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BACKGROUND: This study aims to decipher the genetic basis governing yield components and quality attributes of peanuts, a critical aspect for advancing molecular breeding techniques. Integrating genotype re-sequencing and phenotypic evaluations of seven yield components and two grain quality traits across four distinct environments allowed for the execution of a genome-wide association study (GWAS). RESULTS: The nine phenotypic traits were all continuous and followed a normal distribution. The broad heritability ranged from 88.09 to 98.08%, and the genotype-environment interaction effects were all significant. There was a highly significant negative correlation between protein content (PC) and oil content (OC). The 10× genome re-sequencing of 199 peanut accessions yielded a total of 631,988 high-quality single nucleotide polymorphisms (SNPs), with 374 significant SNP loci identified in association with the nine traits of interest. Notably, 66 of these pertinent SNPs were detected in multiple environments, and 48 of them were linked to multiple traits of interest. Five loci situated on chromosome 16 (Chr16) exhibited pleiotropic effects on yield traits, accounting for 17.64-32.61% of the observed phenotypic variation. Two loci on Chr08 were found to be strongly associated with protein and oil contents, accounting for 12.86% and 14.06% of their respective phenotypic variations, respectively. Linkage disequilibrium (LD) block analysis of these seven loci unraveled five nonsynonymous variants, leading to the identification of one yield-related candidate gene and two quality-related candidate genes. The correlation between phenotypic variation and SNP loci in these candidate genes was validated by Kompetitive allele-specific PCR (KASP) marker analysis. CONCLUSIONS: Overall, molecular markers were developed for genetic loci associated with yield and quality traits through a GWAS investigation of 199 peanut accessions across four distinct environments. These molecular tools can aid in the development of desirable peanut germplasm with an equilibrium of yield and quality through marker-assisted breeding.
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Arachis , Estudo de Associação Genômica Ampla , Arachis/genética , Locos de Características Quantitativas/genética , Melhoramento Vegetal , Mapeamento Cromossômico/métodos , Fenótipo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Storage capacity, average open circuit voltage (OCV), diffusion barrier, lattice parameter changes, etc. are key indicators of whether a material would be suitable for use as a Li-ion or non-Li-ion battery (LIB or NLIB) anode. The rapid development of 2D materials over the past few decades has opened up new possibilities for these metrics. Using first-principles calculations, we prove that two 2D materials, TiB4 and SrB8, show excellent performance in terms of the above metrics when used as anodes for LIBs or NLIBs. As detailed, TiB4 has an Li\Na\K\Ca storage capacity of 588 mA h g-1, 588 mA h g-1, 588 mA h g-1, and 1176 mA h g-1, respectively, and SrB8 has an Li\Na\K\Ca storage capacity of 308 mA h g-1, 308 mA h g-1, 462 mA h g-1, and 616 mA h g-1, respectively, and they show good electrical conductivity whether existing Li, Na, K or Ca is adsorbed or not. The diffusion barriers on both surfaces are low, indicating good rate performance. The average OCV is also very low. In particular, the lattice parameters of the two materials change very little during the embedding of Li\Na\K\Ca. For Ti9B36 the corresponding values are about 0.37% (Li), 0.33% (Na), 0.64% (K) and 0.03% (Ca), and for Sr8B64 the corresponding values are about 0.70% (Li), 0.16% (Na), 0.13% (K) and 0.004% (Ca), which imply zero strain-like character and great cycling performance. All the above results show that TiB4 and SrB8 monolayers are very promising Li\Na\K\Ca ion battery anodes.
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Detecting road cracks is essential for inspecting and assessing the integrity of concrete pavement structures. Traditional image-based methods often require complex preprocessing to extract crack features, making them challenging when dealing with noisy concrete surfaces in diverse real-world scenarios, such as autonomous vehicle road detection. This study introduces an image-based crack detection approach that combines a Random Forest machine learning classifier with a deep convolutional neural network (CNN) to address these challenges. Three state-of-the-art models, namely MobileNet, InceptionV3, and Xception, were employed and trained using a dataset of 30,000 images to build an effective CNN. A systematic comparison of validation accuracy across various base learning rates identified a base learning rate of 0.001 as optimal, achieving a maximum validation accuracy of 99.97%. This optimal learning rate was then applied in the subsequent testing phase. The robustness and flexibility of the trained models were evaluated using 6,000 test photos, each with a resolution of 224 × 224 pixels, which were not part of the training or validation sets. The outstanding results, boasting a remarkable 99.95% accuracy, 99.95% precision, 99.94% recall, and a matching 99.94% F1 Score, unequivocally affirm the efficacy of the proposed technique in precisely identifying road fractures in photographs taken on real concrete surfaces.
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This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 µg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.
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Cistanche , Medicamentos de Ervas Chinesas , Neoplasias , Animais , Camundongos , Farmacologia em Rede , Proteína Beclina-1 , Espécies Reativas de Oxigênio , Extratos Vegetais , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Medicina Tradicional Chinesa , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
Herein, a type of hypervalent iodine compound-iodosobenzene (PhIO)-is proposed to regulate the LiPSs electrochemistry and enhance the performance of Li-S battery. PhIO owns the practical advantages of low-cost, commercial availability, environmental friendliness and chemical stability. The lone pair electrons of oxygen atoms in PhIO play a critical role in forming a strong Lewis acid-base interaction with terminal Li in LiPSs. Moreover, the commercial PhIO can be easily converted to nanoparticles (≈20 nm) and uniformly loaded on a carbon nanotube (CNT) scaffold, ensuring sufficient chemisorption for LiPSs. The integrated functional PhIO@CNT interlayer affords a LiPSs-concentrated shield that not only strongly obstructs the LiPSs penetration but also significantly enhances the electrolyte wettability and Li+ conduction. The PhIO@CNT interlayer also serves as a "vice current collector" to accommodate various LiPSs and render smooth LiPSs transformation, which suppresses insulating Li2 S2 /Li2 S layer formation and facilitates Li+ diffusion. The Li-S battery based on PhIO@CNT interlayer (6 wt% PhIO) exhibits stable cycling over 1000 cycles (0.033% capacity decay per cycle) and excellent rate performance (686.6 mAh g-1 at 3 C). This work demonstrates the great potential of PhIO in regulating LiPSs and provides a new avenue towards the low-cost and sustainable application of Li-S batteries.
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Heterostructures are attracting increasing attention in the field of sodium-ion batteries. However, it is still unclear whether any two monophase components can be used to construct a high-performance heterostructure for sodium-ion batteries, as well as the kind of heterostructures that can boost electrochemical performances. In this study, based on classical semiconductor theories on antiblocking and blocking interfaces, attempts are made to answer the abovementioned queries. For this purpose, NiTe2 -ZnTe antiblocking and CoTe2 -ZnTe blocking heterostructures are synthesized through a bimetal-hexamine framework-derived strategy. The NiTe2 -ZnTe antiblocking heterostructure exhibits excellent high-rate and cycling performances, while the CoTe2 -ZnTe blocking heterostructure performs poorly, even compared to their monophase components. Further, kinetic measurements and theoretical calculation confirm that antiblocking heterointerfaces can boost Na-ion diffusion efficiency and decrease the diffusion barrier, which can be attributed to the highly conductive antiblocking heterointerfaces generated due to electron transfer from NiTe2 to ZnTe. Therefore, this study provides a new perspective to design heterostructures more efficiently, with significantly better Na-ion storage performance.
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Junctophilins (JPH1-JPH4) are expressed in excitable and nonexcitable cells, where they tether endoplasmic/sarcoplasmic reticulum (ER/SR) and plasma membranes (PM). These ER/SR-PM junctions bring Ca-release channels in the ER/SR and Ca as well as Ca-activated K channels in the PM to within 10-25 nm. Such proximity is critical for excitation-contraction coupling in muscles, Ca modulation of excitability in neurons, and Ca homeostasis in nonexcitable cells. JPHs are anchored in the ER/SR through the C-terminal transmembrane domain (TMD). Their N-terminal Membrane-Occupation-Recognition-Nexus (MORN) motifs can bind phospholipids. Whether MORN motifs alone are sufficient to stabilize JPH-PM binding is not clear. We investigate whether S-palmitoylation of cysteine (Cys), a critical mechanism controlling peripheral protein binding to PM, occurs in JPHs. We focus on JPH2 that has four Cys residues: three flanking the MORN motifs and one in the TMD. Using palmitate-alkyne labeling, Cu(I)-catalyzed alkyne-azide cycloaddition reaction with azide-conjugated biotin, immunoblotting, proximity-ligation-amplification, and various imaging techniques, we show that JPH2 is S-palmitoylatable, and palmitoylation is essential for its ER/SR-PM tether function. Palmitoylated JPH2 binds to lipid-raft domains in PM, whereas palmitoylation of TMD-located Cys stabilizes JPH2's anchor in the ER/SR membrane. Binding to lipid-raft domains protects JPH2 from depalmitoylation. Unpalmitoylated JPH2 is largely excluded from lipid rafts and loses the ability to form stable ER/SR-PM junctions. In adult ventricular myocytes, native JPH2 is S-palmitoylatable, and palmitoylated JPH2 forms distinct PM puncta. Sequence alignment reveals that the palmitoylatable Cys residues in JPH2 are conserved in other JPHs, suggesting that palmitoylation may also enhance ER/SR-PM tethering by these proteins.
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Membrana Celular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Musculares/metabolismo , Ácido Palmítico/metabolismo , Retículo Sarcoplasmático/metabolismo , Animais , Células COS , Células Cultivadas , Chlorocebus aethiops , HumanosRESUMO
The monofunctional trinuclear platinum complex (MTPC), as a promising antitumor agent, can form MTPC-DNA adducts via bifunctional and trifunctional cross-links. Molecular dynamics simulations were used to investigate DNA structural distortions of the MTPC-DNA adducts. MTPC coordinating to DNA results in the decrease of base-pair thermal stability and DNA structural distortions. It is found that there are more significant DNA structural distortions in the trifunctional cross-link than in the bifunctional cross-link, in the 1,4-GG than in the 1,3-GG cross-link, and in the intrastrand than in the interstrand cross-link with the same spans. The results provide a better understanding of DNA structural distortions induced by MTPC with various cross-links at the nucleotide level and are helpful for exploring novel Pt-based anticancer drugs.
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Antineoplásicos , Platina , Antineoplásicos/farmacologia , Reagentes de Ligações Cruzadas , DNA , Adutos de DNA , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Compostos Organoplatínicos/farmacologiaRESUMO
The pursuit of high capacity is one of the key challenges for the development of alkaline ion batteries (AIBs, namely Li/Na/K-ion batteries; LIBs, NIBs, or KIBs). Carbon-based anode materials represented by graphite have been widely used in secondary batteries; however, their storage capacity is generally not high. Graphene was once considered a promising candidate, but it has proven to be incapable of interacting strongly with alkali ions. Here, by first-principles calculations, we predict an allotrope of graphene that may soon be experimentally synthesized, called T-graphene, which is a promising anode material for AIBs. We find that when it is used as the anode for NIBs, its theoretical capacity can be as high as 2232 mA h g-1 (Na6C6), which is six times that of graphite. For LIB and KIB anodes, the specific capacities are 744 mA h g-1 and 1116 mA h g-1, corresponding to the Li2C6 and K3C6 chemical formula, respectively. We first demonstrate that the material is mechanically stable. We further show that the material has good electrical conductivity whether it is before or after adsorption of Li(Na or K). We also studied the diffusion of Li(Na or K) on its surface and found that their corresponding diffusion barriers are very low (Li, Na and K are about 0.37 eV, 0.35 eV and 0.25 eV, respectively), which means good rate performance. It is calculated that the average open circuit voltage of the corresponding three half-cells at full charge is also low (LIBs is about 0.20 V, NIBs is about 0.12 V, and KIBs are about 0.37 V), which is beneficial for increasing the operating voltage of the full battery. In addition, during the adsorption of lithium, sodium and potassium, the lattice change of the material is very small (about 1.0% for lithium, about 1.4% for sodium, and about 1.9% for potassium), which means good cycling performance. These results indicate that T-graphene is expected to replace graphene and become a very attractive anode material for AIBs.
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PURPOSE: The meta-analysis aimed to evaluate the effect of gonadotrophin-releasing hormone agonist (GnRH-a) addition for luteal support on pregnancy outcome in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. METHODS: Meta-analysis. RESULTS: A total of 3,584 cycles were identified from 13 randomized controlled trials. The cumulative analysis showed that GnRH-a addition for luteal supports significantly improved live birth rate (relative risk [RR] = 1.52; 95% CI 1.20-1.94; p = 0.0006), the clinical pregnancy rate (RR 1.21; 95% CI 1.11-1.33; p < 0.0001), ongoing pregnancy rate (RR 1.18; 95% CI 1.06-1.32; p = 0.004), pregnancy rate (RR 1.36; 95% CI 1.01-1.82; p = 0.04), implantation rate (RR 1.44; 95% CI 1.17-1.77; p = 0.0007), and multiple pregnancy rate (RR 1.40; 95% CI 1.04-1.88; p = 0.03) in comparison with control, but not for the incidence of ovarian hyperstimulation syndrome (RR 0.96; 95% CI 0.32-2.89; p = 0.94). We also found that GnRH-a addition for luteal support had a tendency to decrease the abortion rate (RR 0.72; 95% CI 0.56-0.93; p = 0.01). CONCLUSIONS: Overall, the current meta-analysis showed a substantial efficacy of GnRH-a addition for luteal support on pregnancy outcomes in women undergoing IVF/ICSI and support the use of GnRH-a in luteal phase to improve the success of IVF/ICSI.
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Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina/agonistas , Fase Luteal/efeitos dos fármacos , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Implantação do Embrião , Feminino , Humanos , Síndrome de Hiperestimulação Ovariana/induzido quimicamente , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: K channel interacting protein 2 (KChIP2), initially cloned as Kv4 channel modulator, is a multi-tasking protein. In addition to modulating several cardiac ion channels at the plasma membrane, it can also modulate microRNA transcription inside nuclei, and interact with presenilins to modulate Ca release through RyR2 in the cytoplasm. However, the mechanism regulating its subcellular distribution is not clear. OBJECTIVE: We tested whether palmitoylation drives KChIP2 trafficking and distribution in cells, and whether the distribution pattern of KChIP2 in cardiac myocytes is sensitive to cellular milieu. METHOD: We conducted imaging and biochemical experiments on palmitoylatable and unpalmitoylatable KChIP2 variants expressed in COS-7 cells and in cardiomyocytes, and on native KChIP2 in myocytes. RESULTS: In COS-7 cells, palmitoylatable KChIP2 clustered to plasma membrane, while unpalmitoylatable KChIP2 exhibited higher cytoplasmic mobility and faster nuclear entry. The same differences in distribution and mobility were observed when these KChIP2 variants were expressed in cardiac myocytes, indicating that the palmitoylation-dependent distribution and trafficking are intrinsic properties of KChIP2. Importantly, acute stress in a rat model of cardiac arrest/resuscitation induced changes in native KChIP2 resembling those of KChIP2 depalmitoylation, promoting KChIP2 nuclear entry. CONCLUSION: The palmitoylation status of KChIP2 determines its subcellular distribution in cardiac myocytes. Stress promotes nuclear entry of KChIP2, diverting it from ion channel modulation at the plasma membrane to other functions in the nuclear compartment.
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Parada Cardíaca/genética , Proteínas Interatuantes com Canais de Kv/genética , Lipoilação/genética , Potássio/metabolismo , Animais , Células COS , Membrana Celular/genética , Chlorocebus aethiops , Citoplasma/genética , Citoplasma/metabolismo , Parada Cardíaca/metabolismo , Parada Cardíaca/patologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Palmitatos/farmacologia , Ratos , Canal de Liberação de Cálcio do Receptor de Rianodina/genéticaRESUMO
The polysulfide shuttle effect and sluggish reaction kinetics hamper the practical applications of lithium-sulfur (Li-S) batteries. Incorporating a functional interlayer to trapping and binding polysulfides has been found effective to block polysulfide migration. Furthermore, surface chemistry at soluble polysulfides/electrolyte interface is a crucial step for Li-S battery in which stable cycling depends on adsorption and reutilization of blocked polysulfides in the electrolyte. A multifunctional catalytic interface composed of niobium nitride/N-doped graphene (NbN/NG) along the soluble polysulfides/electrolyte is designed and constructed to regulate corresponding interface chemical reaction, which can afford long-range electron transfer surfaces, numerous strong chemisorption, and catalytic sites in a working lithium-sulfur battery. Both experimental and theoretical calculation results suggest that a new catalytic interface enabled by metal-like NbN with superb electrocatalysis anchored on NG is highly effective in regulating the blocked polysulfide redox reaction and tailoring the Li2 S nucleation-growth-decomposition process. Therefore, the Li-S batteries with multifunctional NbN/NG barrier exhibit excellent rate performance (621.2 mAh g-1 at 3 C) and high stable cycling life (81.5% capacity retention after 400 cycles). This work provides new insights to promote Li-S batteries via multifunctional catalytic interface engineering.
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Riboswitches are RNA molecules that regulate gene expression using conformation change, affected by binding of small molecule ligands. Although a number of ligand-bound aptamer complex structures have been solved, it is important to know ligand-free conformations of the aptamers in order to understand the mechanism of specific binding by ligands. In this paper, we use dynamics simulations on a series of models to characterize the ligand-free and ligand-bound aptamer domain of the c-di-GMP class I (GEMM-I) riboswitch. The results revealed that the ligand-free aptamer has a stable state with a folded P2 and P3 helix, an unfolded P1 helix and open binding pocket. The first Mg ions binding to the aptamer is structurally favorable for the successive c-di-GMP binding. The P1 helix forms when c-di-GMP is successive bound. Three key junctions J1/2, J2/3 and J1/3 in the GEMM-I riboswitch contributing to the formation of P1 helix have been found. The binding of the c-di-GMP ligand to the GEMM-I riboswitch induces the riboswitch's regulation through the direct allosteric communication network in GEMM-I riboswitch from the c-di-GMP binding sites in the J1/2 and J1/3 junctions to the P1 helix, the indirect ones from those in the J2/3 and P2 communicating to P1 helix via the J1/2 and J1/3 media.
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Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , GMP Cíclico/análogos & derivados , Riboswitch , Regulação Alostérica , Sítio Alostérico , GMP Cíclico/metabolismo , Ligantes , Modelos Moleculares , Simulação de Dinâmica Molecular , Conformação de Ácido NucleicoRESUMO
Two-dimensional binary hydrogen-bonded organic frameworks constructed from 1,3,5-benzenetricarboxylic acid (TMA) and 4,4'-biphenyldicarboxylic acid (BDA) on highly oriented pyrolytic graphite (HOPG) were investigated by scanning tunneling microscopy (STM) in heptanoic acid and octanoic acid solvents. High-resolution STM observations demonstrated that various assemblies of hydrogen-bonded networks are strongly dependent on the nature of the solvent. Well-ordered porous rectangular flowerlike networks were revealed at the heptanoic acid/HOPG interface, whereas two different coexisting densely packed guest-host BDA/TMA structures were observed at the octanoic acid/HOPG interface. It is suggested that the stabilization of the binary networks is possibly associated with the solvent chain length, and longer-chain solvents favored the formation of porous polymorphic networks.
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Two dimensional (2D) materials have great potential for application in energy storage due to their unique structural characteristics. Here we propose for the first time a density functional theory study into the scientific feasibility of using g-Mg3N2, which is a novel graphene-like 2D material, as a high-capacity anode material for Li-ion batteries (LIBs). The favorable Li-adsorption geometries and the Li adsorption thermodynamics are explored in detail. It is found that monolayer g-Mg3N2 can be lithiated up to Li7Mg3N2 that offers a super high theoretical capacity of 1858 mA h g-1 and the average intercalation potential ranging from 0.2 to 0.7 V is suitable for anode applications. The metallic electronic structures of LixMg3N2, in combination with the low Li-ion diffusion energy barriers on the honeycomb structure, promote high electron and Li-ion conductivity to ensure fast charge/discharge cycling. The excellent structural stability of Mg3N2 is good for the cycling performance. These results predict that g-Mg3N2 can serve as a high-performance anode material for LIBs.
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MicroRNA (miR) 429 has been shown to inhibit epithelial-to-mesenchymal transition (EMT) in cancer cells. However, the role of miR429 in EMT in non-cancer cells has not been defined, especially in the kidneys. The present study determined whether miR429 participated in angiotensin (ANG) II-induced EMT and fibrogenesis in renal cells. In NRK-52E cells, a rat proximal tubular cell line, incubation of ANG II (10-9 M) for 24 h significantly reduced the level of miR429 by 60% and increased the protein levels of mesenchymal markers α-smooth muscle actin and fibroblast-specific protein-1 by threefold and decreased epithelial marker E-cadherin by 60%, which was blocked by losartan, an AT1 receptor antagonist. Treatment of cells with miR429 inhibitor produced similar changes in the above EMT markers to that induced by ANG II. In cells overexpressed with miR429 transgene, ANG II-induced increases in collagen were abolished. Male Sprague-Dawley rats were infused with ANG II (200 ng·kg-1·min-1) for 12 days, and the levels of miR429 in the kidneys were reduced by 75%. Intrarenal transfection of lentivirus expressing miR429 also reversed the ANG II-induced changes in the EMT markers and collagen in the kidneys. The ANG II-induced increase in urinary albumin was significantly inhibited by miR429 transgene. There was no difference in the increases of blood pressure between ANG II- and ANG II+miR429 transgene-treated rats. These data suggest that ANG II-induced inhibition of miR429 contributes to ANG II-induced transdifferentiation and fibrogenesis in renal cells and that miR429 protects against ANG II-induced kidney damages.
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Albuminúria/induzido quimicamente , Angiotensina II/toxicidade , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , MicroRNAs/metabolismo , Podócitos/efeitos dos fármacos , Actinas/metabolismo , Albuminúria/genética , Albuminúria/metabolismo , Albuminúria/patologia , Animais , Caderinas/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular , Transdiferenciação Celular/efeitos dos fármacos , Colágeno/metabolismo , Regulação para Baixo , Fibrose , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , MicroRNAs/genética , Podócitos/metabolismo , Podócitos/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To explore the influence of body fat percentage (BF%) and body mass index (BMI) on the semen quality of adult males. METHODS: A total of 125 randomly selected male infertility patients underwent examinations of semen quality, BMI and BF% on the day of enrollment. With BMI ≥28 kg/m2 as the criterion of obesity, 50 of the patients fell into the category of obesity and 75 into that of non-obesity, while with BF% >25% as the criterion, 69 belonged to the obesity and 56 to the non-obesity type. We compared the semen parameters of the subjects between the obesity and non-obesity groups based on the two criteria and analyzed the correlation of semen quality with age, BF% and BMI. RESULTS: With BF% as the criterion, the obesity patients, as compared with the non-obesity men, showed significantly lower semen volume (ï¼»2.94 ± 1.15ï¼½ vs ï¼»3.51 ± 1.27ï¼½ ml, P < 0.05), percentage of grade a+b sperm (ï¼»33.37 ± 19.80ï¼½% vs ï¼»41.87 ± 15.43ï¼½%, P < 0.05) and sperm motility (ï¼»56.31 ± 22.26ï¼½% vs ï¼»64.95 ± 18.22ï¼½%, P < 0.05). Similar results were observed with BMI as the criterion in the semen volume (ï¼»2.86 ± 1.11ï¼½ vs ï¼»3.34 ± 1.26ï¼½ ml, P < 0.05), percentage of grade a sperm (ï¼»16.33 ± 13.80ï¼½% vs ï¼»25.09 ± 15.06ï¼½%, P < 0.05), percentage of grade a+b sperm (ï¼»30.10 ± 18.43ï¼½% vs ï¼»39.80 ± 17.50ï¼½%, P < 0.05) and sperm motility (ï¼»53.62 ± 21.56ï¼½% vs ï¼»62.83 ± 20.47ï¼½%, P < 0.05). Age was correlated negatively with sperm motility (r = ï¼0.20,P < 0.05), BF% negatively with the semen volume (r = ï¼0.21, P < 0.05), the percentage of grade a sperm (r = ï¼0.21, P < 0.05) and the percentage of grade a+b sperm (r = ï¼0.18, P <0.05), and BMI negatively with the semen volume (r = ï¼0.26, P < 0.01), percentage of grade a sperm (r = ï¼0.23, P<0.01) and percentage of grade a+b sperm (r = ï¼0.18, P < 0.05). Further multivariate analysis also showed that BF% was negatively correlated with the semen volume and percentage of grade a+b sperm after exclusion of age and other factors. CONCLUSIONS: Obesity affects the semen volume, percentage of grade a sperm, percentage of grade a+b sperm and sperm motility in male infertility patients. And BF% can be used as an indicator in the diagnosis of obesity.
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Índice de Massa Corporal , Infertilidade Masculina , Obesidade , Análise do Sêmen , Sêmen , Tecido Adiposo , Adulto , Humanos , Infertilidade Masculina/complicações , Masculino , Obesidade/complicações , Contagem de Espermatozoides , Motilidade dos Espermatozoides , EspermatozoidesRESUMO
To search a novel analgesic characterizes the effects on human sperm motility as minimal as possible. A new class of endomorphin-1 (EM-1) analogues was synthesized by combining successful chemical modifications including N-terminal guanidino modification, Phe4 was chlorinated, replaced of l-Pro2-Trp3 by d-Ala2-Gly3 or d-Pro2-Gly3 at position 2 and 3. Their bioactivities were measured by radioligand binding assay, metabolic stability, antinociception activity and sperm motility effects. In radioligand binding assays, analogue GAGP shown a µ-opioid receptor affinity about 17.7-fold higher and a 57.3-fold higher δ-opioid receptor affinity than EM-1. In the metabolic stability assays, GAGP had the longest half-lives and 16.6-fold higher than EM-1. In the tail-flick test in mice, GAGP showed the best analgesia. In sperm motility assays, the group of GAGP (10-5, 10-7mol/L) decreased of the percentage of a+b grade, and no significant when compared with initial value. In GAGP (10-6mol/L) group, sperm motility was progressively increased, although it was not statistically significant. But at the groups of morphine (10-7mol/L) and GAGD (10-7mol/L), these caused significant reduction between 0 and 90 min. We found that analogues GAGP, activating µ-opioid receptor and partial δ-opioid receptor, exhibit good analgesic effects with minimal implications for human sperm motility. It might be important in potential application as drug candidates of analgesic without implications for human sperm motility.
Assuntos
Analgésicos Opioides/química , Oligopeptídeos/química , Sequência de Aminoácidos , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/toxicidade , Animais , Meia-Vida , Humanos , Camundongos , Oligopeptídeos/farmacocinética , Oligopeptídeos/toxicidade , Receptores Opioides delta/química , Receptores Opioides delta/metabolismo , Receptores Opioides mu/química , Receptores Opioides mu/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacosRESUMO
A new class of endomorphin-1 analogues was synthesized by combining successful chemical modifications including N-terminal guanidino modification, Phe4 was chlorinated, D-Ala-Gly Substituted L-Pro2. Their bioactivities were measured by radioligand binding assay, metabolic stability and the tail-flick test. In radioligand binding assays, analogue GAGPC (Nα-Amidino-Tyr-D-Ala-Gly-Trp-p-Cl-Phe-NH2), shown a µ-opioid receptor affinity about 1.42-fold higher and a 2.51-fold higher δ-opioid receptor affinity than EM-1. In the metabolic stability assays, GAGPC had the longest half-lives which was 284min and 53-fold higher than that of EM-1. In the tail-flick test in mice, GAGPC chloride modification increases the lipid content of the drug, thus increases the permeability of the blood brain barrier, and has a higher analgesic activity. It might be of importance in potential application as drug candidates as analgesic.
Assuntos
Analgésicos Opioides/farmacologia , Oligopeptídeos/farmacologia , Analgésicos Opioides/síntese química , Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacocinética , Animais , Barreira Hematoencefálica/metabolismo , Membrana Celular/metabolismo , Meia-Vida , Masculino , Camundongos , Naloxona/administração & dosagem , Naloxona/farmacologia , Oligopeptídeos/síntese química , Oligopeptídeos/metabolismo , Oligopeptídeos/farmacocinética , Ensaio Radioligante , Ratos Wistar , Receptores Opioides delta/metabolismo , Receptores Opioides mu/metabolismoRESUMO
Inflammasomes activate caspase-1 to produce interleukin (IL)-1ß. Activation of the NLRP3 inflammasome is involved in various renal pathological conditions. It remains unknown whether the NLRP3 inflammasome activation participates in the abnormal renal response to high-salt (HS) diet in Dahl salt-sensitive (S) rats. In addition, our lab recently showed that transplantation of mesenchymal stem cells (MSCs) attenuated HS-induced inflammation in the renal medulla in Dahl S rat. However, it is unclear whether the anti-inflammatory action of MSCs is associated with inhibition of the NLRP3 inflammasome. The present study determined the response of the NLRP3 inflammasome to HS intake and the effect of MSC transplantation on the NLRP3 inflammasome in the renal medulla in Dahl S rats. Immunostaining showed that the inflammasome components NLRP3, ASC, and caspase-1 were mainly present in distal tubules and collecting ducts. Interestingly, the renal medullary levels of these inflammasome components were remarkably increased after a HS diet in Dahl S rats, while remaining unchanged in normal rats. This HS-induced activation of the NLRP3 inflammasome was significantly blocked by MSC transplantation into the renal medulla in Dahl S rats. Furthermore, infusion of a caspase-1 inhibitor into the renal medulla significantly attenuated HS-induced hypertension in Dahl S rats. These data suggest that HS-induced activation of the NLRP3 inflammasome may contribute to renal medullary dysfunction in Dahl S rats and that inhibition of inflammasome activation may be one of the mechanisms for the anti-inflammatory and anti-hypertensive effects of stem cells in the renal medulla in Dahl S rats.