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1.
Nanomaterials (Basel) ; 14(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38607169

RESUMO

Amorphous alloys or metallic glasses (MGs) thin films have attracted extensive attention in various fields due to their unique functional properties. Here, we use in situ heating transmission electron microscopy (TEM) to investigate the thermal stability and crystallization behavior of Pd-Au-Si thin films prepared by a pulsed laser deposition (PLD) method. Upon heating treatment inside a TEM, we trace the structural changes in the Pd-Au-Si thin films through directly recording high-resolution images and diffraction patterns at different temperatures. TEM observations reveal that the Pd-Au-Si thin films started to nucleate with small crystalline embryos uniformly distributed in the glassy matrix upon approaching the glass transition temperature Tg=625K, and subsequently, the growth of crystalline nuclei into sub-10 nm Pd-Si nanocrystals commenced. Upon further increasing the temperature to 673K, the thin films transformed to micro-sized patches of stacking-faulty lamellae that further crystallized into Pd9Si2 and Pd3Si intermetallic compounds. Interestingly, with prolonged thermal heating at elevated temperatures, the Pd9Si2 transformed to Pd3Si. Simultaneously, the solute Au atoms initially dissolved in glassy alloys and eventually precipitated out of the Pd9Si2 and Pd3Si intermetallics, forming nearly spherical Au nanocrystals. Our TEM results reveal the unique thermal stability and crystallization processes of the PLD-prepared Pd-Au-Si thin films as well as demonstrate a possibility of producing a large quantity of pure nanocrystals out of amorphous solids for various applications.

2.
Waste Manag ; 182: 63-73, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38640752

RESUMO

The incineration bottom ash (IBA) was impregnated with nickel to catalyze toluene (tar surrogate) steam reforming. A toluene conversion of >80 % was achieved at 800℃ without activity decay in a 100-h test for 15 %Ni/IBA. An activation stage was observed for Ni/IBA catalysts in the initial 50 âˆ¼ 400 min under different reaction conditions. A series of experiments and characterizations were performed to explore the possible mechanisms for the activation. It was found that the iron species in IBA gradually migrated to the catalyst surface and formed a Ni-FeOx complex owing to the metal-support interaction. The synergy of Ni-FeOx played an important role in improving the activity of Ni/IBA due to the enhanced lattice oxygen activity. Additionally, Ni/IBA catalysts showed a much lower coke deposition rate than Ni/Al2O3 (1.12 vs. 3.45 mg-C/gcat∙h) because of the variable states of FeOx and the abundant basic sites caused by the alkali and alkaline earth metals contained in IBA.

3.
ACS Appl Mater Interfaces ; 16(15): 19247-19253, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38591143

RESUMO

Two-dimensional (2D) transitional metal dichalcogenides (TMDs) have garnered significant attention due to their potential for next-generation electronics, which require device scaling. However, the performance of TMD-based field-effect transistors (FETs) is greatly limited by the contact resistance. This study develops an effective strategy to optimize the contact resistance of WSe2 FETs by combining contact doping and 2D metallic electrode materials. The contact regions were doped using a laser, and the metallic TaSe2 flakes were stacked on doped WSe2 as electrodes. Doping the contact areas decreases the depletion width, while introducing the TaSe2 contact results in a lower Schottky barrier. This method significantly improves the electrical performance of the WSe2 FETs. The doped WSe2/TaSe2 contact exhibits an ultralow Schottky barrier height of 65 meV and a contact resistance of 11 kΩ·µm, which is a 50-fold reduction compared to the conventional Cr/Au contact. Our method offers a way on fabricating high-performance 2D FETs.

4.
J Mater Chem B ; 12(15): 3636-3658, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38529593

RESUMO

Cancer is a growing worldwide health problem with the most broadly studied treatments, in which immunotherapy has made notable advancements in recent years. However, innumerable patients have presented a poor response to immunotherapy and simultaneously experienced immune-related adverse events, with failed therapeutic results and increased mortality rates. Consequently, it is crucial to develop alternate tactics to boost therapeutic effects without producing negative side effects. Ultrasound is considered to possess significant therapeutic potential in the antitumor field because of its inherent characteristics, including cavitation, pyrolysis, and sonoporation. Herein, this timely review presents the comprehensive and systematic research progress of ultrasound-enhanced cancer immunotherapy, focusing on the various ultrasound-related mechanisms and strategies. Moreover, this review summarizes the design and application of current sonosensitizers based on sonodynamic therapy, with an attempt to provide guidance on new directions for future cancer therapy.


Assuntos
Neoplasias , Terapia por Ultrassom , Humanos , Terapia por Ultrassom/métodos , Ultrassonografia , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neoplasias/patologia , Terapia Combinada , Imunoterapia
5.
Food Chem ; 441: 138289, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38176141

RESUMO

Octenyl succinic anhydride-modified chitosan (OSA-CS) was synthesized and applied as a coating material to enhance the stability of docosahexaenoic acid (DHA)-loaded nanoemulsion. Due to the presence of the positively charged OSA-CS coating, the nanoemulsion exhibited a high positive zeta potential and two different layers. Compared with natural CS-coated nanoemulsion, OSA-CS-coated nanoemulsion showed improved storage stability (physical and chemical stability) and stability against environmental stresses (ionic strengths, temperatures and pH). Besides, OSA-CS-coated nanoemulsion protected encapsulated DHA from simulated gastric fluid damage better than that of natural CS-coated nanoemulsion, suggesting that OSA-CS-coated nanoemulsion had the potential to deliver more DHA into the small intestine. In conclusion, based on the comparison of two coating materials, natural chitosan and OSA-CS, it was found that the encapsulated nutrient was better protected by the OSA-CS coating. Such a finding will provide insights to broaden the application of modified chitosan in food delivery systems.


Assuntos
Quitosana , Amido , Ácidos Docosa-Hexaenoicos , Anidridos Succínicos , Emulsões
6.
Hum Cell ; 37(2): 435-450, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218754

RESUMO

Continuously progressive hepatic fibrosis might cause chronic liver diseases, resulting in hepatic failure. The activation of hepatic stellate cells (HSCs) residing in the liver might induce and influence hepatic fibrosis. In the present study, microRNA 3074 (miR-3074) was found increased within transforming growth factor-ß (TGF-ß)-activated HSCs and enriched within the TGF-ß signaling. In activated HSCs by TGF-ß, miR-3074 overexpression aggravated TGF-ß-induced fibrotic changes, whereas miR-3074 inhibition exerted opposite effects. miR-3074 directly targeted bone morphogenetic protein 7 (BMP7) and inhibited BMP7 expression. Under TGF-ß induction, overexpressed BMP7 notably attenuated the promotive roles of miR-3074 overexpression in TGF-ß-activated HSCs. Within carbon tetrachloride (CCl4)-caused liver fibrosis murine model, miR-3074 agomir administration promoted, while LV-BMP7 administration alleviated CCl4-induced fibrotic changes; LV-BMP7 significantly attenuated the effects of miR-3074 agomir. Lastly, mmu-miR-3074 also targeted mouse BMP7 and inhibited mouse BMP7 expression. In conclusion, the miR-3074/BMP7 axis regulates TGF-ß-caused activation of HSCs in vitro and CCl4-caused murine liver fibrosis in vivo. BMP7-mediated Smad1/5/8 activation might be involved.


Assuntos
Células Estreladas do Fígado , MicroRNAs , Animais , Camundongos , Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/efeitos adversos , Proteína Morfogenética Óssea 7/metabolismo , Células Estreladas do Fígado/patologia , Fígado/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/induzido quimicamente , MicroRNAs/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
7.
Biosens Bioelectron ; 247: 115935, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38128319

RESUMO

Long-chain fatty acyl-CoAs (LCACoAs) are intermediates in lipid metabolism that exert a wide range of cellular functions. However, our knowledge about the subcellular distribution and regulatory impacts of LCACoAs is limited by a lack of methods for detecting LCACoAs in living cells and tissues. Here, we report our development of LACSerHR, a genetically encoded fluorescent biosensor that enables precise measurement of subtle fluctuations in the levels of endogenous LCACoAs in vivo. LACSerHR significantly improve the fluorescent brightness and analyte affinity, in vitro and in vivo testing showcased LACSerHR's large dynamic range. We demonstrate LACSerHR's capacity for real-time evaluation of LCACoA levels in specific subcellular compartments, for example in response to disruption of ACSL enzyme function in HEK293T cells. Moreover, we show the application of LACSerHR for sensitive measurement of elevated LCACoA levels in the livers of mouse models for two common metabolic diseases (NAFLD and type 2 diabetes). Thus, our LACSerHR sensor is a powerful, broadly applicable tool for studying LCACoAs metabolism and disease.


Assuntos
Técnicas Biossensoriais , Diabetes Mellitus Tipo 2 , Humanos , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Células HEK293 , Fígado , Metabolismo dos Lipídeos , Acil Coenzima A/metabolismo
8.
ACS Sens ; 8(12): 4484-4493, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38079595

RESUMO

Inositol hexakisphosphate (IP6), a naturally occurring metabolite of inositol with specific functions in different organelles or tissues, participates in numerous physiological processes and plays a key role in mammalian metabolic regulation. However, current IP6 detection methods, i.e., high-performance liquid chromatography and gel electrophoresis, require sample destruction and lack spatiotemporal resolution. Here, we construct and characterize a genetically encoded fluorescence biosensor named HIPSer that enables ratiometric quantitative IP6 detection in HEK293T cells and subcellular compartments. We demonstrate that HIPSer has a high sensitivity and relative selectivity for IP6 in vitro. We also provide proof-of-concept evidence that HIPSer can monitor IP6 levels in real time in HEK293T cells and can be targeted for IP6 detection in the nucleus of HEK293T cells. Moreover, HIPSer could also detect changes in IP6 content induced by chemical inhibition of IP6-metabolizing enzymes in HEK293T cells. Thus, HIPSer achieves spatiotemporally precise detection of fluctuations in endogenous IP6 in live cells and provides a versatile tool for mechanistic investigations of inositol phosphate functions in metabolism and signaling.


Assuntos
Fosfatos de Inositol , Ácido Fítico , Humanos , Fluorescência , Células HEK293 , Fosfatos de Inositol/química , Fosfatos de Inositol/metabolismo , Ácido Fítico/química , Ácido Fítico/metabolismo
9.
Nanomaterials (Basel) ; 13(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37947673

RESUMO

The structure of a material is an important factor in determining its physical properties. Here, we adjust the structure of the Ni50Mn37Ga13 spun ribbons by changing the wheel speed to regulate the exchange bias effect of the material. The characterization results of micromorphology and structure show that as the wheel speed increases, the martensite lath decreases from 200 nm to 50 nm, the structure changed from the NM to a NM and 10M mixed martensitic structure containing mainly NM, then changed to NM and 10M where 10M and NM are approaching. Meanwhile, HE first increased and then decreased as the wheel speed increased. The optimum exchange bias effect (HE = 7.2 kOe) occurs when the wheel speed is 25 m∙s-1, mainly attributed to the enhanced ferromagnetism caused by part of 10M in NM martensite, which enhanced the exchange coupling of ferromagnetism and antiferromagnetism. This work reveals the structural dependence of exchange bias and provides a way to tune the magnitude of the exchange bias of Heusler alloys.

10.
Mar Drugs ; 21(10)2023 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-37888481

RESUMO

The purpose of the study was to investigate the stability and oral delivery of DHA-encapsulated Pickering emulsions stabilized by soy protein isolate-chitosan (SPI-CS) nanoparticles (SPI-CS Pickering emulsions) under various conditions and in the simulated gastrointestinal (GIT) model. The stability of DHA was characterized by the retention rate under storage, ionic strength, and thermal conditions. The oral delivery efficiency was characterized by the retention and release rate of DHA in the GIT model and cell viability and uptake in the Caco-2 model. The results showed that the content of DHA was above 90% in various conditions. The retention rate of DHA in Pickering emulsions containing various nanoparticle concentrations (1.5 and 3.5%) decreased to 80%, while passing through the mouth to the stomach, and DHA was released 26% in 1.5% Pickering emulsions, which was faster than that of 3.5% in the small intestine. After digestion, DHA Pickering emulsions proved to be nontoxic and effectively absorbed by cells. These findings helped to develop a novel delivery system for DHA.


Assuntos
Quitosana , Nanopartículas , Humanos , Proteínas de Soja , Emulsões , Células CACO-2 , Digestão , Tamanho da Partícula
11.
Ecotoxicol Environ Saf ; 265: 115510, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37742572

RESUMO

Fluopyram, a SDH inhibitor fungicide, is widely used in agriculture to control fungi and nematodes. However, fluopyram has been proved toxic that caused damage to organs through oxidative stress. The development of natural extracts that can reduce oxidative damage is a promising method. Lentinan is isolated from Lentinus edodes and has been verified its antioxidant activity. In this study, Caenorhabditis elegans was used to evaluate the protective effects of lentinan against fluopyram-induced toxicity and the possible mechanisms. Results showed that lentinan pretreatment notably increased the survival rate of N2 nematodes by 15.0 % and extended the lifespan by 91.5 %, compared with the fluopyram treatment. Lentinan pretreatment reverted the inhibition of the locomotion and reproduction of C. elegans under the fluopyram stress. In addition, lentinan pretreatment significantly decreased the contents of ROS and MDA in N2 nematodes. Moreover, pretreated with lentinan significantly recovered the decreased activities of CAT, SOD, GST and SDH induced by fluopyram. Lentinan pretreatment enhanced the mRNA levels of daf-16 and skn-1 and their downstream genes in the nematodes compared with the fluopyram group. In daf-16 and skn-1 mutants, the lifespan, ROS and related genes expression were not significantly changed in lentinan pretreatment. Pretreated with lentinan significantly enhanced the fluorescence intensity of SOD-3::GFP and GST-4::GFP, and promoted the nuclear translocation of DAF-16 and SKN-1 under the fluopyram stress. In summary, these findings indicated that lentinan protected C. elegans from fluopyram-induced toxicity via DAF-16 and SKN-1.

12.
Foods ; 12(18)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37761058

RESUMO

Chitooligosaccharides (COS), a high-value chitosan derivative, have many applications in food, pharmaceuticals, cosmetics and agriculture owing to their unique biological activities. Chitosanase, which catalyzes the hydrolysis of chitosan, can cleave ß-1,4 linkages to produce COS. In this study, a chitosanase-producing Bacillus paramycoides BP-N07 was isolated from marine mud samples. The chitosanase enzyme (BpCSN) activity was 2648.66 ± 20.45 U/mL at 52 h and was able to effectively degrade chitosan. The molecular weight of purified BpCSN was approximately 37 kDa. The yield and enzyme activity of BpCSN were 0.41 mg/mL and 8133.17 ± 47.83 U/mg, respectively. The optimum temperature and pH of BpCSN were 50 °C and 6.0, respectively. The results of the high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) of chitosan treated with BpCSN for 3 h showed that it is an endo-chitosanase, and the main degradation products were chitobiose, chitotriose and chitotetraose. BpCSN was used for the preparation of oligosaccharides: 1.0 mg enzyme converted 10.0 g chitosan with 2% acetic acid into oligosaccharides in 3 h at 50 °C. In summary, this paper reports that BpCSN has wide adaptability to temperature and pH and high activity for hydrolyzing chitosan substrates. Thus, BpCSN is a chitosan decomposer that can be used for producing chitooligosaccharides industrially.

13.
J Med Chem ; 66(16): 11282-11293, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37535016

RESUMO

2'-Deoxy-2'-ß-fluoroadenosines bearing 4'-azido or 4'-ethynyl groups designed for the treatment of HIV-1 infection have been synthesized. All these compounds possess nanomolar anti-HIV-1 activity, with the 4'-ethynyl-2-fluoroadenosine analog 1c (CL-197) being the most potent compound with low cytotoxicity (EC50 = 0.9 nM, CC50 > 100 µM). It also shows potent inhibitory activities on drug resistant and clinical HIV-1 strains. Oral administration of 1c to Beagle dogs resulted in high levels of its bioactive form 1c-TP in peripheral blood mononuclear cells, the HIV-1 target cells, where the resulting triphosphate exhibited a long-term intracellular retention and could prevent HIV-1 infection for an extended time. 1c displayed low in vivo toxicity and favorable pharmacokinetics profiles in Sprague-Dawley rats. The preclinical data support further development of 1c as a highly potent and orally bioavailable clinical candidate to treat HIV-1 infection. Currently, CL-197 is in clinical trials in China (registration number: CXHL2200529).


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Ratos , Animais , Cães , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Leucócitos Mononucleares , Ratos Sprague-Dawley , Infecções por HIV/tratamento farmacológico
14.
Prev Med Rep ; 35: 102329, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37554353

RESUMO

This study explores the status quo of preventive care use and social capital among middle-aged and elderly people (≥45 years old) in China, and employs a multi-level model to analyze whether social capital at different levels is associated with preventive care use. The data are derived from the 2018 China Health and Retirement Longitudinal Study (CHARLS), which includes 11,503 respondents and 450 communities. Preventive care use covers the utilization of routine physical examination services. Individual social capital is measured by the level of social network and social activities participation. Social network includes contacting with children or other people, for example, by phone, text message. Social activities participation is measured by the involvement in social activities, for example, playing mahjong, going to community club. Community social capital is evaluated by the richness of community facilities. Results reveals that the utilization of preventive care is 48.94% among middle-aged and elderly in China. The most used preventive service is routine blood test. The intra-class correlation (ICC) coefficient indicates that preventive health behaviors of the respondents are clustered at communities where they live. Multi-level regression shows that influence of social network is not significant to preventive care use (p ï¼ž 0.05). Community facilities and individual social activities participation are significantly associated with preventive care use (p < 0.05). The association between social capital and preventive care use could be considered as an important factor when making policies to promote preventive care use.

15.
Environ Sci Pollut Res Int ; 30(40): 91794-91802, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37479935

RESUMO

Fluopimomide is a novel pesticide intensively used in agricultural pest control; however, its excessive use may have toxicological effects on non-target organisms. In this study, Caenorhabditis elegans was used to evaluate the toxic effects of fluopimomide and its possible mechanisms. The effects of fluopimomide on the growth, pharyngeal pumping, and antioxidant systems of C. elegans were determined. Furthermore, the gene expression levels associated with mitochondria in the nematodes were also investigated. Results indicated that fluopimomide at 0.2, 1.0, and 5.0 mg/L notably (p < 0.001) decreased body length, pharyngeal pumping, and body bends in the nematodes compared to the untreated control. Additionally, fluopimomide at 0.2, 1.0, and 5.0 mg/L notably (p < 0.05) increased the content of malondialdehyde by 3.30-, 21.24-, and 33.57-fold, respectively, while fluopimomide at 1.0 and 5.0 mg/L significantly (p < 0.001) increased the levels of reactive oxygen species (ROS) by 49.14% and 77.06% compared to the untreated control. In contrast, fluopimomide at 1.0 and 5.0 mg/L notably reduced the activities of target enzyme succinate dehydrogenase and at 5.0 mg/L reduced the activities of antioxidant enzyme superoxide dismutase. Further evidence revealed that fluopimomide at 1.0 and 5.0 mg/L significantly inhibited oxygen consumption and at 0.2, 1.0, and 5.0 mg/L significantly inhibited ATP level in comparison to the untreated control. The expression of genes related to the mitochondrial electron transport chain mev-1 and isp-1 was significantly downregulated. ROS levels in the mev-1 and isp-1 mutants after fluopimomide treatments did not change significantly compared with the untreated mutants, suggesting that mev-1 and isp-1 may play critical roles in the toxicity induced by fluopimomide. Overall, the results demonstrate that oxidative stress and mitochondrial damage may be involved in toxicity of fluopimomide in C. elegans.


Assuntos
Caenorhabditis elegans , Praguicidas , Animais , Praguicidas/toxicidade , Antioxidantes , Espécies Reativas de Oxigênio , Estresse Oxidativo
16.
Food Chem ; 429: 136871, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37478609

RESUMO

The purpose of this work was to prepare Pickering emulsion stabilized by bacteriostatic whey protein isolate-vanillin (WPI-Van) nanoparticles as a carrier for encapsulating vitamin E. The particle size, ζ potential, PDI were used to study the optimal preparation conditions of nanoparticles. The results showed that the optimal preparation condition was achieved at WPI/Van mass ratio of 3:1. FTIR spectra demonstrated the complexation of WPI and Van. SEM image showed spherical and slightly rough surface of nanoparticles. Inhibitory effects of nanoparticles on E. coli and S. aureus were also observed. After storage of 21 days at 4 °C, the retention rate of vitamin E in the emulsions remained 43% higher than that of unencapsulated vitamin E. Moreover, the release rate of vitamin E encapsulated in emulsions in the small intestine was 81%, indicating excellent bioaccessibility. The research can provide a new insight for production and application of antibacterial Pickering emulsions.


Assuntos
Escherichia coli , Nanopartículas , Emulsões , Proteínas do Soro do Leite , Staphylococcus aureus , Vitamina E , Tamanho da Partícula
17.
Phys Chem Chem Phys ; 25(25): 16962-16967, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37334887

RESUMO

Monolayer (ML) NiCl2 exhibits a strong biquadratic exchange interaction between the first neighboring magnetic atoms (B1), as demonstrated by the spin spiral model in J. Ni et al., Phys. Rev. Lett., 2021, 127, 247204. This interaction is crucial for stabilizing the ferromagnetic collinear order within the ML NiCl2. However, they neither point out the role of B1 nor discuss the dispersion relation from spin orbit coupling (SOC) in the spin spiral. As we have done in this work, these parameters might theoretically potentially be derived directly by fitting the calculated spin spiral dispersion relation. Here, we draw attention to the fact that B1 is equivalent to half of J3 in Heisenberg linear interactions and that the positive B1 partially counteracts the negative J3's impact on the spin spiral to make the ML NiCl2 ferromagnetic. The comparatively small J3 + 1/2B1 from the spin spiral led us to believe that J3 could be substituted by B1, yet it still exists and plays a crucial function in magnetic semiconductors or insulators. The dispersion relation, which we also obtain from SOC, displays weak antiferromagnetic behavior in the spin spiral.

18.
BMC Public Health ; 23(1): 1209, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349685

RESUMO

OBJECTIVE: To analyze the risk factors associated with different levels of eye discomfort due to video terminal use among college students at different altitudes. METHODS: This cross-sectional study was conducted to assess the prevalence and extent of eye discomfort by distributing an questionnaire to university students via the Internet. To analyze the causes and risk factors of eye discomfort among college students at different altitudes after using video terminals. RESULTS: A total of 647 participants who met the criteria were included in this survey, of whom 292 (45.1%) were males and 355 (54.9%) were females. The results of the survey showed 194 (30.0%) participants without eye discomfort and 453 (70.0%) participants with eye discomfort. The results of the univariate comparison of the degree of eye discomfort in the study subjects with different characteristics showed that the differences in the degree of eye discomfort were statistically significant (P < 0.05) for the 7 groups of indicators: gender, region, wearing corneal contact lenses for more than 2 h per day, frequent use of eye drops, sleep time, total time of VDT use per day, and total time per VDT use, while the remaining indicators, including age, profession, and whether refractive surgery or other eye surgery was performed, whether frame glasses were worn for a long time, and duration of daily mask wear were not statistically significant. The results of multi-factor logistic analysis of the degree of eye discomfort in the study subjects with different characteristics showed that gender, region, frequent use of eye drops, sleep time, and total time of VDT use per day were the risk factors affecting the degree of eye discomfort. CONCLUSIONS: Female, high altitude, frequent use of eye drops, shorter daily sleep duration and longer daily VDT use were associated risk factors for the development of severe eye discomfort, where the severity of eye discomfort was significantly negatively correlated with increased sleep duration and significantly positively correlated with increased total time of VDT use.


Assuntos
Altitude , Lágrimas , Masculino , Humanos , Feminino , Estudos Transversais , Inquéritos e Questionários , Estudantes , Terminais de Computador
19.
Acta Pharm Sin B ; 13(4): 1686-1698, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37139408

RESUMO

Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the ß-catenin level, and accordingly inhibit the Wnt/ß-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.

20.
Brain Res ; 1811: 148375, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37146745

RESUMO

With the approval of s-ketamine nasal spray as a novel antidepressant, its robust antidepressant effects have been intensively examined in clinical trials. However, the therapeutic efficacy and mechanisms of repeated intermittent drug administration remain unclear. In the present study, we applied a classic chronic unpredictable mild stress (CUMS) model to induce depressive-like behaviors of mice and evaluated the role of repeated s-ketamine administration (10 mg/kg, 7 consecutive days) in ameliorating depressive-like behaviors and modulating related molecular pathways. A battery of behavioral tests were performed to assess CUMS-induced depression. The protein expressions of GluN1, GluN2A, GluN2B, GluR1, CaMKIIα, phosphorylated CaMKIIα (p-CaMKIIα), BDNF, TrkB, phosphorylated TrkB (p-TrkB), mTOR, and phosphorylated mTOR (p-mTOR) as well as modification of synaptic ultrastructure was identified in hippocampal tissues. It turned out that s-ketamine manifested evident antidepressant effects with improved synaptic plasticity. Meanwhile, the results suggested that s-ketamine could differentially modulate glutamate receptors with upregulated GluN1 and GluR1 levels and downregulated GluN2B levels. CUMS-induced elevation of CaMKIIα phosphorylation and decline of BDNF, TrkB phosphorylation and mTOR could also be reversed through s-ketamine treatment. Together, our study provided evidence that selectively modulated glutamate receptors as well as CaMKIIα and mTOR signaling were involved in repeated s-ketamine administration.


Assuntos
Antidepressivos , Fator Neurotrófico Derivado do Encéfalo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Antidepressivos/uso terapêutico , Hipocampo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Receptores de Glutamato/metabolismo , Estresse Psicológico/metabolismo , Modelos Animais de Doenças
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