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1.
Nat Commun ; 15(1): 5792, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987247

RESUMEN

The construction of a large-scale quantum internet requires quantum repeaters containing multiple entangled photon sources with identical wavelengths. Semiconductor quantum dots can generate entangled photon pairs deterministically with high fidelity. However, realizing wavelength-matched quantum-dot entangled photon sources faces two difficulties: the non-uniformity of emission wavelength and exciton fine-structure splitting induced fidelity reduction. Typically, these two factors are not independently tunable, making it challenging to achieve simultaneous improvement. In this work, we demonstrate wavelength-tunable entangled photon sources based on droplet-etched GaAs quantum dots through the combined use of AC and quantum-confined Stark effects. The emission wavelength can be tuned by ~1 meV while preserving an entanglement fidelity f exceeding 0.955(1) in the entire tuning range. Based on this hybrid tuning scheme, we finally demonstrate multiple wavelength-matched entangled photon sources with f > 0.919(3), paving the way towards robust and scalable on-demand entangled photon sources for quantum internet and integrated quantum optical circuits.

2.
Discov Oncol ; 15(1): 285, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012378

RESUMEN

BACKGROUND: Unlike human epidermal growth factor receptor 2 (HER2) amplification or exon 20 insertions, missense mutations in the extracellular domain (ECD), transmembrane domain (TMD), and intracellular domain (ICD) of the HER2 protein have been implicated as oncogenic in non-small cell lung cancer (NSCLC). However, their molecular subtypes, structural disparities, and clinical responses to current medical treatments, particularly HER2-targeted tyrosine kinase inhibitors (TKIs), remain unclear in NSCLC and warrant investigation. METHODS: A real-world observational ATLAS study was conducted to gather and analyze therapeutic outcomes of chemotherapy or TKIs for heterogeneous HER2 missense mutations in NSCLC. Computational models of typical ECD, TMD, and ICD mutations were utilized to explore their structural variances. RESULTS: We screened 37 eligible patients with HER2-activating missense mutations, of which 35 patients who had received chemotherapy or HER2-targeted TKIs as first-line therapy were available for response assessment. The median progression-free survival (PFS) for chemotherapy was 4.43 months (95% confidence interval [CI], 3.77-5.10), with an objective response rate (ORR) of 26.1% (6/23) and a disease control rate (DCR) of 17/23 (73.9%). The administration of afatinib, dacomitinib, and pyrotinib, HER2-targeted TKIs, achieved a median PFS of 4.65 months, with an ORR of 33.3% (4/12) and a DCR of 83.3% (10/12). Molecular modeling and computational simulations of ECD, TMD, and ICD mutations revealed their distinct structural characteristics. CONCLUSION: In comparison to chemotherapy, HER2-targeted TKIs demonstrated similar activity and PFS benefits for HER2-activating missense mutations in NSCLC.

3.
ACS Appl Mater Interfaces ; 16(27): 35752-35760, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38917413

RESUMEN

Metal halide perovskite materials with excellent carrier transport properties have been regarded as a new class of catalysts with great application potential. However, their development is hampered by their instability in polar solvents and high temperatures. Herein, we report a solution-processed Cs2MoCl6 perovskite nanocrystals (NCs) capped with the Mo6+, showing high thermostability in polar solvents. Furthermore, the Pd single atoms (PdSA) can be anchored on the surface of Cs2MoCl6 NCs through the unique coordination structure of Pd-Cl sites, which exhibit excellent semihydrogenation of different alkyne derivatives with high selectivity at full conversion at room temperature. Moreover, the activity could be improved greatly under Xe lamp irradiation. Detailed experimental characterization and DFT calculations indicate the improved activity under light illumination is due to the synergistic effect of photo-to-heat conversion and photoinduced electron transfer from Cs2MoCl6 to PdSA, which facilitates the activation of the C≡C group. This work not only provides a new catalyst for high selective semihydrogenation of alkyne derivatives but also opens a new avenue for metal halides as photothermal catalysts.

4.
Nat Commun ; 15(1): 4901, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851779

RESUMEN

Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 µg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.


Asunto(s)
Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Animales , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/química , Humanos , Familia de Multigenes , Ratones , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/metabolismo , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Bacteriana/efectos de los fármacos , Genoma Bacteriano/genética , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Biología Computacional/métodos , Cisteína/metabolismo , Cisteína/química
5.
J Dent ; 146: 105046, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38729285

RESUMEN

OBJECTIVES: The high prevalence of antibiotic-resistant bacteria poses a threat to the global public health. The appropriate use of adjuvants to restore the antimicrobial activity of antibiotics against resistant bacteria could be an effective strategy for combating antibiotic resistance. In this study, we investigated the counteraction of Triton X-100 (TX-100) and the mechanisms underlying the antibiotic resistance of Enterococcus faecalis (E. faecalis). METHODS: Standard, wild-type (WT), and induced antibiotic-resistant E. faecalis strains were used in this study. In vitro antibacterial experiments were conducted to evaluate the antimicrobial activities of gentamicin sulfate and ciprofloxacin hydrochloride in the presence and absence of 0.02 % TX-100 against both planktonic and biofilm bacteria. Transcriptomic and untargeted metabolomic analyses were performed to explore the molecular mechanisms of TX-100 as an antibiotic adjuvant. Additionally, membrane permeability, membrane potential, glycolysis-related enzyme activity, intracellular adenosine triphosphate (ATP), and expression levels of virulence genes were assessed. The biocompatibility of different drug combinations was also evaluated. RESULTS: A substantially low TX-100 concentration improved the antimicrobial effects of gentamicin sulfate or ciprofloxacin hydrochloride against antibiotic-resistant E. faecalis. Mechanistic studies demonstrated that TX-100 increased cell membrane permeability and dissipated membrane potential. Moreover, antibiotic resistance and pathogenicity of E. faecalis were attenuated by TX-100 via downregulation of the ABC transporter, phosphotransferase system (PTS), and ATP supply. CONCLUSIONS: TX-100 enhanced the antimicrobial activity of gentamicin sulfate and ciprofloxacin hydrochloride at a low concentration by improving antibiotic susceptibility and attenuating antibiotic resistance and pathogenicity of E. faecalis. CLINICAL SIGNIFICANCE: These findings provide a theoretical basis for developing new root canal disinfectants that can reduce antibiotic resistance.


Asunto(s)
Antibacterianos , Biopelículas , Ciprofloxacina , Farmacorresistencia Bacteriana , Enterococcus faecalis , Gentamicinas , Pruebas de Sensibilidad Microbiana , Octoxinol , Enterococcus faecalis/efectos de los fármacos , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Ciprofloxacina/farmacología , Gentamicinas/farmacología , Octoxinol/farmacología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Humanos , Adenosina Trifosfato/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Glucólisis/efectos de los fármacos
6.
Colloids Surf B Biointerfaces ; 240: 113978, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38810466

RESUMEN

Photodynamic therapy (PDT) is an effective method for bacterial infection control in root canals of teeth with a broad-spectrum antibacterial activity. However, its application in root canal treatment is limited due to its inefficiency under hypoxic conditions and dentin staining. Triton X-100 (TX) shows great potential in enhancing the efficiency of antimicrobial agents through improving bacterial membrane permeability. The present study employed a combination of toluidine blue O (TB)-mediated PDT with TX to target the Enterococcus faecalis (E. faecalis), a bacterium with strong resistance to various antibacterial agents and mostly detected in infected root canals. PDT combined with TX showed enhanced antibacterial efficiency against both planktonic cells and biofilms of E. faecalis. At the same time, TX enhanced the antibacterial effect in dentinal tubules and reduced the incubation time. Mechanism studies revealed that TX improved reactive oxygen species (ROS) production through increasing the proportion of TB monomers. Additionally, increased membrane permeability and wettability were also observed. The findings demonstrated the PDT combined with TX could be used as a highly effective method for the root canal disinfection of teeth.


Asunto(s)
Antibacterianos , Biopelículas , Enterococcus faecalis , Octoxinol , Fotoquimioterapia , Especies Reactivas de Oxígeno , Enterococcus faecalis/efectos de los fármacos , Fotoquimioterapia/métodos , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Octoxinol/química , Octoxinol/farmacología , Especies Reactivas de Oxígeno/metabolismo , Cloruro de Tolonio/farmacología , Cloruro de Tolonio/química , Humanos , Pruebas de Sensibilidad Microbiana , Cavidad Pulpar/microbiología , Cavidad Pulpar/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química
7.
Arch Toxicol ; 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796608

RESUMEN

Disruption of the thyroid hormone (TH) system is connected with diverse adverse health outcomes in wildlife and humans. It is crucial to develop and validate suitable in vitro assays capable of measuring the disruption of the thyroid hormone (TH) system. These assays are also essential to comply with the 3R principles, aiming to replace the ex vivo tests often utilised in the chemical assessment. We compared the two commonly used assays applicable for high throughput screening [Luminol and Amplex UltraRed (AUR)] for the assessment of inhibition of thyroid peroxidase (TPO, a crucial enzyme in TH synthesis) using several cell lines and 21 compounds from different use categories. As the investigated cell lines derived from human and rat thyroid showed low or undetectable TPO expression, we developed a series of novel cell lines overexpressing human TPO protein. The HEK-TPOA7 model was prioritised for further research based on the high and stable TPO gene and protein expression. Notably, the Luminol assay detected significant peroxidase activity and signal inhibition even in Nthy-ori 3-1 and HEK293T cell lines without TPO expression, revealing its lack of specificity. Conversely, the AUR assay was specific to TPO activity. Nevertheless, despite the different specificity, both assays identified similar peroxidation inhibitors. Over half of the tested chemicals with diverse structures and from different use groups caused TPO inhibition, including some widespread environmental contaminants suggesting a potential impact of environmental chemicals on TH synthesis. Furthermore, in silico SeqAPASS analysis confirmed the high similarity of human TPO across mammals and other vertebrate classes, suggesting the applicability of HEK-TPOA7 model findings to other vertebrates.

8.
Phys Rev Lett ; 132(16): 160801, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38701444

RESUMEN

A solid-state approach for quantum networks is advantageous, as it allows the integration of nanophotonics to enhance the photon emission and the utilization of weakly coupled nuclear spins for long-lived storage. Silicon carbide, specifically point defects within it, shows great promise in this regard due to the easy of availability and well-established nanofabrication techniques. Despite of remarkable progresses made, achieving spin-photon entanglement remains a crucial aspect to be realized. In this Letter, we experimentally generate entanglement between a silicon vacancy defect in silicon carbide and a scattered single photon in the zero-phonon line. The spin state is measured by detecting photons scattered in the phonon sideband. The photonic qubit is encoded in the time-bin degree of freedom and measured using an unbalanced Mach-Zehnder interferometer. Photonic correlations not only reveal the quality of the entanglement but also verify the deterministic nature of the entanglement creation process. By harnessing two pairs of such spin-photon entanglement, it becomes straightforward to entangle remote quantum nodes at long distance.

9.
Curr Res Food Sci ; 8: 100748, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38764976

RESUMEN

Limosilactobacillus (L.) fermentum is widely utilized for its beneficial properties, but lysogenic phages can integrate into its genome and can be induced to enter the lysis cycle under certain conditions, thus accomplishing lysis of host cells, resulting in severe economic losses. In this study, a lysogenic phage, LFP03, was induced from L. fermentum IMAU 32510 by UV irradiation for 70 s. The electron microscopy showed that this phage belonged to Caudoviricetes class. Its genome size was 39,556 bp with a GC content of 46.08%, which includes 20 functional proteins. Compared with other L. fermentum phages, the genome of phage LFP03 exhibited deletions, inversions and translocations. Biological analysis showed that its optimal multiplicity of infection was 0.1, with a burst size of 133.5 ± 4.9 PFU/infective cell. Phage LFP03 was sensitive to temperature and pH value, with a survival rate of 48.98% at 50 °C. It could be completely inactivated under pH 2. The adsorption ability of this phage was minimally affected by temperature and pH value, with adsorption rates reaching 80% under all treated conditions. Divalent cations could accelerate phage adsorption, while chloramphenicol expressed little influence. This study might expand the related knowledge of L. fermentum phages, and provide some theoretical basis for improving the stability of related products and establishing phage control measures.

10.
Heliyon ; 10(9): e30312, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707278

RESUMEN

A775_G776insYVMA, the typical and predominant HER2 exon 20 insertion variant in non-small cell lung cancer, exhibits relative insensitivity to covalent HER2-targeted tyrosine kinase inhibitors. However, other less common insertions have shown better responses to HER2-targeted inhibitors. M774delinsWLV is a rare HER2 exon 20 insertion subtype and its clinical sensitivity to HER2-targeted inhibitors remains unclear. Furthermore, there is a lack of current studies to elucidate its structure and predict its sensitivity to HER2-targeted tyrosine kinase inhibitors. Herein, we presented a case of non-small cell lung cancer harboring M774delinsWLV who derived favorable response and significant survival benefit from HER2-targeted tyrosine kinase inhibitors. A 60-year-old male with metastatic lung adenocarcinoma carrying M774delinsWLV received pyrotinib monotherapy as first-line treatment. After rapid disease progression at three months, sequential combination therapy with pyrotinib and bevacizumab yielded promising antitumor activity and sustained progression-free survival benefits for nearly a year. Subsequent dacomitinib monotherapy displayed significant activity against this uncommon insertion, resulting in a rapid decrease in tumor markers and partial response, along with progression-free survival of one year. The molecular simulation revealed no significant differences in the overall protein structure and binding pocket region between M774delinsWLV and the HER2 wild type. Drug binding dynamics simulation indicated that dacomitinib exhibited the most potent binding activity compared to afatinib, pyrotinib and poziotinib. Conclusively, dacomitinib exhibited promising efficacy against the rare HER2 exon 20 insertion M774delinsWLV. Extensive investigation is needed to elucidate the effects of HER2-targeted tyrosine kinase inhibitors on non-small cell lung cancer with different HER2 insertion subtypes.

11.
Angew Chem Int Ed Engl ; 63(25): e202403927, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632085

RESUMEN

All-inorganic metal halides with afterglow emission have attracted increasing attention due to their significantly longer afterglow duration and higher stability compared to their organic-inorganic hybrid counterparts. However, their afterglow colors have not yet reached the blue spectral region. Here, we report all-inorganic copper-doped Rb2AgBr3 single crystals with ultralong blue afterglow (>300 s) by modulating defect states through doping engineering. The introduction of copper(I) ions into Rb2AgBr3 facilitates the formation of bromine vacancies, thus increasing the density of trap states available for charge storage and enabling bright, persistent emission after ceasing the excitation. Moreover, cascade energy transfer between distinct emissive centers in the crystals results in ultra-broadband photoluminescence, not only covering the whole white light with near-unity quantum yield but also extending into the near-infrared region. This 'cocktail' of exotic light-emission properties, in conjunction with the excellent stability of copper-doped Rb2AgBr3 crystals, allowed us to demonstrate their implementation to solid-state lighting, night vision, and intelligent anti-counterfeiting.

12.
Pestic Biochem Physiol ; 201: 105848, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685210

RESUMEN

Fusarium asiaticum is a destructive phytopathogenic fungus that causes Fusarium head blight of wheat (FHB), leading to serious yield and economic losses to cereal crops worldwide. Our previous studies indicated that target-site mutations (K216R/E, S217P/L, or E420K/G/D) of Type I myosin FaMyo5 conferred high resistance to phenamacril. Here, we first constructed one sensitive strain H1S and three point mutation resistant strains HA, HC and H1R. Then we conducted comparative transcriptome analysis of these F. asiaticum strains after 1 and 10 µg·mL-1 phenamacril treatment. Results indicated that 2135 genes were differentially expressed (DEGs) among the sensitive and resistant strains. The DEGs encoding ammonium transporter MEP1/MEP2, nitrate reductase, copper amine oxidase 1, 4-aminobutyrate aminotransferase, amino-acid permease inda1, succinate-semialdehyde dehydrogenase, 2, 3-dihydroxybenzoic acid decarboxylase, etc., were significantly up-regulated in all the phenamacril-resistant strains. Compared to the control group, a total of 1778 and 2097 DEGs were identified in these strains after 1 and 10 µg·mL-1 phenamacril treatment, respectively. These DEGs involved in 4-aminobutyrate aminotransferase, chitin synthase 1, multiprotein-bridging factor 1, transcriptional regulatory protein pro-1, amino-acid permease inda1, ATP-dependent RNA helicase DED1, acetyl-coenzyme A synthetase, sarcoplasmic/endoplasmic reticulum calcium ATPase 2, etc., showed significantly down-regulated expression in phenamacril-sensitive strain but not in resistant strains after phenamacril treatment. In addition, cyanide hydratase, mating-type protein MAT-1, putative purine nucleoside permease, plasma membrane protein yro2, etc., showed significantly co-down-regulated expression in all the strains after phenamacril treatment. Taken together, This study provides deep insights into the resistance regulation mechanism and the inhibitory effect of fungicide phenamacril and these new annotated proteins or enzymes are worth for the discovery of new fungicide targets.


Asunto(s)
Farmacorresistencia Fúngica , Fungicidas Industriales , Fusarium , Fusarium/efectos de los fármacos , Fusarium/genética , Fungicidas Industriales/farmacología , Farmacorresistencia Fúngica/genética , Perfilación de la Expresión Génica , Transcriptoma/efectos de los fármacos , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Enfermedades de las Plantas/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
13.
Phys Rev Lett ; 132(8): 083601, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38457704

RESUMEN

Quantum non-Gaussianity, a more potent and highly useful form of nonclassicality, excludes all convex mixtures of Gaussian states and Gaussian parametric processes generating them. Here, for the first time, we conclusively test quantum non-Gaussian coincidences of entangled photon pairs with the Clauser-Horne-Shimony-Holt-Bell factor S=2.328±0.004 from a single quantum dot with a depth up to 0.94±0.02 dB. Such deterministically generated photon pairs fundamentally overcome parametric processes by reducing crucial multiphoton errors. For the quantum non-Gaussian depth of the unheralded (heralded) single-photon state, we achieve the value of 8.08±0.05 dB (19.06±0.29 dB). Our Letter experimentally certifies the exclusive quantum non-Gaussianity properties highly relevant for optical sensing, communication, and computation.

14.
J Adv Res ; 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38211884

RESUMEN

INTRODUCTION: The prevention and treatment of chronic obstructive pulmonary disease (COPD) is closely tied to antioxidation and anti-inflammation. Phycocyanin (PC) has numerous pharmacological effects, such as antioxidation and anti-inflammation. However, it remains unclear whether PC can play a therapeutic role in COPD. OBJECTIVE: As inflammation and oxidative stress can aggravate COPD, this study is to explore the effect of PC on COPD mice and its mechanisms. METHODS: The COPD mice model was established by exposing them to lipopolysaccharide (LPS) and cigarette smoke (CS); PC was administrated in a concentration of 50 mg/kg for 30 days. On the last day, lung function was measured, and bronchoalveolar lavage fluid (BALF) was obtained and classified for cells. Lung tissue pathological change was analyzed, and organ indices statistics were measured. Based on molecular docking, the mechanism was explored with Western blotting, immunohistochemical, and immunofluorescence in vivo and in vitro. RESULTS: PC significantly ameliorated the pulmonary function of COPD mice and reduced inflammation of the lung (p < 0.05), and hematoxylin and eosin (H&E) staining showed PC depressed lung inflammatory cell accumulation and emphysema. Periodic acid Schiff (PAS) and Masson staining revealed that PC retarded goblet cells metaplasia and collagen deposition (p < 0.05). In addition, in vivo PC regulated Heme oxygenase 1 (HO-1) (p < 0.05) and NAD(P)H dehydrogenase quinone 1 (NQO1) level (p < 0.01) in the lung, as well as NOX2 level in pulmonary macrophages. Molecular docking results indicate that phycocyanobilin (PCB) in PC had a good binding site in Keap1 and NOX2 proteins; the phycocyanobilin-bound phycocyanin peptide (PCB-PC-peptide) was obtained for further studies. In vitro, PCB-PC-peptide could depress the phospho-NF-E2-related factor 2 (p-Nrf2) and NQO1 protein expression in RAW264.7 cells induced by cigarette smoke extract (CSE) (p < 0.05). CONCLUSION: PC exerts beneficial effects on COPD via anti-inflammatory and antioxidative stress, which may be achieved through PCB.

15.
Orthop Surg ; 16(2): 462-470, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38086608

RESUMEN

OBJECTIVE: Osteosarcoma is a primary malignancy originating from mesenchymal tissue characterized by rapid growth, early metastasis and poor prognosis. Ginsenoside Rg5 (G-Rg5) is a minor ginsenoside extracted from Panax ginseng C.A. Meyer which has been discovered to possess anti-tumor properties. The objective of current study was to explore the mechanism of G-Rg5 in the treatment of osteosarcoma by network pharmacology and molecular docking technology. METHODS: Pharmmapper, SwissTargetPrediction and similarity ensemble approach databases were used to obtain the pharmacological targets of G-Rg5. Related genes of osteosarcoma were searched for in the GeneCards, OMIM and DrugBank databases. The targets of G-Rg5 and the related genes of osteosarcoma were intersected to obtain the potential target genes of G-Rg5 in the treatment of osteosarccoma. The STRING database and Cytoscape 3.8.2 software were used to construct the protein-protein interaction (PPI) network, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. AutoDock vina software was used to perform molecular docking between G-Rg5 and hub targets. The hub genes were imported into the Kaplan-Meier Plotter online database for survival analysis. RESULTS: A total of 61 overlapping targets were obtained. The related signaling pathways mainly included PI3K-Akt signaling pathway, Proteoglycans in cancer, Lipid and atherosclerosis and Kaposi sarcoma-associated herpesvirus infection. Six hub targets including PIK3CA, SRC, TP53, MAPK1, EGFR, and VEGFA were obtained through PPI network and targets-pathways network analyses. The results of molecular docking showed that the binding energies were all less than -7 kcal/mol. And the results of survival analysis showed TP53 and VEGFA affect the prognosis of sarcoma patients. CONCLUSION: This study explored the possible mechanism of G-Rg5 in the treatment of osteosarcoma using network pharmacology method, suggesting that G-Rg5 has the characteristics of multi-targets and multi-pathways in the treatment of osteosarcoma, which lays a foundation for the follow-up experimental and clinical researches on the therapeutic effects of G-Rg5 on osteosarcoma.


Asunto(s)
Neoplasias Óseas , Medicamentos Herbarios Chinos , Ginsenósidos , Osteosarcoma , Humanos , Simulación del Acoplamiento Molecular , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Osteosarcoma/tratamiento farmacológico , Neoplasias Óseas/tratamiento farmacológico
16.
Adv Mater ; 36(2): e2302140, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37801733

RESUMEN

Metal halide nanocrystals (NCs) with high photoluminescence quantum yield (PLQY) are desirable for lighting, display, and X-ray detection. Herein, the novel lanthanide-based halide NCs are committed to designing and optimizing the optical and scintillating properties, so as to unravel the PL origin, exciton dynamics, and optoelectronic applications. Sb-doped zero-dimensional (0D) Cs3 TbCl6 NCs exhibit a green emission with a narrow full width of half maximum of 8.6 nm, and the best PLQY of 48.1% is about three times higher than that of undoped NCs. Experiments and theoretical calculations indicate that 0D crystalline and electronic structures make the exciton highly localized on [TbCl6 ]3- octahedron, which boosts the Cl- -Tb3+ charge transfer process, thus resulting in bright Tb3+ emission. More importantly, the introduction of Sb3+ not only facilitates the photon absorption transition, but also builds an effective thermally boosting energy transfer channel assisted by [SbCl6 ]3- -induced self-trapped state, which is responsible for the PL enhancement. The high luminescence efficiency and negligible self-absorption of the Cs3 TbCl6 : Sb nanoscintillator enable a more sensitive X-ray detection response compared with undoped sample. The study opens a new perspective to deeply understand the excited state dynamics of metal halide NCs, which helps to design high-performance luminescent lanthanide-based nanomaterials.

17.
Prog Biophys Mol Biol ; 186: 39-52, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38030044

RESUMEN

Algae, which are ubiquitous in ecosystems, have evolved a variety of light-harvesting complexes to better adapt to diverse habitats. Phycobilisomes/phycobiliproteins, unique to cyanobacteria, red algae, and certain cryptomonads, compensate for the lack of chlorophyll absorption, allowing algae to capture and efficiently transfer light energy in aquatic environments. With the advancement of microscopy and spectroscopy, the structure and energy transfer processes of increasingly complex phycobilisomes have been elucidated, providing us with a vivid portrait of the dynamic adaptation of their structures to the light environment in which algae thrive: 1) Cyanobacteria living on the surface of the water use short, small phycobilisomes to absorb red-orange light and reduce the damage from blue-violet light via multiple methods; 2) Large red algae inhabiting the depths of the ocean have evolved long and dense phycobilisomes containing phycoerythrin to capture the feeble blue-green light; 3) In far-red light environments such as caves, algae use special allophycocyanin cores to optimally utilize the far-red light; 4) When the environment shifts, algae can adjust the length, composition and density of their rods to better adapt; 5) By carefully designing the position of the pigments, phycobilisomes can transfer light energy to the reaction center with nearly 100% efficiency via three energy transfer processes.


Asunto(s)
Cianobacterias , Ficobilisomas , Ficobilisomas/química , Ecosistema
18.
Phys Chem Chem Phys ; 25(46): 32002-32009, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-37975722

RESUMEN

The high photostability of DNAs and RNAs is inextricably related to the photochemical and photophysical properties of their building blocks, nucleobases and nucleosides, which can dissipate the absorbed UV light energy in a harmless manner. The deactivation mechanism of the nucleosides, especially the decay pathways of cytidine (Cyd), has been a matter of intense debate. In the current study, we employ high-level electronic structure calculations combined with excited state non-adiabatic dynamic simulations to provide a clear picture of the excited state deactivation of Cyd in both gas phase and aqueous solution. In both environments, a barrierless decay path driven by the ring-puckering motion and a relaxation channel with a small energy barrier driven by the elongation motion of CO bond are assigned to <200 fs and sub-picosecond decay time component, respectively. The presence of ribose group has a subtle effect on the dynamic behavior of Cyd in gas phase as the ribose-to-base hydrogen/proton transfer process is energetically inaccessible with a sizable energy barrier of about 1.4 eV. However, this energy barrier is significantly reduced in water, especially when an explicit water molecule is present. Therefore, we argue that the long-lived decay channel found in aqueous solution could be assigned to the Cyd-water intermolecular hydrogen/proton transfer process. The present study postulates a novel scenario toward deep understanding the intrinsic photostability of DNAs and RNAs and provides solid evidence to disclose the long history debate of cytidine excited-state decay mechanism, especially for the assignment of experimentally observed time components.

19.
J Agric Food Chem ; 71(41): 15132-15144, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37797200

RESUMEN

With the improvement in sow prolificacy, formula feeding has been increasingly used in the pig industry. Diarrhea remains a serious health concern in formula-fed (FF) piglets. Fecal microbiota transplantation (FMT) is an efficacious strategy to reshape gut microbiota and the metabolic profile for treating diarrhea. This study aims to investigate whether FMT from breast-fed piglets could alleviate diarrhea in FF piglets. The piglets were randomly assigned to the control (CON) group, FF group, and FMT group. Our results showed that FF piglets exhibited a higher diarrhea incidence, damaged colonic morphology, and disrupted barrier function. In contrast, FMT treatment normalized the morphology and barrier function. FMT suppressed the JNK/MAPK pathway and production of proinflammatory cytokines. Additionally, FF piglets had a lower abundance of the beneficial bacterial genus Bifidobacterium compared to CON piglets. Following FMT administration, Bifidobacterium was restored. Meanwhile, 5-HIAA, a metabolite of tryptophan, and AHR-responsive CYP1A1 and CYP1B1 were upregulated. Importantly, integrated multiomics analysis revealed a strong positive correlation between Bifidobacterium and 5-HIAA. In vitro, 5-HIAA supplementation reversed the LPS-induced disruption of tight junctions and production of proinflammatory cytokines in IPEC-J2 cells. In conclusion, FMT reduced diarrhea incidence and improved growth performance. The alleviative effect of FMT on diarrhea was associated with Bifidobacterium and 5-HIAA.


Asunto(s)
Microbioma Gastrointestinal , Porcinos , Animales , Femenino , Ácido Hidroxiindolacético , Receptores de Hidrocarburo de Aril/genética , Diarrea/terapia , Diarrea/veterinaria , Diarrea/microbiología , Citocinas/genética
20.
J Phys Chem Lett ; 14(43): 9646-9654, 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37870498

RESUMEN

Lead-free halide perovskites are promising materials for solar energy applications. However, their efficiency is hindered by poor light absorption in the visible-near-infrared region. Herein, we introduce vanadium (V) with low-lying ground/excited-state energy levels to form two types of stable lead-free V-based perovskite (Cs2NaVCl6 and Cs3V2Cl9) colloidal nanocrystals (NCs) with strong light absorption covering the ultraviolet to near-infrared region. We find the absorption can be further enhanced by structural regulation, in which the zero-dimensional (0D) Cs3V2Cl9 NCs show stronger and red-shifted (up to 1400 nm) light absorption compared to the three-dimensional Cs2NaVCl6 NCs. In 0D Cs3V2Cl9 NCs, [V2Cl9]3- dimers play a vital role in governing strong visible-near-infrared light absorption. We demonstrated their application for photocatalytic CO2 reduction. Our work sheds light on the structure-property relationship governing the absorption behavior, providing a novel route for tuning the light absorption ability of lead-free halide perovskites.

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