly biofuel ethanol, which provides a solution to solve the shortage of raw materials and environmental protection problems in the paper products industry.
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Celulasa , Enzimas Inmovilizadas , Enzimas Inmovilizadas/metabolismo , Celulosa/metabolismo , Celulasa/metabolismo , Temperatura , Polímeros , HidrólisisRESUMEN
Osteoarthritis (OA) is a chronic joint disease that causes pathological changes in articular cartilage, synovial membrane, or subchondral bone. Conventional treatments for OA include surgical and non-surgical methods. Surgical treatment is suitable for patients in the terminal stage of OA. It is often the last choice because of the associated risks and high cost. Medication of OA mainly includes non-steroidal anti-inflammatory drugs, analgesics, hyaluronic acid, and cortico-steroid anti-inflammatory drugs. However, these drugs often have severe side effects and cannot meet the needs of patients. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Apoptosis is programmed cell death, which is a kind of physiologic cell suicide determined by heredity and conserved by evolution. Inhibition of apoptosis-related pathways has been found to prevent and treat a variety of diseases. Excessive apoptosis can destroy cartilage homeostasis and aggravate the pathological process of OA. Therefore, inhibition of apoptosis-related factors or signaling pathways has become an effective means to treat OA. Phytochemicals are active ingredients from plants, and it has been found that phytochemicals can play an important role in the prevention and treatment of OA by inhibiting apoptosis. We summarize preclinical and clinical studies of phytochemicals for the treatment of OA by inhibiting apoptosis. The results show that phytochemicals can treat OA by targeting apoptosis-related pathways. On the basis of improving some phytochemicals with low bioavailability, poor water solubility, and high toxicity by nanotechnology-based drug delivery systems, and at the same time undergoing strict clinical and pharmacological tests, phytochemicals can be used as a potential therapeutic drug for OA and may be applied in clinical settings.
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Osteoartritis , Humanos , Osteoartritis/tratamiento farmacológico , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Apoptosis , Antiinflamatorios no Esteroideos , Disponibilidad BiológicaRESUMEN
Hypothyroidism as a long-term complication in cancer survivors has been an issue, but few studies have focused on changes in thyroid hormone levels during chemotherapy for leukaemia. This retrospective study was conducted to assess the characteristics of children with acute lymphoblastic leukaemia (ALL) and hypothyroidism during induction chemotherapy and to investigate the prognostic value of hypothyroidism in ALL. Patients with a detailed thyroid hormone profile at ALL diagnosis were enrolled. Hypothyroidism was defined as low serum levels of free tetraiodothyronine (FT4) and/or free triiodothyronine (FT3). The Kaplan-Meier method was used to create survival curves, and multivariate Cox regression analysis was used to screen prognostic factors associated with progression-free survival (PFS) and overall survival (OS). There were 276 children eligible for the study, and 184 patients (66.67%) were diagnosed with hypothyroidism, including 90 cases (48.91%) with functional central hypothyroidism and 82 cases (44.57%) with low T3 syndrome. Hypothyroidism was correlated with the dosages of L-Asparaginase (L-Asp) (P = .004) and glucocorticoids (P = .010), central nervous system (CNS) status (P = .012), number of severe infections (grade 3, 4 or 5) (P = .026) and serum albumin level (P = .032). Hypothyroidism was an independent prognostic factor for PFS in ALL children (P = .024, 95% CI: 1.1-4.1). We conclude that hypothyroidism is commonly present in ALL children during induction remission, which is related to chemotherapy drugs and severe infections. Hypothyroidism was a predictor of poor prognosis in childhood ALL.
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Hipotiroidismo , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Niño , Quimioterapia de Inducción/efectos adversos , Estudios Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pronóstico , Hipotiroidismo/inducido químicamenteRESUMEN
Functionalizing single-walled carbon nanotubes (SWNTs) with light-harvesting molecules is a facile way to construct donor-acceptor nanoarchitectures with intriguing optoelectronic properties. Magnesium-centered bacteriochlorin (MgBC), chlorin (MgC), and porphyrin (MgP) are a series of tetrapyrrole macrocycles comprising a central metal and four coordinated aromatic or antiaromatic five-membered rings linked by methine units, which show excellent visible light absorption. To delineate the effects of the aromaticity of coordinated rings on the optoelectronic properties of the nanocomposites, the photoinduced energy and charge transfer dynamics between Mg-centered tetrapyrroles and SWNTs are explored. The results show that excited energy transfer (EET) can occur within MgP@SWNT ascribed to the stabilization of the highest occupied molecular orbital (HOMO) in MgP with the increase of aromatic coordinated rings, while only electron transfer can take place in MgBC@SWNT and MgC@SWNT. Non-adiabatic dynamics simulations demonstrate that electron and hole transfer from MgP to SWNT is asynchronous. The electron transfer is ultrafast with a timescale of ca. 50 fs. By contrast, the hole transfer is significantly suppressed, although it can be accelerated to some extent when using a lower excitation energy of 2.2 eV as opposed to 3.1 eV. Further analysis reveals that the large energy gaps between charge-donor and charge-acceptor states play a crucial role in regulating photoexcited state relaxation dynamics. Our theoretical insights elucidate the structure-functionality interrelations between Mg-centered tetrapyrroles and SWNTs and provide a comprehensive understanding of the underlying charge transfer mechanism within MgP@SWNT nanocomposites, which paves the way for the forthcoming development of SWNT-based photo-related functional materials with targeted applications.
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PURPOSE: The purpose of this study was to determine the prevalence of medical adhesive-related skin injury (MARSI) at the site of central venous access device (CVAD) implantation in patients with cancer, identify risk factors associated with MARSI in patients with cancer, and create a nomogram for predicting risk of MARSI. DESIGN: Retrospective, single-center study. SUBJECTS AND SETTING: The sample comprised 1172 consecutive patients who underwent CVAD implantation between February 2018 and February 2019; their mean age was 55.7 years (SD: 13.9). Data were collected at the First Affiliated Hospital of Xi'an Jiaotong University, located in Xi'an, China. METHODS: Demographic and pertinent clinical data were collected from patient records. Routine dressing changes were performed every 7 days for peripherally inserted central venous catheters (PICCs) or 28 days for ports except in patients with existing skin injuries. Skin injuries related to use of medical adhesives and persisting for more than for 30 minutes were classified MARSI. Data were used to develop a nomogram for predicting MARSI. The accuracy of the nomogram was verified by calculating the concordance index (C-index) and drawing a calibration curve. RESULTS: Among the 1172 patients, 330 (28.2%) had undergone PICC implantation, and 282 (24.1%) experienced 1 or more MARSIs representing an incidence rate of 1.7 events per 1000 CVAD days. Statistical analysis identified previous MARSI history, the need for total parenteral nutrition support, other catheter-related complications, a history of allergy, and PICC implantation as associated with a higher likelihood of developing for MARSI. Based on these factors, we established a nomogram for predicting the risk of developing MARSI in patients with cancer who underwent CVAD implantation. The C-index of the nomogram was 0.96, and the calibration curve of the nomogram showed that the predictive ability of the nomogram was strong. CONCLUSIONS: We evaluated patients with cancer who were undergoing CVAD and identified that previous MARSI history, patients needing total parenteral nutrition support, other catheter-related complications, allergic history, and PICC implantation (compared with ports) were associated with a higher likelihood for developing MARSI. The nomogram we developed showed a good ability for predicting the risk of developing MARSI and may assist nurses to predict MARSI in this population.
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Infecciones Relacionadas con Catéteres , Catéteres Venosos Centrales , Neoplasias , Enfermedades de la Piel , Humanos , Persona de Mediana Edad , Adhesivos/efectos adversos , Estudios Retrospectivos , Incidencia , Enfermedades de la Piel/epidemiología , Neoplasias/complicaciones , Factores de Riesgo , Catéteres Venosos Centrales/efectos adversosRESUMEN
Food waste has become a significant challenge faced by the community with a shared future for mankind, and it has also caused a considerable impact on China's food security. Scholars across disciplines, international organizations, and especially policymakers are increasingly interested in food waste. Policies are seen as a powerful factor in reducing food waste, but current research on related policies is more scattered. This paper summarizes and analyzes the experiences of food waste policy development and implementation by systematically reviewing the studies on food waste reduction policies. The results of this paper's analysis show that current global food waste policies are focused at the national strategic level, with approaches such as legislation, food donation, waste recycling, awareness and education, and data collection. At the same time, we find that the current experience of developed countries in policy formulation and implementation is beneficial for policy formulation in developing countries. And taking China as an example, we believe that developing countries can improve food waste policies in the future by improving legislation, guiding the development of food banks, promoting social governance, and strengthening scientific research projects. These policies will all contribute strongly to global environmental friendliness. In addition, we discuss some of the factors that influence the development of food waste policies and argue that in the future, more consideration needs to be given to the effects of policy implementation and that case studies should focus more on developing countries. This will contribute to the global sustainable development process. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-023-03132-0.
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The outbreak of COVID-19 epidemic has enabled the establishment and application of various rapid detection methods. It is particularly important to establish a fast and accurate detection method for enterovirus, which will be beneficial for clinical diagnosis, epidemic prevention and control, and timely traceability. Through establishing an ultra-fast reverse transcription-polymerase chain reaction (RT-PCR) equipment, this study aimed to evaluate the sensitivity and specificity of the testing method of enterovirus nucleic acids based on ultra-fast real-time fluorescence RT-PCR technology. A total of 61 cases were sampled, which were then transported and preserved. After the nucleic acid extraction, the nucleic acids of the same sample were tested with the enterovirus nucleic acid detection kit produced by Guangzhou Da An Gene Company and the ultra-fast RT-PCR equipment system established in this study. ABI7500Fast and Ahram biosystems S1 fast equipment were used for amplification detection. If the sample had an S-shaped amplification curve in the FAM channel and the Ct value ≤40.00, the result was positive. The sensitivity, precision, and accuracy of the detection method were then verified. This study established a novel testing method to achieve enterovirus nucleic acid detection within 24 min. The sensitivity detection limit of the method was 1.0 × 102 copies/ml. The coefficients of variation for repeated detection of the high, medium, and low concentration samples were 2.644%, 1.674%, and 4.281%, respectively, with good detection repeatability. In addition, a total of 29 cases were positive by the ultra-fast RT-PCR detection method in 61 suspected samples, which was consistent with the conventional fluorescent RT-PCR method. The established rapid detection method can greatly shorten the time for providing a detection report, which may greatly improve the efficiency of diagnosis and treatment.
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COVID-19 , Infecciones por Enterovirus , Enterovirus , Ácidos Nucleicos , COVID-19/diagnóstico , Enterovirus/genética , Infecciones por Enterovirus/diagnóstico , Humanos , Proyectos Piloto , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , TecnologíaRESUMEN
An integrated method combining network pharmacology and in vivo experiment was performed to investigate the therapeutic mechanism of capsaicin (Cap) against acute lung injury. The potential key genes and signaling pathways involved in the therapeutic effect of Cap were predicted by the network pharmacology analyses. Additionally, the histological assessment, ELISA, and RT-qPCR were performed to confirm the therapeutic effect and the potential mechanism action involved. Our findings showed that TNF, IL-6, CXCL1, CXCL2, and CXCL10 were part of the top 50 genes. Enrichment analysis revealed that those potential genes were enriched in the TNF signaling pathway and IL-17 signaling pathway. In vivo experiment results showed that Cap alleviated histopathological changes, decreased inflammatory infiltrated cells and inflammatory cytokines, and improved antioxidative enzyme activities in the bronchoalveolar lavage fluid (BALF). Furthermore, Cap treatment effectively downregulated TNF, IL-6, NF-κB, CXCL1, CXCL2, and CXCL10 in lung tissue. Thus, our findings demonstrated that Cap has the therapeutic effect on LPS-induced acute lung injury in neonatal rats via suppression of the TNF signaling pathway and IL-17 signaling pathway.
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Lesión Pulmonar Aguda , Lipopolisacáridos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/patología , Animales , Líquido del Lavado Bronquioalveolar , Capsaicina/efectos adversos , Citocinas/metabolismo , Lipopolisacáridos/farmacología , Pulmón/metabolismo , FN-kappa B/metabolismo , Farmacología en Red , RatasRESUMEN
Poplar is not only an important woody plant, but also a model species for molecular plant studies. We identified PagGRF11 (pAxG07Gg0005700), a homolog of the Arabidopsis AtGRF1 (AT4G37740) and AtGRF2 (AT2G22840) gene. We transformed the poplar clone "84K" with PagGRF11, and the transgenic overexpressed plants (PagGRF11-OE) showed plant height reduction (dwarfing), stem diameter increase, internode shortening, and larger leaf area. The Arabidopsis overexpression line grf-oe (Overexpression of PagGRF11 in Arabidopsis), mutant line atgrf (a loss-of-function mutant of the AtGRF1 gene of Arabidopsis thaliana), and mutant trans-complementary line atgrf+oe (overexpression of PagGRF11 in mutant plants (atgrf)) also showed different leaf size phenotypes. Further, tissue sections revealed that increased xylem production was the main cause of stem thickening. Transcriptome differential expression analysis of PagGRF11 overexpressed and control plants showed that PagGRF11 promoted CCCH39(C3H39) expression. The expression profile of CCCH39 in different tissues showed that it was highly expressed in xylem. Yeast single hybrid and instantaneous double luciferase assay results showed that PagGRF11 directly transcribed and activated CCCH39 expression through interaction with cis-acting element GARE (TCTGTTG), thus promoting xylem development. This is the first finding that GRF positively regulates xylem development through CCCH39 expression activation and further suggests that PagGRF11 is a potential target for increasing wood yield.
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Arabidopsis , Populus , Arabidopsis/genética , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Populus/metabolismo , Madera/genética , Xilema/metabolismoRESUMEN
KEY MESSAGE: TwPDR1, a PDR transporter from Tripterygium wilfordii Hook.f., was proved to efflux triptolide and its stability could be enhanced by A1033T mutation. Triptolide, an abietane-type diterpene in Tripterygium wilfordii Hook.f., possesses many pharmacological activities. However, triptolide is in short supply and very expensive because it is present at low amounts in natural plants and lack alternative production methods. Transporter engineering, which increases the extracellular secretion of secondary metabolites in in vitro culture systems, is an effective strategy in metabolic engineering but is rarely reported. In this study, TwPDR1, a pleiotropic drug resistance-type ATP binding cassette transporter, was identified as the best efflux pump candidate for diterpenoids through bioinformatics analysis. TwPDR1 was located in the plasma membrane, highly expressed in adventitious roots, and induced by methyl jasmonate. The triptolide efflux function of TwPDR1 was confirmed by transient expression in tobacco BY-2 cells and by downregulation via RNA interference in the native host. However, the overexpression of TwPDR1 had a limited effect on the secretion of triptolide. As shown by previous studies, a single amino acid mutation might increase the abundance of TwPDR1 by increasing protein stability. We identified the A1033 residue in TwPDR1 by sequence alignment and confirmed that A1033T mutation could increase the expression of TwPDR1 and result in the higher release ratio of triptolide (78.8%) of the mutants than that of control (60.1%). The identification and functional characterization of TwPDR1 will not only provide candidate gene material for the metabolic engineering of triptolide but also guide other transporter engineering researches in the future.
Asunto(s)
Diterpenos/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Fenantrenos/metabolismo , Proteínas de Plantas/metabolismo , Tripterygium/metabolismo , Secuencia de Aminoácidos , Transporte Biológico , Línea Celular , Compuestos Epoxi/metabolismo , Proteínas de Transporte de Membrana/química , Mutagénesis/genética , Filogenia , Proteínas de Plantas/química , Plantas Modificadas Genéticamente , Estabilidad Proteica , Protoplastos/metabolismo , Nicotiana/genética , Transcripción Genética , Tripterygium/genéticaRESUMEN
Growing studies have paid attention to the relationships between childhood trauma, resilience and depressive symptoms. Depression is more common in girls, while gender differences in these associations have been rarely studied. Yet the study will be beneficial for prevention and intervention of depression in adolescents. The aim of this study is to examine gender differences in the effects of different types of childhood trauma and resilience on depressive symptoms. Data was collected from 6510 students (3408 males, aged 10-17 years) in Wuhan, Hubei, China from 2015 to 2016. Participants completed a self-report questionnaire assessing childhood trauma, resilience, and depressive symptoms. Multiple regression analysis was used to determine gender differences in the relationships between childhood trauma, resilience and depressive symptoms. We found that childhood trauma was positively related to depressive symptoms for both genders, but the relationship in females was stronger than in males. No significant gender difference was found in the independent effect of resilience to depressive symptoms. Resilience moderated the effects of emotional abuse, physical abuse and sexual abuse on depressive symptoms in both males and females. However, the interaction effect of resilience with emotional abuse on depressive symptoms was stronger in females compared to males. Our findings revealed gender differences in the links between childhood trauma and depressive symptoms among adolescents, and the interaction effect of resilience and childhood emotional abuse on depressive symptoms was gender-specific. These provide the basis for gender-special prevention and intervention measures for depressive symptoms in adolescents.
Asunto(s)
Maltrato a los Niños , Depresión , Adolescente , Niño , China/epidemiología , Depresión/epidemiología , Femenino , Humanos , Masculino , Caracteres Sexuales , Factores Sexuales , Estudiantes , Encuestas y CuestionariosRESUMEN
An ultrasensitive and versatile assay for biomarkers has been developed using graphene/gold nanoparticles (AuNPs) composites and single-particle inductively-coupled plasma/mass spectrometry (spICP-MS). Thrombin was chosen as a model biomarker for this study. AuNPs modified with thrombin aptamers were first non-selectively adsorbed onto the surface of graphene oxide (GO) to form GO/AuNPs composites. In the presence of thrombin, the AuNPs desorbed from the GO/AuNPs composites due to a conformation change of the thrombin aptamer after binding with thrombin. The desorbed AuNPs were proportional to the concentration of thrombin and could be quantified by spICP-MS. By counting the individual AuNPs in the spICP-MS measurement, the concentration of thrombin could be determined. This assay achieved an ultralow detection limit of 4.5 fM with a broad linear range from 10 fM to 100 pM. The method also showed excellent selectivity and reproducibility when a complex protein matrix was evaluated. Furthermore, the diversity and ready availability of ssDNA ligands make this method a versatile new technique for ultrasensitive detection of a wide variety of biomarkers in clinical diagnostics.