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In this work, poly(l-lactic acid) (PLLA) Janus shape memory membranes with uniform vertically penetrative channels (SMEUVs) with slit pores have been fabricated with the help of template-assisting spray-coating and uniaxial tension at high temperature. During fog collection, superhydrophobic and hydrophilic surfaces act as the front (fog-facing) side and back side, respectively, in which the structural characteristics play essential roles. On one hand, the vertically penetrative channels in SMEUVs and the special pore geometry contribute to lower resistance, accelerating the transport of captured water through membranes (from the superhydrophobic side to the hydrophilic side). On the other hand, the movement of water droplets along the back side has been guided by the oriented structures of slit pores, promoting the detachment of droplets from the hydrophilic surface. Their synergistic effect removes captured water in a timely manner and provides fresh sites for the subsequent nucleation of water, enhancing fog collection performance. As a result, the optimal specimen (Janus SMEUVs with a draw ratio of 2.5, placed in the parallel direction) exhibits a much higher water collection rate (â¼6×) relative to references (superhydrophobic and hydrophilic membranes). Our results are significant for sustainable development in view of both fog collection in arid regions and the biodegradability of PLLA.
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Seminal plasma extracellular vesicles (SPEVs) play an important role in regulating sperm motility by delivering various cargoes, such as miRNAs, mRNAs, proteins and metabolites. However, information on the lipid compositions of SPEVs and their roles in semen quality is limited. Here, we performed high-throughput transcriptomic and lipidomic analysis on SPEVs isolated from 20 boars with high or low sperm motility. Then, we evaluated the lipid composition and gene expression characteristics of SPEVs and identified the specific lipids and genes related to sperm motility. As a result, a total of 26 lipid classes were identified in SPEVs, and five subclasses, CerG2, CerG3, LPE, LPS and TG, were significantly different in boars with high and low sperm motility. In addition, 195 important lipids and 334 important genes were identified by weighted gene coexpression analysis (WGCNA) and differential expression analysis. We observed that several important genes and lipids in SPEVs potentially influence sperm motility via glycerophospholipid metabolism, glycerolipid metabolism, the sphingolipid signaling pathway and the ferroptosis pathway. Furthermore, we found a significant correlation between the content of 22 lipids and the expression levels of 67 genes (|cor|â¯>â¯0.8, Pâ¯<â¯0.05). Moreover, we observed that three important gene-lipid linkages (CerG1 (d22:0/24:0) - RCAN3, Cer (d18:1/24:0) - SCFD2 and CerG1 (d18:0/24:1) - SCFD2) were strongly correlated with sperm motility. Based on the results, some genes and lipids in SPEVs may play important roles in sperm motility by interacting with sperm through important pathways.
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Hollow natural polysaccharide microcapsules have broad applications in drug delivery field due to their excellent biocompatibility and drug loading efficiency. In this paper, pH/near-infrared (NIR) dual-responsive microcapsules composed of hyaluronic acid (HA), chitosan (CS) and hollow CuS (HA/CS/HA@CuS) had been fabricated via a layer-by-layer (LbL) approach. The negative charge, rough surface and hollow structure of microcapsules are very favorable for loading positively charged DOX. As a result, hollow microcapsules display a high drug loading efficiency of 91.15 %. The variation in the degree of amino ionization at different pH values leads to the changes in the electrostatic force between CS/HA multilayers, resulting in the structural change in microcapsules. Therefore, microcapsules exhibit significant pH-responsive drug release properties. In addition, hollow CuS nanoparticles with excellent photothermal conversion ability are capped on the multilayer surface, enabling microcapsules to exhibit excellent NIR-responsive drug delivery properties. Overall, hyaluronic acid/chitosan-based hollow microcapsules with notable pH/NIR dual-responsiveness have been prepared, which can be used as a potential drug carrier for controlled drug delivery and photothermal chemical combination therapy.
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Cápsulas , Quitosana , Liberação Controlada de Fármacos , Ácido Hialurônico , Nanopartículas , Quitosana/química , Ácido Hialurônico/química , Concentração de Íons de Hidrogênio , Nanopartículas/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Humanos , Sistemas de Liberação de Medicamentos , CobreRESUMO
SCOPE: Depression, a prevalent mental disorder, has significantly impacted the lives of 350 million people, yet it holds promise for amelioration through food-derived phenolics. Raspberries, renowned globally for their delectable flavor, harbor a phenolic compound known as raspberry ketone (RK). However, the impact of RK on depressive symptoms remains ambiguous. This study aims to investigate the impact of RK on lipopolysaccharide (LPS)-induced depressed mice and elucidates its potential mechanisms, focusing on the gut-brain axis. METHODS AND RESULTS: Through behavioral tests, RK exerts a notable preventive effect on LPS-induced depression-like behaviors in mice. RK proves capable of attenuating gut inflammation, repairing gut barrier impairment, modulating the composition of the gut microbiome (Muribaculaceae, Streptococcus, Lachnospiraceae, and Akkermansia), and promoting the production of short-chain fatty acids. Furthermore, RK alleviates neuroinflammation by suppressing the TLR-4/NF-κB pathway and bolsters synaptic function by elevating levels of neurotrophic factors and synapse-associated proteins. CONCLUSION: The current study provides compelling evidence that RK effectively inhibits the TLR-4/NF-κB pathway via the gut-brain axis, leading to the improvement of LPS-induced depression-like behaviors in mice. This study addresses the research gap in understanding the antidepressant effects of RK and illuminates the potential of utilizing RK as a functional food for preventing depression.
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Eixo Encéfalo-Intestino , Depressão , Microbioma Gastrointestinal , Lipopolissacarídeos , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Depressão/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Masculino , Camundongos , Eixo Encéfalo-Intestino/efeitos dos fármacos , Eixo Encéfalo-Intestino/fisiologia , Butanonas/farmacologia , Camundongos Endogâmicos C57BL , Comportamento Animal/efeitos dos fármacos , Antidepressivos/farmacologiaRESUMO
BACKGROUND: Chemoresistance is a major cause of treatment failure in gastric cancer (GC). Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is an N6-methyladenosine (m6A)-binding protein involved in a variety of cancers. However, whether m6A modification and hnRNPA2B1 play a role in GC chemoresistance is largely unknown. In this study, we aimed to investigate the role of hnRNPA2B1 and the downstream mechanism in GC chemoresistance. METHODS: The expression of hnRNPA2B1 among public datasets were analyzed and validated by quantitative PCR (qPCR), Western blotting, immunofluorescence, and immunohistochemical staining. The biological functions of hnRNPA2B1 in GC chemoresistance were investigated both in vitro and in vivo. RNA sequencing, methylated RNA immunoprecipitation, RNA immunoprecipitation, and RNA stability assay were performed to assess the association between hnRNPA2B1 and the binding RNA. The role of hnRNPA2B1 in maintenance of GC stemness was evaluated by bioinformatic analysis, qPCR, Western blotting, immunofluorescence, and sphere formation assays. The expression patterns of hnRNPA2B1 and downstream regulators in GC specimens from patients who received adjuvant chemotherapy were analyzed by RNAscope and multiplex immunohistochemistry. RESULTS: Elevated expression of hnRNPA2B1 was found in GC cells and tissues, especially in multidrug-resistant (MDR) GC cell lines. The expression of hnRNPA2B1 was associated with poor outcomes of GC patients, especially in those who received 5-fluorouracil treatment. Silencing hnRNPA2B1 effectively sensitized GC cells to chemotherapy by inhibiting cell proliferation and inducing apoptosis both in vitro and in vivo. Mechanically, hnRNPA2B1 interacted with and stabilized long noncoding RNA NEAT1 in an m6A-dependent manner. Furthermore, hnRNPA2B1 and NEAT1 worked together to enhance the stemness properties of GC cells via Wnt/ß-catenin signaling pathway. In clinical specimens from GC patients subjected to chemotherapy, the expression levels of hnRNPA2B1, NEAT1, CD133, and CD44 were markedly elevated in non-responders compared with responders. CONCLUSION: Our findings indicated that hnRNPA2B1 interacts with and stabilizes lncRNA NEAT1, which contribute to the maintenance of stemness property via Wnt/ß-catenin pathway and exacerbate chemoresistance in GC.
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Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B , Ribonucleoproteínas Nucleares Heterogêneas , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , RNA Longo não Codificante/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
In this work, hierarchically porous PLA (polylactic acid) shape memory nonwovens were prepared by electrospinning its blend solution with PEO (polyethylene oxide) and subsequent water etching. Based on shape memory effect resulting from tiny crystals and the amorphous matrix of PLA, the switch between compact and porous surfaces has been achieved via cyclical hot-pressing and recovery in a hot water bath. After hot-pressing, the disappearance of hierarchical pores contributes to compact surface, enabling embedding of the target molecule in PLA nonwoven (i.e., CLOSE state). Upon exposure to heat, PLA nonwoven recovers to its permanent shape and exhibits a porous surface, providing a penetrative diffusion pathway for small molecules (i.e., OPEN state). The hierarchically porous structure and shape memory effect endow PLA nonwoven with the capability of rapid release. Our results provide a good candidate for some potential applications, such as temperature-controlled quick-release of catalysts and drugs.
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A strongly declining aerosol radiative effect has been observed in China since 2013 after implementing the clean air action, yet its impact on wheat (Triticum aestivum L.) production remains unclear. We use satellite measures and a biophysical crop model to assess the impact of aerosol-induced radiative perturbations on winter wheat production in the agricultural belt of Henan province from 2013 to 2018. After calibrating parameters with the extended Fourier Amplitude Sensitivity Test (EFAST) and the generalized likelihood uncertainty estimation (GLUE) method, the DSSAT CERES-Wheat model was able to simulate crop biomass and yield more accurately. We found that the aerosol negatively impacted wheat biomass by 21.87% and yield by 22.48% from 2006 to 2018, and the biomass effects from planting to anthesis were more significant compared to anthesis to maturity. Due to the strict clean air action, under all-sky conditions, the surface solar shortwave radiation (SSR) in 2018 increased by about 7.08% over 2006-2013 during the wheat growing seasons. As a result of the improvement of crop photosynthesis, winter wheat biomass and yield increased by an average of 5.46% and 2.9%, respectively. Our findings show that crop carbon uptake and yield will benefit from the clean air action in China, helping to ensure national food and health security.
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Agricultura , Triticum , Estações do Ano , Biomassa , ChinaRESUMO
BACKGROUND: In the context of Corona Virus Disease 2019 (COVID-19) global pandemic, Its impact on male reproductive function should be concerned. METHODS: Our study is a prospective cohort study that recruited participants infected or uninfected with COVID-19 between December 2022 and March 2023. All laboratory tests and questionnaire data were completed at the First Affiliated Hospital of Nanchang University. A total of 132 participants were enrolled, with 78 COVID-19 positive patients as the positive group and 54 COVID-19 negative participants as the negative group. Semen quality was assessed by the fifth World Health Organization criteria. The general characteristics of semen samples were assessed using CASA (computer-assisted sperm analysis). DNA damage and the high density stainability was assessed by sperm chromatin structure analysis (SCSA) based on flowcytometry. RESULTS: The sperm concentration, progressive motility and motility in COVID-19 negative group were significantly higher than positive group. In the following DNA damage analysis, a remarkably lower sperm DNA fragmentation index (DFI) in the COVID-19 negative group. In the positive group, unhealthy lifestyles had no significant effect on semen parameters, DNA fragmentation and nuclear compaction. CONCLUSIONS: After excluding the interference of unhealthy lifestyle, the COVID-19 infection can have a significant impact on the quality of semen, especially the DFI,. Therefore, it shows that COVID-19 can adversely affects male fertility, and this result provides advisory guidance for clinicians.
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COVID-19 , Sêmen , Humanos , Masculino , Análise do Sêmen , Estudos Prospectivos , Motilidade dos Espermatozoides , DNA , Fragmentação do DNA , CromatinaRESUMO
The ancient traditional Chinese drink Bian-Que Triple-Bean Soup made by fermentation (FTBS) of Lactococcus lactis subsp. lactis YM313 and Lacticaseibacillus casei YQ336 is a potential functional drink. The effect of fermentation on the flavor and biological activity of FTBS was evaluated by analyzing its chemical composition. Five volatile flavors were detected in modified FTBS. Fermentation decreased the proportion of nonanal (beany flavor substances) but significantly increased the total flavone contents, phenol contents and many bioactive small molecule substances in FTBS. The changes of these substances led to the significant improvement of FTBS sensory evaluation, antioxidant activity and prebiotic potential. This research provides a theoretical basis for the application of Lactic acid bacteria (LAB) in the fermentation of edible plant-based foods and transformation from traditional food to industrial production.
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BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy that causes significant maternal and perinatal morbidity and mortality. Circular RNA (circRNA) hsa_circ_0015382 is associated with the pathogenesis of PE, but its underlying regulatory mechanism remains to be explored. METHODS: Relative RNA levels of hsa_circ_0015382, microRNA-616-3p and thrombospondin-2 (THBS2) were detected by quantitative reverse transcription-polymerase chain reaction. In vitro regulatory effects of hsa_circ_0015382 on the proliferation, migration, invasion and angiogenesis of trophoblasts were evaluated by CCK-8, flow cytometry for cell cycle, EdU, transwell, wound healing and HUVEC tube formation assays, respectively. Targeting interaction was verified by dual-luciferase reporter and RNA immunoprecipitation assays. RESULTS: Hsa_circ_0015382 was highly expressed in placental tissues from PE patients. Upregulation of hsa_circ_0015382 repressed trophoblast proliferation, migration, invasion and lowered trophoblast-induced HUVEC tube formation. Hsa_circ_0015382 was validated as a miR-616-3p sponge and miR-616-3p targeted THBS2. Hsa_circ_0015382 could mediate trophoblast proliferation, migration, invasion and regulate trophoblast-induced HUVEC tube formation by sponging miR-616-3p and regulating THBS2 expression. CONCLUSION: Hsa_circ_0015382 is associated with the pathogenesis of PPE by regulating the miR-616-3p/THBS2 axis. HIGHLIGHTS: Hsa_circ_0015382 is overexpressed in preeclampsia patients. Hsa_circ_0015382 inhibits trophoblast proliferation, migration, invasion and decreases trophoblast-induced HUVEC tube formation. Hsa_circ_0015382 interacts with miR-616-3p to regulate THBS2 expression.
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Hipertensão , MicroRNAs , Pré-Eclâmpsia , Feminino , Gravidez , Humanos , Pré-Eclâmpsia/genética , Placenta , Trombospondinas/genética , MicroRNAs/genéticaRESUMO
Although 1-hydroxy-4-quinolone derivatives, such as 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), aurachin C, and floxacrine, have been reported as effective cytochrome bc1 complex inhibitors, the bioactivity of these products is not ideal, presumably due to their low bioavailability in tissues, particularly their poor solubility and low mitochondrial accumulation. In order to overcome the drawbacks of these compounds and develop their use as agricultural fungicides acting by cytochrome bc1 inhibition, in this study, three novel mitochondria-targeting quinolone analogs (mitoQNOs) were designed and synthesized by conjugating triphenylphosphonium (TPP) with quinolone. They exhibited greatly enhanced fungicidal activity compared to the parent molecule, especially mitoQNO11, which showed high antifungal activity against Phytophthora capsici and Sclerotinia sclerotiorum with EC50 values of 7.42 and 4.43 µmol/L, respectively. In addition, mitoQNO11 could inhibit the activity of the cytochrome bc1 complex of P. capsici in a dose-dependent manner and effectively depress its respiration and ATP production. The greatly decreased mitochondrial membrane potential and massively generated reactive oxygen species (ROS) strongly suggested that the inhibition of complex III led to the leakage of free electrons, which resulted in the damage of the pathogen cell structure. The results of this study indicated that TPP-conjugated QNOs might be used as agricultural fungicides by conjugating them with TPP.
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The design of metal-organic frameworks (MOF) derived composites with multiple loss mechanisms and multi-scale micro/nano structures is an important research direction of microwave absorbing materials. Herein, multi-scale bayberry-like Ni-MOF@N-doped carbon composites (Ni-MOF@NC) are obtained by a MOF assisted strategy. By utilizing the special structure of MOF and regulating its composition, the effective improvement of Ni-MOF@NC's microwave absorption performance has been achieved. The nanostructure on the surface of core-shell Ni-MOF@NC can be regulated and N doping on carbon skeleton by adjusting the annealing temperature. The optimal reflection loss of Ni-MOF@NC is -69.6 dB at 3 mm, and the widest effective absorption bandwidth is 6.8 GHz. This excellent performance can be attributed to the strong interface polarization caused by multiple core-shell structures, the defect and dipole polarization caused by N doping, and the magnetic loss caused by Ni. Meanwhile, the coupling of magnetic and dielectric properties enhances the impedance matching of Ni-MOF@NC. The work proposes a particular idea of designing and synthesizing an applicable microwave absorption material that possesses excellent microwave absorption performance and promising application potential.
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BACKGROUND: Succinate dehydrogenase inhibitors (SDHIs) are the fastest growing agricultural fungicides at present, but their rapidly growing resistance is a serious problem for their application. Previously, we screened out a fungicidal lead compound CBUA-TPP (1) through triphenylphosphonium (TPP)-driven mitochondrial-targeting strategy. The targeting led to the rapid accumulation of 1 in mitochondria and the saturation inhibition of complex II in a short time, resulting in electron leakage and the explosion of reactive oxygen species (ROS). However, the contribution of biphenyl-2-amines to the activity of these compounds and their structure-activity relationship are still unknown. RESULTS: Two series of CBUA-TPP (1) analogues (series 2 and 3) were designed and synthesized. The bioassay results indicated that series 2 compounds generally showed much higher fungicidal activities than series 3, suggesting the crucial contribution of the biarylamine module in these targeted molecules and the pyridinyl substitution of phenyl is unfavorable to their activities. Interestingly, these two series of compounds displayed almost opposite substituent effects. Several compounds showed excellent fungicidal activities in vitro, among which compound 2-1 exhibited excellent field control efficacy on potato late blight. CONCLUSION: By optimizing the lead compound, the contribution of biarylamine in CBUA-TPP (1) analogs to the fungicidal activity is clarified. Several compounds, represented by 2-1, have great potential as fungicide candidates. They exhibit high and broad-spectrum fungicidal activities and are highly effective against common pathogenic fungi infecting vegetables and fruits both in vitro and field control. It not only provided a new choice for controlling these diseases, but its low resistance tendency also provided a better scheme for resistance management. © 2023 Society of Chemical Industry.
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Ascomicetos , Fungicidas Industriais , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Amidas/farmacologia , Relação Estrutura-AtividadeRESUMO
Keloid is a common dermis tumor, occurring repeatedly, affecting the quality of patients' life. Long non-coding RNAs (lncRNAs) have crucial regulatory capacities in skin scarring formation and subsequent scar carcinogenesis. The intention of this study was to investigate the mechanism and function of GNAS antisense-1 (GNAS-AS1) in keloids. Clinical samples were collected to evaluate the expression of GNAS-AS1, RUNX2, and miR-188-5p by qRT-PCR. The proliferation, migration, and invasion of HKF cells were detected by CCK-8, wound healing, and Transwell assays. The expression levels of mRNA and protein were examined through qRT-PCR and Western blot assay. Luciferase reporter assay was used to identify the binding relationship among GNAS-AS1, miR-188-5p, and Runt-related transcription factor 2 (RUNX2). GNAS-AS1 and RUNX2 expressions were remarkably enhanced, and miR-188-5p expression was decreased in keloid clinical tissues and HKF cells. GNAS-AS1 overexpression promoted cells proliferation, migration, and invasion, while GNAS-AS1 knockdown had the opposite trend. Furthermore, overexpression of GNAS-AS1 reversed the inhibitory effect of 5-FU on cell proliferation, migration, and invasion. MiR-188-5p inhibition or RUNX2 overexpression could enhance the proliferation, migration, and invasion of HKF cells. GNAS-AS1 targeted miR-188-5p to regulate RUNX2 expression. In addition, the inhibition effects of GNAS-AS1 knockdown on HKF cells could be reversed by inhibition of miR-188-5p or overexpression of RUNX2, while RUNX2 overexpression eliminated the suppressive efficaciousness of miR-188-5p mimics on HKF cells growth. GNAS-AS1 knockdown could regulate the miR-188-5p/RUNX2 signaling axis to inhibit the growth and migration in keloid cells. It is suggested that GNAS-AS1 may become a new target for the prevention and treatment of keloid.
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Queloide , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Queloide/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Cromograninas/genética , Cromograninas/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismoRESUMO
Ecological environment assessment, which forms the basis for the survival and development of human society, is a crucial measure for the sustainable development of society and economy. However, current quantitative assessment models such as EI, EQI, RSEI et al. are insufficient to meet the requirements of dynamic research in large areas, long time series and dense time intervals. Therefore, in this paper, we constructed the comprehensive ecological environment quality index model SCEQI that can meet these needs by applying the remote sensing big data as the data source. The SCEQI aggregated the ecological indices NDVI, NDBSI, Lst and Wet by full-sequence dynamic dimensionless, automated principal component analysis and multi-temporal average method. In order to verify the spatial and temporal accuracy of the model, we took Henan Province as an example to compare the result of SCEQI with that of EI, EQI, RSEI and proved that SCEQI performed better in both time and space. Also, we verified the superiority of time, space, and precision of SCEQI with profiles, samples, and cluster analysis.
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Ecossistema , Monitoramento Ambiental , Humanos , Tecnologia de Sensoriamento Remoto , Meio Ambiente , Modelos Teóricos , ChinaRESUMO
In this work, poly (vinylidene fluoride) (PVDF) hierarchically porous membranes (HPMs) with isolated large pores and continuous narrow nano-pores have been fabricated from its blend with poly (methyl methacrylate) (PMMA) based on the combination of crystallization template with chemical or supercritical CO2 foaming. On the one hand, the decomposition of azodicarbonamide (ADC, chemical foaming agent) or the release of CO2 can produce isolated large pores. On the other hand, PMMA is expelled during the isothermal crystallization of PVDF in their miscible blend, yielding narrow nano-pores upon etching with a selective solvent. In the case of supercritical CO2, the attained PVDF HPMs fail to improve separation performance because of the compact wall of isolated-large-pore and consequent poor connectivity of hierarchical pores. In the case of ADC, the optimal HPM exhibits much higher flux (up to 20 times) without any loss of selectivity compared with the reference only with nano-pores. The enhanced permeability can be attributed to the shorter diffusion length and lower diffusion barrier from isolated large pores, while the comparable selectivity is determined by narrow nano-pores in THE matrix.
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Objective To investigate the expression of N6-methyladenosine (m6A) binding protein hnRNPA2B1 in various tumors and its relationship with prognosis and immune infiltration. Methods We investigated the expression of hnRNPA2B1 in different tumors and verified it in gastric cancer (GC) tissue microarray using immunohistochemistry. Univariate COX regression and Kaplan-Meier survival analysis were used to identify the prognostic value of hnRNPA2B1 in pan-cancer. In addition, we explored the correlation between the expression of hnRNPA2B1 and immune cell infiltration, immune checkpoint genes, tumor mutational burden (TMB) as well as microsatellite instability (MSI). Results The expression of hnRNPA2B1 was higher in tumor tissues than in corresponding normal tissues in most cancers. In GC tissue microarray, the expression of hnRNPA2B1 in GC tissues was significantly higher than that in paired adjacent normal tissues. High expression of hnRNPA2B1 was significantly associated with poor prognosis in 7 types of tumors. Moreover, the expression of hnRNPA2B1 was positively correlated with immune cell infiltration in a variety of tumors. In addition, hnRNPA2B1 was notably associated with immune checkpoint related genes, TMB and MSI. Conclusion The expression of hnRNPA2B1 is ubiquitously elevated in a variety of tumors and is associated with poor prognosis. Furthermore, hnRNPA2B1 is closely related to the immune cell infiltration and tumor microenvironment.
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Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/genética , Adenosina , Estimativa de Kaplan-MeierRESUMO
ß-Methoxyacrylate fungicides as complex III Qo site inhibitors play a crucial role in the control of crop diseases. In this study, the triphenylphosphonium (TPP)-driven mitochondrion-targeting strategy was used to modify the kresoxim-methyl scaffold at the toxicophore or side chain to develop novel mitochondrion-targeted QoI fungicides. These kresoxim-methyl analogues exhibited different fungicidal activities, depending on the position of TPP conjugation and the linker length. Among them, 2A-5 and 2C-4 showed excellent characteristics superior to kresoxim-methyl as candidate fungicides, in which the activity enhancement against Phytophthora capsici was the most remarkable, with an EC50 value of about 5 µM. Notably, both hyphal and zoospore structures of the pathogens were severely damaged after treatment with them. The action mechanism approach revealed that they might cause a significant decrease in ATP synthesis and ROS outbreak in different ways. The results also provided a new insight into the contribution of targeting group TPP to the fungicidal activity in TPP-driven fungicides.
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Fungicidas Industriais , Fungicidas Industriais/química , Complexo III da Cadeia de Transporte de Elétrons , Espécies Reativas de Oxigênio , Mitocôndrias , Trifosfato de AdenosinaRESUMO
With the rapid development of electric power, lithium materials, as a rare metal material, will be used up in 50 years. Sodium, in the same main group as lithium in the periodic table, is abundant in earth's surface. However, in the study of sodium-ion batteries, there are still problems with their low-temperature performance. Its influencing factors mainly include three parts: cathode material, anode material, and electrolyte. In the cathode, there are Prussian blue and Prussian blue analogues, layered oxides, and polyanionic-type cathodes in four parts, as this paper discusses. However, in the anode, there is hard carbon, amorphous selenium, metal selenides, and the NaTi2(PO4)3 anode. Then, we divide the electrolyte into four parts: organic electrolytes; ionic liquid electrolytes; aqueous electrolytes; and solid-state electrolytes. Here, we aim to find electrode materials with a high specific capacity of charge and discharge at lower temperatures. Meanwhile, high-electrical-potential cathode materials and low-potential anode materials are also found. Furthermore, their stability in air and performance degradation in full cells and half-cells are analyzed. As for the electrolyte, despite the aspects mentioned above, its electrical conductivity in low temperatures is also reported.
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Neuromyelitis optica spectrum disorders (NMOSD) are rare, debilitating autoimmune diseases of the central nervous system. Many NMOSD patients have antibodies to Aquaporin-4 (AQP4). Prior studies show associations of NMOSD with individual Human Leukocyte Antigen (HLA) alleles and with mutations in the complement pathway and potassium channels. HLA allele associations with NMOSD are inconsistent between populations, suggesting complex relationships between the identified alleles and risk of disease. We used a retrospective case-control approach to identify contributing genetic variants in patients who met the diagnostic criteria for NMOSD and their unaffected family members. Potentially deleterious variants identified in NMOSD patients were compared to members of their families who do not have the disease and to existing databases of human genetic variation. HLA sequences from patients from Belgrade, Serbia, were compared to the frequency of HLA haplotypes in the general population in Belgrade. We analyzed exome sequencing on 40 NMOSD patients and identified rare inherited variants in the complement pathway and potassium channel genes. Haplotype analysis further detected two haplotypes, HLA-A*01, B*08, DRB1*03 and HLA-A*01, B*08, C*07, DRB1*03, DQB1*02, which were more prevalent in NMOSD patients than in unaffected individuals. In silico modeling indicates that HLA molecules within these haplotypes are predicted to bind AQP4 at several sites, potentially contributing to the development of autoimmunity. Our results point to possible autoimmune and neurodegenerative mechanisms that cause NMOSD, and can be used to investigate potential NMOSD drug targets.