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Some people, entirely untrained in music, can listen to a song and replicate it on a piano with unnerving accuracy. What enables some to "hear" music so much better than others? Long-standing research confirms that part of the answer is undoubtedly neurological and can be improved with training. However, are there structural, physical, or engineering attributes of the human hearing mechanism apparatus (i.e., the hair cells of the internal ear) that render one human innately superior to another in terms of propensity to listen to music? In this work, we investigate a physics-based model of the electromechanics of the hair cells in the inner ear to understand why a person might be physiologically better poised to distinguish musical sounds. A key feature of the model is that we avoid a "black-box" systems-type approach. All parameters are well-defined physical quantities, including membrane thickness, bending modulus, electromechanical properties, and geometrical features, among others. Using the two-tone interference problem as a proxy for musical perception, our model allows us to establish the basis for exploring the effect of external factors such as medicine or environment. As an example of the insights we obtain, we conclude that the reduction in bending modulus of the cell membranes (which for instance may be caused by the usage of a certain class of analgesic drugs) or an increase in the flexoelectricity of the hair cell membrane can interfere with the perception of two-tone excitation.
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Música , Percepção da Fala , Humanos , Percepção Auditiva , Audição , Física , Percepção da Fala/fisiologia , Percepção da Altura Sonora/fisiologiaRESUMO
Chemistry-alone approach has recently been applied for incepting pluripotency in somatic cells, representing a breakthrough in biology. However, chemical reprogramming is hampered by low efficiency, and the underlying molecular mechanisms remain unclear. Particularly, chemical compounds do not have specific DNA-recognition domains or transcription regulatory domains, and then how do small molecules work as a driving force for reinstating pluripotency in somatic cells? Furthermore, how to efficiently clear materials and structures of an old cell to prepare the rebuilding of a new one? Here, we show that small molecule CD3254 activates endogenous existing transcription factor RXRα to significantly promote mouse chemical reprogramming. Mechanistically, CD3254-RXRα axis can directly activate all the 11 RNA exosome component genes (Exosc1-10 and Dis3) at transcriptional level. Unexpectedly, rather than degrading mRNAs as its substrates, RNA exosome mainly modulates the degradation of transposable element (TE)-associated RNAs, particularly MMVL30, which is identified as a new barrier for cell-fate determination. In turn, MMVL30-mediated inflammation (IFN-γ and TNF-α pathways) is reduced, contributing to the promotion of successful reprogramming. Collectively, our study provides conceptual advances for translating environmental cues into pluripotency inception, particularly, identifies that CD3254-RXRα-RNA exosome axis can promote chemical reprogramming, and suggests modulation of TE-mediated inflammation via CD3254-inducible RNA exosome as important opportunities for controlling cell fates and regenerative medicine.
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Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Camundongos , Animais , Reprogramação Celular/genética , Fatores de Transcrição/metabolismo , Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo , Ácidos Cumáricos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismoRESUMO
Chemical compounds have recently been introduced as alternative and non-integrating inducers of pluripotent stem cell fate. However, chemical reprogramming is hampered by low efficiency and the molecular mechanisms remain poorly characterized. Here, we show that inhibition of spleen tyrosine kinase (Syk) by R406 significantly promotes mouse chemical reprogramming. Mechanistically, R406 alleviates Syk / calcineurin (Cn) / nuclear factor of activated T cells (NFAT) signaling-mediated suppression of glycine, serine, and threonine metabolic genes and dependent metabolites. Syk inhibition upregulates glycine level and downstream transsulfuration cysteine biosynthesis, promoting cysteine metabolism and cellular hydrogen sulfide (H2 S) production. This metabolic rewiring decreased oxidative phosphorylation and ROS levels, enhancing chemical reprogramming. In sum, our study identifies Syk-Cn-NFAT signaling axis as a new barrier of chemical reprogramming and suggests metabolic rewiring and redox homeostasis as important opportunities for controlling cell fates.
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Fibroblastos/metabolismo , Sulfeto de Hidrogênio/metabolismo , Quinase Syk/antagonistas & inibidores , Animais , Calcineurina/metabolismo , Células Cultivadas , Cisteína/metabolismo , Fibroblastos/efeitos dos fármacos , Glicina/metabolismo , Camundongos , Fatores de Transcrição NFATC/metabolismo , Oxazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues, and regulates obesity related diseases, however the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein 1 (UCP1) and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1 and mitochondrial complex expression. These findings demonstrate that NPR-C deficiency enhances metabolic health by boosting energy expenditure in WAT, emphasizing the potential of NPR-C inhibition for treating obesity and related metabolic disorders.
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BACKGROUND: Current randomized trial evidence for the effects of physical activity intervention on weight change in adults was mainly from western countries, with little reliable evidence from low- and middle-income countries, such as China, where lifestyle factors and obesity patterns differ substantially from those in western countries. We examined the effects of physical activity intervention on weight change using cluster randomized trial data among Chinese older adults. METHODS: The cluster randomized controlled trial included an 8-week physical activity intervention period and was followed up to 24 months. Eight villages were randomly assigned to the intervention group (4 villages, n = 240) or the control group (4 villages, n = 268). The intervention group received physical activity intervention based on the socio-ecological model, while the control group did not. The intervention involved three levels: individual, interpersonal, and community levels, which aimed to promote leisure-time physical activity of participants. The primary outcome of the present study was the difference in percentage weight change at 24 months from baseline. We used Tanita BC-601 analyzer scales to measure weight and recorded it to the nearest 0.1 kg. RESULTS: Among the 508 participants, the mean age was 70.93 (SD, 5.69) years, and 55.5% were female. There were significant differences in percentage weight change between the intervention group and the control group with a mean change of -1.78% (95% CI, -2.67% to -0.90%; p < 0.001) in the total sample, -1.94% (95% CI, -3.14% to -0.73%; p = 0.002) in participants with overweight/obesity, and -1.45% (95% CI, -2.73% to -0.18%; p = 0.027) among participants with underweight/healthy weight in favor of the intervention group at 24 months. CONCLUSIONS: Physical activity intervention resulted in weight loss in rural older sample at 24 months. This suggested that physical activity interventions are feasible for weight loss among older adults, especially for those with overweight/obesity or aged under 80. TRIAL REGISTRATION: The study has been registered on the Chinese Clinical Trial Registry on April 20, 2021 (ChiCTR2100045653), https://www.chictr.org.cn/showproj.html?proj=123704 .
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BACKGROUND: The treatment of spinal cord injury (SCI) has always been a significant research focus of clinical neuroscience, with inhibition of microglia-mediated neuro-inflammation as well as oxidative stress key to successful SCI patient treatment. Caffeic acid phenethyl ester (CAPE), a compound extracted from propolis, has both anti-inflammatory and anti-oxidative effects, but its SCI therapeutic effects have rarely been reported. METHODS: We constructed a mouse spinal cord contusion model and administered CAPE intraperitoneally for 7 consecutive days after injury, and methylprednisolone (MP) was used as a positive control. Hematoxylin-eosin, Nissl, and Luxol Fast Blue staining were used to assess the effect of CAPE on the structures of nervous tissue after SCI. Basso Mouse Scale scores and footprint analysis were used to explore the effect of CAPE on the recovery of motor function by SCI mice. Western blot analysis and immunofluorescence staining assessed levels of inflammatory mediators and oxidative stress-related proteins both in vivo and in vitro after CAPE treatment. Further, reactive oxygen species (ROS) within the cytoplasm were detected using an ROS kit. Changes in mitochondrial membrane potential after CAPE treatment were detected with 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide. Mechanistically, western blot analysis and immunofluorescence staining were used to examine the effect of CAPE on the SIRT1/PGC1α/DRP1 signaling pathway. RESULTS: CAPE-treated SCI mice showed less neuronal tissue loss, more neuronal survival, and reduced demyelination. Interestingly, SCI mice treated with CAPE showed better recovery of motor function. CAPE treatment reduced the expression of inflammatory and oxidative mediators, including iNOS, COX-2, TNF-α, IL-1ß, 1L-6, NOX-2, and NOX-4, as well as the positive control MP both in vitro and in vivo. In addition, molecular docking experiments showed that CAPE had a high affinity for SIRT1, and that CAPE treatment significantly activated SIRT1 and PGC1α, with down-regulation of DRP1. Further, CAPE treatment significantly reduced the level of ROS in cellular cytoplasm and increased the mitochondrial membrane potential, which improved normal mitochondrial function. After administering the SIRT1 inhibitor nicotinamide, the effect of CAPE on neuro-inflammation and oxidative stress was reversed.On the contrary, SIRT1 agonist SRT2183 further enhanced the anti-inflammatory and antioxidant effects of CAPE, indicating that the anti-inflammatory and anti-oxidative stress effects of CAPE after SCI were dependent on SIRT1. CONCLUSION: CAPE inhibits microglia-mediated neuro-inflammation and oxidative stress and supports mitochondrial function by regulating the SIRT1/PGC1α/DRP1 signaling pathway after SCI. These effects demonstrate that CAPE reduces nerve tissue damage. Therefore, CAPE is a potential drug for the treatment of SCI through production of anti-inflammatory and anti-oxidative stress effects.
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Ácidos Cafeicos , Doenças Mitocondriais , Álcool Feniletílico , Traumatismos da Medula Espinal , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Metilprednisolona/farmacologia , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/metabolismo , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Álcool Feniletílico/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Dinaminas/efeitos dos fármacosRESUMO
Horizontal gene transfer (HGT) is a major driving force in the evolution of prokaryotic and eukaryotic genomes. Despite recent advances in distribution and ecological importance, the extensive pattern, especially in seed plants, and post-transfer adaptation of HGT-acquired genes in land plants remain elusive. We systematically identified 1150 foreign genes in 522 land plant genomes that were likely acquired via at least 322 distinct transfers from nonplant donors and confirmed that recent HGT events were unevenly distributed between seedless and seed plants. HGT-acquired genes evolved to be more similar to native genes in terms of average intron length due to intron gains, and HGT-acquired genes containing introns exhibited higher expression levels than those lacking introns, suggesting that intron gains may be involved in the post-transfer adaptation of HGT in land plants. Functional validation of bacteria-derived gene GuaD in mosses and gymnosperms revealed that the invasion of foreign genes introduced a novel bypass of guanine degradation and resulted in the loss of native pathway genes in some gymnosperms, eventually shaping three major types of guanine metabolism in land plants. We conclude that HGT has played a critical role in land plant evolution.
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Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time-consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.
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Inteligência Artificial , Hepatopatia Gordurosa não Alcoólica , Humanos , Algoritmos , Tecnologia , HepatócitosRESUMO
Hyperlipidemia is a common metabolic disorder that can lead to cardiovascular disease. PDK4 is a key enzyme that regulates glucose and fatty acid metabolism and homeostasis. The aim of this study is to explore the correlation between PDK4 expression and dyslipidemia in obese children, and to find new therapeutic targets for hyperlipidemia in children. The expression of PDK4 in serum was detected by qRT-PCR. Receiver operating characteristic curve was used to analyze the relationship between PDK4 and dyslipidemia. Upstream miRNAs of PDK4 were predicted by the database and verified by dual luciferase reporter gene assay and detected by qRT-PCR. The hyperlipidemia mouse model was established by high-fat diet (HFD) feeding, and the metabolic disorders of mice were detected. PDK4 is poorly expressed in the serum of obese children. The upstream of PDK4 may be inhibited by miR-107, miR-27a-3p, and miR-106b-5p, which are highly expressed in the serum of obese children. Overexpression of PDK4 improves lipid metabolism in HFD mice. miR-27a-3p silencing upregulates PDK4 to improve lipid metabolism. In conclusion, PDK4 has a diagnostic effect on dyslipidemia in children, while lipid metabolism in hyperlipidemic mice could be mitigated by upregulation of PDK4, which was inhibited by miR-107, miR-27a-3p and miR-106b-5p on upstream.
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Dislipidemias , Hiperlipidemias , MicroRNAs , Obesidade Infantil , Humanos , Criança , Camundongos , Animais , Metabolismo dos Lipídeos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Dislipidemias/genéticaRESUMO
INTRODUCTION: How education affects the relationship between sedentary behavior and cognitive function remains unclear. The aim of this study was to investigate the relationship between mentally active sedentary behavior and cognitive function in rural older Chinese across different levels of education. METHODS: Data from 517 participants aged 60 years and older in rural China at baseline, 4 weeks, 8 weeks, 6 months, 12 months, and 24 months were analyzed. Univariate analysis was carried out using descriptive statistical techniques and bivariate analysis was performed using linear mixed effects models. RESULTS: Total mentally active sedentary behavior time and playing cards/mahjong time were significantly associated with global cognition (0.25 points [95% CI, 0.15-0.35], p < 0.001; 0.27 points [95% CI, 0.16-0.37], p < 0.001, respectively), the attention dimension (0.07 points [95% CI, 0.01-0.12], p = 0.025; 0.08 points [95% CI, 0.02-0.14], p = 0.011, respectively), and the memory dimension (0.20 points [95% CI, 0.13-0.26], p < 0.001; 0.18 points [95% CI, 0.12-0.25], p < 0.001, respectively). Such associations were more pronounced in illiterate participants. CONCLUSION: Our study suggested a positive association between mentally active sedentary behavior and cognitive function, with the association being more pronounced among illiterate older adults compared to the relatively well-educated. Future cognitive interventions should focus more on mentally active behavior. In addition, education-specific intervention strategy may be considered in cognitive interventions.
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PURPOSE: To evaluate microvasculature alterations of the peripapillary retina and macula and to assess whether the changes can detect preclinical retinopathy in systemic lupus erythematosus patients. METHODS: Cross-sectional study of 32 systemic lupus erythematosus patients without retinopathy and 22 normal controls. Optical coherence tomography angiography was used to measure the microvasculature of the peripapillary retina and macula. Vessel densities (VD, %) and fractal dimensions of superficial capillary plexus (SCP) and deep capillary plexus were calculated. RESULTS: Compared with controls, macular vessel densities of the whole image SCP (macular vessel density of SCP-wi) and macular vessel density of inferior SCP (macular vessel density of SCP-i) were significantly reduced in systemic lupus erythematosus patients ( P < 0.05). The peripapillary vessel densities (peripapillary vessel density [pVD]) of a 2.5-mm circle of SCP (pVD of SCP Φ2.5 ), pVD of SCP Φ3.5 , and pVD of inferior region of the inner circle of SCP (pVD of SCP-ii) were significantly reduced in patients treated with hydroxychloroquine >5 years. Macular vessel density of SCP-wi declined with age (ß = -0.12; P < 0.01) and pVD of SCP-ii declined with hydroxychloroquine cumulative dose (ß = -0.01; P < 0.01). Macular vessel density of SCP-i had the best discrimination power of 0.77 ( P < 0.01). CONCLUSION: Systemic lupus erythematosus patients without ocular involvement had microvasculature alterations that were particularly evident in the SCP. Peripapillary retina microvasculature may be reduced in patients with longer hydroxychloroquine treatment.
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Lúpus Eritematoso Sistêmico , Doenças Retinianas , Humanos , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Vasos Retinianos/diagnóstico por imagem , Estudos Transversais , Hidroxicloroquina , Retina , Microvasos , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológicoRESUMO
PURPOSE: The study aimed to examine the consistency of vertebral bone quality (VBQ) scores for assessing osteoporosis across different etiologies and explore the predictive value of various VBQ scores for fragility vertebral fractures. METHODS: Patients with fragility fractures were matched by age and sex to patients with lumbar degeneration. VBQ scores were calculated in T1- and T2-weighted magnetic resonance imaging. Differential analysis of bone quality was performed based on etiology. RESULTS: A total of 96 inpatients were retrospectively enrolled. VBQT1 scores were only sensitive to osteoporotic bone in degenerative group (p < 0.01), failing to identify osteoporosis in fractured group (p > 0.05). For the degenerative group, the area under the curve (AUC) using the VBQT1 scores to differentiate osteoporosis was 0.72. After controlling the confounding variables, only VBQT2 scores were significantly higher in fractured group than degenerative group, with a greater AUC of 0.82 predicting fragility fractures. VBQT1 scores moderately correlated with femoral neck T-scores in degenerative group (r = -0.45, p < 0.01) but not in fractured group (r = -0.24, p > 0.05). VBQT2 scores were not associated with femoral neck T-scores (p > 0.05). CONCLUSION: This study is the first to evaluate the effectiveness of VBQs scores in assessing osteoporosis post-fracture. Only non-fractured patients' bone quality is fully susceptible to VBQT1 scores. While VBQT1 scores may not correlate with fragility fractures, VBQT2 scores present a viable alternative.
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Osteoporose , Fraturas por Osteoporose , Humanos , Fraturas por Osteoporose/diagnóstico por imagem , Estudos Retrospectivos , Densidade Óssea , Vértebras Lombares/diagnóstico por imagem , Osteoporose/complicações , Osteoporose/diagnóstico por imagem , Imageamento por Ressonância Magnética/efeitos adversosRESUMO
PURPOSE: To compare the morphometry of paraspinal muscles in patients with degenerative spondylolisthesis (DS), isthmic spondylolisthesis (IS), and healthy individuals. METHODS: Thirty-seven pairs of DS patients were selected using propensity score matching with IS patients, while 37 healthy individuals matched for age, sex, and BMI were selected as controls. The relative cross-sectional area (rCSA), and relative functional cross-sectional area (rfCSA) of paraspinal muscles were measured, and the degree of fatty infiltration (FI) was calculated. Based on occupational differences, the patients were also divided into worker and farmer groups, and the same measurements were taken on them. RESULTS: At the L3/L4 level, the multifidus (MF) FI was greater in the DS and IS groups than in the control group, the erector spinae (ES) rfCSA was higher in the IS group than in the DS and control groups. At the L4/L5 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS and control groups. At the L5/S1 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS group. At the L3/L4, L4/L5 level, MF rfCSA were higher in the worker group than in the farmer group (p < 0.05). CONCLUSION: The morphological changes in paraspinal muscles in patients with DS were dominated by selective atrophy of the MF, while in patients with IS, the morphological changes in paraspinal muscle showed selective atrophy of the MF accompanied by compensatory hypertrophy of the ES. The surgeon should consider the morphological differences in paraspinal muscle between different types of lumbar spondylolisthesis when establishing the appropriate surgical program.
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Vértebras Lombares , Músculos Paraespinais , Pontuação de Propensão , Espondilolistese , Humanos , Espondilolistese/diagnóstico por imagem , Espondilolistese/patologia , Músculos Paraespinais/patologia , Músculos Paraespinais/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Adulto , Estudos de Casos e Controles , Imageamento por Ressonância MagnéticaRESUMO
As an electromechanical coupling between strain gradients and polarization, flexoelectricity is largely enhanced at the nanoscale. However, directly observing the evolution of flexoelectric fields at the nanoscale usually suffers from the difficulty of producing strain gradients and probing electrical responses simultaneously. Here, we introduce nanocracks in SrTiO3, Ba0.67Sr0.33TiO3, and TiO2 samples and apply continuously varying mechanical loading to them, and as a result, huge strain gradients appear at the crack tip and result in a significant flexoelectric effect. Then, using atomic force microscopy, we successfully measure the evolution of flexoelectricity around the crack tips. For the case of SrTiO3, the maximum induced electric field reaches 11 kV/m due to the tensile load increasing. The proposed method provides a reliable way to identify the significance of the flexoelectric effect. It may also open a new avenue for the study of flexoelectricity involving multiple physics phenomena including flexoelectronics, the flexo-photovoltaic effect, and others.
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Chemical doping of sodium is an indispensable means to optimize thermoelectric properties of PbTe materials, while a bottleneck is that an aliovalent atom doping leads to spontaneous intrinsic defects in the PbTe matrix, resulting in low dopant solubility. Therefore, it is urgent to improve the doping efficiency of Na for maximizing optimization. Here, an amazing new insight that the intentionally introduced Pb vacancies can promote Na solubility in ternary Pb1- x Nax Te is reported. Experimental analysis and theoretical calculations provide new insights into the inherent mechanism of the enhancement of Na solubility. The Pb vacancies and the resultant more dissolved Na not only synergistically optimize the carrier concentration and further facilitate the band convergence, but also induce a large number of dense dislocations in the grains. Consequently, benefiting from the self-enhancement of Seebeck coefficient and the minimization of lattice thermal conductivity, an 18% growth is obtained for the figure of merit zT in vacancy-containing Pb0.95 Na0.04 Te sample, reaching maximum zTmax ≈ 2.0 at 823 K, which achieves an ultra-high performance in only Na-doped ternary Pb1- x Nax Te materials. The strategy utilized here provides a novel route to optimize PbTe materials and represents an important step forward in manipulating thermoelectrics to improve dopant solubility.
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Melatonin (N-acetyl-5-methoxytryptamine) is a potent reactive oxygen species (ROS) scavenger that increases the biotic and abiotic stress tolerance in plants. The signaling and regulation pathways of melatonin in plants remain elusive. Here, we report that transgenic apple (Malus domestica) plants overexpressing the transcription factor gene, MdWRKY17, have higher melatonin contents and lower ROS levels than those of control, while the MdWRKY17 RNA interference (RNAi) lines show the reversed phenotype. The binding of MdWRKY17 to N-acetylserotonin O-methyltransferase7 (MdASMT7) directly promotes the MdASMT7 expression in the in vitro and in vivo. MdASMT7 is a melatonin synthase that localizes to the plasma membrane. MdASMT7 overexpression rescued the lower melatonin contents of MdWRKY17-RNAi lines, confirming the role of MdWRKY17-MdASMT7 module in melatonin biosynthesis in apple. Furthermore, melatonin treatment activated the mitogen-activated kinases (MPKs) MdMPK3 and MdMPK6, which phosphorylate MdWRKY17 to promote transcriptional activation of MdASMT7. RNAi-mediated silencing of MdMPK3/6 decreases MdASMT7 expression in transgenic apple plants overexpressing MdWRKY17, which further confirms MdMPK3/6 fine-tunes MdWRKY17-mediated MdASMT7 transcription. This also forms a positive loop that melatonin activates MdMPK3/6 and thus accelerates the biosynthesis of itself via triggering MdMPK3/6-MdWRKY17-MdASMT7 pathway. This novel melatonin regulatory pathway not only have dissected the molecular mechanisms of melatonin biosynthesis but also provided an alternative approach for generating transgenic melatonin-rich apples which may benefits to human health.
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Malus , Melatonina , Humanos , Melatonina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ativação Transcricional , Plantas Geneticamente Modificadas/genética , Estresse Fisiológico , Malus/genética , Malus/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Water-soluble synthetic polymers (WSPs) are distinct from insoluble plastic particles, which are both critical components of synthetic polymers. In the history of human-made macromolecules, WSPs have consistently portrayed a crucial role and served as the ingredients of a variety of products (e.g., flocculants, thickeners, solubilizers, surfactants, etc.) commonly used in human society. However, the environmental exposures and risks of WSPs with different functions remain poorly understood. This paper provides a critical review of the usage, environmental fate, environmental persistence, and biological consequences of multiple types of WSPs in commercial and industrial production. Investigations have identified a wide market of applications and potential environmental threats of various types of WSPs, but we still lack the suitable assessment tools. The effects of physicochemical properties and environmental factors on the environmental distribution as well as the transport and transformation of WSPs are further summarized. Evidence regarding the degradation of WSPs, including mechanical, thermal, hydrolytic, photoinduced, and biological degradation is summarized, and their environmental persistence is discussed. The toxicity data show that some WSPs can cause adverse effects on aquatic species and microbial communities through intrinsic toxicity and physical hazards. This review may serve as a guide for environmental risk assessment to help develop a sustainable path for WSP management.
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Purificação da Água , Água , Humanos , Abastecimento de Água , Polímeros , PlásticosRESUMO
Pectate lyases (Pels) have a vital function in degradation of the primary plant cell wall and the middle lamella and have been widely used in the industry. In this study, two pectate lyase genes, IDSPel16 and IDSPel17, were cloned from a sheep rumen microbiome. The recombinant enzymes were expressed in Escherichia coli and functionally characterized. Both IDSPel16 and IDSPel17 proteins had an optimal temperature of 60 â, and an optimal pH of 10.0. IDSPel16 was relatively stable below 60 °C, maintaining 77.51% residual activity after preincubation at 60 °C for 1 h, whereas IDSPel17 denatured rapidly at 60 °C. IDSPel16 was relatively stable between pH 6.0 and 12.0, after pretreatment for 1 h, retaining over 60% residual activity. IDSPel16 had high activity towards polygalacturonic acid, with a Vmax of 942.90 ± 68.11, whereas IDSPel17 had a Vmax of only 28.19 ± 2.23 µmol/min/mg. Reaction product analyses revealed that IDSPel17 liberated unsaturated digalacturonate (uG2) and unsaturated trigalacturonate (uG3) from the substrate, indicating a typical endo-acting pectate lyase (EC 4.2.2.2). In contrast, IDSPel16 initially generated unsaturated oligogalacturonic acids, then converted these intermediates into uG2 and unsaturated galacturonic acid (uG1) as end products, a unique depolymerization profile among Pels. To the best of our knowledge, the IDSPel16 discovered with both endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities. These two pectate lyases, particularly the relatively thermo- and pH-stable IDSPel16, will be of interest for potential application in the textile, food, and feed industries. KEY POINTS: ⢠Two novel pectate lyase genes, IDSPel16 and IDSPel17, were isolated and characterized from the sheep rumen microbiome. ⢠Both IDSPel16 and IDSPel17 are alkaline pectate lyases, releasing unsaturated digalacturonate and unsaturated trigalacturonate from polygalacturonic acid. ⢠IDSPel16, a bifunctional pectate lyase with endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities, could be a potential candidate for industrial application.
Assuntos
Polissacarídeo-Liases , Rúmen , Animais , Ovinos , Rúmen/metabolismo , Polissacarídeo-Liases/metabolismo , Clonagem MolecularRESUMO
Citrus fruit were easily infected by Penicillium digitatum, and caused green mold rapidly, resulting in enormous post-harvest losses. ε-poly-l-lysine (ε-PL) was generally regarded as a safe (GRAS) substance. Besides, it was proved to have a dual effect on harming fungi and triggering fruit defense responses. Fatty acid metabolism is closely related to fruit defense response. However, little is known about how ε-PL affected fatty acid metabolism in citrus fruit. Here, we found that ε-PL increased the expression of CsFATA, CsACSL, CsFAD2, CsFAD3, CsLOX2S, and CsHPL in fatty acid metabolism, decreasing oleic acid levels and enhancing linoleic and linolenic acid levels. Additionally, ε-PL enriched the activities of LOX and HPL during the oxidative decomposition of fatty acids, and activating C9 aldehyde biosynthesis. Interestingly, ε-PL combined with (2E,4E)-nonadienal (C9 aldehyde) would improve the inhibitory effect against Penicillium digitatum. And the combined bio-fungicide significantly delayed the citrus green mold compared to single concentrations of the individual components. These results suggested that ε-PL improved citrus fruit defense responses through fatty acid-mediated defense responses. Combined bio-fungicide consisting of ε-PL and (2E,4E)-nonadienal have an excellent prospect for controlling citrus green mold.
Assuntos
Citrus , Fungicidas Industriais , Fungicidas Industriais/metabolismo , Polilisina/farmacologia , Citrus/metabolismo , Citrus/microbiologia , Frutas/microbiologia , Ácidos Graxos , Doenças das Plantas/microbiologiaRESUMO
The biocontrol effectiveness of Metschnikowia citriensis relies on its production of pulcherriminic acid (PA), which forms insoluble and stable pulcherrimin pigments by chelating iron ions, this inhibits pathogen growth by preventing their utilization of chelated Fe3+. In this study, ΔM. citriensis, which did not produce PA, was used as a control to examine changes in its biocontrol effectiveness by adding tryptophan to the medium. Tryptophan was shown to have no discernible impact on the growth and PA production of ΔM. citriensis; moreover, the PA synthesis-related genes PULs, Snf2, and leucyl-tRNA synthesis-related genes A3136 and A3022 were all down-regulated in ΔM. citriensis. The PA-free ΔM. citriensis eventually showed a much poorer inhibition zone against the pathogens in vitro, and a noticeably decreased control efficiency against postharvest diseases in citrus fruit. Tryptophan was added to the medium, which had no appreciable impact on inhibitory zone of ΔM. citriensis against pathogens in vitro, but enhanced its ability to control citrus postharvest diseases. Additionally, the control effects of culture broth of M. citriensis and ΔM. citriensis on postharvest diseases in citrus fruit were assessed. It was found that both culture broth of M. citriensis and ΔM. citriensis exhibited remarkable control effects against citrus postharvest diseases, with culture broth of M. citriensis which containing PA being more effective in controlling the disease. Last but not least, we extracted and dissolved pulcherrimin to obtain PA extracts, which were then injected to citrus fruits to assess the biocontrol effectiveness. The findings demonstrated that postharvest diseases of citrus fruit can be effectively controlled by PA extracts. This research suggested a new biological strategy for the management of citrus postharvest diseases.