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The higher viscosity and lower pH in lysosomes of cancer cells highlight their potential as biomarkers for cancer. Therefore, the development of acid-activated viscosity fluorescent probes is significant for the early diagnosis and treatment of cancer. Based on this, we have designed and synthesized a near-infrared fluorescent probe based on the 2-(2-hydroxyphenyl)benzothiazole (HBT) group, namely HBTH, to monitor the viscosity changes within lysosomes. It has been demonstrated that HBTH was extremely sensitive to viscosity, with a strong linear relationship between fluorescence intensity and log(viscosity) within the range of (logη) = 0-3.06 (a correlation coefficient of 0.98), proving its capability for quantitative viscosity measurement. In particular, the most obvious fluorescence enhancement of HBTH was only efficiently triggered by the combined effect of low pH and high viscosity. Furthermore, HBTH can rapidly localize to lysosomes by wash-free procedure at a low concentration (100 nM) and achieve high-fidelity imaging within 20 s. It can also monitor the dynamic processes of lysosomes in cells, viscosity changes under drug stimuli, and lysosomal behavior during mitophagy. Importantly, HBTH is capable of identifying tumors in tumor-bearing nude mice through in vivo imaging. These features make HBTH a powerful tool for the early diagnosis and treatment of cancer.
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Corantes Fluorescentes , Lisossomos , Camundongos Nus , Neoplasias , Lisossomos/metabolismo , Lisossomos/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Animais , Viscosidade , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Camundongos , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Benzotiazóis/química , Benzotiazóis/farmacologia , Camundongos Endogâmicos BALB C , Imagem Óptica , Mitofagia/efeitos dos fármacosRESUMO
BACKGROUND: Lipid droplets (LDs) polarity is intricately linked to diverse biological processes and diseases. The visualization of LDs-polarity is of vital importance but challenging due to the lack of high-specificity, high-sensitivity and large-Stokes shift probes for real-time tracking LDs-polarity in biological systems. RESULTS: Four D-π-A based fluorescent probes (TPA-TCF1-TPA-TCF4) have been developed by combining tricyanofuran (an electron acceptor, A) and triphenylamine (an electron donor, D) derivatives with different terminal groups. Among them, TPA-TCF1 and TPA-TCF4 exhibit excellent polar sensitivity, large Stokes shift (≥182 nm in H2O), and efficient LDs targeting ability. In particular, TPA-TCF4 is capable of monitoring the change of LDs-polarity during ferroptosis, inflammation, apoptosis of cancer cell, and fatty liver. SIGNIFICANCE: All these features render TPA-TCF4 a versatile tool for pharmacodynamic evaluation of anti-cancer drugs, in-depth understanding of the biological effect of LDs on ferroptosis, and medical diagnosis of LDs-polarity related diseases.
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Fígado Gorduroso , Ferroptose , Corantes Fluorescentes , Inflamação , Gotículas Lipídicas , Gotículas Lipídicas/química , Gotículas Lipídicas/metabolismo , Humanos , Ferroptose/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Corantes Fluorescentes/química , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Animais , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Estrutura MolecularRESUMO
By co-culturing two endophytic fungi (Chaetomium virescens and Xylaria grammica) collected from the medicinal and edible plant Smilax glabra Roxb. and analyzing them with MolNetEnhancer module on GNPS platform, seven undescribed chromone-derived polyketides (chaetoxylariones A-G), including three pairs of enantiomer ones (2a/2b, 4a/4b and 6a/6b) and four optical pure ones (1, 3, 5 and 7), as well as five known structural analogues (8-12), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray diffraction, 13C NMR calculation and DP4+ probability analyses, as well as the comparison of the experimental electronic circular dichroism (ECD) data. Structurally, compound 1 featured an unprecedented chromone-derived sulfonamide tailored by two isoleucine-derived δ-hydroxy-3-methylpentenoic acids via the acylamide and NO bonds, respectively; compound 2 represented the first example of enantiomeric chromone derivative bearing a unique spiro-[3.3]alkane ring system; compound 3 featured a decane alkyl side chain that formed an undescribed five-membered lactone ring between C-7' and C-10'; compound 4 contained an unexpected highly oxidized five-membered carbocyclic system featuring rare adjacent keto groups; compound 7 featured a rare methylsulfonyl moiety. In addition, compound 10 showed a significant inhibition towards SW620/AD300 cells with an IC50 value of PTX significantly decreased from 4.09 µM to 120 nM, and a further study uncovered that compound 10 could obviously reverse the MDR of SW620/AD300 cells.
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Antineoplásicos , Chaetomium , Cromonas , Ensaios de Seleção de Medicamentos Antitumorais , Policetídeos , Xylariales , Cromonas/química , Cromonas/farmacologia , Cromonas/isolamento & purificação , Policetídeos/química , Policetídeos/farmacologia , Policetídeos/isolamento & purificação , Estrutura Molecular , Xylariales/química , Chaetomium/química , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Técnicas de Cocultura , Proliferação de Células/efeitos dos fármacosRESUMO
This study aims to understand how socioeconomic status and the family environment impact students' academic achievement through the mediation of parental involvement in rural China. To achieve this, a cross-sectional design was adopted, and a total of 525 parents of rural junior high school students from S province in southwest China were surveyed. The proposed conceptual framework was tested by structural equation modeling. The results claimed that both socioeconomic status and the family environment are important factors affecting the academic achievement of rural students, and the role of the family environment is more pronounced. Furthermore, parental involvement has a significant mediating effect between socioeconomic status and academic achievement, especially between the family environment and academic achievement. The findings highlighted the importance of the family environment and parental involvement to compensate for the negative impact of disadvantaged family socioeconomic status on academic achievement.
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Organic light-emitting materials (OLEMs) are emerging contaminants in the environment and have been detected in various environment samples. However, limited information is available regarding their contamination within the human body. Here, we developed a novel QuEChERS (quick, easy, cheap, effective, rugged, and safe) method coupled with triple quadrupole/high-resolution mass spectrometry to determine OLEMs in breast milk samples, employing both target and suspect screening strategies. Our analysis uncovered the presence of seven out of the 39 targeted OLEMs in breast milk samples, comprising five liquid crystal monomers and two OLEMs commonly used in organic light-emitting diode displays. The cumulative concentrations of the seven OLEMs in each breast milk sample ranged from ND to 1.67 × 103 ng/g lipid weight, with a mean and median concentration of 78.76 and 0.71 ng/g lipid weight, respectively, which were higher compared to that of typical organic pollutants such as polychlorinated biphenyls and polybrominated diphenyl ethers. We calculated the estimated daily intake (EDI) rates of OLEMs for infants aged 0-12 months, and the mean EDI rates during lactation were estimated to range from 30.37 to 54.89 ng/kg bw/day. Employing a suspect screening approach, we additionally identified 66 potential OLEMs, and two of them, cholesteryl hydrogen phthalate and cholesteryl benzoate, were further confirmed using pure reference standards. These two substances belong to cholesteric liquid crystal materials and raise concerns about potential endocrine-disrupting effects, as indicated by in silico predictive models. Overall, our present study established a robust method for the identification of OLEMs in breast milk samples, shedding light on their presence in the human body. These findings indicate human exposure to OLEMs that should be further investigated, including their health risks.
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Poluentes Ambientais , Bifenilos Policlorados , Lactente , Feminino , Humanos , Leite Humano/química , Poluentes Ambientais/análise , Bifenilos Policlorados/análise , Espectrometria de Massas , LipídeosRESUMO
The development of environmentally friendly, degradable piezoelectric materials is of great significance for the environment. Poly(L-lactic acid) (PLLA) is a promising piezoelectric material as a degradable material. Here, we have introduced a series of ionic liquids (ILs) into PLLA spinning solution, and the PLLA/IL composite nanofiber membranes are prepared by electrospinning method. When the conductivity of the spinning solution is below 400 µS·cm-1, the addition of ILs, especially [EMIm][PF6], can significantly improve the morphology and piezoelectric properties of the PLLA/IL composite nanofiber membrane with the output voltage of 2.3 V under the pressure of 5 N, which is 4 times that of the PLLA nanofiber membrane. The improvement of the piezoelectric properties of PLLA/IL nanofiber membrane may be due to the high dipole moment generated by the C=O dipole after the interaction between the O atom in C=O on the PLLA molecular chain and the [EMIm]+ cation in the IL. This work has elucidated the effects of ILs on the properties of spinning solution and the piezoelectric properties of PLLA, which can provide a theoretical basis for the selection of the preparation system of piezoelectric polymer and inspire the development of environmentally friendly flexible piezoelectric materials.
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Estrogen-induced intrahepatic cholestasis (IHC) is a mild but potentially serious risk and urges for new therapeutic targets and effective treatment. Our previous study demonstrated that RORγt and CXCR3 signaling pathway of invariant natural killer T (iNKT) 17 cells play pathogenic roles in 17α-ethinylestradiol (EE)-induced IHC. Ursodeoxycholic acid (UDCA) and 18ß-glycyrrhetinic acid (GA) present a protective effect on IHC partially due to their immunomodulatory properties. Hence in present study, we aim to investigate the effectiveness of UDCA and 18ß-GA in vitro and verify the accessibility of the above targets. Biochemical index measurement indicated that UDCA and 18ß-GA presented efficacy to alleviate EE-induced cholestatic cytotoxicity. Both UDCA and 18ß-GA exhibited suppression on the CXCL9/10-CXCR3 axis, and significantly restrained the expression of RORγt in vitro. In conclusion, our observations provide new therapeutic targets of UDCA and 18ß-GA, and 18ß-GA as an alternative treatment for EE-induced cholestasis.
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Colestase , Ácido Glicirretínico , Células T Matadoras Naturais , Receptores CXCR3 , Ácido Ursodesoxicólico , Colestase/induzido quimicamente , Colestase/tratamento farmacológico , Etinilestradiol/toxicidade , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacologia , Ácido Glicirretínico/uso terapêutico , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Receptores CXCR3/genética , Receptores CXCR3/metabolismo , Transdução de Sinais , Ácido Ursodesoxicólico/farmacologia , Ácido Ursodesoxicólico/uso terapêutico , Animais , CamundongosRESUMO
Flexible conductive films based on light-to-heat conversion are promising for the next-generation electronic devices. A flexible waterborne polyurethane composite film (PU/MA) with excellent photothermal conversion performance was obtained by combination of PU and silver nanoparticle decorated MXene (MX/Ag). The silver nanoparticles (AgNPs) uniformly decorated on the MXene surface by γ-ray irradiation induced reduction. Because of the synergistic effect of MXene with outstanding light-to-heat conversion efficiency and the AgNPs with plasmonic effect, the surface temperature of the PU/MA-II (0.4%) composite with lower MXene content increased from room temperature to 60.7 °C at 5 min under 85 mW cm-2 light irradiation. Besides, the tensile strength of PU/MA-II (0.4%) increased from 20.9 MPa (pure PU) to 27.5 MPa. The flexible PU/MA composite film shows great potential in the field of thermal management of flexible wearable electronic devices.
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BACKGROUND: Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. METHODS: Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. RESULTS: In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. CONCLUSIONS: Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis.
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Propofol , Humanos , Camundongos , Animais , Propofol/farmacologia , Hipóxia , Células Endoteliais da Veia Umbilical Humana , Miócitos Cardíacos , Estresse Oxidativo , Apoptose/fisiologia , Chaperonina com TCP-1RESUMO
Since the COVID-19 pandemic, polypropylene melt-blown nonwovens (MBs) have been widely used in disposable medical surgical masks and medical protective clothing, seriously threatening the environment. As a bio-based biodegradable polymer, polylactic acid (PLA) has attracted great attention in fabricating MBs. However, there are still issues with the undesirable spinnability of PLA and the limited filtration and antibacterial performance of PLA MBs. Herein, a high-efficiency, low-resistance, and antibacterial PLA filter is fabricated by melt-blown spinning and electret postprocessing technology. The irradiation technique is used to tune PLA chain structure, improving its spinnability. Further, silica (SiO2) nanoparticles are added to enhance the charge storage stability of PLA MBs. With a constant airflow rate of 32 L min-1, the PLA-based MBs exhibit a high particulate filtration efficiency of 94.8 ± 1.5%, an ultralow pressure drop of 14.1 ± 1.8 Pa, and an adequate bacterial filtration efficiency of 98 ± 1.2%, meeting the medical protective equipment standard. In addition, the zinc oxide (ZnO) masterbatches are doped into the blend and the antibacterial rate of PLA-based MBs against Escherichia coli and Staphylococcus aureus is higher than 99%. This successful preparation and modification method paves the way for the large-scale production of PLA MBs as promising candidates for high-efficacy and antibacterial filters.
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A mild, modular and efficient synthetic method with broad substrate scope was developed for aspulvinones. Nine natural aspulvinones were synthesized, six of which were for the first time. The aldol condensation delivered Z-configuration products predominantly in MeCN. Meanwhile, alkoxy exchange occurred in MeOH and EtOH. Aspulvinone O and E, and substrate 49, 50, and 51 exhibited modest anti-SARS-CoV-2 activity in a high-throughput screening and enzyme kinetics assay.
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Objective:The purpose of this study was to investigate the clinical characteristics and risk factors of adult recurrent acute infectious epiglottitis. Methods:All patients diagnosed with acute infectious epiglottitis hospitalized in the Department of Otolaryngology, Hai'an People's Hospital, Nantong University from January 2012 to December 2019 were included. Results:The recurrence rate of 331 adult patients with acute infectious epiglottitis was 4.2% ï¼14/331ï¼, including 10 cases of once recurrence and 4 cases of twice recurrence. The onset time of all patients was within 48 hours. The most common main complaint in the recurrent group was sore throat ï¼42.9%ï¼, and dysphagia in the non-recurrent group ï¼42.0%ï¼. The frequency of drinking in recurrent group was higher than that in non-recurrent group ï¼P=0.009ï¼. The incidence of chronic obstructive pulmoriary diseaseï¼COPDï¼, diabetes, cyst and gastroesophageal reflux disease/laryngopharyngeal reflux disease in recurrent group was higher than that in non-recurrent group. There was no significant difference in other clinical features, treatment and prognosis between the two groups except tongue tonsil infection under laryngoscope. Multivariate analysis showed that frequent drinking ï¼more than twice a weekï¼, COPD, diabetes, cysts and lingual tonsillar infection were the risk factors for recurrence. Conclusion:Adult acute infectious epiglottitis has a proportion of single or multiple recurrence. Frequent drinking, COPD, diabetes, cyst and lingual tonsillar infection are the risk factors for the recurrence.
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Cistos , Epiglotite , Refluxo Laringofaríngeo , Doença Pulmonar Obstrutiva Crônica , Humanos , Adulto , Epiglotite/diagnóstico , Epiglotite/terapia , Fatores de Risco , Doença AgudaRESUMO
(-)-Guaiol is a sesquiterpenoid found in many traditional Chinese medicines with potent antitumor activity. However, its therapeutic effect and mechanism in non-small cell lung cancer (NSCLC) have not been fully elucidated. In this study, (-)-Guaiol was found to induce immunogenic cell death (ICD) in NSCLC in vitro. Using (-)-Guaiol in vivo, we found that (-)-Guaiol could suppress tumor growth, increase dendritic cell activation, and enhance T-cell infiltration. Vaccination experiments suggest that cellular immunoprophylaxis after (-)-Guaiol intervention can suppress tumor growth. Previous studies have found that (-)-Guaiol induces apoptosis and autophagy in NSCLC. Apoptosis and autophagy are closely related to ICD. To explore whether autophagy and apoptosis are involved in (-)-Guaiol-induced ICD, we used inhibitors of apoptosis and autophagy. The results showed that the release of damage-associated molecular patterns (DAMPs) was partly reversed after inhibition of apoptosis and autophagy. In conclusion, these results suggested that the (-)-Guaiol triggers immunogenic cell death and inhibits tumor growth in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/patologia , Morte Celular Imunogênica , Linhagem Celular Tumoral , Apoptose , AutofagiaRESUMO
BACKGROUND: Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. METHODS: Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. RESULTS: In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. CONCLUSIONS: Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis. Highlights Microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs) exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes. Microvesicles from propofol post-treated HUVECs ((HR + P)-EMVs) induced diminished oxidative stress and apoptosis in IR-injured cardiomyocytes compared with microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs). lncCCT4-2 was significantly highly expressed in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs, and reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. lncCCT4-2 inhibited HR-EMVs induced oxidative stress and apoptosis in HR-injured AC16 cells by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in AC16 cells.
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Humanos , Animais , Camundongos , Propofol/farmacologia , Apoptose/fisiologia , Estresse Oxidativo , Miócitos Cardíacos , Chaperonina com TCP-1 , Células Endoteliais da Veia Umbilical Humana , HipóxiaRESUMO
Two acid-catalyzed tandem reactions between 4-hydroxy-1-methylquinolin-2(1H)-one and propargylic alcohols are described. Depending mainly on the propargylic alcohol used, these tandem reactions proceed via either a Friedel-Crafts-type allenylation followed by 6-endo-dig cyclization sequence to form pyrano[3,2-c]quinolones or a Friedel-Crafts-type alkylation and 5-exo-dig ring closure sequence to afford furo[3,2-c]quinolones in moderate-to-high yields. The pyrano[3,2-c]quinolones products could be further transformed to tetracyclic 4,9-dihydro-5H-cyclopenta[lmn]phenanthridin-5-one derivatives.
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The illustration of the correlation between lipid droplets (LDs) variation and nonalcoholic fatty liver disease (NAFLD) is a challenging and important work in biomedical research. Herein, a red emission fluorophore LD-HW containing donor-π-bridge-acceptor (D-π-A) structure was readily constructed and systematically investigated. It was found that LD-HW could selectively identify polarity variation accompanying with an obvious blue-shift (around 80 nm) in fluorescence spectra, and a sharp enhancement (about 440-fold) in fluorescence quantum yield (QY) over the solvent polarity ranging from water (polarity parameter Δf = 0.3200) to 1,4-dioxane (Δf = 0.0205). In addition, probe LD-HW could precisely light up LDs within a short time (≤5 min) through a wash-free procedure and real-time monitor the dynamic behavior of cellular LDs. More importantly, LD-HW exhibited an excellent performance in differentiating fatty liver through in vivo imaging the change of cellular LDs. The in situ fluorescence spectra of corresponding tissue section proved that polarity level in the liver of NAFLD mice was lower than that in normal mice. Taken together, probe LD-HW presented great potential in non-invasive diagnosis of fatty liver through in vivo imaging.
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Técnicas Biossensoriais , Hepatopatia Gordurosa não Alcoólica , Animais , Corantes Fluorescentes/química , Ionóforos , Gotículas Lipídicas/química , Camundongos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Solventes , Água/análiseRESUMO
BACKGROUND: By analyzing the risk factors of postoperative complications in elderly patients with hip replacement, We aimed to develop a nomogram model based on preoperative and intraoperative variables and verified the sensitivity and specificity for risk stratification of postoperative complications in elderly with total hip replacement patients. AIM: To develop a nomogram model for risk stratification of postoperative complications in elderly with total hip replacement patients. METHODS: A total of 414 elderly patients who underwent surgical treatment for total hip replacement hospitalized at the Affiliated Hospital of Guangdong Medical University from March 1, 2017 to August 31, 2019 were included into this study. Univariate and multivariate logistic regression were conducted to identify independent risk factors of postoperative complication in the 414 patients. A nomogram was developed by R software and validated to predict the risk of postoperative complications. RESULTS: Multivariate logistic regression analysis revealed that age (OR = 1.05, 95%CI: 1.00-1.09), renal failure (OR = 0.90, 95%CI: 0.83-0.97), Type 2 diabetes (OR = 1.05, 95%CI: 1.00-1.09), albumin (ALB) (OR = 0.91, 95%CI: 0.83-0.99) were independent risk factors of postoperative complication in elderly patients with hip replacement (P < 0.05). For validation of the nomogram, receive operating characteristic curve revealed that the model predicting postoperative complication in elderly patients with hip replacement was the area under the curve of 0.8254 (95%CI: 0.78-0.87), the slope of the calibration plot was close to 1 and the model passed Hosmer-Lemeshow goodness of fit test (χ 2 = 10.16, P = 0.4264), calibration in R Emax = 0.176, Eavg = 0.027, which all demonstrated that the model was of good accuracy. CONCLUSION: The nomogram predicting postoperative complications in patients with total hip replacement constructed based on age, type 2 diabetes, renal failure and ALB is of good discrimination and accuracy, which was of clinical significance.
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New Delhi metallo-ß-lactamase-1 (NDM-1) can hydrolyze almost all antibiotics of the ß-lactam group, resulting in the generation of multidrug resistant bacteria. Besides its broad hydrolytic activity, pathogens expressing NDM-1 often harbor other antibiotic-resistant genes, further promoting the pervasion of multi-resistant clinical isolates and making clinically available drugs scantier. Despite the urgent need for NDM-1 inhibitors, there is no approved drug in clinic. Here, we summarize NDM-1 inhibitors developed since 2018, classify these compounds by chemical scaffolds, and propose some inconsistencies and notable problems among these studies, which are expected to benefit future research.
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Farmacorresistência Bacteriana Múltipla , beta-Lactamases , Antibacterianos/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , beta-Lactamases/química , beta-Lactamases/genéticaRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignant tumor whose effective treatment has not been found. The redox state and proliferative activity of PDAC cells are maintained by the conversion of aspartic acid in the cytoplasm into oxaloacetate though aspartate aminotransferase 1 (GOT1). Therefore, GOT1 inhibitors as a potential approach for treating PDAC have attracted more attention of researchers. Ziprasidone effectively inhibited GOT1 in a non-competitive manner. The potential cytotoxicity and anti-proliferation effects of ziprasidone against PDAC cells in vitro and in vivo were evaluated. Ziprasidone can induce glutamine metabolism disorder and redox state imbalance of PDAC cells by targeting GOT1, thereby inhibiting proliferation, preventing migration, and inducing apoptosis. Ziprasidone displayed significant in vivo antitumor efficacy in SW1990 cell-derived xenografts. What's more, knockdown of GOT1 in SW1990 reduced the anti-proliferative effects of ziprasidone. As a novel GOT1 inhibitor, ziprasidone may be a lead compound for the treatment of PDAC. KEY MESSAGES: Small molecule inhibitors targeting GOT1 may provide a therapeutic target in PDAC. Ziprasidone effectively inhibited GOT1 enzyme in a non-competitive manner. Ziprasidone repressed glutamine metabolism and inhibited the growth of tumor in vivo. Knockdown of GOT1 decreased the anti-proliferative effects of ziprasidone.