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1.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38261339

RESUMEN

Various methods have been proposed to reconstruct admixture histories by analyzing the length of ancestral chromosomal tracts, such as estimating the admixture time and number of admixture events. However, available methods do not explicitly consider the complex admixture structure, which characterizes the joining and mixing patterns of different ancestral populations during the admixture process, and instead assume a simplified one-by-one sequential admixture model. In this study, we proposed a novel approach that considers the non-sequential admixture structure to reconstruct admixture histories. Specifically, we introduced a hierarchical admixture model that incorporated four ancestral populations and developed a new method, called HierarchyMix, which uses the length of ancestral tracts and the number of ancestry switches along genomes to reconstruct the four-way admixture history. By automatically selecting the optimal admixture model using the Bayesian information criterion principles, HierarchyMix effectively estimates the corresponding admixture parameters. Simulation studies confirmed the effectiveness and robustness of HierarchyMix. We also applied HierarchyMix to Uyghurs and Kazakhs, enabling us to reconstruct the admixture histories of Central Asians. Our results highlight the importance of considering complex admixture structures and demonstrate that HierarchyMix is a useful tool for analyzing complex admixture events.


Asunto(s)
Pueblo de Asia Central , Genética de Población , Humanos , Teorema de Bayes , Pueblo de Asia Central/genética , Simulación por Computador , Cromosomas/genética , Genética de Población/métodos
2.
Plant Physiol ; 194(3): 1498-1511, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-37956105

RESUMEN

Drought and heat stresses usually occur concomitantly in nature, with increasing frequency and intensity of both stresses expected due to climate change. The synergistic agricultural impacts of these compound climate extremes are much greater than those of the individual stresses. However, the mechanisms by which drought and heat stresses separately and concomitantly affect dynamic photosynthesis have not been thoroughly assessed. To elucidate this, we used tomato (Solanum lycopersicum) seedlings to measure dynamic photosynthesis under individual and compound stresses of drought and heat. Individual drought and heat stresses limited dynamic photosynthesis at the stages of diffusional conductance to CO2 and biochemistry, respectively. However, the primary limiting factor for photosynthesis shifted to mesophyll conductance under the compound stresses. Compared with the control, photosynthetic carbon gain in fluctuating light decreased by 38%, 73%, and 114% under the individual drought, heat, and compound stresses, respectively. Therefore, compound stresses caused a greater reduction in photosynthetic carbon gain in fluctuating light conditions than individual stress. These findings highlight the importance of mitigating the effects of compound climate extremes on crop productivity by targeting mesophyll conductance and improving dynamic photosynthesis.


Asunto(s)
Sequías , Solanum lycopersicum , Agricultura , Carbono , Cambio Climático , Fotosíntesis
3.
Chem Rev ; 123(1): 1-30, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36342422

RESUMEN

The functions of interfacial synergy in heterojunction catalysts are diverse and powerful, providing a route to solve many difficulties in energy conversion and organic synthesis. Among heterojunction-based catalysts, the Mott-Schottky catalysts composed of a metal-semiconductor heterojunction with predictable and designable interfacial synergy are rising stars of next-generation catalysts. We review the concept of Mott-Schottky catalysts and discuss their applications in various realms of catalysis. In particular, the design of a Mott-Schottky catalyst provides a feasible strategy to boost energy conversion and chemical synthesis processes, even allowing realization of novel catalytic functions such as enhanced redox activity, Lewis acid-base pairs, and electron donor-acceptor couples for dealing with the current problems in catalysis for energy conversion and storage. This review focuses on the synthesis, assembly, and characterization of Schottky heterojunctions for photocatalysis, electrocatalysis, and organic synthesis. The proposed design principles, including the importance of constructing stable and clean interfaces, tuning work function differences, and preparing exposable interfacial structures for designing electronic interfaces, will provide a reference for the development of all heterojunction-type catalysts, electrodes, energy conversion/storage devices, and even super absorbers, which are currently topics of interest in fields such as electrocatalysis, fuel cells, CO2 reduction, and wastewater treatment.

4.
Nano Lett ; 24(15): 4691-4701, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38588212

RESUMEN

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.


Asunto(s)
Neoplasias , Microambiente Tumoral , Humanos , Inmunoterapia , Radioinmunoterapia , Glucosa , Glucosa Oxidasa , Inmunosupresores , Ácido Láctico , Neoplasias/terapia , Línea Celular Tumoral
5.
Plant Mol Biol ; 114(3): 36, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38598012

RESUMEN

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.


Asunto(s)
Arabidopsis , MicroARNs , ARN Largo no Codificante , ARN Endógeno Competitivo , ARN Largo no Codificante/genética , Ácido Abscísico/farmacología , Arabidopsis/genética , Manitol , MicroARNs/genética , ARN Mensajero , Triticum/genética , Ceras
6.
Anal Chem ; 96(22): 9026-9033, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38771095

RESUMEN

Precise detection of a trace substance that intrinsically possesses weak chemical activity and less-distinctive spatial structure is of great significance, but full of challenges, as it could not be effectively recognized via either an active covalent reaction process or multiple noncovalent interactions toward its simple structure. Here, the electronic-effect-driven recognition strategy was proposed to visually sense an illicit drug, γ-hydroxybutyric acid (GHB), which was treated as an analyte model due to its inherent simple structure. In particular, a sensing system composed of two probes substituted by the nitro (-NO2) and the hydrogen (-H), was constructed with the characteristic yellow coloring and blue fluorescence, as well as high sensitivity (0.586 ng/mL), fast response (0.2 s), and specific recognition, even in the presence of 22 interferents. In addition, a portable eyeshadow box-like sensing chip was fabricated and proven to be reliable and feasible in sensing GHB disguised in liquors for self-protection in a covert manner. Hence, this work developed an electronic-effect-driven modulation strategy of the recognition interaction between the probe and the analyte and, thus, would open up a new thought for detecting the analyte with weak activity and a simple structure, as well as propel the relevant application in real scenarios.

7.
Small ; : e2401024, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38597755

RESUMEN

Exposing different facets on metal-organic frameworks (MOFs) is highly desirable to enhance the performance for various applications, however, exploiting a concise and effective approach to achieve facet-controlled synthesis of MOFs remains challenging. Here, by modulating the ratio of metal precursors to ligands, the facet-engineered iron-based MOFs (Fe-MOFs) exhibits enhanced catalytic activity for Fenton reaction are explored, and the mechanism of facet-dependent performance is revealed in detail. Fully exposed (101) and (100) facets on spindle-shaped Fe-MOFs enable rapid oxidation of colorless o-phenylenediamine (OPD) to colored products, thereby establishing a dual-mode platform for the detection of hydrogen peroxide (H2O2) and triacetone triperoxide (TATP). Thus, a detection limit as low as 2.06 nm is achieved, and robust selectivity against a wide range of common substances (>16 types) is obtained, which is further improved by incorporating a deep learning architecture with an SE-VGG16 network model, enabling precise differentiation of oxidizing agents from captured images. The present strategy is expected will shine light on both the rational synthesis of nanomaterials with modulated morphologies and the exploitation of high-performance trace chemical sensors.

8.
J Transl Med ; 22(1): 173, 2024 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-38369516

RESUMEN

Lung cancer, a prevalent and aggressive disease, is characterized by recurrence and drug resistance. It is essential to comprehend the fundamental processes and discover novel therapeutic objectives for augmenting treatment results. Based on our research findings, we have identified a correlation between methylation of cg09897064 and decreased expression of ZBP1, indicating a link to unfavorable prognosis in patients with lung cancer. Furthermore, these factors play a role in macrophage polarization, with ZBP1 upregulated in M1 macrophages compared to both M0 and M2 polarized macrophages. We observed cg09897064 methylation in M2 polarization, but not in M0 and M1 polarized macrophages. ATACseq analysis revealed closed chromatin accessibility of ZBP1 in M0 polarized macrophages, while open accessibility was observed in both M1 and M2 polarized macrophages. Our findings suggest that ZBP1 is downregulated in M0 polarized macrophages due to closed chromatin accessibility and downregulated in M2 polarized macrophages due to cg09897064 methylation. Further investigations manipulating cg09897064 methylation and ZBP1 expression through overexpression plasmids and shRNAs provided evidence for their role in modulating macrophage polarization and tumor growth. ZBP1 inhibits M2 polarization and suppresses tumor growth, while cg09897064 methylation promotes M2 polarization and macrophage-induced tumor growth. In mechanism investigations, we found that cg09897064 methylation impairs CEBPA binding to the ZBP1 promoter, leading to decreased ZBP1 expression. Clinical experiments were conducted to validate the correlation between methylation at cg09897064, ZBP1 expression, and macrophage M2 polarization. Targeting these factors may hold promise as a strategy for developing innovative checkpoint inhibitors in lung cancer treatment.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Proteínas de Unión al ARN , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Cromatina/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Macrófagos/metabolismo , Metilación , Proteínas de Unión al ARN/genética
9.
Phys Rev Lett ; 132(15): 150603, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38682974

RESUMEN

Ground state preparation is classically intractable for general Hamiltonians. On quantum devices, shallow parametrized circuits can be effectively trained to obtain short-range entangled states under the paradigm of variational quantum eigensolver, while deep circuits are generally untrainable due to the barren plateau phenomenon. In this Letter, we give a general lower bound on the variance of circuit gradients for arbitrary quantum circuits composed of local 2-designs. Based on our unified framework, we prove the absence of barren plateaus in training finite local-depth circuits (FLDC) for the ground states of local Hamiltonians. FLDCs are allowed to be deep in the conventional circuit depth to generate long-range entangled ground states, such as topologically ordered states, but their local depths are finite, i.e., there is only a finite number of gates acting on individual qubits. This characteristic sets FLDC apart from shallow circuits: FLDC in general cannot be classically simulated to estimate local observables efficiently by existing tensor network methods in two and higher dimensions. We validate our analytical results with extensive numerical simulations and demonstrate the effectiveness of variational training using the generalized toric code model.

10.
Phys Rev Lett ; 132(24): 240402, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38949339

RESUMEN

In the context of measurement-induced entanglement phase transitions, the influence of quantum noises, which are inherent in real physical systems, is of great importance and experimental relevance. In this Letter, we present a comprehensive theoretical analysis of the effects of both temporally uncorrelated and correlated quantum noises on entanglement generation and information protection. This investigation reveals that entanglement within the system follows q^{-1/3} scaling for both types of quantum noises, where q represents the noise probability. The scaling arises from the Kardar-Parisi-Zhang fluctuation with effective length scale L_{eff}∼q^{-1}. More importantly, the information protection timescales of the steady states are explored and shown to follow q^{-1/2} and q^{-2/3} scaling for temporally uncorrelated and correlated noises, respectively. The former scaling can be interpreted as a Hayden-Preskill protocol, while the latter is a direct consequence of Kardar-Parisi-Zhang fluctuations. We conduct extensive numerical simulations using stabilizer formalism to support the theoretical understanding. This Letter not only contributes to a deeper understanding of the interplay between quantum noises and measurement-induced phase transition but also provides a new perspective to understand the effects of Markovian and non-Markovian noises on quantum computation.

11.
Chemistry ; 30(25): e202303989, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38345999

RESUMEN

Benzobicyclo[3.2.1]octane is a cage-like unique motif containing a bicyclo[3.2.1]octane structure fused with at least one benzene ring. It is found in various natural products that exhibit structural complexities and important biological activities. The total synthesis of natural products possessing this challenging structure has received considerable attention, and great advances have been made in this field during the past 15 years. This review summarizes thus far achieved chemical syntheses and synthetic studies of natural compounds featuring the benzobicyclo[3.2.1]octane core. It focuses on strategic approaches constructing the bridged structure, aiming to provide a useful reference for inspiring further advancements in strategies and total syntheses of natural products with such a framework.

12.
Chemistry ; 30(8): e202303519, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38018776

RESUMEN

Three unusual ajmaline-macroline type bisindole alkaloids, alsmaphylines A-C, together with their postulated biogenetic precursors, were isolated from the stem barks and leaves of Alstonia macrophylla via the building blocks-based molecular network (BBMN) strategy. Alsmaphyline A represents a rare ajmaline-macroline type bisindole alkaloid with an S-shape polycyclic ring system. Alsmaphylines B and C are two novel ajmaline-macroline type bisindole alkaloids with N-1-C-21' linkages, and the former possesses an unconventional stacked conformation due to the presence of intramolecular noncovalent interactions. The chemical structures including absolute configurations of alsmaphylines A-C were established by comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray crystallography. In addition, a plausible biosynthetic pathway of these bisindole alkaloids as well as their ability to promote the protein synthesis on HT22 cells were discussed.


Asunto(s)
Alcaloides , Alstonia , Oxindoles , Alstonia/química , Ajmalina , Alcaloides Indólicos/química , Estructura Molecular , Alcaloides/química
13.
Inorg Chem ; 63(20): 9288-9296, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38724469

RESUMEN

A novel 3D europium-based cationic framework (Eu-CMOF) has been constructed solvothermally by employing a viologen derivative as an organic functional building unit. Notably, Eu-CMOF demonstrates its capability as a proficient aqueous-phase ion-exchange host, facilitating the remarkable rapid chromatographic column separation of new coccine and malachite green (NC3-/MG+), as well as new coccine and methylene blue (NC3-/MLB+), in mere 2 to 4 min. Adsorption thermodynamics and kinetics of anionic dyes demonstrate that Eu-CMOF exhibits a higher adsorption capacity for NC3-, as evaluated by the Langmuir model, reaching a value of 173 mg·g-1. The pseudo-second-order rate constant is determined to be 3.84 × 10-3 mg-1·g·min-1. Additionally, Eu-CMOF displays reversible photochromic and amine- and ammonia-induced vapochromic behaviors. Further mechanistic studies reveal that these chromic behaviors are primarily attributed to the generation of free viologen radical stimulated by Xe-light or electron-rich amine/ammonia. This research contributes to the development of advanced materials with applications in rapid chromatographic separation and stimuli-responsive chromic properties, showcasing the potential of Eu-CMOF as a versatile platform for practical applications.

14.
Fish Shellfish Immunol ; 145: 109364, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199264

RESUMEN

Micropterus salmoides rhabdovirus (MSRV) is one of the main pathogens of largemouth bass, leading to serious economic losses. The G protein, as the only envelope protein present on the surface of MSRV virion, contains immune-related antigenic determinants, thereby becoming the primary target for the design of MSRV vaccines. Here, we displayed the G protein on the surface of yeast cells (named EBY100/pYD1-G) and conducted a preliminary assessment of the protective efficacy of the recombinant yeast vaccine. Upon oral vaccination, a robust immune response was observed in systemic and mucosal tissue. Remarkably, following the MSRV challenge, the relative percent survival of EBY100/pYD1-G treated largemouth bass significantly increased to 66.7 %. In addition, oral administration inhibited viral replication and alleviated the pathological symptoms of MSRV-infected largemouth bass. These results suggest that EBY100/pYD1-G could be used as a potential oral vaccine against MSRV infection.


Asunto(s)
Lubina , Enfermedades de los Peces , Rhabdoviridae , Animales , Saccharomyces cerevisiae , Vacunación , Proteínas Fúngicas , Vacunas Sintéticas
15.
J Chem Inf Model ; 64(9): 3640-3649, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38359459

RESUMEN

The accurate identification and analysis of chemical structures in molecular images are prerequisites of artificial intelligence for drug discovery. It is important to efficiently and automatically convert molecular images into machine-readable representations. Therefore, in this paper, we propose an automated molecular optical image recognition model based on deep learning, called Image2InChI. Additionally, the proposed Image2InChI introduces a novel feature fusion network with attention to integrate image patch and InChI prediction. The improved SwinTransformer as an encoder and the Transformer Decoder as a decoder with patch embedding are applied to predict the image features for the corresponding InChI. The experimental results showed that the Image2InChI model achieves an accuracy of InChI (InChI acc) of 99.8%, a Morgan FP of 94.1%, an accuracy of maximum common structures (MCS acc) of 94.8%, and an accuracy of longest common subsequence (LCS acc) of 96.2%. The experiments demonstrated that the proposed Image2InChI model improves the accuracy and efficiency of molecular image recognition and provided a valuable reference about optical chemical structure recognition for InChI.


Asunto(s)
Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador/métodos , Descubrimiento de Drogas/métodos , Imagen Óptica/métodos
16.
BMC Infect Dis ; 24(1): 45, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38172766

RESUMEN

BACKGROUND: This study aimed to assess and compare procalcitonin (PCT) and C-reactive protein (CRP) levels between COVID-19 and non-COVID-19 sepsis patients. Additionally, we evaluated the diagnostic efficiency of PCT and CRP in distinguishing between Gram-positive (GP) and Gram-negative (GN) bacterial infections. Moreover, we explored the associations of PCT with specific pathogens in this context. METHODS: The study included 121 consecutive sepsis patients who underwent blood culture testing during the COVID-19 epidemic. PCT and CRP were measured, and reverse transcriptase-polymerase chain reaction (RT-PCR) was employed for the detection of COVID-19 nucleic acid. The Mann-Whitney U-test was used to compare PCT and CRP between the COVID-19 and non-COVID-19 groups. Receiver operating characteristic (ROC) curves were generated to compare PCT and CRP levels in the GN group versus the GP group for assessing the diagnostic efficiency. The kruskal-Wallis H test was applied to assess the impact of specific pathogen groups on PCT concentrations. RESULTS: A total of 121 sepsis patients were categorized into a COVID-19 group (n = 25) and a non-COVID-19 group (n = 96). No significant differences in age and gender were observed between the COVID-19 and non-COVID-19 groups. The comparison of biomarkers between these groups showed no statistically significant differences. The optimal cut-off values for PCT and CRP in differentiating between GP and GN infections were 1.03 ng/mL and 34.02 mg/L, respectively. The area under the ROC curve was 0.689 (95% confidence interval (CI) 0.591-0.786) for PCT and 0.611 (95% CI 0.505-0.717) for CRP. The diagnostic accuracy was 69.42% for PCT and 58.69% for CRP. The study found a significant difference in PCT levels among specific groups of pathogens (P < 0.001), with the highest levels observed in Escherichia coli infections. The frequency of Staphylococcus spp. positive results was significantly higher (36.0%) in COVID-19 compared to non-COVID-19 sepsis patients (P = 0.047). CONCLUSION: Sepsis patients with COVID-19 revealed a significantly higher culture positivity for staphylococcus spp. than the non-COVID-19 group. Both PCT and CRP showed moderate diagnostic efficiency in differentiating between GP and GN bacterial infections. PCT showed potential utility in identifying E. coli infections compared to other pathogens.


Asunto(s)
COVID-19 , Infecciones por Escherichia coli , Infecciones por Bacterias Gramnegativas , Sepsis , Humanos , Proteína C-Reactiva/análisis , Polipéptido alfa Relacionado con Calcitonina , Escherichia coli/metabolismo , Calcitonina , Estudios Retrospectivos , COVID-19/diagnóstico , Sepsis/microbiología , Biomarcadores , Curva ROC , Infecciones por Bacterias Gramnegativas/microbiología , Staphylococcus , Prueba de COVID-19
17.
Phys Chem Chem Phys ; 26(9): 7269-7275, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38193864

RESUMEN

On the basis of variable-temperature single-crystal X-ray diffraction, rotational energy barrier analysis, variable-temperature/frequency dielectric response, and molecular dynamics simulations, here we report a new crystalline supramolecular rotor (CH3NH3)(18-crown-6)[CuCl3], in which the (H3C-NH3)+ ion functions as a smallest dual-wheel rotator showing bisected rotation dynamics, while the host 18-crown-6 macrocycle behaves as a stator that is not strictly stationary. This study also provides a helpful insight into the dynamics of ubiquitous -CH3/-NH3 groups confined in organic or organic-inorganic hybrid solids.

18.
Bioorg Chem ; 150: 107596, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38941699

RESUMEN

A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC.

19.
Acta Pharmacol Sin ; 45(6): 1201-1213, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38491160

RESUMEN

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.


Asunto(s)
Vía de Señalización Hippo , Interleucina-6 , Regeneración Hepática , Ratones Endogámicos C57BL , Proteínas Serina-Treonina Quinasas , Receptor de Angiotensina Tipo 2 , Transducción de Señal , Animales , Masculino , Ratones , Acetaminofén , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Interleucina-6/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Regeneración Hepática/efectos de los fármacos , Regeneración Hepática/fisiología , Ratones Noqueados , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Proteínas Señalizadoras YAP/metabolismo
20.
Environ Res ; 247: 118255, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38266890

RESUMEN

Lewis acids of solid catalysts have been featured for a pivotal role in promoting various reactions. Regarding the oxidation protocol to remove formaldehyde, the inherent drawback of the best-studied MnO2 materials in acidic sites has eventually caused deficiency of active hydroxyls to sustain low-temperature activity. Herein, the cryptomelane-type MnO2 was targeted and it was tuned via incorporation of Zr metal, exhibiting great advances in not only the complete HCHO-to-CO2 degradation but also cycling performance. Zr species were existent in doping state in the MnO2 lattice, rendering lower crystallinity and breaking the regular growth of MnO2 crystallites, which thereby tripled surface area and created larger volume of smaller mesopores. Meantime, the local electronic properties of Mn atoms were also changed by Zr doping, i.e., more low-valence Mn species were formed due to the electron transfer from Zr to Mn. The results of infrared studies demonstrate the higher possession of Lewis acid sites on ZrMn, and this high degree of electrophilic agents favored the production of hydroxyl species. Furthermore, the reactivity of surface hydroxyls, as investigated by CO temperature programmed reduction and temperature programmed desorption of adsorbed O2, was obviously improved as well after Zr modification. It is speculated jointly with the characterizations of the post-reaction catalysts that the accelerated production of active hydroxyls helped rapidly convert formaldehyde into key intermediate-formate, which was then degraded into CO2, avoiding the side reaction path with undesired intermediate-hydrocarbonate-over the pristine MnO2, where active sites were blocked and formaldehyde oxidation was inhibited. Additionally, Zr decoration could stabilize Lewis acidity to be more resistant to heat degeneration, and this merit brought about advantageous thermal recyclability for cycled application.


Asunto(s)
Ácidos de Lewis , Óxidos , Óxidos/química , Compuestos de Manganeso/química , Dióxido de Carbono , Formaldehído/química , Catálisis
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