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Lithium-oxygen batteries (LOBs) have been widely studied because of their ultra-high energy density (â¼3500 Wh kg-1). However, the reversibility and stability of LOBs are greatly limited by the sluggish kinetics of oxygen reduction/evolution reactions (ORR/OER) and severely parasitic reactions on oxygen electrodes. Electrolyte in LOBs plays an important role in the transport of reactive oxygen species and Li+, which greatly affects the kinetics and reversibility of the charging and discharging processes of batteries. In this work, perfluorooctane (PFO) is used as the additive in 1.0 M LiTFSI/TEGDEM electrolyte for LOBs to regulate the kinetics of oxygen electrode reactions. Due to the strong adsorption ability of PE toward oxygen, the oxygen concentration inside the electrolyte is greatly increased after the addition of PE. In addition, the PE-added electrolyte also exhibits superior electrochemical stability and is capable of triggering solution-mediated Li2O2 growth pathway during the discharge process of the LOBs. Therefore, with the increased oxygen concentration and the optimized electrode/electrolyte interface, the ORR/OER kinetics on the oxygen electrode is significantly promoted, which enables the LOBs with excellent energy efficiency and cycling life. This work provides a new idea for the design of oxygen-rich and high-performance electrolyte for lithium-oxygen batteries.
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As an alternative to traditional dietary fibers with prebiotic effects, the interaction between resistant starch III (RS3) and gut microbiota is worth exploring. In this study, the effects of RS3 on the proliferation of Bifidobacterium adolescentis (B. adolescentis) and their structural changes before and after fermentation were investigated. Autoclaved-debranched resistant starch (ADRS) demonstrated the best proliferative effect for B. adolescentis and the highest roughness (Ra = 21.90 nm; Rq = 16.00 nm). The rough surface of ADRS was the key for B. adolescentis proliferation. B. adolescentis produced an extracellular amylase to assist degradation and showed the highest activity in ADRS. Fermentation disrupted short-range ordered structure and reduced R1047 cm-1/1022 cm-1 by 20.74 % and R995 cm-1/1022 cm-1 by 30.85 %. The extracellular amylase was essential substance for ADRS degradation. These findings help optimize RS3 structure and promote the proliferation of intestinal probiotics.
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Bifidobacterium adolescentis , Fermentación , Probióticos , Almidón , Zea mays , Zea mays/química , Zea mays/microbiología , Zea mays/metabolismo , Almidón/metabolismo , Almidón/química , Bifidobacterium adolescentis/metabolismo , Probióticos/metabolismo , Probióticos/química , Microbioma Gastrointestinal , Humanos , Amilasas/metabolismo , Almidón Resistente/metabolismoRESUMEN
Chromosomal inversions (INVs) are particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage-sensitive genes in cis Short-read genome sequencing (srGS) can only resolve â¼70% of cytogenetically visible inversions referred to clinical diagnostic laboratories, likely due to breakpoints in repetitive regions. Here, we study 12 inversions by long-read genome sequencing (lrGS) (n = 9) or srGS (n = 3) and resolve nine of them. In four cases, the inversion breakpoint region was missing from at least one of the human reference genomes (GRCh37, GRCh38, T2T-CHM13) and a reference agnostic analysis was needed. One of these cases, an INV9 mappable only in de novo assembled lrGS data using T2T-CHM13 disrupts EHMT1 consistent with a Mendelian diagnosis (Kleefstra syndrome 1; MIM#610253). Next, by pairwise comparison between T2T-CHM13, GRCh37, and GRCh38, as well as the chimpanzee and bonobo, we show that hundreds of megabases of sequence are missing from at least one human reference, highlighting that primate genomes contribute to genomic diversity. Aligning population genomic data to these regions indicated that these regions are variable between individuals. Our analysis emphasizes that T2T-CHM13 is necessary to maximize the value of lrGS for optimal inversion detection in clinical diagnostics. These results highlight the importance of leveraging diverse and comprehensive reference genomes to resolve unsolved molecular cases in rare diseases.
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The performance of BiOBr in photocatalytic nitrogen (N2) fixation is suboptimal, attributed to the weak chemisorption and activation of N2 by surface atoms. In our study, we achieved the formation of two-dimensional (2D) bismuth (Bi) on BiOBr nanosheets through in situ annealing in hydrogen atmosphere and successfully constructed a unique 2D-2D Bi/BiOBr ohmic heterojunction using a one-step method. Notably, the Bi/BiOBr heterojunction was utilized for photocatalytic N2 fixation under visible light (λ > 400 nm) in ultrapure water, demonstrating an exceptional N2 fixation rate of 376.16 µmol g-1 h-1. This rate is 7.7 and 4.1 times higher than those of BiOBr and BiOBr-OVs, respectively. The improved photocatalytic efficiency is attributed to the significantly enhanced N2 adsorption capability and more effective separation of photogenerated carriers, both stemming from the distinctive 2D/2D architecture of the Bi/BiOBr heterojunction. This work demonstrates that 2D Bi offers active sites that facilitate photocatalytic N2 fixation and introduces an approach to the design and construction of 2D/2D photocatalysts for applications spanning catalysis, optoelectronics, electronics, and beyond.
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OBJECTIVE: Gastric cancer is malignant cancer with high morbidity and mortality worldwide. Milk fat globule EGF and factor V/VIII domain containing (MFGE8) was involved in many cancers. Nevertheless, the role of MFGE8 in gastric cancer remained indistinct. To probe the role of MFGE8 in gastric cancer and further explore the regulating mechanism. METHODS: GEPIA was employed for analysis of MFGE8 expression and survival of gastric cancer patients. MFGE8 expression in gastric cancer was determined by immunohistochemistry, PCR, and western blot. The effect of MFGE8 on gastric cancer cells were evaluated by a series of cell function experiments. The mechanism of MFGE8 on gastric cancer was analyzed by GSEA and verified by in vitro and in vivo experiments. RESULTS: MFGE8 was over-expressed in gastric cancer. Silence of MFGE8 suppressed cell viability, proliferated ability, migrated and invasive ability, and EMT, but accelerated cell apoptosis. The opposite results were obtained in MFGE8-overexpressed gastric cancer cells. Zinc finger and BTB domain containing 7â¯A (ZBTB7A) was a transcription factor of MFGE8. ZBTB7A overexpression eliminated the effect of MFGE8 on gastric cancer cells. MFGE8 activated the IL-6/JAK/STAT3 signaling. Inhibition of IL-6/JAK/STAT3 signaling by Stattic (pathway inhibitor) could eliminate the promoting effect of MFGE8 on IL-6/JAK/STAT3 signaling. In addition, MFGE8 shRNA inhibited tumor growth. CONCLUSION: MFGE8 promoted cell proliferation, EMT progress, and tumor growth of gastric cancer by activating the IL-6/JAK/STAT3 signaling.
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Annual glacier melting alters hydrothermal conditions of the foreland alpine meadows, and causes significant fluctuations in methane (CH4) flux. Previously we found that Tibetan glacier foreland alpine meadow shifts to CH4 source from sink during the melting season, but the potential mechanisms remain unclear. This study, via combination of in-situ measurement of seasonal CH4 flux and survey of microbial species that may involve in CH4 metabolism, explores the causes of glacier melting on CH4 flux in a glacier foreland alpine meadow on Tibetan Plateau. We determined a pronounced CH4 emission (13.95 µg·m-2·h-1) in August (melting season) but CH4 uptake in June (-3.76 µg·m-2·h-1) and October (-17.77 µg·m-2·h-1), and 1.4-fold higher soil moisture in August than the other two months. This showed a direct correlation of CH4 flux with glacier melting increased soil water. Additionally, glacier melting caused more CH4 fluxes increase in hollows than in hummocks. Amplicon sequencing determined 126-fold higher abundance of mcrA, the methanogenic marker gene, in August than in June and October, and a higher relative abundance of a fungal phylum Mortierellomycota and syntrophic bacteria that convert the fatty acids, the degradation intermediates of organic complexes to CO2 and acetate, the methanogenic substrates like in August. However, no seasonal variation of pmoA, the marker gene of aerobic methanotrophs, was observed. It appears that glacier melting promotes the CH4 producing but not the consuming microorganisms, thus leading to increased CH4 emission. The findings of this work indicate that global warming resulted glacier melting would increase global CH4 emissions, and in turn worsens global warming, so an alarming positive feedback loop.
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Metallothioneins (MTs) are small proteins that coordinate d-block metal ions in sulfur-metal clusters to control metal ion concentrations within the cell. Here we study metal cluster formation in the MT of the periwinkle Littorina littorea (LlMT) by nuclear magnetic resonance (NMR). We demonstrate that the three Cd2+ ions in each domain are taken up highly cooperatively, that is, in an all-or-none fashion, with a four- to six-fold higher affinity for the C-terminal domain. During the transfer of metal ions from Cd2+-loaded MT to apo MT, Cd2+ is most efficiently transferred from the metalated protein to the apo C-terminal domain. This behavior might be connected to unique structural motifs in the C-terminal domain, such as two double-CXC motifs and an increased proportion of positively charged residues. In Cd2+/Zn2+ metal exchange experiments, the N-terminal domain displayed the most efficient inter-molecular metal exchange. Amide hydrogen exchange reveals fewer protected amides for the N-terminal domain, suggesting the structure might more easily "open up" to facilitate metal exchange. Experiments with a physical separation of donor and acceptor species demonstrate that metal exchange and transfer require protein-protein contacts. These findings provide insights into the mechanism of metal uptake and metal transfer, which are important processes during metal detoxification in snail MTs.
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Cadmio , Metalotioneína , Metalotioneína/química , Metalotioneína/metabolismo , Cadmio/química , Cadmio/metabolismo , Zinc/metabolismo , Zinc/química , Resonancia Magnética Nuclear Biomolecular , Metaloproteínas/química , Metaloproteínas/metabolismo , Modelos MolecularesRESUMEN
Williams syndrome (WS) is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23, characterized by intellectual disability, distinctive craniofacial and dental features, and cardiovascular problems. Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes. Here, we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2, as well as one patient with a 167 kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2. To investigate the potential involvement of RFC2 in WS pathogenicity, we generate a rfc2 knockout (KO) zebrafish using CRISPR-Cas9 technology. Additionally, we generate a KO zebrafish of its paralog gene, rfc5, to better understand the functions of these RFC genes in development and disease. Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS, including small head and brain, jaw and dental defects, and vascular problems. RNA-seq analysis reveals that genes associated with neural cell survival and differentiation are specifically affected in rfc2 KO zebrafish. In addition, heterozygous rfc2 KO adult zebrafish demonstrate an anxiety-like behavior with increased social cohesion. These results suggest that RFC2 may contribute to the pathogenicity of Williams syndrome, as evidenced by the zebrafish model.
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Mercury (Hg), a ubiquitous atmospheric trace metal posing serious health risks, originates from natural and anthropogenic sources. India, the world's second-largest Hg emitter and a signatory to the Minamata Convention, is committed to reducing these emissions. However, critical gaps exist in our understanding of the spatial and temporal distribution of Hg across the vast Indian subcontinent due to limited observational data. This study addresses this gap by employing the GEOS-Chem model with various emission inventories (UNEP2010, WHET, EDGAR, STREETS, and UNEP2015) to simulate Hg variability across the Asian domain, with a specific focus on India from 2013 to 2017. Model performance was evaluated using ground-based GMOS observations and available literature data. Emission inventory performance varied across different observational stations. Hence, we employed ensemble results from all inventories. The maximum relative bias for Total Gaseous Mercury (TGM) and Gaseous Elemental Mercury (GEM; Hg0) concentrations is about ±20%, indicating simulations with sufficient accuracy. Total Hg wet deposition fluxes are highest over the Western Ghats and the Himalayan foothills due to higher rainfall. During the monsoon, the Hg wet deposition flux is about 65.4% of the annual wet deposition flux. Moreover, westerly winds cause higher wet deposition in summer over Northern and Eastern India. Total Hg dry deposition flux accounts for 72-74% of total deposition over India. Hg0 dry deposition fluxes are higher over Eastern India, which correlates strongly with the leaf area index. Excluding Indian anthropogenic emissions from the model simulations resulted in a substantial decrease (21.9% and 33.5%) in wet and total Hg deposition fluxes, highlighting the dominant role of human activities in Hg pollution in India.
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Introduction: Maize photosensitivity and the control of flowering not only are important for reproduction, but also play pivotal roles in the processes of domestication and environmental adaptation, especially involving the utilization strategy of tropical maize in high-latitude regions. Methods: In this study, we used a linkage mapping population and an inbred association panel with the photoperiod sensitivity index (PSI) phenotyped under different environments and performed transcriptome analysis of T32 and QR273 between long-day and short-day conditions. Results: The results showed that PSIs of days to tasseling (DTT), days to pollen shedding (DTP), and days to silking (DTS) indicated efficacious interactions with photoperiod sensitivity for maize latitude adaptation. A total of 48 quantitative trait loci (QTLs) and 252 quantitative trait nucleotides (QTNs) were detected using the linkage population and the inbred association panel. Thirteen candidate genes were identified by combining the genome-wide association study (GWAS) approach, linkage analysis, and transcriptome analysis, wherein five critical candidate genes, MYB163, bif1, burp8, CADR3, and Zm00001d050238, were significantly associated with photoperiod sensitivity. Discussion: These results would provide much more abundant theoretical proofs to reveal the genetic basis of photoperiod sensitivity, which would be helpful to understand the genetic changes during domestication and improvement and contribute to reducing the barriers to use of tropical germplasm.
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Erwinia amylovora, the causative agent of fire blight, causes significant economic losses for farmers worldwide by inflicting severe damage to the production and quality of plants in the Rosaceae family. Historically, fire blight control has primarily relied on the application of copper compounds and antibiotics, such as streptomycin. However, the emergence of antibiotic-resistant strains and growing environmental concerns have highlighted the need for alternative control methods. Recently, there has been a growing interest in adopting bacteriophages (phages) as a biological control strategy. Phages have demonstrated efficacy against the bacterial plant pathogen E. amylovora, including strains that have developed antibiotic resistance. The advantages of phage therapy includes its minimal impact on microbial community equilibrium, the lack of a detrimental impact on plants and beneficial microorganisms, and its capacity to eradicate drug-resistant bacteria. This review addresses recent advances in the isolation and characterization of E. amylovora phages, including their morphology, host range, lysis exertion, genomic characterization, and lysis mechanisms. Furthermore, this review evaluates the environmental tolerance of E. amylovora phages. Despite their potential, E. amylovora phages face certain challenges in practical applications, including stability issues and the risk of lysogenic conversion. This comprehensive review examines the latest developments in the application of phages for controlling fire blight and highlights the potential of E. amylovora phages in plant protection strategies.
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Bacteriófagos , Erwinia amylovora , Especificidad del Huésped , Enfermedades de las Plantas , Erwinia amylovora/virología , Bacteriófagos/fisiología , Bacteriófagos/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Genoma Viral , Rosaceae/microbiología , Rosaceae/virología , Terapia de Fagos/métodosRESUMEN
Objective: To evaluate the association between systemic inflammatory markers and clinical outcomes (all-cause mortality, cardiovascular mortality, and rehospitalization) in patients with heart failure with preserved ejection fraction (HFpEF). Methods: We conducted a comprehensive literature search in PubMed, Embase, and Ovid Medline databases from inception to June 27, 2024. Studies were included if they were observational clinical studies involving HFpEF patients over 18 years old, with exposure to systemic inflammatory markers and reporting on adverse prognosis outcomes. The Newcastle-Ottawa Scale (NOS) was used to assess study quality. Results: Eight studies ultimately included in the meta-analysis which involved 9,744 participants from six countries. The meta-analysis showed that systemic inflammatory markers were significantly associated with all-cause mortality (HR 1.43, 95% CI 1.19-1.72, p < 0.05), cardiovascular mortality (HR 2.04, 95% CI 1.33-3.12, p < 0.05), and cardiovascular rehospitalization (HR 2.83, 95% CI 0.92-8.67, p < 0.05) in HFpEF patients. Low heterogeneity was observed across studies (I2 = 0.00%). Sensitivity and publication bias analyses indicated that the results were robust. Conclusion: Systemic inflammatory markers demonstrate significant predictive value for adverse clinical outcomes in HFpEF patients. The findings suggest that monitoring systemic inflammation may provide valuable prognostic information for clinicians managing HFpEF patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=562698, identifier (CRD42024562698).
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BACKGROUND: Hyperuricemia (HUA) and gout have been demonstrated as independent risk factors for cardiovascular disease. The relationship between the recently updated Life's Essentials 8 (LE8), which measures ideal cardiovascular health (CVH), and HUA and gout remains unclear. The aim of this study was to explore the relationship between CVH and the prevalence of HUA and gout among a nationally representative sample of US adults. METHODS: This study utilized cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) for the years 2007 to 2018. The CVH scores and their corresponding components were defined according to the guidelines established by the American Heart Association. The association between the LE8 score and both HUA and gout was assessed using weighted multivariable logistic and restricted cubic spline (RCS) models. RESULTS: Among the 21,155 participants aged 20 years and older, the prevalence of HUA was 17.20% (95% CI, 16.05-18.36%), and the prevalence of gout was 3.58% (95% CI, 3.13-4.02%). After adjusting for potential confounders, compared to participants exhibiting low CVH, the multivariable adjusted odds ratio (OR) for HUA was 0.65 (95% CI, 0.56-0.75) in those with moderate CVH, and 0.25 (95% CI, 0.20-0.31) in those with high CVH. Additionally, compared to participants with low CVH, the multivariable adjusted OR for gout was 0.66 (95% CI, 0.53-0.81) in those with moderate CVH and 0.32 (95% CI, 0.20-0.50) in those with high CVH. The LE8 score exhibited a significant nonlinear negative association with HUA and linear negative correlation with gout. In subgroup analyses focusing on HUA, significant interactions were observed between LE8 score and age, sex, and CKD (P for interaction < 0.05). For gout, only a significant interaction between LE8 score and sex was observed (P for interaction < 0.05). CONCLUSIONS: Among adults, there was a significant negative correlation between LE8 score and the prevalence of HUA and gout. Maintaining an ideal CVH may be beneficial in reducing the burden of HUA and gout.
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Enfermedades Cardiovasculares , Gota , Hiperuricemia , Encuestas Nutricionales , Humanos , Gota/epidemiología , Hiperuricemia/epidemiología , Masculino , Femenino , Estudios Transversales , Adulto , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Prevalencia , Estados Unidos/epidemiología , Factores de Riesgo , Anciano , Adulto Joven , Estado de SaludRESUMEN
INTRODUCTION: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been established as an effective treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high lactate level. Moreover, studies have suggested that the rate of complications early after surgery directly increased with elevated lactate levels. Glucose-insulin-potassium (GIP), a potent cardioprotective intervention, has been demonstrated to adjust blood glucose (BG) levels and reduce lactate levels. However, the insulin-glucose ratio should be adjusted according to the surgery performed. Here, we aimed to evaluate the advantages of using modified GIP during CRS/HIPEC to reduce the lactate level at the end of surgery and further reduce the incidence of early postoperative complications. METHODS AND ANALYSIS: The modified GIP versus conventional management during surgery study is a single-center, randomized, single-blinded outcome assessment clinical trial of 80 patients with PC who are between 18 and 64 years old and undergoing CRS/HIPEC. Participants will be randomly allocated to receive modified GIP or conventional treatment (1:1). The primary outcome will be the plasma lactate level at the end of surgery. The secondary outcomes will include the highest levels and fluctuation ranges of lactate and BG during surgery, extubation time, APACHE-II score 24 h after surgery, postoperative defecation and exhaust time, postoperative lactate clearance time, postoperative liver and kidney function, incidence of complications within 7 days after surgery, length of intensive care unit stay (LIS), length of hospital stay (LHS), and total cost of hospitalization. ETHICS AND DISSEMINATION: The trial protocol was approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University, approval number sjtky11-1x-2022(118). The results will be published in international peer-reviewed journals. TRIAL REGISTRATION: ChiCTR2200057258. Registered on March 5, 2022.
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Procedimientos Quirúrgicos de Citorreducción , Glucosa , Quimioterapia Intraperitoneal Hipertérmica , Insulina , Ácido Láctico , Neoplasias Peritoneales , Potasio , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Quimioterapia Intraperitoneal Hipertérmica/efectos adversos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/sangre , Insulina/administración & dosificación , Glucosa/administración & dosificación , Potasio/sangre , Adulto , Persona de Mediana Edad , Ácido Láctico/sangre , Ácido Láctico/administración & dosificación , Método Simple Ciego , Femenino , Masculino , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Resultado del Tratamiento , Adulto Joven , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , AdolescenteRESUMEN
Previous studies have reported that senolytic drugs can reverse obesity-mediated accumulation of senescent cells in the ovary and protect against cisplatin-induced ovarian injury by removing senescent cells. Early intervention with ABT-263 has been shown to mitigate ovarian aging. However, it remains unknown whether treatment with ABT-263 could rejuvenate the aged ovary in reproductively old females. Therefore, the current study was aimed to investigate whether advanced age intervention with ABT-263 could ameliorate age-related decline in ovarian function. Fourteen 16-month-old mice with a C57/BL6 background were treated with ABT-263 (N = 7) or vehicle (N = 7) for two weeks. Mice were initially treated with ABT-263 (60 mg/kg/d) or vehicle for 7 consecutive days. After a 7-day break, the treatment was repeated for another 7 consecutive days. Six 2-month-old mice with C57BL/6 were used as a young control. The hormonal levels, estrus cycles, ovarian reserve, ovarian cell proliferation and apoptosis, ovarian fibrosis, and steroidogenic gene expression of ovarian stromal cells were evaluated. ABT-263 treatment did not rescue abnormal estrus cycles and sex hormonal levels, or inhibit the formation of multinucleated giant cells and ovarian stromal cell apoptosis in aged ovaries. However, it reduced ovarian fibrosis and preserved the steroidogenic gene expression of ovarian stromal cells in aged ovaries. Importantly, ABT-263 treatment further depleted ovarian follicles in aged mice. In conclusion, ABT-263 treatment accelerated the depletion of ovarian follicles in aged mice, suggesting that senolytic drugs for reproductively old female may adversely affect female fertility.
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Envejecimiento , Compuestos de Anilina , Apoptosis , Ratones Endogámicos C57BL , Ovario , Sulfonamidas , Animales , Femenino , Ratones , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patología , Sulfonamidas/farmacología , Envejecimiento/efectos de los fármacos , Compuestos de Anilina/farmacología , Apoptosis/efectos de los fármacos , Senoterapéuticos/farmacología , Proliferación Celular/efectos de los fármacos , Reserva Ovárica/efectos de los fármacos , Ciclo Estral/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Células del Estroma/metabolismo , Células del Estroma/efectos de los fármacosRESUMEN
Osteoarthritis and sports injuries often lead to cartilage defects. How to promote its repair and rebuild the smooth cartilage surface has been a hot spot of research in recent years. Kartogenin (KGN), a small molecule discovered in recent years, has been shown to promote the proliferation and chondrogenic differentiation of mesenchymal stem cells (MSCs). As more and more studies have been conducted on KGN, its mechanism of action has been gradually revealed. However, KGN is insoluble in water and therefore easily removed by body fluids. In order to address such issues, a number of systems for efficient intra-articular delivery of KGN have been developed. In addition, due to the complex pathology of cartilage repair, KGN is often used in combination with other drugs to target different stages. In addition, with the rapid development of tissue engineering, scholars have combined KGN with various scaffolds by physical or chemical methods. In this paper, we firstly introduce the general properties of KGN followed by a review of the latest advances in the intra-articular delivery modes of KGN. Finally, we discuss the prospects for the application of KGN in cartilage regeneration, which is aimed at providing a new idea and target for the treatment of cartilage defects.
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We investigated the light-absorption properties of brown carbon (BrC) as part of the Georgia Wildland-Fire Simulation Experiment. We constructed fuel beds representative of three ecoregions in the Southeastern U.S. and varied the fuel-bed moisture content to simulate either prescribed fires or drought-induced wildfires. Based on decreasing fire radiative energy normalized by fuel-bed mass loading (FREnorm), the combustion conditions were grouped into wildfire (Wild), prescribed fire (Rx), and wildfire involving duff ignition (WildDuff). The emitted BrC ranged from weakly absorbing (WildDuff) to moderately absorbing (Rx and Wild) with the imaginary part of the refractive index (k) values that were well-correlated with FREnorm. We apportioned the BrC into water-soluble (WSBrC) and water-insoluble (WIBrC). Approximately half of the WSBrC molecules detected using electrospray-ionization mass spectrometry were potential chromophores. Nevertheless, k of WSBrC was an order of magnitude smaller than k of WIBrC. Furthermore, k of WIBrC was well-correlated with FREnorm while k of WSBrC was not, suggesting different formation pathways between WIBrC and WSBrC. Overall, the results signify the importance of combustion conditions in determining BrC light-absorption properties and indicate that variables in wildland fires, such as moisture content and fuel-bed composition, impact BrC light-absorption properties to the extent that they influence combustion conditions.
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Gaudichaudione H (GH) is a natural small molecular compound isolated from Garcinia oligantha Merr. (Clusiaceae). Being an uncommon rare caged polyprenylated xanthone, the potential pharmacological functions of GH remain to be fully elucidated currently. In this study, we primarily focused on identifying potential bioavailable targets and elucidating related therapeutic actions. Herein, the network pharmacology analysis, metabolomics analysis and genome-wide mRNA transcription assay were performed firstly to predict the major pharmacological action and potential targets of GH. To confirm the hypothesis, gene knockout model was created using CRISPR/Cas9 method. The pharmacological action of GH was evaluated in vitro and in vivo. Firstly, our results of network pharmacology analysis and omics assay indicated that GH significantly activated NRF2 signaling pathway, and the function could be associated with liver disease treatment. Then, the pharmacological action of GH was evaluated in vitro and in vivo. The treatment with GH significantly increased the protein levels of NRF2 and promoted the transcription of NRF2 downstream genes. Further analysis suggested that GH regulated NRF2 through an autophagy-mediated non-canonical mechanism. Additionally, the administration of GH effectively protected the liver from carbon tetrachloride (CCl4)-induced liver fibrosis and inflammation, which depended on the activation of NRF2 in hepatic stellate cells and inflammatory cells respectively. Collectively, our findings underscore the potential therapeutic effect of GH on alleviating hepatic fibrosis and inflammation through the augmentation of NRF2 signaling pathway, providing a promising avenue for the treatment of liver fibrosis and inflammation in clinical settings.
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A Bayesian optimisation algorithm for deep learning crystal structure prediction software (CBD-GM) is used to predict the structures of Cu(I) and Cu(II) oxides of 2D and 3D materials. Two known 2D structures and two known 3D structures were anticipated, in addition to the prediction of 5 novel structures. All nine structures were optimised and analysed using density-functional theory (DFT). Firstly, DFT calculations using the PBE functional indicate that the structures should be thermodynamically and dynamically stable. Secondly, we calculated the elastic constants using the "stress-strain" method, and the predicted Young's modulus and Poisson's ratios of the materials suggest that they all should have excellent ductile mechanical properties. Calculations of the band structure of the materials performed using the Heyd-Scuseria-Ernzerhof (HSE) hybrid functional indicate that some of the materials should be semiconductors with useful bandgaps. The results therefore provide inspiration for the synthesis of new copper oxides for industrial applications.