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Parkinson's disease (PD) is a mitochondria-related neurodegenerative disease characterized by locomotor deficits and loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Majority of PD research primarily focused on neuronal dysfunction, while the roles of astrocytes and their mitochondria remain largely unexplored. To bridge the gap and investigate the roles of astrocytic mitochondria in PD progression, we constructed a specialized optogenetic tool, mitochondrial-targeted anion channelrhodopsin, to manipulate mitochondrial membrane potential in astrocytes. Utilizing this tool, the depolarization of astrocytic mitochondria within the SNc in vivo led to the accumulation of γ-aminobutyric acid (GABA) and glutamate in SNc, subsequently resulting in excitatory/inhibitory imbalance and locomotor deficits. Consequently, in vivo calcium imaging and interventions of neurotransmitter antagonists demonstrated that GABA accumulation mediated movement deficits of mice. Furthermore, 1 h/day intermittent astrocytic mitochondrial depolarization for 2 weeks triggered spontaneous locomotor dysfunction, α-synuclein aggregation, and the loss of DA neurons, suggesting that astrocytic mitochondrial depolarization was sufficient to induce a PD-like phenotype. In summary, our findings suggest the maintenance of proper astrocytic mitochondrial function and the reinstatement of a balanced neurotransmitter profile may provide a new angle for mitigating neuronal dysfunction during the initial phases of PD.
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Reactions of Co(OAc)2·4H2O, N'N'-bis(3-pyridylmethyl)oxalamide (L) and 4,4'-sulfonyldibenzoic acid (H2SDA) afforded four coordination polymers with the same mixed ligands, {[Co(L)(SDA)(H2O)2]·H2O·CH3OH}n, 1, {[Co(L)0.5(SDA)]·2H2O·0.5L}n, 2, {[Co(L)1.5(SDA)(H2O)]·H2O}n, 3, and {[Co2(L)1.5(SDA)2(H2O)2]·4H2O}n, 4, which have been structurally characterized using single-crystal X-ray crystallography. Complexes 1-4 are 2D layers, revealing topologies of sql, 2,6L1, (4,4)Ia, and 6L12, respectively, and demonstrating that the metal-to-ligand ratio, solvent system, and reaction temperature are important in determining the structural diversity. The immersion of these complexes into various solvents shows that the structural types govern the chemical stabilities of 1-4. Reversible structural transformation is shown for complexes 1 and 2 upon solvent removal and adsorption, while those of 3 and 4 are irreversible.
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Climate warming and air pollution are the main environmental problems in China. This study used China's Carbon Accounting Database, energy economic model, and air quality model to analyze the potential carbon emission peaking path and synergistic air quality improvement gain in the industrial sector in Hunan Province. Based on China's Carbon Accounting Database and the local industry/energy statistical yearbooks in Hunan, the total CO2 emissions in Hunan Province in 2019 were 310.6 Mt, of which the industrial sector accounted for over 70% of the emissions, mainly from the production and supply of electricity, steam, and heat; the production of non-metallic minerals; and the smelting and pressing of ferrous metals. Three potential industrial carbon emission peaking scenarios were analyzed using the LEAP energy economic model, including the business-as-usual scenario (peaking by 2030), moderate emission reduction scenario (peaking by 2028), and aggressive emission reduction scenario (peaking by 2025), by employing different economic growth rates, energy technology progress, and energy structures of the industrial sector. Furthermore, by combining the anthropogenic air pollutant emission inventory and the regional air quality model WRF-Chem, we analyzed the air quality improvement associated with various carbon emission peak paths. The results showed that the annual mean concentrations of major air pollutants had decreased in the three scenarios, especially in the Chang-Zhu-Tan Region. The aggressive emission reduction scenario was the most effective scenario, followed by the moderate emission reduction scenario and the business-as-usual scenario. Manufacturing was the sector with the most significant synergistic effect of pollution and carbon reduction. When carbon emission peaks were achieved, the annual average concentrations of PM2.5 and PM10 in Hunan Province could be synergistically reduced by 0.6-1.8 µg·m-3 and 1.8-8.9 µg·m-3, respectively. Our findings offer important insights into carbon emission peaking and can provide useful information for potential mitigation actions.
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Residual canopy transpiration (Emin_canop) is a key physiological trait that determines trees' survival time under drought after stomatal closure and after trees have limited access to soil water. Emin_canop mainly depends on leaf minimum conductance (gmin) and vapor pressure deficit. Here we determined the seasonal variation of gmin and how gmin is related to interspecies variation in leaf cuticular and stomatal traits for nine European tree species in a mature forest. In addition, we determined the species-specific temperature responses of gmin. With this newly obtained insight, we calculated Emin_canop for the nine species for one day at our research site during the 2022 central European hot drought. Our results show that at ambient temperatures gmin ranged from 0.8 to 4.8 mmol m-2 s-1 across the nine species and was stable in most species throughout the growing season. The interspecies variation of gmin was associated with leaf cuticular and stomatal traits. Additionally, gmin exhibited strong temperature responses and increased, depending on species, by a factor of two to four in the range of 25-50 °C. For the studied species at the site, during a single hot drought day, Emin_canop standardized by tree size (stem basal area) ranged from 2.0 to 36.7 L m-2, and non-standardized Emin_canop for adult trees ranged from 0.3 to 5.3 L. Emin_canop also exhibited species-specific rapid increases under hotter temperatures. Our results suggest that trees, depending on species, need reasonable amounts of water during a drought, even when stomates are fully closed. Species differences in gmin and ultimately Emin_canop can, together with other traits, affect the ability of a tree to keep its tissue hydrated during a drought and is likely to contribute to species-specific differences in drought vulnerability.
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Árvores , Água , Árvores/fisiologia , Água/fisiologia , Secas , Folhas de Planta/fisiologia , FlorestasRESUMO
Food and predators are the most noteworthy objects for the basic survival of wild animals, and both are often deviant in both spatial and temporal domains and quickly attract an animal's attention. Although stimulus-specific adaptation (SSA) is considered a potential neural basis of salient sound detection in the temporal domain, related research on visual SSA is limited and its relationship with temporal saliency is uncertain. The avian nucleus isthmi pars magnocellularis (Imc), which is central to midbrain selective attention network, is an ideal site to investigate the neural correlate of visual SSA and detection of a salient object in the time domain. Here, the constant order paradigm was applied to explore the visual SSA in the Imc of pigeons. The results showed that the firing rates of Imc neurons gradually decrease with repetitions of motion in the same direction, but recover when a motion in a deviant direction is presented, implying visual SSA to the direction of a moving object. Furthermore, enhanced response for an object moving in other directions that were not presented ever in the paradigm is also observed. To verify the neural mechanism underlying these phenomena, we introduced a neural computation model involving a recoverable synaptic change with a "center-surround" pattern to reproduce the visual SSA and temporal saliency for the moving object. These results suggest that the Imc produces visual SSA to motion direction, allowing temporal salient object detection, which may facilitate the detection of the sudden appearance of a predator.
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Mesencéfalo , Neurônios , Animais , Mesencéfalo/fisiologia , Neurônios/fisiologia , Columbidae , Estimulação LuminosaRESUMO
Carbon emission peaking and air quality improvement is an urgent issue in the research of the atmospheric environment. Here, the emission factor method was used to compile the city-level greenhouse gas emission inventory of Jiangsu Province from 2010 to 2019, which was then combined with greenhouse gas-air pollutant synergy analysis and WRF-Chem air quality model simulation to analyze the synergistic gain of air quality improvement under different carbon emission reduction scenarios. The results revealed that the annual mean CO2 emission in Jiangsu Province from 2010 to 2019 was 701.74-897.47 Mt. Suzhou, Xuzhou, and Nanjing had the highest emissions (91.19-182.12 Mt·a-1); Yangzhou, Suqian, and Lianyungang had the lowest emissions (13.19-32.54 Mt·a-1); and majority of the cities had a continuous upward trend in the CO2 emissions. Energy activities were the main source of CO2 emissions, accounting for nearly 90%, whereas industrial production processes contributed to the remaining 10%. This study designed three types of CO2 emission reduction conditions according to different emission reduction priorities, namely, sector-wide collaborative, energy priority, and industrial priority. Each type of emission reduction condition included a different intensity of CO2 emission reduction (10%, 20%, and 40%). The condition-based simulation results demonstrated that, taking 2017 as the base year, the average annual decrease in PM2.5 concentration in sector-wide collaborative, energy priority, and industrial priority emission reduction was 6.7-21.1, 3.1-12.0, and 3.4-14.3 µg·m-3, respectively. Sector-wide collaborative emission reduction had the most notable improvement in PM2.5 pollution. Under the condition of the sector-wide collaborative emission reduction of 40%, the average annual PM2.5 concentration of all cities, excluding Xuzhou and Suqian, met the national â ¡ standard (35 µg·m-3). The change responses of PM10, SO2, NO2, and CO were similar to that of PM2.5, but O3 pollution increased under the conditions of energy and industrial priorities.
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Myocardial infarction (MI) has the characteristics of high mortality rate, strong suddenness and invisibility. There are problems such as the delayed diagnosis, misdiagnosis and missed diagnosis in clinical practice. Electrocardiogram (ECG) examination is the simplest and fastest way to diagnose MI. The research on MI intelligent auxiliary diagnosis based on ECG is of great significance. On the basis of the pathophysiological mechanism of MI and characteristic changes in ECG, feature point extraction and morphology recognition of ECG, along with intelligent auxiliary diagnosis method of MI based on machine learning and deep learning are all summarized. The models, datasets, the number of ECG, the number of leads, input modes, evaluation methods and effects of different methods are compared. Finally, future research directions and development trends are pointed out, including data enhancement of MI, feature points and dynamic features extraction of ECG, the generalization and clinical interpretability of models, which are expected to provide references for researchers in related fields of MI intelligent auxiliary diagnosis.
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Eletrocardiografia , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/diagnóstico , Reconhecimento PsicológicoRESUMO
A Cu-2.35Ni-0.69Si alloy with low La content was designed in order to study the role of La addition on microstructure evolution and comprehensive properties. The results indicate that the La element demonstrates a superior ability to combine with Ni and Si elements, via the formation of La-rich primary phases. Owing to existing La-rich primary phases, restricted grain growth was observed, due to the pinning effect during solid solution treatment. It was found that the activation energy of the Ni2Si phase precipitation decreased with the addition of La. Interestingly, the aggregation and distribution of the Ni2Si phase, around the La-rich phase, was observed during the aging process, owing to the attraction of Ni and Si atoms by the La-rich phase during the solid solution. Moreover, the mechanical and conductivity properties of aged alloy sheets suggest that the addition of the La element showed a slight reducing effect on the hardness and electrical conductivity. The decrease in hardness was due to the weakened dispersion and strengthening effect of the Ni2Si phase, while the decrease in electrical conductivity was due to the enhanced scattering of electrons by grain boundaries, caused by grain refinement. More notably, excellent thermal stabilities, including better softening resistance ability and microstructural stability, were detected for the low-La-alloyed Cu-Ni-Si sheet, owing to the delayed recrystallization and restricted grain growth caused by the La-rich phases.
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Helicobacter pylori infection is an important issue worldwide, and several guidelines have been published for clinicians to achieve successful eradication. However, there are still some patients who remain infected with H. pylori after treatment. Clinicians should identify the reasons that caused treatment failure and find strategies to manage them. We have searched and organized the literature and developed methods to overcome factors that contribute to prior treatment failure, such as poor compliance, inadequate intragastric acid suppression, and antibiotic resistance. To improve compliance, telemedicine or smartphone applications might play a role in the modern world by increasing doctor-patient relationships, while concomitant probiotics could be administered to reduce adverse effects and enhance adherence. For better acid suppression, high-potency and high-dose proton-pump inhibitors or potassium-competitive acid blockers have preferable efficacy. To overcome antibiotic resistance, susceptibility tests either by culture or by genotyping are the most commonly used methods and have been suggested for antibiotic selection before rescue therapy, but empirical therapy according to detailed medical history could be an alternative. Eradication with a longer treatment period (14 days) has a better outcome than shorter period (7 or 10 days). Ultimately, clinicians should select antibiotics based on the patient's history of drug allergy, previous antibiotic exposure, local antibiotic resistance, available medications, and cost. In addition, identifying patients with a high risk of cancer and shared decision-making are also essential for those who have experienced eradication failure.
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The thin-wall heat pipe is an efficient heat transfer component that has been widely used in the field of heat dissipation of high-power electronic equipment in recent years. In this study, the orange peel morphology defect of thin-wall heat pipes after bending deformation was analyzed both for the macro-3D profile and for the micro-formation mechanism. The morphology and crystal orientations of the grains and annealing twins were carefully characterized utilizing optical metallography and the electron backscatter diffraction technique. The results show that after high-temperature sintering treatment, the matrix grains of the heat pipe are seriously coarsened and form a strong Goss texture, while certain annealing twins with the unique copper orientation are retained. The distribution of the Schmid factor value subjected to the uniaxial stress indicates that inhomogeneity in the intergranular deformation exists among the annealing twins and matrix grains. The annealing twin exhibits a "hard-oriented" component during the deformation; thus, it plays a role as a barrier and hinders the slipping of dislocation. As the strain accumulates, part of the annealing twins may protrude from the surface of the heat pipe, forming a large-scale fluctuation of the surface as the so-called "orange peel" morphology. The 3D profile shows the bulged twins mostly perpendicular to the drawing direction, about 200-300 in width and 10-20 µm in height.
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Engineered magnetic nanoparticles combining diagnosis and therapy functions into one entity hold great potential to rejuvenate cancer treatment; however, they are still constrained by the "always on" signals and unsatisfactory therapeutic effect. Here, we report an intelligent theranostic probe based on Mn3O4 tetragonal bipyramids (MnTBs), which simultaneously respond to H+ and glutathione (GSH) with high sensitivity and quickly decompose to release Mn2+ in mild acidic and reductive intracellular environments. Mn2+ binds to the surrounding proteins to achieve a remarkable relaxivity amplification and selectively brighten the tumors. Particularly, this MR signal improvement is also effective in the detection of millimeter-sized liver metastases, with an ultrahigh contrast of 316%. Moreover, Mn2+ would trigger chemodynamic therapy (CDT) by exerting the Fenton-like activity to generate ËOH from H2O2. Subsequently, a significant tumor suppression effect can be achieved by the GSH depletion-enhanced CDT. Besides, MnTBs manifest efficient urinary and hepatic excretions with biodegradability and minimal systemic toxicity. A pH/GSH dual responsive nanoprobe that integrates tumor diagnostic and therapeutic activities was developed to provide a new paradigm for precise diagnosis and treatment of tumors and metastases.
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Nanopartículas , Neoplasias , Humanos , Linhagem Celular Tumoral , Peróxido de Hidrogênio/metabolismo , Neoplasias/tratamento farmacológico , Nanopartículas/uso terapêutico , Glutationa/metabolismo , Imageamento por Ressonância Magnética , Concentração de Íons de Hidrogênio , Microambiente TumoralRESUMO
Neurons responding sensitively to motions in several rather than all directions have been identified in many sensory systems. Although this directional preference has been demonstrated by previous studies to exist in the isthmi pars magnocellularis (Imc) of pigeon (Columba livia), which plays a key role in the midbrain saliency computing network, the dynamic response characteristics and the physiological basis underlying this phenomenon are unclear. Herein, dots moving in 16 directions and a biologically plausible computational model were used. We found that pigeon Imc's significant responses for objects moving in preferred directions benefit the long response duration and high instantaneous firing rate. Furthermore, the receptive field structures predicted by a computational model, which captures the actual directional tuning curves, agree with the real data collected from population Imc units. These results suggested that directional preference in Imc may be internally prebuilt by elongating the vertical axis of the receptive field, making predators attack from the dorsal-ventral direction and conspecifics flying away in the ventral-dorsal direction, more salient for avians, which is of great ecological and physiological significance for survival.
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DAHP synthase catalyzes the first step in the shikimate pathway, deriving the biosynthesis of aromatic amino acids (Trp, Phe and Tyr), phenazine-1-carboxamide, folic acid, and ubiquinone in Pseudomonas chlororaphis. In this study, we identified and characterized one DAHP synthase encoding gene phzC, which differs from the reported DAHP synthase encoding genes aroF, aroG and aroH in E. coli. PhzC accounts for approximately 90% of the total DAHP synthase activities in P. chlororaphis HT66 and plays the most critical role in four DAHP synthases in the shikimate pathway. Inactivation of phzC resulted in the reduction of PCN production by more than 90%, while the absence of genes aroF, aroG and aroH reduced PCN yield by less than 15%, and the production of PCN was restored after the complementation of gene phzC. Moreover, the results showed that phzC in P. chlororaphis HT66 is not sensitive to feedback inhibition. This study demonstrated that gene phzC is essential for PCN biosynthesis. The expression level of both phzC and phzE genes are not inhibited in feedback by PCN production due to the absence of a loop region required for allosteric control reaction. This study highlighted the importance of PhzC and applying P. chlororaphis for shikimate pathway-derived high-value biological production.
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An important step in brain image analysis is to divide specific brain regions by matching brain slices to standard brain reference atlases, and perform statistical analysis on the labeled neurons in each brain region. Taking mouse fluorescently labeled brain slices as an example, due to the noise and distortion introduced during the preparation of brain slices, and the modal differences with standard brain atlas, the brain slices cannot directly establish an accurate one-to-one correspondence with the brain atlas, which in turn affects the accuracy of the number of labeled neurons in each brain region. This paper introduces the idea of image representation, uses neural networks to realize the registration of different modal mouse brain slices and brain atlas, completes the regional localization of the brain slices, and uses threshold segmentation to detect and count the labeled neurons in each brain region. The method proposed in this paper can effectively solve the problem of large deviation of neurons count caused by the inaccurate division of brain regions in large deformed brain slices, and can automatically realize accurate count of labeled neurons in each brain region of brain slices. The whole framework of method for counting labeled neurons in mouse brain regions based on image representation and registration.
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Encéfalo , Processamento de Imagem Assistida por Computador , Animais , Encéfalo/diagnóstico por imagem , Cabeça , Imageamento por Ressonância Magnética , Camundongos , Redes Neurais de Computação , NeurôniosRESUMO
The intermediate and deep layers of the optic tectum (OT) contain neurons that are sensitive to small continuously moving targets. The sensitivity of these neurons to continuously moving targets suggests directed energy accumulation in the dendrite field of these neurons. Considering that the activation of a single dendrite can induce somatic spikes in vitro, we suggest the mechanism underlying the sequential probability activation of soma. The simulation model of these neurons constructed in combination with the above assumptions qualitatively reproduces the response characteristics of neurons to multi-sized stimuli and continuous sensitivity stimuli observed in physiological experiments. We used the characteristics of continuous motion-sensitive neurons that prefer long-lasting motion and single dendrite activation to induce somatic spikes as the entry point to construct the neuron encoding model. This model will enhance our understanding of the information-processing mechanism of the OT area of bird neurons in perceiving weak targets, and has important theoretical and practical significance for the construction of new brain-like algorithms.
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Percepção de Movimento , Colículos Superiores , Animais , Encéfalo , Columbidae , Percepção de Movimento/fisiologia , Neurônios Motores , Colículos Superiores/fisiologiaRESUMO
Engineered magnetic nanoparticles have been extensively explored for magnetic resonance imaging (MRI) diagnosis of a tumor to improve the visibility. However, most of these nanoparticles display "always-on" signals without tumor specificity, causing insufficient contrast and false positives. Here, we provide a new paradigm of MRI diagnosis using MnCO3 nanorhombohedras (MnNRs) as an ultrasensitive T1-weighted MRI contrast agent, which smartly enhances the MR signal in response to the tumor microenvironment. MnNRs would quickly decompose and release Mn2+ at mild acidity, one of the pathophysiological parameters associated with cancer malignancy, and then Mn2+ binds to surrounding proteins to achieve a remarkable amplification of T1 relaxivity. In vivo MRI experiments demonstrate that MnNRs can selectively brighten subcutaneous tumors from the edge to the interior may be because of the upregulated vascular permeation at the tumor edge, where cancer cell proliferation and angiogenesis are more active. Specially, benefiting from the T2 shortening effect in normal liver tissues, MnNRs can detect millimeter-sized liver metastases with an ultrahigh contrast of 294%. The results also indicate an effective hepatic excretion of MnNRs through the gallbladder. As such, this pH-activatable MRI strategy with facility, biocompatibility, and excellent efficiency may open new avenues for tumor malignancy and metastasis diagnosis and holds great promise for precision medicine.
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Carbonatos/química , Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Manganês/química , Nanopartículas/química , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Teste de Materiais , Metástase NeoplásicaRESUMO
Cushion plants' significant role for alpine biodiversity has been demonstrated in particular through their positive effects on plant diversity. However, their effects on higher trophic levels (e.g. insects) remain largely unclear. In this study, by field sampling in the Hengduan Mountains (HDM) in southwestern China, we evaluated the effects of an alpine gynodioecious cushion species, Arenaria polytrichoides (Carophyllaceae), on insect richness, abundance and population dynamics at two different elevations (4427 m vs. 4732 m) separately at two time periods (day vs. night) and in two growing seasons (early vs. late). The results showed that the total insect diversity decreases from low to high elevation sites. Some insect species were exclusively detected within A. polytrichoides cushions, leading to an increase in local insect richness from 7% to 35%. The positive effects of cushions on insect diversity could be attributed to unique biotic properties provided by cushions. Firstly, the effects were determined by the sexual dimorphism of the cushion with hermaphroditic cushions supporting higher insect diversity than female cushions. This could be because hermaphroditic cushions provide more resources, such as nectar and pollen grains, for insects than female cushions. Secondly, the cushions' associated beneficiary plants can also provide extra resources for attracting more insects, but this effect was mediated by the micro-environmental conditions. Finally, the magnitude of cushions' positive effects on insect dynamics were stronger under higher than under lower environmental stress. This study confirmed that facilitation by A. polytrichoides cushions in HDM plays an important role in constructing the alpine insect community and further regulating its dynamics. Moreover, the positive effects of cushions on insect dynamics increase with increasing environmental stress. Therefore, the distribution range of insects would quite possibly be expanded into higher elevation under future climate changes, which will induce new challenges for the local alpine ecosystems.
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Altitude , Ecossistema , Animais , Biodiversidade , China , Insetos , PlantasRESUMO
In recent years, there has been increasing interest in microbial biotechnology for the production of value-added compounds from renewable resources. Pseudomonas species have been proposed as a suitable workhorse for high-value secondary metabolite production because of their unique characteristics for fast growth on sustainable carbon sources, a clear inherited background, versatile intrinsic metabolism with diverse enzymatic capacities, and their robustness in an extreme environment. It has also been demonstrated that metabolically engineered Pseudomonas strains can produce several industrially valuable aromatic chemicals and natural products such as phenazines, polyhydroxyalkanoates, rhamnolipids, and insecticidal proteins from renewable feedstocks with remarkably high yields suitable for commercial application. In this review, we summarize cell factory construction in Pseudomonas for the biosynthesis of native and non-native bioactive compounds in P. putida, P. chlororaphis, P. aeruginosa, as well as pharmaceutical proteins production by P. fluorescens. Additionally, some novel strategies together with metabolic engineering strategies in order to improve the biosynthetic abilities of Pseudomonas as an ideal chassis are discussed. Finally, we proposed emerging opportunities, challenges, and essential strategies to enable the successful development of Pseudomonas as versatile microbial cell factories for the bioproduction of diverse bioactive compounds.
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Microbiologia Industrial , Engenharia Metabólica , Pseudomonas/metabolismo , Produtos Biológicos , Glicolipídeos , Inseticidas , Fenazinas , Poli-Hidroxialcanoatos , Metabolismo Secundário , Biologia SintéticaRESUMO
The cathode ray tube (CRT) is a common and important tool that has been in use for decades, with which behavioral and visual neuroscientists deliver specific visual images generated by computers. Considering the operating principle of the CRT, the image it presents can flick at a constant rate, which will introduce distractions to the visual experiments on subjects with higher temporal resolutions. While this entrainment has been proved common in recordings of the primary visual cortex of mammals, it is uncertain whether it also exists in the intermediate to deep layers of pigeon's optic tectum, which is relevant to the spatial attention. Here, we present continuous visual stimuli with different refresh rates and luminances couples shown on a CRT to pigeons. The recordings in the intermediate to deep layers of optic tectum were significantly phase locking to the refresh of the CRT, and lower refresh rates of the CRT with higher brightness more likely introduced artifacts in electrophysiological recordings of pigeons, which may seriously damage their visual information perception.