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1.
Nature ; 612(7939): 246-251, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36385532

RESUMO

A step towards the next generation of high-capacity, noise-resilient communication and computing technologies is a substantial increase in the dimensionality of information space and the synthesis of superposition states on an N-dimensional (N > 2) Hilbert space featuring exotic group symmetries. Despite the rapid development of photonic devices and systems, on-chip information technologies are mostly limited to two-level systems owing to the lack of sufficient reconfigurability to satisfy the stringent requirement for 2(N - 1) degrees of freedom, intrinsically associated with the increase of synthetic dimensionalities. Even with extensive efforts dedicated to recently emerged vector lasers and microcavities for the expansion of dimensionalities1-10, it still remains a challenge to actively tune the diversified, high-dimensional superposition states of light on demand. Here we demonstrate a hyperdimensional, spin-orbit microlaser for chip-scale flexible generation and manipulation of arbitrary four-level states. Two microcavities coupled through a non-Hermitian synthetic gauge field are designed to emit spin-orbit-coupled states of light with six degrees of freedom. The vectorial state of the emitted laser beam in free space can be mapped on a Bloch hypersphere defining an SU(4) symmetry, demonstrating dynamical generation and reconfiguration of high-dimensional superposition states with high fidelity.


Assuntos
Comunicação , Tecnologia da Informação , Fótons , Tecnologia
2.
Planta ; 259(3): 68, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38337086

RESUMO

MAIN CONCLUSION: Overexpression and loss of function of OsGEX3 reduce seed setting rates and affect pollen fertility in rice. OsGEX3 positively regulates osmotic stress response by regulating ROS scavenging. GEX3 proteins are conserved in plants. AtGEX3 encodes a plasma membrane protein that plays a crucial role in pollen tube guidance. However, the function of its homolog in rice, OsGEX3, has not been determined. Our results demonstrate that OsGEX3 is localized in the plasma membrane and the nucleus as shown by a transiently transformed assay using Nicotiana benthamiana leaves. The up-regulation of OsGEX3 was detected in response to treatments with polyethylene glycol (PEG) 4000, hydrogen peroxide, and abscisic acid (ABA) via RT-qPCR analysis. Interestingly, we observed a significant decline in the seed setting rates of OsGEX3-OE lines and mutants, compared to the wild type. Further investigations reveal that overexpression and loss of function of OsGEX3 affect pollen maturation. TEM observation revealed a significant decrease in the fertile pollen rates of OsGEX3-OE transgenic lines and Osgex3 mutants due to a delay in pollen development at the late vacuolated stage. Overexpression of OsGEX3 improved osmotic stress and oxidative stress tolerance by enhancing reactive oxygen species (ROS) scavenging in rice seedlings, whereas Osgex3 mutants exhibited an opposite phenotype in osmotic stress. These findings highlight the multifunctional roles of OsGEX3 in pollen development and the response to abiotic stress. The functional characterization of OsGEX3 provides a fundamental basis for rice molecular breeding and can facilitate efforts to cultivate drought resistance and yield-related varieties.


Assuntos
Oryza , Espécies Reativas de Oxigênio/metabolismo , Oryza/fisiologia , Pressão Osmótica , Reprodução , Estresse Oxidativo , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/genética , Regulação da Expressão Gênica de Plantas , Secas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Phys Rev Lett ; 132(25): 256902, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996261

RESUMO

Non-Hermitian degeneracies reveal intriguing and nontrivial behaviors in open physical systems. Examples like parity-time (PT) symmetry breaking, topological encircling chirality, and enhanced sensing near an exceptional point (EP) are often associated with the abrupt nature of the phase transition around these degeneracies. Here we experimentally observe a cavity-enhanced second-harmonic frequency (SHG) conversion on a PT symmetry line, i.e., a set consisting of open-ended isofrequency or isoloss lines, both terminated at EPs on the Riemann surface in parameter space. The enhancement factor can reach as high as 300, depending on the crossing point whether in the symmetry or the broken phase of the PT line. Moreover, such enhancement of SHG enables sensitive distance sensing with a nanometer resolution. Our works may pave the way for practical applications in sensing, frequency conversion, and coherent wave control.

4.
Acta Pharmacol Sin ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39284877

RESUMO

Palmitoyl-protein thioesterase 1 (PPT1) is a lysosomal depalmitoylation enzyme that mediates protein posttranslational modifications. Loss-of-function mutation of PPT1 causes a failure of the lysosomal degradation of palmitoylated proteins and results in a congenital disease characterized by progressive neuronal degeneration referred to as infantile neuronal ceroid lipofuscinosis (INCL). A mouse knock-in model of PPT1 (PPT1-KI) was established by introducing the R151X mutation into exon 5 of the PPT1 gene, which exhibited INCL-like pathological lesions. We previously reported that hippocampal γ oscillations were impaired in PPT1 mice. Hippocampal γ oscillations can be enhanced by selective activation of the dopamine D4 receptor (DR4), a dopamine D2-like receptor. In this study, we investigated the changes in DR expression and the effects of dopamine and various DR agonists on neural network activity, cognition and motor function in PPT1KI mice. Cognition and motor defects were evaluated via Y-maze, novel object recognition and rotarod tests. Extracellular field potentials were elicited in hippocampal slices, and neuronal network oscillations in the gamma frequency band (γ oscillations) were induced by perfusion with kainic acid (200 nM). PPT1KI mice displayed progressive impairments in γ oscillations and hippocampus-related memory, as well as abnormal expression profiles of dopamine receptors with preserved expression of DR1 and 3, increased membrane expression of DR4 and decreased DR2 levels. The immunocytochemistry analysis revealed the colocalization of PPT1 with DR4 or DR2 in the soma and large dendrites of both WT and PPT1KI mice. Immunoprecipitation confirmed the interaction between PPT1 and DR4 or DR2. The impaired γ oscillations and cognitive functions were largely restored by the application of exogenous dopamine, the selective DR2 agonist quinpirole or the DR4 agonist A412997. Furthermore, the administration of A412997 (0.5 mg/kg, i.p.) significantly upregulated the activity of CaMKII in the hippocampus of 5-month-old PPT1KI mice. Collectively, these results suggest that the activation of D2-like dopamine receptors improves cognition and network activity in PPT1KI mice and that specific DR subunits may be potential targets for the intervention of neurodegenerative disorders, such as INCL.

5.
Acta Pharmacol Sin ; 45(6): 1287-1304, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38360930

RESUMO

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Humanos , Feminino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Farmacologia em Rede , Modelos Biológicos , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Camundongos , Linhagem Celular Tumoral , Metástase Neoplásica
6.
Chirality ; 36(1): e23628, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37926465

RESUMO

The chiral media is crucial to the chiral recognition and separation of enantiomers. In this study, we report the preparation of novel chiral carbon nanoparticles (CCNPs) via surface passivation using glucose as the carbon source and S-(-)-α-methylbenzylamine as the chiral ligand. The structures of the obtained CCNPs are characterized via FT-IR, Raman spectroscopy, DLS, XPS, XRD, TEM, and zeta potential analysis. These CCNPs could be employed as the chiral adsorbent and used for the enantioselective adsorption of the ibuprofen enantiomers. The results demonstrated that the CCNPs could selectively adsorb R-enantiomer from ibuprofen racemate solution and give an enantiomeric excess (e.e.) of about 50% under an optimal adsorption condition. Moreover, the regeneration efficiency of the CCNPs remained above e.e. of 43% after the fifth cycle. The present work confirmed that the prepared CCNPs show great potential in the enantioselective separation of ibuprofen racemate.


Assuntos
Ibuprofeno , Nanopartículas , Estereoisomerismo , Adsorção , Espectroscopia de Infravermelho com Transformada de Fourier , Carbono
7.
Langenbecks Arch Surg ; 409(1): 64, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363369

RESUMO

BACKGROUND: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment. METHODS: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I2), to analyze the clinical outcome of FSG. RESULTS: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups. CONCLUSIONS: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk.


Assuntos
Pé Diabético , Transplante de Pele , Cicatrização , Animais , Humanos , Derme Acelular , Doença Crônica , Pé Diabético/cirurgia , Peixes , Transplante de Pele/métodos , Resultado do Tratamento
8.
J Clin Nurs ; 33(3): 1012-1021, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38156743

RESUMO

AIMS: This study aims to investigate the impact of nurses' experiences of hospital violence on resilience, the mediating effect of trust in patients and the moderating effect of organizational trust. BACKGROUND: Despite belonging to the central part of health care worldwide and being the leading provider of medical services, nurses are often subjected to hospital violence, which affects their physical and mental well-being. Trust is a high-order mechanism that encourages positive thinking and personal and professional development. However, research into the impact of trust on resilience concerning nurses' experiences of hospital violence is limited. METHODS: The participants were 2331 nurses working in general hospitals in China. A cross-sectional survey was conducted, and data were collected via questionnaires from July to October 2022 and analysed using SPSS 25.0 and SPSS PROCESS 3.3 macros. This study was prepared and reported according to the STROBE checklist. RESULTS: Mean trust in patients was 48.00 ± 10.86 (12-60), mean organizational trust was 56.19 ± 8.90 (13-65) and mean resilience was 78.63 ± 19.26 (0-100). Nurses' experience of hospital violence had a direct negative effect on resilience (ß = -.096, p = .871), a significant adverse effect on trust in patients (ß = -3.022, p < .001) and a significant positive effect on trust in patients on resilience (ß = 1.464, p < .001). Trusting patients played a mediating role. The significant moderating effect of organizational trust between experience of hospital violence and trust in patients was moderated by a mediating effect index of -0.1867 (95% CI = [-0.3408, -0.0345]). CONCLUSIONS: Nurses' experience of hospital violence exerted a negative effect on resilience, trust in patients had a fully mediated effect and organizational trust had a significant moderating influence in the pathway from nurses' experience of hospital violence to patients' trust-mediated resilience. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study highlights the impact of nurses' experiences of hospital violence on resilience and explores the importance of trust from the nurses' perspective. Measures taken by managers to provide nurses with a safe, trusting and positive work environment can be highly beneficial in enhancing nurse resilience.


Assuntos
Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Resiliência Psicológica , Humanos , Estudos Transversais , Hospitais , Violência , Inquéritos e Questionários , Satisfação no Emprego
9.
Int J Mol Sci ; 25(20)2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39456760

RESUMO

Camellia flavida var. flavida, commonly known as "Jinhua Tea", has its flowers and leaves traditionally utilized as tea and functional food sources. However, there is limited knowledge about its bioactive components and their biological activities. This study isolated ten previously unidentified glycoside compounds from the flowers of Camellia flavida, including three oleanane-type triterpenoid saponins (compounds 1-3) and seven flavonoid glycosides (compounds 4-10), collectively named flavidosides A-J. This study assessed the cytotoxicity of these compounds against a panel of human cancer cell lines and their α-glucosidase inhibitory activities. Notably, flavidoside C showed significant cytotoxicity against BEL-7402 and MCF-7 cell lines, with IC50 values of 4.94 ± 0.41 and 1.65 ± 0.39 µM, respectively. Flavidoside H exhibited potent α-glucosidase inhibitory activity, with an IC50 value of 1.17 ± 0.30 mM. These findings underscore the potential of Camellia flavida in the development of functional foods.


Assuntos
Camellia , Flavonoides , Flores , Inibidores de Glicosídeo Hidrolases , Glicosídeos , Saponinas , Humanos , Saponinas/farmacologia , Saponinas/química , Camellia/química , Glicosídeos/farmacologia , Glicosídeos/química , Flores/química , Flavonoides/farmacologia , Flavonoides/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Linhagem Celular Tumoral , Triterpenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células MCF-7 , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , alfa-Glucosidases/metabolismo
10.
Plant J ; 110(5): 1397-1414, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35322500

RESUMO

La proteins are found widely in eukaryotes and play a variety of vital roles. AtLa1 has been identified as an La protein that is necessary for embryogenesis in Arabidopsis; however, the existence and biological functions of La proteins in rice (Oryza sativa L.) remain unclear. In this study, we identified and characterized two La proteins in rice that are homologous to AtLa1 and named them OsLa1 and OsLa2. Both the OsLa1 and OsLa2 genes encode RNA-binding proteins with an La domain and two RNA-binding domains. Mutant OsLa1 reduced grain length and pollen fertility, whereas OsLa1 overexpression caused the opposite phenotypes. Further experiments indicated that OsLa1 modulates grain size by influencing cell expansion. Interestingly, mutant OsLa2 resulted in thin grains with decreased weight and a low seed-setting rate. We also found that OsLa1 interacted with OsLa2 and that both OsLa1 and OsLa2 interacted with OseIF6.1, a eukaryotic translation initiation factor involved in ribosome biogenesis. In addition, OsLa1 was able to bind to OseIF6.1 mRNA to modulate its expression. Complete OseIF6.1 knockout caused lethality and OseIF6.1/oseif6.1 heterozygous plants displayed low fertility and low seed setting. Together, our results enrich our knowledge of the role of La proteins in rice growth and development, as well as the relationship between La and eIF6 in rice.


Assuntos
Arabidopsis , Oryza , Arabidopsis/genética , Grão Comestível/genética , Grão Comestível/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Sementes/metabolismo
11.
Phys Rev Lett ; 131(22): 223801, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101337

RESUMO

We present an approach to achieve zero modes in lattice models that do not rely on any symmetry or topology of the bulk, which are robust against disorder in the bulk of any type and strength. Such symmetry-free zero modes (SFZMs) are formed by attaching a single site or small cluster with zero mode(s) to the bulk, which serves as the "nucleus" that expands to the entire lattice. We identify the requirements on the couplings between this boundary and the bulk, which reveals that this approach is intrinsically non-Hermitian. We then provide several examples with either an arbitrary or structured bulk, forming spectrally embedded zero modes in the bulk continuum, midgap zero modes, and even restoring the "zeroness" of coupling or disorder-shifted topological corner states. Focusing on viable realizations using photonic lattices, we show that the resulting SFZM can be observed as the single lasing mode when optical gain is applied to the boundary.

12.
Phys Rev Lett ; 130(26): 263801, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37450823

RESUMO

Topological effects in photonic non-Hermitian systems have recently led to extraordinary discoveries including nonreciprocal lasing, topological insulator lasers, and topological metamaterials, to mention a few. These effects, although realized in non-Hermitian systems, are all stemming from their Hermitian components. Here we experimentally demonstrate the topological skin effect and boundary sensitivity, induced by the imaginary gauge field in a two-dimensional laser array, which are fundamentally different from any Hermitian topological effects and intrinsic to open systems. By selectively and asymmetrically injecting gain into the system, we have synthesized an imaginary gauge field on chip, which can be flexibly reconfigured on demand. We show not only that the non-Hermitian topological features remain intact in a nonlinear nonequilibrium system, but also that they can be harnessed to enable persistent phase locking with intensity morphing. Our work lays the foundation for a dynamically reconfigurable on-chip coherent system with robust scalability, attractive for building high-brightness sources with arbitrary intensity profiles.


Assuntos
Lasers , Fótons
13.
Mol Biol Rep ; 50(1): 889-897, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36367659

RESUMO

Helicobacter pylori (H. pylori) is a common pathogen that infects more than half of the world's population. Its infection can not only lead to a variety of gastrointestinal diseases, such as chronic gastritis and gastric cancer (GC) but also be associated with many extra-gastrointestinal diseases. Exosomes, as a new intercellular information transmission medium, can carry biological signal molecules such as microRNAs (miRNAs) to regulate a variety of cellular physiological activities and are involved in multiple cancer processes. In this article, we provide a systematic review on the role of exosomal miRNAs in H. pylori-associated GC.


Assuntos
Exossomos , Infecções por Helicobacter , MicroRNAs , Neoplasias Gástricas , Humanos , Exossomos/genética , Mucosa Gástrica , Infecções por Helicobacter/genética , Infecções por Helicobacter/complicações , Helicobacter pylori , MicroRNAs/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia
14.
J Nat Prod ; 86(7): 1793-1800, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37358590

RESUMO

Six new ursane-type triterpenes with a phenylpropanoid unit and five known oleanane-type triterpenes were isolated from the leaves of Camellia ptilosperma. The undescribed compounds were identified by analysis of 1D and 2D NMR and HRESIMS spectroscopic data as ptilospermanols A-F. The cytotoxicity of new compounds against six human cancer cell lines and three mouse tumor cell lines was evaluated by MTT assay.


Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Camellia , Triterpenos , Humanos , Animais , Camundongos , Triterpenos/farmacologia , Triterpenos/química , Camellia/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Estrutura Molecular , Linhagem Celular Tumoral
15.
Int J Mol Sci ; 24(23)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38069101

RESUMO

Plasmodiophora brassicae (P. brassicae) is a soil-born pathogen worldwide and can infect most cruciferous plants, which causes great yield decline and economic losses. It is not well known how microbial diversity and community composition change during P. brassicae infecting plant roots. Here, we employed a resistant and a susceptible pakchoi cultivar with and without inoculation with P. brassicae to analyze bacterial and fungal diversity using 16S rRNA V3-V4 and ITS_V1 regions, respectively. 16S rRNA V3-V4 and ITS_V1 regions were amplified and sequenced separately. Results revealed that both fungal and bacterial diversity increased, and composition was changed in the rhizosphere soil of the susceptible pakchoi compared with the resistant cultivar. In the four groups of R_mock, S_mock, R_10d, and S_10d, the most relatively abundant bacterium and fungus was Proteobacteria, accounting for 61.92%, 58.17%, 48.64%, and 50.00%, respectively, and Ascomycota, accounting for 75.11%, 63.69%, 72.10%, and 90.31%, respectively. A total of 9488 and 11,914 bacteria were observed uniquely in the rhizosphere soil of resistant and susceptible pakchoi, respectively, while only 80 and 103 fungi were observed uniquely in the correlated soil. LefSe analysis showed that 107 and 49 differentially abundant taxa were observed in bacteria and fungi. Overall, we concluded that different pakchoi cultivars affect microbial diversity and community composition, and microorganisms prefer to gather around the rhizosphere of susceptible pakchoi. These findings provide a new insight into plant-microorganism interactions.


Assuntos
Microbiota , Micobioma , Plasmodioforídeos , Microbiota/genética , Plasmodioforídeos/genética , RNA Ribossômico 16S/genética , Rizosfera , Fungos/genética , Microbiologia do Solo , Bactérias/genética , Solo , Raízes de Plantas/microbiologia
16.
Molecules ; 28(20)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37894536

RESUMO

Phytochemical investigation of the leaves of Camellia ptilosperma S. Y. Liang et Q. D. Chen led to the isolation of ten undescribed compounds, including six new triterpenes (1-6) and four new pheophorbide-related compounds (7-10). Meanwhile, the cytotoxic activity of the six triterpenes against six cancer cell lines was evaluated by MTT assay. Compound 2 showed potent cytotoxicity toward HepG2 cells with an IC50 value of 2.57 µM. Compounds 4 and 5 exhibited cytotoxicity against MDA-MB231 cells, with IC50 values of 11.31 and 5.52 µM, respectively. Additionally, the cytotoxicity of four new pheophorbides against these cancer cells was evaluated both in the presence and absence of light treatment. Compound 7 exhibited exceptional photocytotoxicity against Hela, MCF-7, and A549 cells, with IC50 values of 0.43 µM, 0.28 µM, and 0.92 µM, respectively. Compound 10 demonstrated significant photodynamic cytotoxic activity against BEL-7402 and HepG2 cells with IC50 values of 0.77 µM and 0.33 µM, respectively. The photodynamic antibacterial activity of 7-10 was also tested for S. aureus, E. coli, K. pneumoniae, and P. aeruginosa under direct illumination. Compounds 8 and 10 exhibited sensitivity to E. coli and demonstrated a photodynamic antibacterial effect, with a MIC value of 0.625 µM.


Assuntos
Antineoplásicos , Camellia , Triterpenos , Humanos , Triterpenos/química , Camellia/química , Staphylococcus aureus , Escherichia coli , Estrutura Molecular , Antibacterianos/química , Células HeLa , Antineoplásicos/farmacologia
17.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(5): 781-792, 2023 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-37807730

RESUMO

OBJECTIVE: To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients. METHODS: By exploring the half maximum inhibitory concentration (IC50) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance. RESULTS: Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC50 were significantly higher than those of the sensitive cell lines (10.99 µmol/L, P < 0.01; 11.96 µmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 µmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib. CONCLUSION: ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Axitinibe/farmacologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteína X Associada a bcl-2 , Proteínas Nucleares , Linhagem Celular Tumoral , Apoptose , Proliferação de Células
18.
Int Nurs Rev ; 70(4): 518-526, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37584307

RESUMO

AIM: The purpose of this study was to explore whether clinical ethical climate mediates the relationship between resilience and moral courage in a population of clinical nurses during COVID-19, and if moral distress faced by nurses is a moderating factor. BACKGROUND: Resilience can help nurses maintain their personal health during COVID-19 when they face great physical and psychological shock and are prone to health problems. Moral courage, as an ethical competency, helps nursing staff in adhering to the principles and values of professional ethics. There is a strong correlation between resilience and moral courage, but the mechanism by which resilience contributes to moral courage is unclear. METHOD: A cross-sectional study research is designed. Three hundred thirty clinical nurses from six hospitals in Beijing, Sichuan, and Fujian of China were included between August 2021 and March 2022. The survey instruments include the Nurses' Moral Courage Scale (NMCS), Connor-Davidson Resilience Scale (CD-RISC), Moral Distress Scale-Revised (MDS-R), and Hospital Ethical Climate Scale (HECS). RESULTS: Ethical climate mediates 15% of the relationship between resilience and moral courage. The association between resilience and ethical climate, as well as the indirect relationship between resilience and moral courage, was modified by moral distress. DISCUSSION: This study investigated the mechanisms by which resilience affects moral courage in clinical nurses in the context of COVID-19, suggesting that moral courage can be increased by alleviating moral distress and increasing ethical climate. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study confirms the mediating effect of moral climate on the relationship between resilience and moral courage, as well as the moderating effect of moral distress. Hospital policymakers should value nurses' psychological resilience and moral courage, develop effective policies to prevent and manage stressors, build social support systems, and create a positive ethical climate.


Assuntos
COVID-19 , Coragem , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Resiliência Psicológica , Humanos , COVID-19/epidemiologia , Estudos Transversais , Princípios Morais , Enfermeiras e Enfermeiros/psicologia , Recursos Humanos de Enfermagem Hospitalar/psicologia , Inquéritos e Questionários
19.
Int Ophthalmol ; 43(12): 4921-4931, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37837486

RESUMO

OBJECTIVES: To investigate the current surgery strategies for bilateral proliferative diabetic retinopathy (PDR), as well as the surgical outcomes of patients with bilateral PDR who underwent pars plana vitrectomy (PPV). MATERIALS: Patients undergoing bilateral vitrectomy for PDR from January 2019 to December 2020 at The Eye Hospital of Wenzhou Medical University were enrolled. Clinical data were collected from the electronic medical records. Factors associated with the time interval between the surgeries on two eyes and postoperative visual outcomes were analyzed. RESULTS: In total, 152 patients with bilateral PDR who underwent bilateral PPV were included in this analysis. Mean age was 53.7 ± 11.4 years. Compared with second-surgery eyes, 60.5% of first-surgery eyes had worse preoperative best-corrected visual acuity (BCVA). The overall PPV time (median, quartile range) between first and second surgeries eye was 1.40 (0.70, 3.15) months. Multivariate analysis showed that the preoperative BCVA of the second-surgery eye had a significant effect on the inter-surgery time interval (P = 0.048). First-surgery eyes had greater vision improvement than second-surgery eyes (Difference of the logarithm of the minimum angle of resolution [LogMAR] BCVA: - 1.00 [- 1.48, - 0.12] versus 0.00 [- 1.30, 0.00], respectively, P < 0.001), especially when eyes with poorer BCVA underwent PPV first (- 1.15 [- 1.87, - 0.54] versus 0.00 [- 0.70, 0.00], respectively, P < 0.001). CONCLUSIONS: Visual acuity is a significant factor that influences surgical strategies, including both surgery order and interval, for patients with bilateral PDR. The eyes operated upon first show more vision improvement due to prompt surgery.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Vitreorretinopatia Proliferativa , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Retinopatia Diabética/complicações , Vitrectomia , Olho , Acuidade Visual , Estudos Retrospectivos
20.
Phys Rev Lett ; 129(24): 243901, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36563238

RESUMO

An imaginary gauge transformation is at the core of the non-Hermitian skin effect. Here, we show that such a transformation can be performed in momentum space as well, which reveals that certain gain- and loss-modulated systems in their parity-time (PT) symmetric phases are equivalent to Hermitian systems with real potentials. Our analysis in momentum space also distinguishes two types of exceptional points (EPs) in the same system. Besides the conventional type that leads to a PT transition upon the continuous increase of gain and loss, we find real-valued energy bands connected at a Dirac EP in hybrid dimensions, consisting of a spatial dimension and a synthetic dimension for the gain and loss strength.

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