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1.
Angew Chem Int Ed Engl ; : e202404109, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624089

RESUMO

Lithium (Li) metal batteries (LMBs) with nickel (Ni)-rich layered oxide cathodes exhibit twice the energy density of conventional Li-ion batteries. However, their lifespan is limited by severe side reactions caused by high electrode reactivity. Fluorinated solvent-based electrolytes can address this challenge, but they pose environmental and biological hazards. This work reports on the molecular engineering of fluorine (F)-free ethers to mitigate electrode surface reactivity in high-voltage Ni-rich LMBs. By merely extending the alkyl chains of traditional ethers, we effectively reduce the catalytic reactivity of the cathode towards the electrolyte at high voltages, which suppresses the oxidation decomposition of the electrolyte, microstructural defects and rock-salt phase formation in the cathode, and gas release issues. The high-voltage Ni-rich NCM811-Li battery delivers capacity retention of 80% after 250 cycles with a high Coulombic efficiency of 99.85%, even superior to that in carbonate electrolytes. Additionally, this strategy facilitates passivation of the Li anode by forming a robust solid-electrolyte interphase, boosting the Li reversibility to 99.11% with a cycling life of 350 cycles, which outperforms conventional F-free ether electrolytes. Consequently, the lifespan of practical LMBs has been prolonged by over 100% and 500% compared to those in conventional carbonate- and ether-based electrolytes, respectively.

2.
JAMA Neurol ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466274

RESUMO

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

3.
Int J Biol Macromol ; 261(Pt 2): 129874, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307430

RESUMO

Bletilla Striata (BS) Polysaccharide (BSP) is one of the main components of the traditional Chinese medicinal plant Bletilla striata Rchb. F. BSP has been widely used in antimicrobial and hemostasis treatments in clinics. Despite its use in skin disease treatment and cosmetology, the effects of BSP on wound healing remain unclear. Here we investigated the anti-inflammatory, antioxidant, and analgesic effects of BSP and explored its impact on morphological changes and inflammatory mediators during wound healing. A carrageenan-induced mouse paw edema model was established to evaluate the anti-inflammatory effect of BSP. Antioxidant indicators, including NO, SOD, and MDA, were measured in the blood and liver. The increased pain threshold induced by BSP was also determined using the hot plate test. A mouse excisional wound model was applied to evaluate the wound healing rate, and HE staining and Masson staining were used to detect tissue structure changes. In addition, ELISA was employed to detect the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß in serum. BSP significantly decreased the concentration of NO and MDA in serum and liver while increasing SOD activity. It exhibited a notable improvement in mouse paw edema induced by carrageenan. BSP dose-dependently delayed the appearance of licking behavior in mice, indicating its analgesic effect. Compared to the control group, the wound healing rate was significantly improved in the BSP treatment group. HE and Masson staining results showed that the BSP and 'Jingwanhong' ointment groups had slightly milder inflammatory responses and significantly promoted more new granulation tissue formation. The levels of serum inflammatory mediators TNF-α, IL-1ß, and IL-6 were reduced to varying degrees. The results demonstrated that BSP possesses anti-inflammatory, antioxidant, analgesic, and wound healing properties, and it may promote wound healing through inhibition of inflammatory cytokine synthesis and release.


Assuntos
Antioxidantes , Fator de Necrose Tumoral alfa , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carragenina/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Interleucina-6 , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Citocinas/metabolismo , Superóxido Dismutase/farmacologia , Cicatrização , Edema/induzido quimicamente , Edema/tratamento farmacológico , Mediadores da Inflamação/farmacologia
4.
Protein Expr Purif ; 218: 106447, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38369031

RESUMO

Diaminopropionate ammonia-lyase transforms D and L isomers of 2,3-diaminopropionate to pyruvate and ammonia. It catalyzes D- and l-serine less effectively. L-2,3-diaminopropionate is a precursor in the biosynthesis of oxalyl diaminopropionate as a neurotoxin in certain legume species. In this work, we cyclized the diaminopropionate ammonia-lyase from Salmonella typhimurium in vitro using the redox-responsive split intein, and identified that backbone cyclization afforded the enzyme with the improved activity, thermal stability and resistance to the exopeptidase proteolysis, different from effects of the incorporated sequence recognized by tobacco vein mottling virus protease at C-terminus. Using analyses of three fluorescent dyes including 8-anilino-1-naphthalenesulfonic acid, N-phenyl-1-naphthylamine, and thioflavin T, the same amounts of the cyclic protein displayed less fluorescence than those of the linear protein upon the heat treatment. The cyclic enzyme displayed the enhanced activity in Escherichia coli cells using the designed novel reporter. In this system, d-serine was added to the culture and transported into the cytoplasm. It was transformed by pre-overexpression of the diaminopropionate ammonia-lyase, and untransformed d-serine was oxidized by the coproduced human d-amino acid oxidase to generate hydrogen peroxide. This oxidant is monitored by the HyPer indicator. The current results presented that the cyclized enzyme could be applied as a better candidate to block the neurotoxin biosynthesis in certain plant species.


Assuntos
Amônia-Liases , Neurotoxinas , Salmonella typhimurium , Humanos , Ciclização , Escherichia coli/genética , Serina
5.
J Am Chem Soc ; 145(39): 21646-21660, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37733759

RESUMO

R-loops and guanine quadruplexes (G4s) are secondary structures of nucleic acids that are ubiquitously present in cells and are enriched in promoter regions of genes. By employing a bioinformatic approach based on overlap analysis of transcription factor chromatin immunoprecipitation sequencing (ChIP-seq) data sets, we found that many splicing factors, including U2AF1 whose recognition of the 3' splicing site is crucial for pre-mRNA splicing, exhibit pronounced enrichment at endogenous R-loop- and DNA G4-structure loci in promoter regions of human genes. We also revealed that U2AF1 binds directly to R-loops and DNA G4 structures at a low-nM binding affinity. Additionally, we showed the ability of U2AF1 to undergo phase separation, which could be stimulated by binding with R-loops, but not duplex DNA, RNA/DNA hybrid, DNA G4, or single-stranded RNA. We also demonstrated that U2AF1 binds to promoter R-loops in human cells, and this binding competes with U2AF1's interaction with 3' splicing site and leads to augmented distribution of RNA polymerase II (RNAPII) to promoters over gene bodies, thereby modulating cotranscriptional pre-mRNA splicing. Together, we uncovered a group of candidate proteins that can bind to both R-loops and DNA G4s, revealed the direct and strong interactions of U2AF1 with these nucleic acid structures, and established a biochemical rationale for U2AF1's occupancy in gene promoters. We also unveiled that interaction with R-loops promotes U2AF1's phase separation, and our work suggests that U2AF1 modulates pre-mRNA splicing by regulating RNAPII's partition in transcription initiation versus elongation.


Assuntos
Estruturas R-Loop , Precursores de RNA , Humanos , Fator de Processamento U2AF/genética , Fator de Processamento U2AF/metabolismo , Precursores de RNA/metabolismo , Splicing de RNA , Proteínas de Ligação a RNA/metabolismo , DNA/química , RNA/química , Regiões Promotoras Genéticas
6.
Int J Biol Macromol ; 253(Pt 4): 127104, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37769758

RESUMO

Inspired by protein post-translational modification (PTM), post-imprinting modification (PIM) has been proposed and developed to prepare novel molecularly imprinted polymers (MIPs), which are similar to functionalized biosynthetic proteins. The PIM involves site-directed modifications in the imprinted cavity of the MIP, such as introducing high-affinity binding sites and introducing fluorescent signal molecules. This modification makes the MIP further functionalized and improves the shortcomings of general molecular imprinting, such as single function, low selectivity, low sensitivity, and inability to fully restore the complex function of natural antibodies. This paper describes the characteristics of PIM strategies, reviews the latest research progress in the recognition and detection of protein biomarkers such as lysozyme, prostate-specific antigen, alpha-fetoprotein, human serum albumin, and peptides, and further discusses the importance, main challenges, and development prospects of PIM. The PIM technology has the potential to develop a new generation of biomimetic recognition materials beyond natural antibodies. It can be used in bioanalysis and other multitudinous fields for its unique features in molecule recognition.


Assuntos
Materiais Biomiméticos , Impressão Molecular , Humanos , Masculino , Polímeros Molecularmente Impressos , Polímeros/química , Anticorpos/química , Antígeno Prostático Específico
7.
Nucleic Acids Res ; 51(16): 8434-8446, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37427784

RESUMO

High-order chromatin organization plays an important role in biological processes and disease development. Previous studies revealed a widespread occurrence of guanine quadruplex (G4) structures in the human genome, with enrichment in gene regulatory regions, especially in promoters. However, it remains unclear whether G4 structures contribute to RNA polymerase II (RNAPII)-mediated long-range DNA interactions and transcription activity. In this study, we conducted an intuitive overlapping analysis of previously published RNAPII ChIA-PET (chromatin interaction analysis with paired-end tag) and BG4 ChIP-seq (chromatin immunoprecipitation followed by sequencing using a G4 structure-specific antibody) data. We observed a strong positive correlation between RNAPII-linked DNA loops and G4 structures in chromatin. Additionally, our RNAPII HiChIP-seq (in situ Hi-C followed by ChIP-seq) results showed that treatment of HepG2 cells with pyridostatin (PDS), a small-molecule G4-binding ligand, could diminish RNAPII-linked long-range DNA contacts, with more pronounced diminutions being observed for those contacts involving G4 structure loci. RNA sequencing data revealed that PDS treatment modulates the expression of not only genes with G4 structures in their promoters, but also those with promoters being connected with distal G4s through RNAPII-linked long-range DNA interactions. Together, our data substantiate the function of DNA G4s in RNAPII-associated DNA looping and transcription regulation.


Assuntos
Cromatina , Quadruplex G , Humanos , Cromatina/genética , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Cromossomos/metabolismo , DNA/genética
8.
JACS Au ; 3(6): 1650-1657, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37388701

RESUMO

In the presence of monovalent alkali metal ions, G-rich DNA sequences containing four runs of contiguous guanines can fold into G-quadruplex (G4) structures. Recent studies showed that these structures are located in critical regions of the human genome and assume important functions in many essential DNA metabolic processes, including replication, transcription, and repair. However, not all potential G4-forming sequences are actually folded into G4 structures in cells, where G4 structures are known to be dynamic and modulated by G4-binding proteins as well as helicases. It remains unclear whether there are other factors influencing the formation and stability of G4 structures in cells. Herein, we showed that DNA G4s can undergo phase separation in vitro. In addition, immunofluorescence microscopy and ChIP-seq experiments with the use of BG4, a G4 structure-specific antibody, revealed that disruption of phase separation could result in global destabilization of G4 structures in cells. Together, our work revealed phase separation as a new determinant in modulating the formation and stability of G4 structures in human cells.

9.
Front Plant Sci ; 14: 1169386, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37235024

RESUMO

Introduction: Alkaloids are one of the main medicinal components of Dendrobium species. Dendrobium alkaloids are mainly composed of terpene alkaloids. Jasmonic acid (JA) induce the biosynthesis of such alkaloids, mainly by enhancing the expression of JA-responsive genes to increase plant resistance and increase the content of alkaloids. Many JA-responsive genes are the target genes of bHLH transcription factors (TFs), especially the MYC2 transcription factor. Methods: In this study, the differentially expressed genes involved in the JA signaling pathway were screened out from Dendrobium huoshanense using comparative transcriptomics approaches, revealing the critical roles of basic helix-loop-helix (bHLH) family, particularly the MYC2 subfamily. Results and discussion: Microsynteny-based comparative genomics demonstrated that whole genome duplication (WGD) and segmental duplication events drove bHLH genes expansion and functional divergence. Tandem duplication accelerated the generation of bHLH paralogs. Multiple sequence alignments showed that all bHLH proteins included bHLH-zip and ACT-like conserved domains. The MYC2 subfamily had a typical bHLH-MYC_N domain. The phylogenetic tree revealed the classification and putative roles of bHLHs. The analysis of cis-acting elements revealed that promoter of the majority of bHLH genes contain multiple regulatory elements relevant to light response, hormone responses, and abiotic stresses, and the bHLH genes could be activated by binding these elements. The expression profiling and qRT-PCR results indicated that bHLH subgroups IIIe and IIId may have an antagonistic role in JA-mediated expression of stress-related genes. DhbHLH20 and DhbHLH21 were considered to be the positive regulators in the early response of JA signaling, while DhbHLH24 and DhbHLH25 might be the negative regulators. Our findings may provide a practical reference for the functional study of DhbHLH genes and the regulation of secondary metabolites.

10.
Metab Brain Dis ; 38(7): 2369-2381, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37256467

RESUMO

Neuropsychiatric disorders have a high incidence worldwide. Kinesins, a family of microtubule-based molecular motor proteins, play essential roles in intracellular and axonal transport. Variants of kinesins have been found to be related to many diseases, including neurodevelopmental/neurodegenerative disorders. Kinesin-12 (also known as Kif15) was previously found to affect the frequency of both directional microtubule transports. However, whether Kif15 deficiency impacts mood in mice is yet to be investigated. In this study, we used the CRISPR/Cas9 method to obtain Kif15-/- mice. In behavioral tests, Kif15-/- female mice exhibited prominent depressive characteristics. Further studies showed that the expression of BDNF was significantly decreased in the frontal cortex, corpus callosum, and hippocampus of Kif15-/- mice, along with the upregulation of Interleukin-6 and Interleukin-1ß in the corpus callosum. In addition, the expression patterns of AnkG were notably changed in the developing brain of Kif15-/- mice. Based on our previous studies, we suggested that this appearance of altered AnkG was due to the maladjustment of the microtubule patterns induced by Kif15 deficiency. The distribution of PSD95 in neurites notably decreased after cultured neurons treated with the Kif15 inhibitor, but total PSD95 protein level was not impacted, which revealed that Kif15 may contribute to PSD95 transportation. This study suggested that Kif15 may serve as a potential target for future depression studies.


Assuntos
Depressão , Cinesinas , Animais , Feminino , Camundongos , Depressão/genética , Cinesinas/genética , Cinesinas/metabolismo , Microtúbulos/metabolismo , Neurônios/metabolismo
11.
Curr Pharm Biotechnol ; 24(15): 1964-1971, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37070797

RESUMO

BACKGROUND: Sodium new houttuyfonate (SNH) is an adduct of houttuyfonate, which is the main component of the common Chinese medicinal plant Houttuynia cordata. SNH has been widely used in antibacterial and anti-inflammatory treatments in clinics. However, the exact antimicrobial mechanism of SNH is still unclear, despite its mild direct antimicrobial activity in vitro. Objectives: The aim of this study is to investigate the effect and possible mechanism of SNH on macrophages against bacteria in vitro. METHODS: In this study, we assessed the antibacterial and anti-inflammatory effects of SNH on the RAW264.7 macrophage cell line against Pseudomonas aeruginosa, a major opportunistic pathogen. RESULTS: Firstly, we found that SNH showed minimal toxicity on RAW264.7 macrophages. Secondly, our results indicated that SNH effectively inhibited the inflammatory reaction of macrophages stimulated by P. aeruginosa. We also found that SNH improved the phagocytosis and killing effect of RAW264.7 macrophages against P. aeruginosa in vitro. Furthermore, our results revealed that SNH effectively inhibited the expression of the TLR4/NF-кB pathway in macrophage RAW264.7 co-incubated with P. aeruginosa in vitro. CONCLUSION: Based on our findings, SNH can significantly improve the phagocytosis of macrophages and inhibit the excessive release of inflammatory factors by repressing the TLR4/NF-кB pathway.


Assuntos
NF-kappa B , Receptor 4 Toll-Like , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Antibacterianos/farmacologia , Macrófagos , Fagocitose , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia
12.
Microb Cell Fact ; 22(1): 2, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604649

RESUMO

BACKGROUND: Several fusion tags for separation handle have been developed, but the fused tag for simply and cheaply separating the target protein is still lacking. RESULTS: Separation conditions for the human annexin A1 (hanA1) tagged emerald green fluorescent protein (EmGFP) in Escherichia coli were optimized via precipitation with calcium chloride (CaCl2) and resolubilization with ethylenediamine tetraacetic acid disodium salt (EDTA-Na2). The HanA1-EmGFP absorbing with other three affinity matrix was detected, only it was strongly bound to heparin Sepharose. The separation efficiency of the HanA1-EmGFP was comparable with purification efficiency of the His6-tagged HanA1-EmGFP via metal ion affinity chromatography. Three fluorescent proteins for the EmGFP, mCherry red fluorescent protein and flavin-binding cyan-green fluorescent protein LOV from Chlamydomonas reinhardtii were used for naked-eye detection of the separation and purification processes, and two colored proteins including a red protein for a Vitreoscilla hemoglobin (Vhb), and a brown protein for maize sirohydrochlorin ferrochelatase (mSF) were used for visualizing the separation process. The added EDTA-Na2 disrupted the Fe-S cluster in the mSF, but it showed little impact on heme in Vhb. CONCLUSIONS: The selected five colored proteins were efficient for detecting the applicability of the highly selective hanA1 for fusion separation and purification handle. The fused hanA1 tag will be potentially used for simple and cheap affinity separation of the target proteins in industry and diagnosis.


Assuntos
Anexina A1 , Humanos , Proteínas de Fluorescência Verde/metabolismo , Anexina A1/metabolismo , Ácido Edético/metabolismo , Cromatografia de Afinidade/métodos , Escherichia coli/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
14.
CNS Neurosci Ther ; 29(1): 228-238, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36286186

RESUMO

AIMS: This study aimed to evaluate the effects of the depletion of SAM and SH3 domain-containing protein 1 (SASH1) on functional recovery after spinal cord injury (SCI) and to investigate the possible mechanism of SASH1 knockdown in astrocytes facilitating axonal growth. METHODS: SCI model was established in adult rats. SASH1 small interfering RNA (siSASH1) was used to investigate its function. Hindlimb motor function was evaluated by the Basso-Bresnahan-Beattie (BBB) assay. The gene expressions were evaluated by the methods of qRT-PCR, Western-blotting, ELISA, and immunohistochemistry. RESULTS: SASH1 knockdown improved the BBB scores after SCI and significantly reduced GFAP expression. In cultured spinal astrocytes, siSASH1 treatment decreased interferon-γ release and increased brain-derived neurotrophic factor (BDNF) release. When cocultured with SASH1-knockdown astrocytes, axonal growth increased. The neuronal tropomyosin receptor kinase B (BDNF receptor) expression increased, especially in the axonal tips. SASH1 expression increased while NSCs differentiated into glial cells, instead of neurons. After SASH1 depletion, differentiated NSCs maintained a higher level of Nestin protein and an increase in BDNF release. CONCLUSIONS: These results indicate that SASH1 acts as an astrocytic differentiation-maintaining protein, and SASH1 downregulation limits glial activation and contributes toward functional recovery after SCI.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Astrócitos , Traumatismos da Medula Espinal , Animais , Ratos , Astrócitos/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diferenciação Celular , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , RNA Interferente Pequeno/genética , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética
15.
ACS Chem Biol ; 17(12): 3450-3457, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36475596

RESUMO

Mutations in the SOD1 (superoxide dismutase 1) gene are associated with amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. By employing ascorbate peroxidase-based proximity labeling, coupled with LC-MS/MS analysis, we uncovered 43 and 24 proteins exhibiting higher abundance in the proximity proteomes of SOD1G85R and SOD1G93A, respectively, than that of wild-type SOD1. Immunoprecipitation followed by western blot analysis indicated the preferential binding of one of these proteins, exportin 5 (XPO5), toward the two mutants of SOD1 over the wild-type counterpart. In line with the established function of XPO5 in pre-miRNA transport, we observed diminished nucleocytoplasmic transport of pre-miRNAs in cells with ectopic expression of the two SOD1 mutants over those expressing the wild-type protein. On the other hand, RT-qPCR results revealed significant elevations in mature miRNA in cells expressing the two SOD1 mutants, which are attributed to the diminished inhibitory effect of XPO5 on Dicer-mediated cleavage of pre-miRNA to mature miRNA. Together, our chemoproteomic approach led to the revelation of a novel mechanism through which ALS-associated mutants of SOD1 perturb miRNA biogenesis, that is, through aberrant binding toward XPO5.


Assuntos
Esclerose Amiotrófica Lateral , MicroRNAs , Doenças Neurodegenerativas , Humanos , Animais , Camundongos , Superóxido Dismutase-1/genética , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/metabolismo , Cromatografia Líquida , Superóxido Dismutase/metabolismo , Espectrometria de Massas em Tandem , Mutação , MicroRNAs/genética , Carioferinas/genética , Camundongos Transgênicos
16.
Foods ; 11(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36496575

RESUMO

The preparation of fried meat products is prone to the formation of large amounts of heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), and trans fatty acids (TFAs), which are potential risks to human health. Spices contain natural antioxidants that can inhibit the oxidation of fats and oils and the formation of hazardous substances. In this experiment, the effect of adding different levels (0.25%, 0.75%, 1.25%) of ginger or rosemary during meatball preparation on the formation of HCAs, PAHs and TFAs in fried pork balls was investigated. The results showed that the addition of ginger and rosemary reduced the content of HCAs in fried pork balls compared to the control group (no added spices). The inhibition of total HCAs was 63% when 0.25% ginger was added, while the total HCA content was reduced to 59% when 0.25% rosemary was added. The addition of 0.25% and 0.75% rosemary reduced the PAH content in fried pork balls by 30% and 35%. In addition, ginger and rosemary showed significant inhibition of C20:1 11t in TFAs, with a maximum inhibition rate of 40%. Therefore, adding appropriate levels of ginger or rosemary to fried pork balls could simultaneously inhibit the formation of HCAs, PAHs, and TFAs.

17.
Reprod Biol Endocrinol ; 20(1): 164, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36451157

RESUMO

BACKGROUND: Sperm, during epididymal transit, acquires microRNAs(miRNAs), which are crucial for embryonic development. However, whether sperm miRNAs influenced by an obstructive epididymal environment affect embryonic development remains unknown. METHOD: The sham operation and vasectomy were performed in C57BL/6 J mice to create the control group (CON) and the obstructive epididymal environment group(OEE) group, respectively. The morphology of the testis and epididymis was observed using hematoxylin and eosin staining (HE staining) to establish the OEE mice model. The sperm quality test, intracytoplasmic sperm injection (ICSI), and epididymosomes fusion were employed to observe the effect of the obstructive epididymal environment on sperm and resultant embryonic development. The alteration of the sperm small RNA (sRNA) profile was analyzed by sRNA sequencing. RT-qPCR and DNA methylation were applied to observe the effect of obstructive epididymis on the expression of sperm miRNAs. The miRNAs microinjection was used to explore the impacts of sperm miRNAs on embryonic development. RESULTS: We confirmed postoperative 8-week mice as the OEE mice model by examining the morphology of the testis and epididymis. In the OEE group, we observed that sperm quality degraded and the development potential of embryos was reduced, which can be saved by the normal epididymal environment. The sperm sRNA sequencing revealed that the expression of the developmental miR-17-92 cluster and the Sfmbt2 miRNA cluster was downregulated in the OEE group. The expression of these two miRNA clusters in epididymis was also downregulated and regulated by DNA methylation. However, the downregulation of either the miR-17-92 cluster or the Sfmbt2 miRNA cluster in normal zygotes did not impair embryonic development. CONCLUSION: The obstructive epididymal environment influences sperm quality and resultant embryonic development, as well as the abundance of the developmental miR-17-92 cluster and the Sfmbt2 miRNA cluster in sperm, but these miRNA clusters are not the cause of abnormal embryonic development. It implies that epididymis is important in early embryonic development and may play a potential role in sperm epigenome.


Assuntos
Epididimo , MicroRNAs , Masculino , Feminino , Gravidez , Camundongos , Animais , MicroRNAs/genética , Camundongos Endogâmicos C57BL , Sêmen , Espermatozoides , Desenvolvimento Embrionário/genética , Modelos Animais de Doenças , Proteínas Repressoras
18.
Chem Rev ; 122(15): 13043-13107, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35839290

RESUMO

Chemomechanics is an old subject, yet its importance has been revived in rechargeable batteries where the mechanical energy and damage associated with redox reactions can significantly affect both the thermodynamics and rates of key electrochemical processes. Thanks to the push for clean energy and advances in characterization capabilities, significant research efforts in the last two decades have brought about a leap forward in understanding the intricate chemomechanical interactions regulating battery performance. Going forward, it is necessary to consolidate scattered ideas in the literature into a structured framework for future efforts across multidisciplinary fields. This review sets out to distill and structure what the authors consider to be significant recent developments on the study of chemomechanics of rechargeable batteries in a concise and accessible format to the audiences of different backgrounds in electrochemistry, materials, and mechanics. Importantly, we review the significance of chemomechanics in the context of battery performance, as well as its mechanistic understanding by combining electrochemical, materials, and mechanical perspectives. We discuss the coupling between the elements of electrochemistry and mechanics, key experimental and modeling tools from the small to large scales, and design considerations. Lastly, we provide our perspective on ongoing challenges and opportunities ranging from quantifying mechanical degradation in batteries to manufacturing battery materials and developing cyclic protocols to improve the mechanical resilience.


Assuntos
Fontes de Energia Elétrica , Termodinâmica
19.
Front Nutr ; 9: 913297, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719170

RESUMO

Thermal treatment of lipids rich in fatty acids contributes to the formation of lipid oxidation products (LOPs), which have potentially harmful effects on human health. This study included soybean oil (SO), palm oil (PO), olive oil (OO), and lard oil (LO) as the research objects, with an aim to investigate the impact of heating temperature and fatty acid type on the generation of LOPs (α-dicarbonyl compounds, malondialdehyde (MDA), α,ß-unsaturated aldehydes, and 16 volatile aldehydes). Results showed that LOPs increased significantly (p < 0.05) with the increase in temperature (100 ~ 200°C). Furthermore, the amount of 2,3-butanedione (159.53 µg/g), MDA (3.15 µg/g), 4-hydroxy-hexenal (3.03 µg/g), 2-butenal (292.18%), 2-pentenal (102.26%), hexanal (898.72%), and 2,4-heptadienal (E, E) (2182.05%) were more at 200°C in SO rich in polyunsaturated fatty acids (PUFAs) than other oils. Results from heat map analysis indicated that the 2, 4-heptadienal, and glyoxal related to the myristic acid of oil. Moreover, the MDA was in close association with PUFAs. Based on the effect of temperature and fatty acid type on the generation of LOPs, this study could serve as a control method to reduce harmful LOPs.

20.
Nat Commun ; 13(1): 704, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35121768

RESUMO

Single-crystalline nickel-rich cathodes are a rising candidate with great potential for high-energy lithium-ion batteries due to their superior structural and chemical robustness in comparison with polycrystalline counterparts. Within the single-crystalline cathode materials, the lattice strain and defects have significant impacts on the intercalation chemistry and, therefore, play a key role in determining the macroscopic electrochemical performance. Guided by our predictive theoretical model, we have systematically evaluated the effectiveness of regaining lost capacity by modulating the lattice deformation via an energy-efficient thermal treatment at different chemical states. We demonstrate that the lattice structure recoverability is highly dependent on both the cathode composition and the state of charge, providing clues to relieving the fatigued cathode crystal for sustainable lithium-ion batteries.

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