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BACKGROUND AND AIMS: Valve interstitial cells (VICs) undergo a transition to intermediate state cells before ultimately transforming into the osteogenic cell population, which is a pivotal cellular process in calcific aortic valve disease (CAVD). Herein, this study successfully delineated the stages of VIC osteogenic transformation and elucidated a novel key regulatory role of lumican (LUM) in this process. METHODS: Single-cell RNA-sequencing (scRNA-seq) from nine human aortic valves was used to characterize the pathological switch process and identify key regulatory factors. The in vitro, ex vivo, in vivo, and double knockout mice were constructed to further unravel the calcification-promoting effect of LUM. Moreover, the multi-omic approaches were employed to analyse the molecular mechanism of LUM in CAVD. RESULTS: ScRNA-seq successfully delineated the process of VIC pathological transformation and highlighted the significance of LUM as a novel molecule in this process. The pro-calcification role of LUM is confirmed on the in vitro, ex vivo, in vivo level, and ApoE-/-//LUM-/- double knockout mice. The LUM induces osteogenesis in VICs via activation of inflammatory pathways and augmentation of cellular glycolysis, resulting in the accumulation of lactate. Subsequent investigation has unveiled a novel LUM driving histone modification, lactylation, which plays a role in facilitating valve calcification. More importantly, this study has identified two specific sites of histone lactylation, namely, H3K14la and H3K9la, which have been found to facilitate the process of calcification. The confirmation of these modification sites' association with the expression of calcific genes Runx2 and BMP2 has been achieved through ChIP-PCR analysis. CONCLUSIONS: The study presents novel findings, being the first to establish the involvement of lumican in mediating H3 histone lactylation, thus facilitating the development of aortic valve calcification. Consequently, lumican would be a promising therapeutic target for intervention in the treatment of CAVD.
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Noble metallic aerogels with the self-supported hierarchical structure and remarkable activity are promising for methanol fuel cells, but are limited by the severe poisoning and degradation of active sites during electrocatalysis. Herein, the highly stable electrocatalyst of N-doped carbon dots-PtNi (NCDs-PtNi) aerogels is proposed by confining NCDs with alloyed PtNi for methanol oxidation and oxygen reduction reactions. Comprehensive electrocatalytic measurements and theoretical investigations suggest the improvement in structure stability and regulation in electronic structure for better electrocatalytic durability when confining NCDs with PtNi aerogels. Notably, the NCDs-PtNi aerogels perform 12-fold higher activity than that of Pt/C and maintain 52% of their initial activity after 5000 cycles toward acidic methanol oxidation. The enhanced stability and activity of NCDs-PtNi aerogels are also evident for oxygen reduction reactions in different electrolytes. These results highlight the effectiveness of stabilizing metallic aerogels with NCDs, offering a feasible pathway to develop robust electrocatalysts for fuel cells.
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Heterogenizing the molecular catalysts on conductive scaffolds to achieve the isolated molecular dispersion and expected coordination structures is significant yet still challenging. Herein, a sulfur-driving strategy to anchor monodispersed cobalt phthalocyanine on nitrogen and sulfur co-doped graphene (NSG-CoPc) is demonstrated. Experimental and theoretical analysis prove that the incorporation of S dramatically improves the adsorption capability of NSG and evokes the monodispersion of the CoPc molecule, promoting the axial CoâN coordination and the electron delocalization of the Co catalytic center. Benefiting from the reduced activation energy barrier and boosted electron transfer, as well as the maximized active site utilization, NSG-CoPc exhibits outstanding H2O2 oxidization and sensing performance (used as a representative reaction). Moreover, the usage of NSG as a substrate can be readily extended to other metal (Ni, Cu, and Fe) phthalocyanine molecules with molecular-level dispersion. This work clarifies the mechanism of heteroatoms decoration and provides a new paradigm in devising monodispersed molecular catalysts with modulated chemical surroundings for broad applications.
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Targeting the homeostasis of anions and iron has emerged as a promising therapeutic approach for the treatment of cancers. However, single-targeted agents often fall short of achieving optimal treatment efficacy. Herein we designed and synthesized a series of novel dual-functional squaramide-hydroxamic acid conjugates that are capable of synergistically modulating the homeostasis of anions and iron. Among them, compound 16 exhibited the most potent antiproliferative activity against a panel of selected cancer cell lines, and strong in vivo anti-tumor efficacy. This compound effectively elevated lysosomal pH through anion transport, and reduced the levels of intracellular iron. Compound 16 could disturb autophagy in A549 cells and trigger robust apoptosis. This compound caused cell cycle arrest at the G1/S phase, altered the mitochondrial function and elevated ROS levels. The present findings clearly demonstrated that synergistic modulation of anion and iron homeostasis has high potentials in the development of promising chemotherapeutic agents with dual action against cancers.
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Antineoplásicos , Apoptosis , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Homeostasis , Ácidos Hidroxámicos , Hierro , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Hierro/metabolismo , Hierro/química , Proliferación Celular/efectos de los fármacos , Homeostasis/efectos de los fármacos , Relación Estructura-Actividad , Ácidos Hidroxámicos/farmacología , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/síntesis química , Estructura Molecular , Apoptosis/efectos de los fármacos , Aniones/química , Aniones/farmacología , Relación Dosis-Respuesta a Droga , Animales , Línea Celular Tumoral , Ratones , Quinina/análogos & derivadosRESUMEN
IgA nephropathy (IgAN) is the most common glomerulonephritis, characterized by the presence of predominant IgA deposits in the mesangium. Deposition of pathogenic IgA in kidney tissue is a fundamental initiating process that has not been fully studied. Here, we employed optical imaging to directly visualize kidney deposition of IgA with optimized spatial and temporal resolution in BALB/c nude mice. Real-time fluorescence imaging revealed that IgA isolated from patients with IgAN preferentially accumulated in the kidneys, compared with IgA purified from healthy individuals. There was no difference in the distribution of either IgA preparation by the liver. Photoacoustic computed tomography dynamically demonstrated and quantified the enhanced retention of pathological IgA in the kidney cortex. Photoacoustic microscopy tracked IgA deposition in the glomeruli with a resolution down to three microns in a mouse model. Notably, longitudinal fluorescent imaging revealed that galactose-deficient IgA (Gd-IgA), which was elevated in the circulation of patients with IgAN, persisted in the kidney for longer than two weeks, and stable deposition of Gd-IgA induced kidney impairment, including albuminuria and mesangial proliferation. Thus, our study highlights that the aberrant kidney depositional kinetics of Gd-IgA is involved in the pathogenesis of IgAN. Hence, cross-scale optical imaging has potential applications in assessing immune-mediated kidney diseases and uncovering underlying mechanisms of disease.
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Glomerulonefritis por IGA , Animales , Ratones , Glomerulonefritis por IGA/diagnóstico por imagen , Glomerulonefritis por IGA/patología , Galactosa , Ratones Desnudos , Inmunoglobulina A , Imagen ÓpticaRESUMEN
The overactivation of canonical Wnt/ß-catenin pathway is one of the main cascades for the initiation, progression, and recurrence of most human malignancies. As an indispensable coreceptor for the signaling transduction of the canonical Wnt/ß-catenin pathway, LRP5 is up-regulated and exerts a carcinogenic role in most types of cancer. However, its expression level and role in gastric cancer (GC) has not been clearly elucidated. The current work showed that LRP5 was overexpressed in GC tissues and the expression of LRP5 was positively associated with the advanced clinical stages and poor prognosis. Ectopic expression of LRP5 enhanced the proliferation, invasiveness, and drug resistance of GC cells in vitro, and accelerated the tumor growth in nude mice, through activating the canonical Wnt/ß-catenin signaling pathway and up-regulating aerobic glycolysis, thus increasing the energy supply for GC cells. Additionally, the expression of LRP5 and glycolysis-related genes showed an obviously positive correlation in GC tissues. By contrast, the exact opposite results were observed when the endogenous LRP5 was silenced in GC cells. Collectively, these results not only reveal the carcinogenic role of LRP5 during GC development through activating the canonical Wnt/ß-catenin and glycolysis pathways, but also provide a valuable candidate for the diagnosis and treatment of human GC.
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Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad , Neoplasias Gástricas , Vía de Señalización Wnt , Animales , Carcinogénesis , Línea Celular Tumoral , Proliferación Celular/genética , Glucólisis , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Ratones , Ratones Desnudos , Neoplasias Gástricas/patología , beta Catenina/metabolismoRESUMEN
INTRODUCTION AND OBJECTIVES: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). MATERIALS AND METHODS: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. RESULTS: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary ß2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. CONCLUSIONS: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.
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Hepatitis B Crónica , Humanos , Adulto , Tenofovir/efectos adversos , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Estudios Retrospectivos , Alanina/uso terapéutico , Adenina/uso terapéutico , Riñón/fisiología , Antivirales/efectos adversos , Resultado del TratamientoRESUMEN
Atractylodin (ATL) has been reported to exert anti-inflammatory effects. Osteogenic changes induced by inflammation in valve interstitial cells (VICs) play a key role in the development of calcified aortic valve disease (CAVD). This study aimed to investigate the anti-calcification effects of ATL on aortic valves. Human VICs (hVICs) were exposed to osteogenic induction medium (OM) containing ATL to investigate cell viability, osteogenic gene and protein expression, and anti-calcification effects. Gas chromatography-mass spectroscopy (GC-MS) metabolomics analysis was used to detect changes in the metabolites of hVICs stimulated with OM before and after ATL administration. The compound-reaction-enzyme-gene network was used to identify drug targets. Gene interference was used to verify the targets. ApoE-/- mice fed a high-fat (HF) diet were used to evaluate the inhibition of aortic valve calcification by ATL. Treatment with 20 µM ATL in OM prevented calcified nodule accumulation and decreases in the gene and protein expression levels of ALP, RUNX2, and IL-1ß. Differential metabolite analysis showed that D-mannose was highly associated with the anti-calcification effect of ATL. The addition of D-mannose prevented calcified nodule accumulation and inhibited succinate-mediated HIF-1α activation and IL-1ß production. The target of ATL was identified as GLA. Silencing of the GLA gene (si-GLA) reversed the anti-osteogenic differentiation of ATL. In vivo, ATL ameliorated aortic valve calcification by preventing decreases in GLA expression and the up-regulation of IL-1ß expression synchronously. In conclusion, ATL is a potential drug for the treatment of CAVD by targeting GLA to regulate D-mannose metabolism, thereby inhibiting succinate-mediated HIF-1α activation and IL-1ß production.
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Válvula Aórtica , Manosa , Humanos , Ratones , Animales , Manosa/metabolismo , Manosa/farmacología , Ratones Noqueados para ApoE , Diferenciación Celular/genética , Células Cultivadas , OsteogénesisRESUMEN
Atractylenolide-1 (AT-1) is a major octanol alkaloid isolated from Atractylodes Rhizoma and is widely used to treat various diseases. However, few reports have addressed the anticancer potential of AT-1, and the underlying molecular mechanisms of its anticancer effects are unclear. This study aimed to assess the effect of AT-1 on triple-negative breast cancer (TNBC) cell proliferation and migration and explore its potential molecular mechanisms. Cell invasion assays confirmed that the number of migrating cells decreased after AT-1 treatment. Colony formation assays showed that AT-1 treatment impaired the ability of MDA-MB-231 cells to form colonies. AT-1 inhibited the expression of p-p38, p-ERK, and p-AKT in MDA-MB-231 cells, significantly downregulated the proliferation of anti-apoptosis-related proteins CDK1, CCND1, and Bcl2, and up-regulated pro-apoptotic proteins Bak, caspase 3, and caspase 9. The gas chromatography-mass spectroscopy results showed that AT-1 downregulated the metabolism-related genes TPI1 and GPI through the glycolysis/gluconeogenesis pathway and inhibited tumor growth in vivo. AT-1 affected glycolysis/gluconeogenesis by downregulating the expression of TPI1 and GPI, inhibiting the proliferation, migration, and invasion of (TNBC) MDA-MB-231 cells and suppressing tumor growth in vivo.
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Antineoplásicos , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Línea Celular Tumoral , Gluconeogénesis , Antineoplásicos/farmacología , Proliferación Celular , Movimiento CelularRESUMEN
In the process of discovering more neural-system-related bioactive compounds from Xylaria nigripes, xylariamino acid A (1), a new amino acid derivative, and a new isovaleric acid phenethyl ester (2) were isolated and identified. Their structures and absolute configurations were determined by analyses of IR, HRESIMS, NMR spectroscopic data, and gauge-independent atomic orbital (GIAO) NMR calculation, as well as electronic circular dichroism (ECD) calculation. The isolated compounds were evaluated for their neuroprotective effects against damage to PC12 cells by oxygen and glucose deprivation (OGD). Compounds 1 and 2 can increase the viability of OGD-induced PC12 cells at all tested concentrations. Moreover, compound 2 (1 µmol L-1) can significantly reduce the percentage of apoptotic cells.
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Ascomicetos , Xylariales , Animales , Ratas , Xylariales/química , Células PC12 , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
The overactivation of canonical Wnt/ß-catenin pathway and the maintenance of cancer stem cells (CSCs) are essential for the onset and malignant progression of most human cancers. However, their regulatory mechanism in colorectal cancer (CRC) has not yet been well demonstrated. Low-density lipoprotein receptor-related protein 5 (LRP5) has been identified as an indispensable co-receptor with frizzled family members for the canonical Wnt/ß-catenin signal transduction. Herein, we show that activation of LRP5 gene promotes CSCs-like phenotypes, including tumorigenicity and drug resistance in CRC cells, through activating the canonical Wnt/ß-catenin and IL-6/STAT3 signalling pathways. Clinically, the expression of LRP5 is upregulated in human CRC tissues and closely associated with clinical stages of patients with CRC. Further analysis showed silencing of endogenous LRP5 gene is sufficient to suppress the CSCs-like phenotypes of CRC through inhibiting these two pathways. In conclusion, our findings not only reveal a regulatory cross-talk between canonical Wnt/ß-catenin signalling pathway, IL-6/STAT3 signalling pathway and CD133-related stemness that promote the malignant behaviour of CRC, but also provide a valuable target for the diagnosis and treatment of CRC.
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Neoplasias Colorrectales , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/genética , Humanos , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Células Madre Neoplásicas/metabolismo , Fenotipo , Vía de Señalización Wnt/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
Post treatment of metal-organic frameworks (MOFs) is widely employed to develop efficient electrocatalysts with better catalytic properties. But the complex processes of post treatment generally led to the collapse of the original structures of MOFs, making the preservation of their pristine hierarchical porous structure a great challenge. Herein, we propose the strategy of alkali treatment of Ni-MOF to transform it into Ni(OH)2 with similar morphology and enhanced electrocatalytic properties for methanol oxidation reaction (MOR). The structure and electrocatalytic properties of as-obtained Ni(OH)2 nanostructured flowers were seriously depended on the alkali concentrations. As the result, Ni(OH)2 obtained from Ni-MOF treated by 0.25â M NaOH (noted as Ni(OH)2 -0.25) performs 1.5 and 2.5 times larger current density than those of Ni(OH)2 -0.025 and Ni(OH)2 -0.5 for MOR. Moreover, the electrocatalytic process and mechanism of MOR on the catalyst of Ni(OH)2 -0.25 are also revealed. Hence, this ex situ conversion strategy of alkali treatment for Ni-MOF uncovered the transformation of MOFs in alkaline solution and develops robust electrocatalyst for practical application of methanol fuel cells.
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DNA nanotechnology plays an increasingly important role in the biomedical field; however, its application in the design of organic nanomaterials is underexplored. Herein, we report the use of DNA nanotechnology to transport a NIR-II-emitting nanofluorophore across the blood-brain barrier (BBB), facilitating non-invasive imaging of brain tumors. Specifically, the DNA block copolymer, PS-b-DNA, is synthesized through a solid-phase click reaction. We demonstrate that its self-assembled structure shows exceptional cluster effects, among which BBB-crossing is the most notable. Therefore, PS-b-DNA is utilized as an amphiphilic matrix to fabricate a NIR-II nanofluorephore, which is applied in inâ vivo bioimaging. Accordingly, the NIR-II fluorescence signal of the DNA-based nanofluorophore localized at a glioblastoma is 3.8-fold higher than the NIR-II fluorescence signal of the PEG-based counterpart. The notably increased imaging resolution will significantly benefit the further diagnosis and therapy of brain tumors.
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Barrera Hematoencefálica/metabolismo , Colorantes/metabolismo , ADN/química , ADN/metabolismo , Rayos Infrarrojos , Transporte Biológico , Línea Celular , Humanos , Imagen MolecularRESUMEN
Chronic hepatitis B (CHB) remains a major global public health problem. The functional cure is the ideal therapeutic target recommended by the latest guidelines, and pursuing a functional cure has become the key treatment end point of current therapy and for upcoming clinical trials. In this review, based on the latest published clinical research evidence, we analyzed the concept and connotation of clinical cures and elaborated on the benefits of clinical cures in detail. Secondly, we have summarized various potential treatment methods for achieving clinical cures, especially elaborating on the latest research progress of interferon-based optimized treatment strategies in achieving clinical cures. We also analyzed which populations can achieve clinical cures and conducted a detailed analysis of relevant virological and serological markers in screening clinical cure advantage populations and predicting clinical cure achievement. In addition, we also introduced the difficulties that may be encountered in the current pursuit of achieving a clinical cure.
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Antivirales , Hepatitis B Crónica , Interferones , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Interferones/uso terapéutico , Resultado del Tratamiento , Medicina Basada en la Evidencia/métodos , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/inmunología , Quimioterapia CombinadaRESUMEN
Nitric oxide (NO) plays an essential role in regulating various physiological and pathological processes. This has spurred various efforts to develop feasible methods for the detection of NO. Herein we designed and synthesized a novel donor-acceptor fluorescent probe Car-NO for the selective and specific detection of NO. Reaction of Car-NO with NO generated a new donor-acceptor structure with strong intramolecular charge transfer (ICT) effect, and led to remarkable chromogenic change from yellow to blue and dramatic fluorescence quenching. Car-NO exhibited high selectivity, excellent sensitivity, and rapid response for the detection of NO. In addition, the nanoparticles prepared from Car-NO (i.e., Car-NO NPs) showed strong NIR emission and high selectivity/sensitivity. Car-NO NPs was successfully employed to image both endogenous and exogenous NO in HeLa and RAW 264.7 cells. The present findings reveal that Car-NO is a promising probe for the detection and bioimaging of NO.
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Colorantes Fluorescentes , Óxido Nítrico , Ratones , Animales , Humanos , Colorantes Fluorescentes/toxicidad , Colorantes Fluorescentes/química , Células HeLa , Fluorescencia , Células RAW 264.7RESUMEN
Using traditional Chinese medicine residues as raw materials, different biochars (BC) were prepared through oxygen-limited pyrolysis at 300 °C, 500 °C, and 700 °C, and BC was ball-milled to produce ball-milled biochar (BMC). Using these adsorbents to adsorb the allelopathic autotoxic substance quercetin. The physical and chemical properties of various biochars derived from traditional Chinese medicine residues were characterized using the Brunauer-Emmett-Teller-N2 surface areas (BET), scanning electron microscopy (SEM), Fourier transform IR spectroscopy (FTIR), X-ray diffraction (XRD), and Raman spectroscopy (Raman). The study investigated the effects of the initial pH value, different humic acid concentrations, and multiple adsorption-desorption experiments on the removal of quercetin from the solution. The article discusses the adsorption mechanism of quercetin in solution by biochar from a traditional Chinese medicine residue, based on the results of adsorption kinetics and adsorption isotherm fitting. The findings indicate that increasing the pyrolysis temperature reduces the oxygen-containing functional groups of BC, enhances the aromaticity, and stabilizes the carbon structure. The pore structure of BMC becomes more complex after ball milling, which increases the number of oxygen-containing functional groups on the surface. Among the samples tested, BMC700 exhibits the best adsorption performance, with an adsorption capacity of 293.3 mg·g-1 at 318 K. The adsorption process of quercetin by BMC700 follows the pseudo-second-order kinetic model and the Freundlich adsorption isotherm model. The process is primarily a form of multimolecular layer adsorption. Its mechanism involves the pore-filling effect, hydrogen-bonding interaction, electrostatic interaction, and π-π coexistence, as well as the yoke effect. Additionally, they are highly recyclable and show promise in addressing continuous cropping issues.
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Given a graph G, the network collapse problem (NCP) selects a vertex subset S of minimum cardinality from G such that the difference in the values of a given measure function f(G)-f(G∖S) is greater than a predefined collapse threshold. Many graph analytic applications can be formulated as NCPs with different measure functions, which often pose a significant challenge due to their NP-hard nature. As a result, traditional greedy algorithms, which select the vertex with the highest reward at each step, may not effectively find the optimal solution. In addition, existing learning-based algorithms do not have the ability to model the sequence of actions taken during the decision-making process, making it difficult to capture the combinatorial effect of selected vertices on the final solution. This limits the performance of learning-based approaches in non-submodular NCPs. To address these limitations, we propose a unified framework called DT-NC, which adapts the Decision Transformer to the Network Collapse problems. DT-NC takes into account the historical actions taken during the decision-making process and effectively captures the combinatorial effect of selected vertices. The ability of DT-NC to model the dependency among selected vertices allows it to address the difficulties caused by the non-submodular property of measure functions in some NCPs effectively. Through extensive experiments on various NCPs and graphs of different sizes, we demonstrate that DT-NC outperforms the state-of-the-art methods and exhibits excellent transferability and generalizability.
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Algoritmos , Redes Neurales de la Computación , Toma de Decisiones/fisiología , HumanosRESUMEN
Atmospheric fine particulate matter (PM2.5) can trigger the production of cytotoxic reactive oxygen species (ROS), which can trigger or exacerbate oxidative stress and pulmonary inflammation. We collected 111 daily (â¼24 h) ambient PM2.5 samples within an urban region of North China during four seasons of 2019-2020. PM2.5 samples were examined for carbonaceous components, water-soluble ions, and elements, together with their oxidative potential (represent ROS-producing ability) by DTT assay. The seasonal peak DTTv was recorded in winter (2.86 ± 1.26 nmol min-1 m-3), whereas the DTTm was the highest in summer (40.6 ± 8.7 pmol min-1 µg-1). WSOC displayed the highest correlation with DTT activity (r = 0.84, p < 0.0001), but the influence of WSOC on the elevation of DTTv was extremely negligible. Combustion source exhibited the most significant and robust correlation with the elevation of DTTv according to the linear mixed-effects model result. Source identification investigation using positive matrix factorization displayed that combustion source (36.2%), traffic source (30.7%), secondary aerosol (15.7%), and dust (14.1%) were driving the DTTv, which were similar to the results from the multiple linear regression (MLR) analysis. Backward trajectory analysis revealed that the major air masses originate from local and regional transportation, but PM2.5 OP was more susceptible to the influence of short-distance transport clusters. Discerning the influence of chemicals on health-pertinent attributes of PM2.5, such as OP, could facilitate a deep understanding of the cause-and-effect relationship between PM2.5 and impacts.
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A pair of new chromone derivative enantiomers, (+)-xylarichromone A (1a) and (-)-xylarichromone A (1b), were isolated from the solid fermentation of Xylaria nigripes. The planar structure of 1 was determined by extensive NMR spectroscopic data, and its absolute configuration was assigned by comparison the ECD spectra with the known chromone derivatives. Compound 1 was the first chromone derivative reported from this medicinal fungus. The neuroprotective effects of 1 against oxygen and glucose deprivation (OGD) induced pheochromocytoma-12 cells (PC12) injury was investigated.
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Ascomicetos , Cromonas , Cromonas/farmacología , Cromonas/química , Estructura Molecular , Espectroscopía de Resonancia MagnéticaRESUMEN
Hybrid crops often exhibit increased yield and greater resilience, yet the genomic mechanism(s) underlying hybrid vigor or heterosis remain unclear, hindering our ability to predict the expression of phenotypic traits in hybrid breeding. Here, we generated haplotype-resolved T2T genome assemblies of two pear hybrid varieties, 'Yuluxiang' (YLX) and 'Hongxiangsu' (HXS), which share the same maternal parent but differ in their paternal parents. We then used these assemblies to explore the genome-scale landscape of allele-specific expression (ASE) and create a pangenome graph for pear. ASE was observed for close to 6000 genes in both hybrid cultivars. A subset of ASE genes related to aspects of fruit quality such as sugars, organic acids, and cuticular wax were identified, suggesting their important contributions to heterosis. Specifically, Ma1, a gene regulating fruit acidity, is absent in the paternal haplotypes of HXS and YLX. A pangenome graph was built based on our assemblies and seven published pear genomes. Resequencing data for 139 cultivated pear genotypes (including 97 genotypes sequenced here) were subsequently aligned to the pangenome graph, revealing numerous structural variant hotspots and selective sweeps during pear diversification. As predicted, the Ma1 allele was found to be absent in varieties with low organic acid content, and this association was functionally validated by Ma1 overexpression in pear fruit and calli. Overall, these results reveal the contributions of ASE to fruit-quality heterosis and provide a robust pangenome reference for high-resolution allele discovery and association mapping.