Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 586
Filtrar
1.
Proc Natl Acad Sci U S A ; 121(17): e2311075121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38625942

RESUMO

Voltage oscillation at subzero in sodium-ion batteries (SIBs) has been a common but overlooked scenario, almost yet to be understood. For example, the phenomenon seriously deteriorates the performance of Na3V2(PO4)3 (NVP) cathode in PC (propylene carbonate)/EC (ethylene carbonate)-based electrolyte at -20 °C. Here, the correlation between voltage oscillation, structural evolution, and electrolytes has been revealed based on theoretical calculations, in-/ex-situ techniques, and cross-experiments. It is found that the local phase transition of the Na3V2(PO4)3 (NVP) cathode in PC/EC-based electrolyte at -20 °C should be responsible for the oscillatory phenomenon. Furthermore, the low exchange current density originating from the high desolvation energy barrier in NVP-PC/EC system also aggravates the local phase transformation, resulting in severe voltage oscillation. By introducing the diglyme solvent with lower Na-solvent binding energy, the voltage oscillation of the NVP can be eliminated effectively at subzero. As a result, the high capacity retentions of 98.3% at -20 °C and 75.3% at -40 °C are achieved. The finding provides insight into the abnormal SIBs degradation and brings the voltage oscillation behavior of rechargeable batteries into the limelight.

2.
Adv Mater ; : e2400169, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607696

RESUMO

Intrinsically safe sodium-ion batteries (SIBs) are considered a promising candidate for large-scale energy storage systems. However, the high flammability of conventional electrolytes may pose serious safety threats and even explosions. Herein, we propose a strategy of constructing a deep eutectic electrolyte (DEE) to boost the safety and electrochemical performance of succinonitrile (SN)-based electrolyte. The strong hydrogen bond between S = O of 1,3,2-dioxathiolane-2,2-dioxide (DTD) and the α-H of SN endows the enhanced safety and compatibility of SN with Lewis bases. Meanwhile, the DTD participates in the inner Na+ sheath and weakens the coordination number of SN. The unique solvation configuration promotes the formation of robust gradient inorganic-rich electrode-electrolyte interphase, and merits stable cycling of half cells in a wide temperature range, with a capacity retention of 82.8% after 800 cycles (25 °C) and 86.3% after 100 cycles (60 °C). Correspondingly, the full cells deliver tremendous improvement in cycling stability and rate performance. This article is protected by copyright. All rights reserved.

3.
Plant Physiol Biochem ; 210: 108571, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38604011

RESUMO

2-(2-Phenylethyl) chromone (PEC) and its derivatives are markers of agarwood formation and are also related to agarwood quality. However, the biosynthetic and regulatory mechanisms of PECs still remain mysterious. Several studies suggested that type III polyketide synthases (PKSs) contribute to PEC biosynthesis in Aquilaria sinensis. Furthermore, systematic studies on the evolution of PKSs in A. sinensis have rarely been reported. Herein, we comprehensively analyzed PKS genes from 12 plant genomes and characterized the AsPKSs in detail. A unique branch contained only AsPKS members was identified through evolutionary analysis, including AsPKS01 that was previously indicated to participate in PEC biosynthesis. AsPKS07 and AsPKS08, two tandem-duplicated genes of AsPKS01 and lacking orthologous genes in evolutionary models, were selected for their transient expression in the leaves of Nicotiana benthamiana. Subsequently, PECs were detected in the extracts of N. benthamiana leaves, suggesting that AsPKS07 and AsPKS08 promote PEC biosynthesis. The interaction between the promoters of AsPKS07, AsPKS08 and five basic leucine zippers (bZIPs) from the S subfamily indicated that their transcripts could be regulated by these transcription factors (TFs) and might further contribute to PECs biosynthesis in A. sinensis. Our findings provide valuable insights into the molecular evolution of the PKS gene family in A. sinensis and serve as a foundation for advancing PEC production through the bioengineering of gene clusters. Ultimately, this contribution is expected to shed light on the mechanism underlying agarwood formation.

4.
Appl Opt ; 63(4): 1182-1187, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437417

RESUMO

The investigation of atmospheric aerosols holds paramount importance within the environmental realm. This significance arises from the intricate nature of aerosol distribution and size in real-life hazy weather conditions. In this work, we have employed the equivalent radius of the aerosols in haze weather obtained from the volume spectrum, and then the scattering characteristics of these aerosols are obtained using the equivalent radius. Pearson correlation coefficients have been used for revealing a strong correlation by comparing Aeronet website data and simulation results with a minimum value of 0.657.

5.
Chin Med ; 19(1): 37, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429848

RESUMO

BACKGROUND: Osteoarthritis (OA) is a prevalent global health concern associated with the loss of articular cartilage and subchondral bone. The lack of disease-modifying drugs for OA necessitates the exploration of novel therapeutic options. Our previous study has demonstrated that traditional Chinese medical herb Trachelospermum jasminoides (Lindl.) Lem. extract suppressed osteoclastogenesis and identified trachelogenin (TCG) as a representative compound. Here, we delved into TCG's potential to alleviate OA. METHODS: We initially validated the in vivo efficacy of TCG in alleviating OA using a rat OA model. Subsequently, we isolated primary bone marrow-derived macrophages in vitro to investigate TCG's impact on osteoclastogenesis. We further employed a small molecule pull-down assay to verify TCG's binding target within osteoclasts. Finally, we isolated primary mouse chondrocytes in vitro to study TCG's regulatory effects and mechanisms on chondrocyte survival. RESULTS: TCG preserved subchondral bone integrity and protected articular cartilage in a rat OA model. Subsequently, in vitro experiments unveiled TCG's capability to inhibit osteoclastogenesis and function through binding to Ras association proximate 1 (Rap1) and inhibiting its activation. Further study demonstrated that TCG inhibited Rap1/integrin αvß3/c-Src/Pyk2 signaling cascade, and consequently led to failed F-actin ring formation. Besides, TCG promoted the proliferation of mouse primary chondrocytes while suppressing apoptosis in vitro. This is attributed to TCG's ability to upregulate HIF1α, thereby promoting glycolysis. CONCLUSION: TCG exerted inhibitory effects on osteoclastogenesis through binding to Rap1 and inhibiting Rap1 activation, consequently preventing subchondral bone loss. Moreover, TCG enhanced chondrocyte survival by upregulating HIF1α and promoting glycolysis. These dual mechanisms collectively provide a novel approach to prevented against cartilage degradation.

6.
ACS Nano ; 18(13): 9354-9364, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38517038

RESUMO

Na3V2(PO4)3 (NVP) based on the multielectron reactions between V2+ and V5+ has been considered a promising cathode for sodium-ion batteries (SIBs). However, it still suffers from unsatisfactory stability, caused by the poor reversibility of the V5+/V4+ redox couple and structure evolution. Herein, we propos a strategy that combines high-entropy substitution and electrolyte optimization to boost the reversible multielectron reactions of NVP. The high reversibility of the V5+/V4+ redox couple and crystalline structure evolution are disclosed by in situ X-ray absorption near-edge structure spectra and in situ X-ray diffraction. Meanwhile, the electrochemical reaction kinetics of high-entropy substitution NVP (HE-NVP) can be further improved in the diglyme-based electrolyte. These enable HE-NVP to deliver a superior electrochemical performance (capacity retention of 93.1% after 2000 cycles; a large reversible capacity of 120 mAh g-1 even at 5.0 A g-1). Besides, the long cycle life and high power density of the HE-NVP∥natural graphite full-cell configuration demonstrated the superiority of HE-NVP cathode in SIBs. This work highlights that the synergism of high-entropy substitution and electrolyte optimization is a powerful strategy to enhance the sodium-storage performance of polyanionic cathodes for SIBs.

7.
Chem Sci ; 15(13): 4833-4838, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38550702

RESUMO

Sodium metal batteries have attracted increasing interest recently, but suffer from severe dendrite growth caused by uneven Na plating/stripping behavior, which may result in the piercing of the membrane, with short circuiting and even cause explosions. Herein, a conductive and sodiophilic Ag coating layer is introduced to regulate Na deposition behaviors for highly reversible sodium metal batteries. Ag coated Zn foil with enhanced sodiophilicity, rapid Na+ transfer kinetics and superior electronic conductivity guarantee the homogenized Na+ ion and electric field distribution. This enables remarkably low overpotentials and uniform Na plating/stripping behavior with ultrahigh Coulombic efficiency of 99.9% during 500 cycles. As expected, the enhanced electrochemical performance of the anode-less battery and anode-free battery coupled with Prussian blue is achieved with the help of Ag coating. This work emphasizes the role of the conductive and sodiophilic coating layer in regulating the Na deposition behaviors for highly reversible sodium metal batteries.

8.
Chin Med ; 19(1): 42, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38444022

RESUMO

BACKGROUND: Cayratia albifolia C.L.Li (CAC), commonly known as "Jiao-Mei-Gu" in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot. RESULTS: CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA. CONCLUSIONS: We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation.

9.
Clin Cancer Res ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451195

RESUMO

PURPOSE: Disruption of lipid bilayer asymmetry is a common feature observed in cancer cells and offers novel routes for therapeutic targeting. We utilized the natural immune receptor TIM-4 to interrogate for loss of plasma membrane phospholipid polarity in primary acute myelogenous leukemia (AML) samples and evaluated the anti-leukemic activity of TIM-4-L-directed T cell therapy in preclinical AML models. METHODS: We performed FACs analysis on 33 primary AML bone marrow specimens and correlated TIM-4-L expression frequency and intensity with molecular disease characteristics. Using Kasumi-1 and MV-4-11 AML cell lines, we further tested the anti-leukemic effects of TIM-4-L-directed engineered T cells in vitro and in vivo. RESULTS: 86% of untreated AML blasts displayed upregulation of cell surface TIM-4-L. These observations were agnostic to AML genetic classification, as samples with mutations in TP53, ASXL1, and RUNX1 displayed TIM-4-L upregulation similar to that seen in favorable and intermediate subtypes. TIM-4-L dysregulation was also stably present in AML cell lines. To evaluate the potential of targeting upregulated TIM-4-L with adoptive T cell therapy (ACT), we constructed TIM-4-L-directed engineered T cells, which demonstrated potent anti-leukemic effects, effectively eliminating AML cell lines with a range of endogenous TIM-4-L expression levels both in vitro and in vivo. CONCLUSIONS: These results highlight TIM-4-L as a highly prevalent target on AML across a range of genetic classifications and novel target for T cell-based therapy in AML. Further investigations into the role of TIM-4-L in AML pathogenesis and its potential as an anti-leukemic target for clinical development are warranted.

10.
Chem Sci ; 15(11): 4135-4139, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38487247

RESUMO

Na2Fe2(SO4)3 (NFS), as a promising cathode for sodium-ion batteries, is still plagued by its poor intrinsic conductivity. In general, hybridization with carbon materials is an effective strategy to improve the sodium storage performance of NFS. However, the role of carbon materials in the electrochemical performance of NFS cathode materials has not been thoroughly investigated. Herein, the effect of carbon materials was revealed by employing various conductive carbon materials as carbon sources. Among these, the NFS coated with Ketjen Black (NFS@KB) shows the largest specific surface area, which is beneficial for electrolyte penetration and rapid ionic/electronic migration, leading to improved electrochemical performance. Therefore, NFS@KB shows a long cycle life (74.6 mA h g-1 after 1000 cycles), superior rate performance (61.5 mA h g-1 at a 5.0 A g-1), and good temperature tolerance (-10 °C to 60 °C). Besides, the practicality of the NFS@KB cathode was further demonstrated by assembling a NFS@KB//hard carbon full cell. Therefore, this research indicates that a suitable carbon material for the NFS cathode can greatly activate the sodium storage performance.

11.
Nat Commun ; 15(1): 2038, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448448

RESUMO

Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.


Assuntos
Cicatriz Hipertrófica , Humanos , Animais , Feminino , Camundongos , Coelhos , Cicatriz Hipertrófica/tratamento farmacológico , Espécies Reativas de Oxigênio , Disponibilidade Biológica , Diferenciação Celular , Metaloproteinases da Matriz
12.
Chin J Nat Med ; 22(2): 127-136, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38342565

RESUMO

Psoriasis, a prevalent inherited skin condition, involves an inflammatory response as a key pathogenic mechanism. The Optimized Yinxieling Formula (OYF), rooted in traditional Chinese medicine, is extensively utilized in clinical settings to treat psoriasis. Although previous studies have demonstrated OYF's significant anti-inflammatory effects in psoriasis, its potential molecular targets and active components remain unexplored. This study aimed to unveil the anti-psoriasis molecular targets and active components of OYF. Our findings indicated that OYF extract markedly reduced the production of several inflammatory mediators, including IL-23, nitric oxide, TNF-α, and IL-1ß, in LPS-induced RAW264.7 cells. We synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy, known as Target Fishing. The enriched target proteins were subsequently identified via LC-MS/MS, followed by bioinformatics analysis to map the psoriasis-associated pathway-gene network. We identified a total of 76 potential target proteins, which were highly associated with mRNA transcription mechanisms. In particular, pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF extract. We further utilized a target protein-based affinity capture strategy, combined with LC-MS and SPR analysis, to globally screen OYF's active components, focusing on the mRNA transcription regulator, fused in sarcoma (FUS). This process led to the identification of umbelliferone, vanillic acid, protocatechuic acid, gentisic acid, and echinacoside as key compounds targeting FUS to inhibit IL-23 expression. Additionally, we formulated a compound cocktail (CpdC), which significantly reduced psoriasis area and severity index (PASI) scores and the expressions of IL-23 and Ki67 in an imiquimod (IMQ)-induced psoriasis mouse model. Collectively, our study elucidates the primary molecular targets and active components of OYF, offering novel insights for psoriasis treatment.


Assuntos
Medicamentos de Ervas Chinesas , Psoríase , Animais , Camundongos , Cromatografia Líquida , Medicamentos de Ervas Chinesas/uso terapêutico , Espectrometria de Massas em Tandem , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Psoríase/patologia , Interleucina-23/efeitos adversos , RNA Mensageiro , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
13.
J Colloid Interface Sci ; 663: 1074-1086, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38331692

RESUMO

Drug-resistant biofilm infection is an extremely serious clinical problem, that easily leads to failure of antibiotic treatment. Although gold nanoparticles (AuNPs) as photothermal agents have been widely used in biofilm eradication, there are still challenges to be addressed, such as insignificantly redshifted absorption and slow assembly process of aggregated AuNPs. Herein, we developed an acidity-activated dispersion-to-aggregation transition to enhance the accumulation of self-complementary zwitterionic peptide-decorated AuNPs for photothermal eradication of drug-resistant biofilm infections. AuNPs were decorated with self-complementary zwitterionic peptides (ZP1 and ZP2) coupled with pH-sensitive anhydride (DMA) and pH-insensitive anhydride (SA), respectively. ZP2-decorated AuNPs with DMA modification (AuNP@ZP2(DMA)) exhibited prolonged blood circulation and enhanced accumulation in acidic biofilm microenvironment. Moreover, the electrostatic attraction between self-complementary ligands drove AuNPs to form closely packed aggregates with strong near-infrared absorption, leading to in vivo photoacoustic imaging ability and photothermal effect against drug-resistant bacteria and fungus, as well as microbial biofilms. AuNP@ZP2(DMA) with longer charge domains and a polyethylene glycol oligomer spacer showed greater photothermal antimicrobial and biofilm resistance in vitro and in vivo. This study develops an innovative acidity-activated AuNP photothermal agent, which provides an effective approach for treatment of biofilm infections.


Assuntos
Ouro , Nanopartículas Metálicas , Ouro/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes , Anidridos/farmacologia
14.
Phytother Res ; 38(4): 1863-1881, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38358766

RESUMO

Forsythia suspensa tea is a popular traditional Chinese medicine decoction for its healthy and therapeutic benefits. However, its effects in bone metabolism were not clear. In recent study, we uncovered anti-osteoclastogenesis property of Phillygenin (Phi), a compound abundant in Forsythia suspensa leaves, and aimed to investigate the effect and mechanism of Phi on bone metabolism in vivo and in vitro. Lipopolysaccharides-induced murine calvaria osteolysis and ovariectomy-induced bone loss animal models were used to identify the bone-protective effect of Phi in vivo and micro-CT, pQCT, and TRAP staining were applied. We used CCK8, TUNEL, BrdU, and TRAP staining to evaluate the efficacy of Phi on the proliferation and formation of OCs in primary mBMMs. RNA sequence, activity-based protein profiling, molecular docking, G-LISA, and WB were used to inspect the target and underlying mechanism of Phi's actions in mBMMs. We found Phi significantly inhibited bone resorption in vivo and inhibited mBMMs osteoclastogenesis in vitro. Ras homolog gene family member A (RhoA) was identified as the direct target of Phi. It counteracted the effects of RhoA activator and acted as a RhoA inhibitor. By targeting RhoA, Phi modulated Rho-associated coiled-coil containing protein kinase 1 (ROCK1) activity and regulated its downstream NF-κB/NFATc1/c-fos pathway. Furthermore, Phi depressed the disassembling of F-actin ring through cofilin and myosin1a. Our findings provided Phi as a potential option for treating bone loss diseases by targeting RhoA and highlighted the importance of F. suspensa as a preventive approach in bone disorders.


Assuntos
Doenças Ósseas Metabólicas , Reabsorção Óssea , Lignanas , Osteólise , Animais , Feminino , Camundongos , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/prevenção & controle , Diferenciação Celular , Lignanas/farmacologia , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Fatores de Transcrição NFATC/farmacologia , Osteoclastos , Osteogênese , Osteólise/induzido quimicamente
15.
RSC Adv ; 14(2): 1488-1500, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38174284

RESUMO

In this study, fcSe@TiO2 and [Cu2I2(fcSe)2]n@TiO2 nanosystems based on ferrocenylselenoether and its cuprous cluster were developed and characterized by X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray spectroscopy (EDX), and electron paramagnetic resonance (EPR). Under optimized conditions, 0.2 g L-1 catalyst, 20 mM H2O2, and initial pH 7, good synergistic visible light photocatalytic tetracycline degradation and Cr(vi) reduction were achieved, with 92.1% of tetracycline and 64.5% of Cr(vi) removal efficiency within 30 minutes. Mechanistic studies revealed that the reactive species ˙OH, ˙O2-, and h+ were produced in both systems through the mutual promotion of Fenton reactions and photogenerated charge separation. The [Cu2I2(fcSe)2]n@TiO2 system additionally produced 1O2 from Cu+ and ˙O2-. The advantages of the developed nanosystems include an acidic surface microenvironment provided by Se⋯H+, resourceful product formation, tolerance of complex environments, and excellent adaptability in refractory N-cyclic organics.

16.
Chem Sci ; 15(4): 1449-1471, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38274053

RESUMO

The expertise accumulated in deep neural network-based structure prediction has been widely transferred to the field of protein-ligand binding pose prediction, thus leading to the emergence of a variety of deep learning-guided docking models for predicting protein-ligand binding poses without relying on heavy sampling. However, their prediction accuracy and applicability are still far from satisfactory, partially due to the lack of protein-ligand binding complex data. To this end, we create a large-scale complex dataset containing ∼9 M protein-ligand docking complexes for pre-training, and propose CarsiDock, the first deep learning-guided docking approach that leverages pre-training of millions of predicted protein-ligand complexes. CarsiDock contains two main stages, i.e., a deep learning model for the prediction of protein-ligand atomic distance matrices, and a translation, rotation and torsion-guided geometry optimization procedure to reconstruct the matrices into a credible binding pose. The pre-training and multiple innovative architectural designs facilitate the dramatically improved docking accuracy of our approach over the baselines in terms of multiple docking scenarios, thereby contributing to its outstanding early recognition performance in several retrospective virtual screening campaigns. Further explorations demonstrate that CarsiDock can not only guarantee the topological reliability of the binding poses but also successfully reproduce the crucial interactions in crystalized structures, highlighting its superior applicability.

17.
Nat Commun ; 15(1): 73, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168108

RESUMO

Transcription-replication conflicts (TRCs), especially Head-On TRCs (HO-TRCs) can introduce R-loops and DNA damage, however, the underlying mechanisms are still largely unclear. We previously identified a chloroplast-localized RNase H1 protein AtRNH1C that can remove R-loops and relax HO-TRCs for genome integrity. Through the mutagenesis screen, we identify a mutation in chloroplast-localized primase ATH that weakens the binding affinity of DNA template and reduces the activities of RNA primer synthesis and delivery. This slows down DNA replication, and reduces competition of transcription-replication, thus rescuing the developmental defects of atrnh1c. Strand-specific DNA damage sequencing reveals that HO-TRCs cause DNA damage at the end of the transcription unit in the lagging strand and overexpression of ATH can boost HO-TRCs and exacerbates DNA damage. Furthermore, mutation of plastid DNA polymerase Pol1A can similarly rescue the defects in atrnh1c mutants. Taken together these results illustrate a potentially conserved mechanism among organisms, of which the primase activity can promote the occurrence of transcription-replication conflicts leading to HO-TRCs and genome instability.


Assuntos
DNA Primase , Replicação do DNA , DNA Primase/genética , DNA Primase/metabolismo , Replicação do DNA/genética , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Dano ao DNA , Mutação
19.
Proc Natl Acad Sci U S A ; 121(5): e2316914121, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38252828

RESUMO

High-performance sodium storage at low temperature is urgent with the increasingly stringent demand for energy storage systems. However, the aggravated capacity loss is induced by the sluggish interfacial kinetics, which originates from the interfacial Na+ desolvation. Herein, all-fluorinated anions with ultrahigh electron donicity, trifluoroacetate (TFA-), are introduced into the diglyme (G2)-based electrolyte for the anion-reinforced solvates in a wide temperature range. The unique solvation structure with TFA- anions and decreased G2 molecules occupying the inner sheath accelerates desolvation of Na+ to exhibit decreased desolvation energy from 4.16 to 3.49 kJ mol-1 and 24.74 to 16.55 kJ mol-1 beyond and below -20 °C, respectively, compared with that in 1.0 M NaPF6-G2. These enable the cell of Na||Na3V2(PO4)3 to deliver 60.2% of its room-temperature capacity and high capacity retention of 99.2% after 100 cycles at -40 °C. This work highlights regulation of solvation chemistry for highly stable sodium-ion batteries at low temperature.

20.
Plants (Basel) ; 13(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38256813

RESUMO

Cucurbitacins, oxygenated tetracyclic triterpenoids that are found mainly in the Cucurbitaceae family, play essential roles as defensive compounds, serving as allomones against herbivores and pathogens and as signals for insect-parasite recognition. These compounds also exhibit various pharmacological effects. The biosynthesis of cucurbitacins is largely regulated by the bitter (Bi) gene, encoding an oxidosqualene cyclase, which catalyzes the conversion of 2,3-oxidosqualene into cucurbitadienol, a common precursor for cucurbitacin synthesis. Previous studies focused on uncovering the Bi gene clusters in Cucurbitaceae, but their presence in other cucurbitacin-producing plants remained unexplored. Here, the evolutionary history of Bi genes and their clusters were investigated in twenty-one plant genomes spanning three families based on chemotaxonomy. Nineteen Bi genes were identified in fourteen Cucurbitaceae, four Begoniaceae, and one Aquilaria species. Phylogenetic analysis suggested that the genome of Aquilaria sinensis contained the earliest Bi gene clusters in this dataset. Moreover, the genomic analysis revealed a conserved microsynteny of pivotal genes for cucurbitacin biosynthesis in Cucurbitaceae, while interspersed Bi gene clusters were observed in Begoniaceae, indicating rearrangements during plant Bi gene cluster formation. The bitter gene in A. sinensis was found to promote cucurbitadienol biosynthesis in the leaves of Nicotiana benthamiana. This comprehensive exploration of plant Bi genes and their clusters provides valuable insights into the genetic and evolutionary underpinnings of cucurbitacin biosynthesis. These findings offer prospects for a deeper understanding of cucurbitacin production and potential genetic resources for their enhancement in various plants.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...