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1.
Heliyon ; 10(7): e28347, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560201

RESUMO

This research aimed to identify the factors that influence impulse buying behavior during livestreaming and advance the existing literature based on a proposed conceptual framework grounded in the stimulus-organism-response (S-O-R) model. We also tested the moderating effects of price perception and scarcity persuasion. An online self-administered questionnaire was used to collect data from 837 Chinese participants aged over 18 years. The data were analyzed using partial least squares structural equation modeling using Smart-PLS version 4.0. The findings showed that susceptibility to social influence, impulse buying tendency, cognitive reactions, affective reactions, and the urge to buy impulsively are statistically significant predictors of impulse buying during livestreaming, with price perception and scarcity persuasion as moderators. The study expands the S-O-R model for livestreaming impulse buying in e-commerce context, highlighting its multifaceted nature and revealing the mediating role of Urge to Buy Impulsively in translating cognitive and emotional factors into impulse buying behavior. These insights offer practical guidance for marketers to design tailored strategies that leverage psychological triggers and external cues to enhance consumer engagement and encourage desired behaviors, ultimately leading to more effective marketing campaigns and improved consumer experiences.

2.
Dalton Trans ; 53(17): 7470-7476, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38595157

RESUMO

A series of two-dimensional (2D) spin-crossover coordination polymers (SCO-CPs) [FeII(TPE)(NCX)2]·solv (1: X = BH3, solv = H2O·2CH3OH·DMF; 2: X = Se, solv = H2O·2CH3OH·0.5DMF; 3: X = S, solv = H2O·2CH3OH·0.5DMF) were synthesized by employing 1,1,2,2-tetra(pyridin-4-yl)ethene (TPE) and pseudohalide (NCX-) coligands. Magnetic measurements indicated that complexes 1-3 exhibited SCO behaviors with diminishing thermal hysteresis (7/4/0 K) upon decreasing the ligand-field strength. The critical temperatures (Tc) during spin transition were found to be inversely proportional to the coordination ability parameters (a™) with a linear correlation. The guest effect was also investigated in the solvent-exchanged phases 1-SE/2-SE/3-SE wherein the DMF molecules were replaced by methanol molecules. Compared with 1-3, 1-SE/2-SE/3-SE displayed more abrupt and complete single-step SCO behaviors but narrower thermal hysteretic loops. The results reported here demonstrate that the Tc values of these two families were dominated by the ligand-field strength of the NCX- anions (NCBH3 > NCSe > NCS), whereas the guest effect only modulated the kinetic factor of the SCO nature in this system.

3.
Sports Med ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687441

RESUMO

There are several modifiable factors that can be targeted to prevent and manage the occurrence and progression of cancer, and maintaining adequate exercise is a crucial one. Regular physical exercise has been shown to be a beneficial strategy in preventing cancer, potentially amplifying the effectiveness of established cancer therapies, alleviating certain cancer-related symptoms, and possibly mitigating side effects resulting from treatment. Nevertheless, the exact mechanisms by which exercise affects tumors, especially its impact on the tumor microenvironment (TME), remain uncertain. This review aims to present an overview of the beneficial effects of exercise in the context of cancer management, followed by a summary of the exercise parameters, especially exercise intensity, that need to be considered when prescribing exercise for cancer patients. Finally, we discuss the influence of exercise on the TME, including its effects on crucial immune cells (e.g., T cells, macrophages, neutrophils, natural killer cells, myeloid-derived suppressor cells, B cells), intratumor angiogenesis, and cancer metabolism. This comprehensive review provides up-to-date scientific evidence on the effects of exercise training on cancer and offers guidance to clinicians for the development of safe and feasible exercise training programs for cancer patients in clinical practice.

4.
Cancers (Basel) ; 16(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38473249

RESUMO

The strategy of drug repurposing has gained traction in the field of cancer therapy as a means of discovering novel therapeutic uses for established pharmaceuticals. Paroxetine (PX), a selective serotonin reuptake inhibitor typically utilized in the treatment of depression, has demonstrated promise as an agent for combating cancer. Nevertheless, the specific functions and mechanisms by which PX operates in the context of triple-negative breast cancer (TNBC) remain ambiguous. This study aimed to examine the impact of PX on TNBC cells in vitro as both a standalone treatment and in conjunction with other pharmaceutical agents. Cell viability was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, apoptosis was assessed through flow cytometry, and the effects on signaling pathways were analyzed using RNA sequencing and Western blot techniques. Furthermore, a subcutaneous tumor model was utilized to assess the in vivo efficacy of combination therapy on tumor growth. The results of our study suggest that PX may activate the Ca2+-dependent mitochondria-mediated intrinsic apoptosis pathway in TNBC by potentially influencing the PI3K/AKT/mTOR pathway as well as by inducing cytoprotective autophagy. Additionally, the combination of PX and chemotherapeutic agents demonstrated moderate inhibitory effects on 4T1 tumor growth in an in vivo model. These findings indicate that PX may exert its effects on TNBC through modulation of critical molecular pathways, offering important implications for improving chemosensitivity and identifying potential therapeutic combinations for clinical use.

5.
ACS Nano ; 18(12): 9160-9175, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38478910

RESUMO

The activation of multiple Pattern Recognition Receptors (PRRs) has been demonstrated to trigger inflammatory responses and coordinate the host's adaptive immunity during pathogen infections. The use of PRR agonists as vaccine adjuvants has been reported to synergistically induce specific humoral and cellular immune responses. However, incorporating multiple PRR agonists as adjuvants increases the complexity of vaccine design and manufacturing. In this study, we discovered a polymer that can activate both the Toll-like receptor (TLR) pathway and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. The polymer was then conjugated to protein antigens, creating an antigen delivery system for subunit vaccines. Without additional adjuvants, the antigen-polymer conjugates elicited strong antigen-specific humoral and cellular immune responses. Furthermore, the antigen-polymer conjugates, containing the Receptor Binding Domain (RBD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein or the Monkeypox Antigen M1R as the antigens, were found to induce potent antigen-specific antibodies, neutralizing antibodies, and cytotoxic T cells. Immunization with M1R-polymer also resulted in effective protection in a lethal challenge model. In conclusion, this vaccine delivery platform offers an effective, safe, and simple strategy for inducing antigen-specific immunity against infectious diseases.


Assuntos
Adjuvantes Imunológicos , Polímeros , Adjuvantes Imunológicos/farmacologia , Antígenos , Imunidade Celular , Vacinas de Subunidades Antigênicas , Anticorpos Neutralizantes , Imunidade Inata , Anticorpos Antivirais
6.
PLoS One ; 19(2): e0293914, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38359026

RESUMO

The millions-worth revenue derived from large-scale food delivery characterises the service as a relatively established phenomenon with potential growth. The current cross-sectional research examined online food delivery service quality on consumer satisfaction and reuse intention. Service quality was divided into seven categories (i.e., reliability, assurance, security, maintaining food quality, system operation, traceability, and perceived service value). Perceived service value offer the unique understanding of the online food delivery consumer satisfaction. Empirical data were elicited from 1352 valid respondents and subsequently assessed through the partial least square structural equation modelling. Findings revealed that reliability, assurance, maintaining food quality, system operation, traceability, and perceived service value could elevate customer satisfaction and optimize the intention to reuse food delivery services. Specific measures to improve service quality, including staff training, improved after-sales service, and system optimisation, were proposed to increase users' satisfaction and intention to reuse optimally.


Assuntos
Comportamento do Consumidor , Intenção , Humanos , Reprodutibilidade dos Testes , Estudos Transversais , Qualidade dos Alimentos , Satisfação Pessoal
7.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5356-5364, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38114125

RESUMO

This study aims to investigate the mechanism of Linderae Radix water extract(LRWE) in the prevention and treatment of diarrhea-predominant irritable bowel syndrome(IBS-D) based on serum metabolomics. Eighteen 2-week-old male SD rats were randomized into control, IBS-D model, and LRWE groups. The rats in other groups except the control group received gavage of senna concentrate combined with restraint stress for the modeling of IBS-D. The rats in the LRWE group were administrated with LRWE(5.4 g·kg~(-1)) by gavage, and those in the control and IBS-D model groups with an equal volume of distilled water for a total of 14 days. The visceral sensitivity was evaluated by the abdominal withdrawal reflex(AWR) score, and the degree of diarrhea was assessed by the fecal water content(FWC). The morphological changes of the colon and the morphology and number of goblet cells were observed by hematoxylin-eosin(HE) and periodic acid-schiff(PAS) staining, respectively. Ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was used for the screening of the potential biomarkers in the rat serum and their related metabolic pathways. The results showed that LRWE reduced the AWR score, decreased FWC, and alleviated visceral sensitivity and diarrhea symptoms in IBS-D rats. HE and PAS staining showed that LRWE mitigated low-grade intestinal inflammation and increased the number of mature secretory goblet cells in the colonic epithelium of IBS-D rats. A total of 25 potential biomarkers of LRWE in treating IBS-D were screened out in this study, which were mainly involved in riboflavin, tryptophan, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, and cysteine and methionine metabolism. The regulatory effects were the most significant on the riboflavin and tryptophan metabolism pathways. LRWE may alleviate the visceral hypersensitivity by promoting energy metabolism and amino acid metabolism, enhancing intestinal barrier function, and improving intestinal immune function in IBS-D rats.


Assuntos
Síndrome do Intestino Irritável , Ratos , Masculino , Animais , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/metabolismo , Água , Cromatografia Líquida , Triptofano , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Diarreia/tratamento farmacológico , Biomarcadores , Riboflavina
8.
Int J Mol Sci ; 24(24)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38138967

RESUMO

In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration, while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6-deficient mice had smaller neointima. In vitro, IL-1ß induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 reduced IL-1ß-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1ß-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1ß, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1ß decreased the levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs, whereas lack of DUSP6 maintained their high levels, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.


Assuntos
Fosfatases de Especificidade Dupla , Neointima , Lesões do Sistema Vascular , Animais , Camundongos , Caderinas , Movimento Celular , Proliferação de Células , Células Cultivadas , Fosfatases de Especificidade Dupla/genética , Hiperplasia , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso , Neointima/genética , Neointima/prevenção & controle , Lesões do Sistema Vascular/genética
9.
Sci Rep ; 13(1): 15106, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704693

RESUMO

The culture of fast fashion accelerates the consumption rate of individuals but at the expense of significant environmental stress. With a large amount of discarded clothing accumulating in landfills, it is crucial to encourage people to dispose of second-hand clothing (SHC) as sustainably as possible, especially in an emerging economy with large volume consumption. Through a survey of 619 respondents from China, this study explored the factors affecting people's intentions and actual donation behaviors toward SHC. It extends the theory of interpersonal behavior (TIB) with environmental factors to construct a research framework, which included cognitive factors (attitude towards sustainable consumption), social factors (sense of community) and personal factors (perceived hedonic benefit) under TIB and the environment factors refers to problem awareness and ascription responsibility. Partial least squares structural equation modeling was employed to analyze the data. The findings revealed that attitudes toward sustainable consumption, problem awareness, ascription of responsibility, sense of community, and perceived hedonic benefit significantly and positively influenced people's intentions and practices of SHC donation. This study will aid governments and relevant green environmental protection organizations in formulating more precise strategies for sustainable development, and promote relevant research on the sustainable disposal of SHC.

10.
Environ Sci Pollut Res Int ; 30(44): 99855-99874, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37615918

RESUMO

The current global trend in sustainable business practices is to optimize green innovation performance. To protect the environment and maintain their own survival, organizations must strengthen their green innovation capabilities. Drawing on the recourse-based view and ecology modernization theory (EMT), this study examines the direct effect of green strategic orientations, green entrepreneurial orientation, green market orientation, green innovation orientation, and green organizational culture on the firm's green innovation capability, as well as the mediating effect of green innovation capability on the relationship of these four factors and green innovation performance. Besides, this study also explored the moderating effects of green management system implementation and firm size on the association between green innovation capability and green innovation performance. To test the hypothesized model, a questionnaire survey was administered to gather responses from 293 medium-sized and large manufacturing firms operating in Pakistan. The partial least squares method was used for data analysis. The results revealed that green entrepreneurial orientation, green market orientation, green innovation orientation, and green organizational culture positively impacted green innovation capability, which subsequently positively influenced green innovation performance. Moreover, effective implementation of green management systems can bolster the effect of green innovation capability on green innovation performance, and the mediating effect of green innovation capability has also been confirmed. These indicated that the management of medium and large manufacturing firms operating in Pakistan should focus on encouraging green innovation and training employees regarding the latest eco-friendly technologies to attain performance and sustainable development goals. Policymakers should implement green business development programs and offer rewards or penalties for promoting compliance. The present study contributes greatly to the literature by applying EMT as an alternative to address the mediating role of green innovation capability and the moderating effect of green management system implementation in enhancing firms' green innovation performance.


Assuntos
Comércio , Análise de Dados , Humanos , Ecologia , Cultura Organizacional , Paquistão
11.
Curr Zool ; 69(5): 501-513, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37637316

RESUMO

Knowing the diet of endangered wild animals is a prerequisite for species-specific conservation and habitat management. The Sichuan partridge Arborophila rufipectus is a globally endangered Galliformes species endemic to the mountains of southwest China. Existing information on the diet of this species is biased and fragmented owing to traditional observation methods. Little is known about their dietary composition or how they respond to temporal variations in food resources throughout the year. In this study, a dietary analysis was performed on 60 fecal samples using DNA Metabarcoding of invertebrates and plants to determine the primary animal and plant components of the diet across 3 critical periods of adult life history (breeding, postbreeding wandering, and overwintering). Preys from the dipteran order, followed by the lepidopteran and araneaen spp., were the predominant, animal-derived foods. Symplocos, Rubus, Celastrus, Holboellia, and Actinidia spp. supply a large abundance of fruits and seeds for this omnivorous bird. Substantial temporal dietary changes among the 3 periods and a general shift toward lower dietary diversity during the breeding season were observed, suggesting that the Sichuan partridge can adjust their diet according to the availability of food resources and their own needs. Characterizing the composition and seasonal changes in Sichuan partridge diets informs the habitat management of native flora (the plant taxa that can generate berries and seeds, such as Symplocos, Rubus, Celastrus, and Holboellia, which are likely of conservation interest) to achieve full life-cycle conservation.

12.
Sci Rep ; 13(1): 11217, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37433838

RESUMO

This study aims to examine the mediating effect of the intention to use wearable payment devices (WPD) between perceived ease of use (PE), perceived usefulness (PU), social influence (SI), perceived trust (TR), and lifestyle compatibility (CM) on the adoption of WPD. Examination was made on the moderating effect of age and gender to improve the understanding of the adoption of WPD as a new payment system. Empirical data was collected through an online survey from 1094 respondents in Malaysia. Furthermore, this study employed dual-stage data analysis through partial least squares structural equation modelling (PLS-SEM) to test the causal and moderating effects, including artificial neural network (ANN) to examine the predictive power of the selected model. As a result, it was found that PE, PU, TR, and CM had a significant positive influence on the intention to use WPD. Furthermore, facilitating conditions and the intention to use WPD exhibited strong positive impacts on the adoption of WPD among Malaysian youth. The intention to use WPD positively and significantly mediated all predictors of adoption of WPD. Following that, ANN analysis confirmed high prediction accuracy of the data fitness. Overall, the findings for ANN highlighted the importance of PE, CM, and TR on the intention to adopt WPD and the impact of facilitating conditions on the adoption of WPD among Malaysian youth. Theoretically, the study extended UTAUT with two additional determinants (e.g., perceived trust and lifestyle compatibility), which were found to have significant influences on the intention to use WPD. The study results would be able to help payment service providers and the smart wearable device industry offer an innovative spectrum of products and present effective marketing tactics to encourage the prospective consumers of Wearable Payment Devices in Malaysia.


Assuntos
Intenção , Dispositivos Eletrônicos Vestíveis , Adolescente , Humanos , Estudos Prospectivos , Povo Asiático , Redes Neurais de Computação
13.
Arterioscler Thromb Vasc Biol ; 43(8): 1412-1428, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37317853

RESUMO

BACKGROUND: During infectious diseases, proinflammatory cytokines transiently destabilize interactions between adjacent vascular endothelial cells (ECs) to facilitate the passage of immune molecules and cells into tissues. However, in the lung, the resulting vascular hyperpermeability can lead to organ dysfunction. Previous work identified the transcription factor ERG (erythroblast transformation-specific-related gene) as a master regulator of endothelial homeostasis. Here we investigate whether the sensitivity of pulmonary blood vessels to cytokine-induced destabilization is due to organotypic mechanisms affecting the ability of endothelial ERG to protect lung ECs from inflammatory injury. METHODS: Cytokine-dependent ubiquitination and proteasomal degradation of ERG were analyzed in cultured HUVECs (human umbilical vein ECs). Systemic administration of TNFα (tumor necrosis factor alpha) or the bacterial cell wall component lipopolysaccharide was used to cause a widespread inflammatory challenge in mice; ERG protein levels were assessed by immunoprecipitation, immunoblot, and immunofluorescence. Murine Erg deletion was genetically induced in ECs (Ergfl/fl;Cdh5[PAC]-CreERT2), and multiple organs were analyzed by histology, immunostaining, and electron microscopy. RESULTS: In vitro, TNFα promoted the ubiquitination and degradation of ERG in HUVECs, which was blocked by the proteasomal inhibitor MG132. In vivo, systemic administration of TNFα or lipopolysaccharide resulted in a rapid and substantial degradation of ERG within lung ECs but not ECs of the retina, heart, liver, or kidney. Pulmonary ERG was also downregulated in a murine model of influenza infection. Ergfl/fl;Cdh5(PAC)-CreERT2 mice spontaneously recapitulated aspects of inflammatory challenges, including lung-predominant vascular hyperpermeability, immune cell recruitment, and fibrosis. These phenotypes were associated with a lung-specific decrease in the expression of Tek-a gene target of ERG previously implicated in maintaining pulmonary vascular stability during inflammation. CONCLUSIONS: Collectively, our data highlight a unique role for ERG in pulmonary vascular function. We propose that cytokine-induced ERG degradation and subsequent transcriptional changes in lung ECs play critical roles in the destabilization of pulmonary blood vessels during infectious diseases.


Assuntos
Doenças Transmissíveis , Fatores de Transcrição , Humanos , Camundongos , Animais , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Lipopolissacarídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Citocinas/metabolismo , Doenças Transmissíveis/metabolismo , Células Cultivadas , Regulador Transcricional ERG/genética , Regulador Transcricional ERG/metabolismo
14.
PLoS One ; 18(6): e0287699, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37352328

RESUMO

Citrus Huanglongbing (HLB) is one of the most destructive diseases of citrus plants caused by the obligate and phloem-limiting bacterium Candidatus Liberibacter asiaticus (Las). Reliable detection methods are important for successful control of the disease. This study was aimed to develop a rapid and user-friendly on-site detection system for Las using the TaqMan probe-based insulated isothermal polymerase chain reaction (iiPCR) assay. The Las-specific on-site detection system could be completed within one hour by simple DNA extraction coupled with a portable POCKIT device, which can perform PCR amplification and automatically provide qualitative results derived from fluorescence signals. The sensitivity of the TaqMan probe-iiPCR assay could be as low as single copy of Las, comparable to a real-time PCR method. Further testing of the field citrus samples showed 100% agreement between the TaqMan probe-iiPCR assay and the real-time PCR method, and the on-site detection system also demonstrated a great performance of Las detection. With high specificity and sensitivity, the on-site detection system developed in this study becomes a simple, rapid and powerful tool for detecting Las in fields.


Assuntos
Citrus , Rhizobiaceae , Doenças das Plantas/microbiologia , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Citrus/microbiologia , Rhizobiaceae/genética , Liberibacter/genética
15.
Dalton Trans ; 52(16): 5065-5074, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-36960916

RESUMO

Successive structural transformations were observed in a methanolic solution containing 4-iodo-1-methylpyridin-1-ium iodide (IPyMe·I) and bismuth iodide (BiI3). When kept in the solution, the amorphous solid (P_1) obtained immediately on mixing would transform to needle crystals (C_1) in hours, which would convert to prismatic crystals (C_2) in around 2 days. In the presence of hydroiodic acid, the hydrothermal reaction of IPyMe·I and BiI3 also gave rise to C_2, and crystals of C_2 in this solution would transform to a third crystalline product C_3 in ca. 3 days. X-ray single crystal diffraction experiments show C_1 containing one-dimensional {BiI4-}n chains, C_2 as a binuclear Bi2I93- structure, and C_3 consisting of a monomeric BiI63- unit, all with IPyMe+ as counter cations. Halogen bonds exist between IPyMe+ and the iodobismuthate, which may play key roles in the structural transformation. By introducing halogen bonding, the hybrids demonstrate excellent water-resistance. A thermal-induced reversible colour change from yellow to dark red occurred from 100 K to 450 K for all three hybrids, in which lattice expansion over the temperature range may be a reason for the thermochromism. The bandgaps derived from the UV-vis diffusion reflectance for the three complexes were 1.80 eV for C_1, 1.84 eV for C_2 and 2.00 eV for C_3. DTF computations followed by electron density topological analysis were applied to explain the structure-optical property relationship for complexes of diverse iodobismuthate types but the same counter cation. It was found that the nature of the Bi-I bonds rather than the dimensionality of the inorganic iodobismuthates is mainly responsible for the light absorption of the materials.

16.
Clin Exp Metastasis ; 40(2): 161-175, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36952079

RESUMO

Brain metastasis is the main cause of treatment failure and melanoma-related death. Inadequate concentrations of therapeutic drugs in the brain due to the blood-brain barrier (BBB) pose a major challenge in the treatment of brain metastasis. Antipsychotics can cross the BBB to reach the brain. Fluphenazine (FPZ) inhibits the survival of melanoma cells in vitro. However, its efficacy in suppressing the metastasis of melanoma, especially brain metastasis, remains unknown. Therefore, we explored whether fluphenazine (FPZ) can be repurposed for treating melanoma metastasis. A subcutaneous tumor model, and experimental metastasis models that simulate the outgrowth of melanoma cells in the brain, lung, and bone were established to verify the inhibitory effect of FPZ on melanoma cells. FPZ showed potential inhibitory effects against melanoma both in vivo and in vitro. It induced G0/G1 phase arrest and-mitochondrion-mediated intrinsic apoptosis, and inhibited autophagic flux in melanoma cells in vitro. In vivo, subcutaneous tumor, brain, lung, and bone models of metastatic melanoma were established. Intraperitoneal injection of FPZ (8 mg/kg) significantly inhibited melanoma growth in the subcutaneous and experimental metastasis models. In a lung metastasis model, FPZ reduced the proportion of M2 macrophages and increased the proportion of CD8+ T cells and NK cells in vivo, thereby promoting an anticancer immune response. The findings of this study indicate that FPZ is a potential drug candidate for treating metastatic melanoma.


Assuntos
Neoplasias Encefálicas , Melanoma , Humanos , Flufenazina/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular , Linfócitos T CD8-Positivos/patologia , Reposicionamento de Medicamentos , Melanoma/tratamento farmacológico , Melanoma/patologia , Encéfalo/patologia , Neoplasias Encefálicas/tratamento farmacológico , Pulmão/patologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células
17.
bioRxiv ; 2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36798267

RESUMO

Background: During infectious diseases, pro-inflammatory cytokines transiently destabilize interactions between adjacent vascular endothelial cells (ECs) to facilitate the passage of immune molecules and cells into tissues. However, in the lung the resulting vascular hyperpermeability can lead to organ dysfunction. Previous work identified the transcription factor ERG as a master regulator of endothelial homeostasis. Here we investigate whether the sensitivity of pulmonary blood vessels to cytokine-induced destabilization is due to organotypic mechanisms affecting the ability of endothelial ERG to protect lung ECs from inflammatory injury. Methods: Cytokine-dependent ubiquitination and proteasomal degradation of ERG was analyzed in cultured Human Umbilical Vein ECs (HUVECs). Systemic administration of TNFα or the bacterial cell wall component lipopolysaccharide (LPS) was used to cause a widespread inflammatory challenge in mice; ERG protein levels were assessed by immunoprecipitation, immunoblot, and immunofluorescence. Murine Erg deletion was genetically induced in ECs ( Erg fl/fl ;Cdh5(PAC)Cre ERT2 ), and multiple organs were analyzed by histology, immunostaining, and electron microscopy. Results: In vitro, TNFα promoted the ubiquitination and degradation of ERG in HUVECs, which was blocked by the proteasomal inhibitor MG132. In vivo, systemic administration of TNFα or LPS resulted in a rapid and substantial degradation of ERG within lung ECs, but not ECs of the retina, heart, liver, or kidney. Pulmonary ERG was also downregulated in a murine model of influenza infection. Erg fl/fl ;Cdh5(PAC)-Cre ERT2 mice spontaneously recapitulated aspects of inflammatory challenges, including lung-predominant vascular hyperpermeability, immune cell recruitment, and fibrosis. These phenotypes were associated with a lung-specific decrease in the expression of Tek , a gene target of ERG previously implicated in maintaining pulmonary vascular stability during inflammation. Conclusions: Collectively, our data highlight a unique role for ERG in pulmonary vascular function. We propose that cytokine-induced ERG degradation and subsequent transcriptional changes in lung ECs play critical roles in the destabilization of pulmonary blood vessels during infectious diseases.

18.
Environ Entomol ; 52(1): 74-80, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36440698

RESUMO

When the favored host of an herbivorous insect pest is absent, the availability of alternative host plants can maintain insect pest populations. Spodoptera frugiperda (Lepidoptera: Noctuidae) is a major invasive, polyphagous insect pest in China. To investigate the suitability of Chinese cabbage as an alternative host for S. frugiperda, oviposition preferences and life history traits were determined for S. frugiperda on Chinese cabbage, corn, and winter wheat over three generations. Results showed that S. frugiperda females preferred to lay their eggs on corn compared to winter wheat and Chinese cabbage. The survival rate of S. frugiperda decreased after switching from corn to Chinese cabbage, only 6% of individuals successfully pupated in the third generation. In addition, S. frugiperda reared on Chinese cabbage had lower pupal weight and fecundity. Winter wheat was a good host for S. frugiperda; although the survival rate decreased when S. frugiperda switched from corn to winter wheat in the parental generation, the survival rate increased over the next two generations to be as high as those reared on corn. Chinese cabbage is not a good long-term host for S. frugiperda, but it could maintain the pest population for at least two generations when more suitable host plants are unavailable. These results will inform management strategies for S. frugiperda.


Assuntos
Brassica , Mariposas , Feminino , Animais , Spodoptera , Larva , Oviposição , Zea mays
19.
Microorganisms ; 10(12)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36557627

RESUMO

The rice-fish system (RFS), a traditional coculture farming model, was selected as a "globally important agricultural heritage system." Host-associated microbiota play important roles in development, metabolism, physiology, and immune function. However, studies on the gut microbiota of aquatic animals in the RFS are scarce, especially the lack of baseline knowledge of the dynamics of gut microbial communities in rice fish during different developmental stages. In this study, we characterized the microbial composition, community structure, and functions of several sympatric aquatic animals (common carp (Cyprinus carpio), crucian carp (Carassius carassius), and black-spotted frogs (Pelophylax nigromaculatus)), and the environment (water) in the RFS using 16S rRNA gene sequencing. Moreover, we investigated stage-specific signatures in the gut microbiota of common carp throughout the three developmental stages (juvenile, sub-adult, and adult). Our results indicated that the Fusobacteriota, Proteobacteria, and Firmicutes were dominant gut microbial phyla in rice fish. The differences in gut microbial compositions and community structure between the three aquatic species were observed. Although no significant differences in alpha diversity were observed across the three developmental stages, the microbial composition and community structure varied with development in common carp in the RFS, with an increase in the relative abundance of Firmicutes in sub-adults and a shift in the functional features of the community. This study sheds light on the gut microbiota of aquatic animals in the RFS. It deepens our understanding of the dynamics of gut microflora during common carp development, which may help improve aquaculture strategies in the RFS.

20.
Cell Oncol (Dordr) ; 45(6): 1255-1275, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36155886

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. As yet, chemotherapy with drugs such as doxorubicin is the main treatment strategy. However, drug resistance and dose-dependent toxicities restrict their clinical use. Natural products are major sources of anti-tumor drugs. OSW-1 is a natural compound with strong anti-cancer effects in several types of cancer, but its effects on the efficacy of chemotherapy in TNBC and its underlying mechanism remain unclear. METHODS: The inhibitory activities of OSW-1 and its combination with several chemotherapy drugs were tested using in vitro assays and in vivo subcutaneous and metastatic mouse TNBC models. The effects of the mono- and combination treatments on TNBC cell viability, apoptosis, autophagy and related signaling pathways were assessed using MTT, flow cytometry, RNA sequencing and immunology-based assays. In addition, the in vivo inhibitory effects of OSW-1 and (combined) chemotherapies were evaluated in subcutaneous and metastatic mouse tumor models. RESULTS: We found that OSW-1 induces Ca2+-dependent mitochondria-dependent intrinsic apoptosis and cyto-protective autophagy through the PI3K-Akt-mTOR pathway in TNBC cells in vitro. We also found that OSW-1 and doxorubicin exhibited strong synergistic anti-TNBC capabilities both in vivo and in vitro. Combination treatment strongly inhibited spontaneous and experimental lung metastases in 4T1 mouse models. In addition, the combination strategy of OSW-1 + Carboplatin + Docetaxel showed an excellent anti-metastatic effect in vivo. CONCLUSIONS: Our data revealed the mode of action and molecular mechanism underlying the effect of OSW-1 against TNBC, and provided a useful guidance for improving the sensitivity of TNBC cells to conventional chemotherapeutic drugs, which warrants further investigation.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Neoplasias de Mama Triplo Negativas/patologia , Fosfatidilinositol 3-Quinases , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Autofagia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Docetaxel/farmacologia , Docetaxel/uso terapêutico
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