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Bioorthogonal pretargeting optical imaging shows the potential for enhanced diagnosis and prognosis. However, the bioorthogonal handles, known for being "always reactive", may engage in reactions at unintended sites with their counterparts, resulting in nonspecific fluorescence activation and diminishing detection specificity. Meanwhile, despite the importance of detecting senescent cancer cells in cancer therapy, current methods mainly rely on common single senescence-associated biomarkers, which lack specificity for differentiating between various types of senescent cells. Herein, we report a dual-locked enzyme-activatable bioorthogonal fluorescence (DEBOF) turn-on imaging approach for the specific detection of senescent cancer cells. A dual-locked bioorthogonal targeting agent (DBTA) and a bioorthogonally activatable fluorescent imaging probe (BAP) are synthesized as the biorthogonal pair. DBTA is a tetrazine derivative dually caged by two enzyme-cleavable moieties, respectively, associated with senescence and cancer, which ensures that its bioorthogonal reactivity ("clickability") is only triggered in the presence of senescent cancer cells. BAP is a fluorophore caged by trans-cyclooctane (TCO), whose fluorescence is only activated upon bioorthogonal reaction between its TCO and the decaged tetrazine of DBTA. As such, the DEBOF imaging approach differentiates senescent cancer cells from nonsenescent cancer cells or other senescent cells, allowing noninvasive tracking of the population fluctuation of senescent cancer cells in the tumor of living mice to guide cancer therapies. This study thus provides a general molecular strategy for biomarker-activatable in vivo bioorthogonal pretargeting imaging with the potential to be applied to other imaging modalities beyond optics.
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Senescência Celular , Corantes Fluorescentes , Imagem Óptica , Humanos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Animais , Camundongos , Linhagem Celular Tumoral , Neoplasias/diagnóstico por imagem , FluorescênciaRESUMO
Background: Health has effects on children's academic performance. Qi deficiency is generally used to assess an individual's health in the Chinese traditional medicine theory. This study explores the effects of qi deficiency on children's academic performance and examines whether mental fatigue mediates these effects. Methods: A total of 550 students aged 10-13 in fifth-grade were surveyed in a big primary school in Sichuan Province in November 2023 using paper-pencil-based questionnaires. Qi deficiency and mental fatigue were assessed, and exam scores in Chinese and Mathematics were recorded. Pearson's correlation and linear regression analyses were used to test the mediation model and hypotheses. Results: The fifth-grade students had mild qi deficiency (M = 2.09) and a mild state of mental fatigue (M = 2.38) on a five-point Likert scale. The average exam scores in Mathematics and Chinese were 70.07 and 74.44 points out of 100, respectively. Qi deficiency was associated with Mathematics scores (r = -0.37, p < 0.01) and Chinese scores (r = -0.30, p < 0.01), and mental fatigue (r = 0.47, p < 0.01). Furthermore, mental fatigue was associated with Mathematics scores (r = -0.46, p < 0.01) and Chinese scores (r = -0.34, p < 0.01). Linear regression analyses showed that qi deficiency significantly predicted Mathematics scores (ß = -0.26, p < 0.01), Chinese scores (ß = -0.19, p < 0.01), and mental fatigue (ß = 0.41, p < 0.01). When qi deficiency was controlled for, mental fatigue significantly predicted Mathematics scores (ß = -0.28, p < 0.01) and Chinese scores (ß = -0.17, p < 0.01). Conclusion: The mediation model and hypotheses were well supported, indicating that mental fatigue mediated the influence of qi deficiency on academic performance of fifth-grade students. Furthermore, the mediation effect of mental fatigue on Mathematics scores was a little stronger than that on Chinese scores.
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Background: In China, the prevalence of mental health issues among college students is a significant concern in society. This study aims to investigate the impact of early dietary quality on the psychological well-being of college students and elucidate the underlying mechanisms through which these effects occur, specifically focusing on height and qi-deficiency as mediators according to Chinese traditional medicine (CTM). Methods: A total of 655 college students were surveyed in October 2023 using paper-pencil-based questionnaires at four second-tier universities in Sichuan Province. The assessment included mental health, height, and qi-deficiency. Pearson's correlation and linear regression analyses were employed to examine the mediation model and test the hypotheses. Results: The college students exhibited acceptable levels of early diet quality (M = 3.72) and mental health (M = 3.63), while also presenting mild qi-deficiency symptoms (M = 2.25). Their average height was measured at 164.61 cm. Early diet quality demonstrated significant associations with mental health (r = 0.38, p < 0.01), height (r = 0.32, p < 0.01), and qi-deficiency (r = -0.32, p < 0.01). Mental health displayed correlations with height (r = 0.32, p < 0.01) and qi-deficiency (r = -0.49, p < 0.01). The results of linear regression analyses revealed significant associations between early diet quality and mental health (ß = 0.31, p < 0.01), height (ß = 0.21, p < 0.01), as well as qi-deficiency (ß = -0.26, p < 0.01). Furthermore, when early diet quality was included in the regression model, both height (ß = 0.21, p < 0.01) and qi-deficiency (ß = -0.35, p < 0.01) emerged as significant mediators in the relationship with mental health. Conclusion: The mediation model and hypotheses were strongly supported, demonstrating that early diet quality exerted an influence on the mental health of college students through two distinct pathways: height and qi-deficiency. Moreover, the mediating effect of qi-deficiency was found to be more pronounced than that of height in the relationship between early diet quality and mental health among college students.
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Estatura , Dieta , Saúde Mental , Qi , Estudantes , Humanos , Feminino , Estudantes/estatística & dados numéricos , Estudantes/psicologia , Masculino , Universidades , Saúde Mental/estatística & dados numéricos , China , Adulto Jovem , Inquéritos e Questionários , Dieta/estatística & dados numéricos , Adulto , Adolescente , Medicina Tradicional ChinesaRESUMO
BACKGROUND: Previous studies have initially reported accompanying elevated 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) inflammatory activity in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. [68Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [68Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function. METHODS: Twelve AMI rats and six Sham rats serially underwent [68Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [18F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively. RESULTS: The uptake of [68Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak activity in the infarct territory, [68Ga]Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05). CONCLUSIONS: Corresponding with the peaked [68Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential.
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Infarto do Miocárdio , Miocárdio , Remodelação Ventricular , Animais , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Remodelação Ventricular/efeitos dos fármacos , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Ratos Sprague-Dawley , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/química , Ratos , Tomografia por Emissão de PósitronsRESUMO
In this study, the effects of citric acid-autoclaving (CA-A) treatment on physicochemical and digestive properties of the native ginseng starches were investigated. The results showed that ginseng starch exhibited a B-type crystal structure with a low onset pasting temperature of 44.23 ± 0.80 °C, but high peak viscosity and setback viscosity of 5897.34 ± 53.72 cP and 692.00 ± 32.36 cP, respectively. The granular morphology, crystal and short-range ordered structure of ginseng starches were destroyed after CA-A treatment. The more short-chain starches were produced, resulting in the ginseng starches solubility increased. In addition, autoclaving, citric acid (CA) and CA-A treatment promoted polymerization and recrystallization of starch molecules, increased the proportion of amylopectin B1, and B3 chains, and improved molecular weight and resistant starch (RS) content of ginseng starches. The most significant multi-scale structural change was induced by CA-A treatment, which reduced the relative crystallinity of ginseng starch from 28.26 ± 0.24 % to 2.75 ± 0.08 %, and increased the content of RS to 54.30 ± 0.14 %. These findings provided a better understanding of the structure and properties of Chinese ginseng starches and offered new ideas for the deep processing of ginseng foods.
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Ácido Cítrico , Panax , Ácido Cítrico/química , Amido/química , Amilopectina/química , Viscosidade , Amido Resistente , Amilose/químicaRESUMO
Ginseng is widely recognized for its diverse health benefits and serves as a functional food ingredient with global popularity. Ginsenosides with a broad range of pharmacological effects are the most crucial active ingredients in ginseng. This study aimed to derive ginseng glucosyl oleanolate (GGO) from ginsenoside Ro through enzymatic conversion and evaluate its impact on liver cancer in vitro and in vivo. GGO exhibited concentration-dependent HepG2 cell death and markedly inhibited cell proliferation via the MAPK signaling pathway. It also attenuated tumor growth in immunocompromised mice undergoing heterograft transplantation. Furthermore, GGO intervention caused a modulation of gut microbiota composition by specific bacterial populations, including Lactobacillus, Bacteroides, Clostridium, Enterococcus, etc., and ameliorated SCFA metabolism and colonic inflammation. These findings offer promising evidence for the potential use of GGO as a natural functional food ingredient in the prevention and treatment of cancer.
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Ingredientes de Alimentos , Microbioma Gastrointestinal , Ginsenosídeos , Neoplasias Hepáticas , Panax , Camundongos , Animais , Ginsenosídeos/farmacologia , Ginsenosídeos/metabolismo , Panax/metabolismo , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds (1-11), including two γ-aromatic butenolides (γ-AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ-butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish.
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4-Butirolactona , 4-Butirolactona/análogos & derivados , Aspergillus , Família Multigênica , Peptídeo Sintases , Peptídeo Sintases/genética , Estrutura Molecular , 4-Butirolactona/farmacologia , 4-Butirolactona/química , Aspergillus/enzimologia , Aspergillus/química , Aspergillus/genética , Animais , Peixe-ZebraRESUMO
Both metal center active sites and vacancies can influence the catalytic activity of a catalyst. A quantitative model to describe the synergistic effect between the metal centers and vacancies is highly desired. Herein, we proposed a machine learning model to evaluate the synergistic index, PSyn, which is learned from the possible pathways for CH4 production from CO2 reduction reaction (CO2RR) on 26 metal-anchored MoS2 with and without sulfur vacancy. The data set consists of 1556 intermediate structures on metal-anchored MoS2, which are used for training. The 2028 structures from the literature, comprising both single active site and dual active sites, are used for external test. The XGBoost model with 3 features, including electronegativity, d-shell valence electrons of metal, and the distance between metal and vacancy, exhibited satisfactory prediction accuracy on limiting potential. Fe@Sv-MoS2 and Os@MoS2 are predicted to be promising CO2RR catalysts with high stability, low limiting potential, and high selectivity against hydrogen evolution reactions (HER). Based on some easily accessible descriptors, transferability can be achieved for both porous materials and 2D materials in predicting the energy change in the CO2RR and nitrogen reduction reaction (NRR). Such a predictive model can also be applied to predict the synergistic effect of the CO2RR in other oxygen and tungsten vacancy systems.
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As some of the most promising candidates for constituting bioinspired electronics, polymer memristors with analog-type switching behavior exhibit great potential for synaptic mimicking and neuromorphic computing systems. By using highly soluble conjugated polyelectrolyte poly[9,9-bis(6-(3-methyl-1-imidazolium-yl)hexyl)fluorene]-covalently modified black phosphorus (BP) nanomaterial (BP-PF-NMI+Br-) as the active layer, an electronic device with the BP-PF-NMI+Br- film sandwiched between the aluminum and indium tin oxide electrodes is successfully fabricated. This device exhibits an excellent amount of electricity-dependent memristive performance at a small sweep voltage range of ±1 V. With increasing amount of electricity flowing through the device, the device resistance gradually decreased in a linear pattern. The changes in frequency, amplitude, and duration of voltage pulses do not affect the linear relationship between the amount of electricity passing through the device and the resistance value achieved after each state reached equilibrium at different numbers of the same voltage pulse stimulations. Both the synaptic potentiation/depression and learning/memorizing/forgetting functions of biological systems have been emulated. In contrast to BP-PF-NMI+Br-, the pure PF-NMI+Br--based device shows a write-once-read-many-times effect at the same scanning voltage range, while the BP:PF-NMI+Br- blends exhibit very unstable memristive performances.
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Myocardial infarction (MI) results in cardiomyocyte necrosis and conductive system damage, leading to sudden cardiac death and heart failure. Studies have shown that conductive biomaterials can restore cardiac conduction, but cannot facilitate tissue regeneration. This study aims to add regenerative capabilities to the conductive biomaterial by incorporating human endometrial mesenchymal stem cell (hEMSC)-derived exosomes (hEMSC-Exo) into poly-pyrrole-chitosan (PPY-CHI), to yield an injectable hydrogel that can effectively treat MI. In vitro, PPY-CHI/hEMSC-Exo, compared to untreated controls, PPY-CHI, or hEMSC-Exo alone, alleviates H2O2-induced apoptosis and promotes tubule formation, while in vivo, PPY-CHI/hEMSC-Exo improves post-MI cardiac functioning, along with counteracting against ventricular remodeling and fibrosis. All these activities are facilitated via increased epidermal growth factor (EGF)/phosphoinositide 3-kinase (PI3K)/AKT signaling. Furthermore, the conductive properties of PPY-CHI/hEMSC-Exo are able to resynchronize cardiac electrical transmission to alleviate arrythmia. Overall, PPY-CHI/hEMSC-Exo synergistically combines the cardiac regenerative capabilities of hEMSC-Exo with the conductive properties of PPY-CHI to improve cardiac functioning, via promoting angiogenesis and inhibiting apoptosis, as well as resynchronizing electrical conduction, to ultimately enable more effective MI treatment. Therefore, incorporating exosomes into a conductive hydrogel provides dual benefits in terms of maintaining conductivity, along with facilitating long-term exosome release and sustained application of their beneficial effects.
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Quitosana , Exossomos , Células-Tronco Mesenquimais , Infarto do Miocárdio , Humanos , Polímeros/metabolismo , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Pirróis , Exossomos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Preparações de Ação Retardada/farmacologia , Peróxido de Hidrogênio/metabolismo , Infarto do Miocárdio/terapia , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/metabolismo , Miócitos Cardíacos/metabolismoRESUMO
The adjuvant is essential for vaccines because it can enhance or directly induce a strong immune response associated with vaccine antigens. Ginsenoside Rh2 (Rh2) had immunomodulatory effects but was limited by poor solubility and hemolysis. In this study, Rh2 liposomes (Rh2-L) were prepared by ethanol injection methods. The Rh2-L effectively dispersed in a double emulsion adjuvant system to form a Water-in-Oil-in-Water (W/O/W) emulsion and had no hemolysis. The physicochemical properties of the adjuvants were tested, and the immune activity and auxiliary effects indicated by the Foot-and-Mouth disease (FMDV) antigen were evaluated. Compared with the mice vaccinated with the FMD vaccine prepared with the double emulsion adjuvant alone, those with the FMD vaccine prepared with the double emulsion adjuvant containing Rh2-L had significantly higher neutralizing antibody titer and splenocyte proliferation rates and showed higher cellular and humoral immune responses. The results demonstrated that Rh2-L could further enhance the immune effect of the double emulsion adjuvant against Foot-and-Mouth Disease.
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Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Camundongos , Animais , Febre Aftosa/prevenção & controle , Lipossomos , Emulsões , Anticorpos Antivirais , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , ÁguaRESUMO
@#Objective To establish and verify a universal and stable potency test method in vitro for SARS-CoV-2 mRNA vaccine,so as to use it for the quality control of SARS-CoV-2 mRNA vaccine.Methods ELISA kits that could bind well to S protein of SARS-CoV-2 variants,as well as transfected cells,cell plating concentrations and doses for transfection were screened,and then a potency test method for SARS-CoV-2 mRNA vaccine in vitro was established and verified.Results An ELISA kit was found with good binding ability to S protein of each variant,and HEK293T cells were determined as the transfection cells,with the plating concentration of 2.5 × 10~5 cells/mL and the transfection dose of 4 μg/well in the 6-well plate.An universal and stable potency test method for SARS-CoV-2 mRNA vaccine in vitro was established.The verification results showed that the method met the quality control needs.Conclusion The established potency test method in vitro for SARS-CoV-2 mRNA vaccine has good relative accuracy,linearity,intermediate precision and range,and can be applied to the quality control of SARS-CoV-2 mRNA vaccines
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@#Objective To establish and verify a universal and stable potency test method in vitro for SARS-CoV-2 mRNA vaccine,so as to use it for the quality control of SARS-CoV-2 mRNA vaccine.Methods ELISA kits that could bind well to S protein of SARS-CoV-2 variants,as well as transfected cells,cell plating concentrations and doses for transfection were screened,and then a potency test method for SARS-CoV-2 mRNA vaccine in vitro was established and verified.Results An ELISA kit was found with good binding ability to S protein of each variant,and HEK293T cells were determined as the transfection cells,with the plating concentration of 2.5 × 10~5 cells/mL and the transfection dose of 4 μg/well in the 6-well plate.An universal and stable potency test method for SARS-CoV-2 mRNA vaccine in vitro was established.The verification results showed that the method met the quality control needs.Conclusion The established potency test method in vitro for SARS-CoV-2 mRNA vaccine has good relative accuracy,linearity,intermediate precision and range,and can be applied to the quality control of SARS-CoV-2 mRNA vaccines.
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OBJECTIVES: To evaluate high-risk human papillomavirus testing (hrHPV) as an alternative for anal cytology in screening for high-grade anal neoplasia (AIN2-3) among males with HIV. To identify predictive risk factors for AIN2-3 and develop a clinical tool to triage males with HIV for high-resolution anoscopy (HRA) without cytology. DESIGN: Retrospective cohort study of 199 adult cisgender men and transgender women with HIV referred to an anal neoplasia clinic in the Southeastern United States between January 2018 and March 2021. METHODS: Each subject underwent cytology, hrHPV, and HRA. Clinical and sociodemographic risk factors were collected for each subject. Significant risk factors for AIN2-3 were identified using logistic regression, and a triage tool incorporating these factors was developed. Screening test characteristics were calculated for cytology with and without adjunct hrHPV, hrHPV alone, and the triage tool. RESULTS: In multivariate analysis, significant predictors of AIN2-3 were hrHPV positivity (odds ratio [OR] = 11.98, CI = 5.58-25.69) and low CD4 count (OR = 2.70, CI = 1.20-6.11). There was no significant difference in positive or negative predictive values among the tool, stand-alone hrHPV, and anal cytology with adjunct hrHPV. Sensitivity and specificity were not significantly different for stand-alone or adjunctive hrHPV testing. Compared with cytology, stand-alone hrHPV and the novel triage tool reduced unnecessary HRA referrals by 65% and 30%, respectively. CONCLUSIONS: Stand-alone hrHPV would have missed 11 of 74 AIN2-3 and generated 74 fewer unnecessary HRAs than current cytology-based screening patterns, which led to 115 unnecessary HRAs in our cohort. We propose triaging those with low CD4 count, hrHPV positivity, and/or smoking history for HRA.
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Neoplasias do Ânus , Infecções por HIV , Infecções por Papillomavirus , Pessoas Transgênero , Neoplasias do Colo do Útero , Adulto , Masculino , Humanos , Feminino , Triagem , Proctoscopia , Estudos Retrospectivos , Neoplasias do Ânus/diagnóstico , Infecções por HIV/diagnóstico , Infecções por Papillomavirus/diagnóstico , Papillomaviridae , Neoplasias do Colo do Útero/diagnósticoRESUMO
Objective: Anoikis is a type of programmed cell death that occurs in normal epithelial and endothelial cells. However, the specific role of anoikis regulators (ANRs) in bladder cancer (BLCA) remains unknown. Therefore, the objective of this study was to find subgroups that could identify different levels of anoikis resistance in BLCA and construct an anoikis scoring system to assess prognosis. Method: By obtaining ANRs from public datasets, subgroups of BLCA with varying degrees of anoikis resistance were identified, and risk was determined. Result: ANRs affects the occurrence and prognosis of BLCA and can be predicted by establishing risk models. Conclusion: The anoikis scoring system and anoikis-associated risk profiles may help develop more effective and personalized treatment strategies for BLCA patients.
This study investigates lncRNAs' role in predicting bladder cancer patient prognosis and immune response. Anoikis is a key focus. Highly variable genes are identified, suggesting personalized treatment strategies. An anoikis scoring system aids clinicians.
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Anoikis , Neoplasias da Bexiga Urinária , Humanos , Células Endoteliais , Prognóstico , Neoplasias da Bexiga Urinária/genética , Imunidade , Microambiente TumoralRESUMO
An optimized complex multi-component nanomaterial system would help greatly enhance the optical limiting performance and applicability of 2D nanomaterials. By using antimony sulfide-[S-1-dodecyl-S'-(α,α'-dimethyl-α''-acetic acid)trithiocarbonate] (Sb2S3-DDAT) as a reversible addition fragmentation chain transfer (RAFT) agent, a highly soluble poly(N-vinylcarbazole)-covalently modified Sb2S3 (Sb2S3-PVK) was synthesized in situ and embedded into a non-optically active poly(methylmethacrylate) (PMMA) matrix producing a PMMA-based film with good optical quality. In contrast to both the Sb2S3/PMMA and Sb2S3:PVK blends/PMMA films, the Sb2S3-PVK/PMMA film exhibits more superior optical limiting performance. After annealing in N2 at 200 °C for 30 minutes, the achieved nonlinear absorption coefficient and limiting threshold are changed from 411.79 cm GW-1 and 1.93 J cm-2 at 532 nm and 242.79 cm GW-1 and 4.17 J cm-2 at 1064 nm before annealing to 478.04 cm GW-1 and 1.70 J cm-2 at 532 nm and 520.92 cm GW-1 and 1.40 J cm-2 at 1064 nm after annealing, respectively. These advantages make Sb2S3-PVK one of the potential promising candidates for a broadband laser protector in both the visible and near-infrared ranges.
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BACKGROUND: The purpose of this study was to investigate the clinical effect of an intra-articular and local infiltration injection of a compound analgesic mixture of ropivacaine and compound betamethasone on the repair of the triangular fibrocartilage complex under wrist arthroscopy. METHODS: This prospective, double-blind, randomized study involved 20 patients with Atzei type 2 or 3 injuries of the triangular fibrocartilage complex who underwent repair under wrist arthroscopy. Patients were divided into two groups (n = 10) according to the systematic random sampling method. The test group was injected with a "cocktail" mixture for pain relief. The control group was injected with normal saline. The visual analog scale (VAS) pain score, pinch force, wrist joint mobility, wrist joint function score (PRWE score), occurrence of adverse reactions and dosage of analgesic drugs were evaluated before and after the operation in the two groups. RESULTS: The resting pain of the patients in the test group was less severe than that of the control group at 12 h, 24 h and 48 h after the operation (P < 0.05), and the pinch force of the patients in the test group was significantly greater than that of the control group at 1 d, 2 d and 3 d after the operation (P < 0.01). The amount of postoperative analgesics used in the test group was significantly lower than that in the control group (P < 0.01), and the patient satisfaction rate in the test group was higher than that in the control group (P < 0.05). There were no postoperative adverse effects in either group. CONCLUSION: An intra-articular and local infiltration injection of a "cocktail" analgesic mixture in the repair of triangular fibrocartilage complex under wrist arthroscopy can provide good pain control in the early postoperative period and reduce the amount of postoperative analgesic drugs administered, thus improving clinical safety. LEVEL OF EVIDENCE: Level II; Randomized Controlled Trial; Treatment Study.
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Liver cancer continues to be a focus of scientific research due to its low five-year survival rate. One of its main core issues is the high metastasis of cells, for which there is no effective treatment. Neferine was originally isolated from Plumula nelumbinis and demonstrated to have a good antitumor effect. In order to extract high-purity Neferine in a more efficient and environmentally friendly manner, response surface methodology (RSM) was used to optimize the isolation and purification procedures in this study. The extract conditions of a 7:3 ratio for the eluent of dichloromethane: methanol, 1:60 for the mass ratio of the extract amount: silica gel, and 3 mL/min of the elution flow rate were shown to be the optimal conditions. These conditions resulted in the highest yield of 6.13 mg per 66.60 mg of starting material, with productivity of 8.76% and purity of 87.04%. Compared with the previous methods, this method can prepare Neferine in large quantities more quickly. We subsequently evaluated the antitumor activity of the purified Neferine against HepG2 hepatic cancer cells. The purified Neferine was found to inhibit the proliferation of HepG2 cells through the CCK-8 assay, with an IC50 of 33.80 µM in 24 h, 29.47 µM in 48 h, 24.35 µM in 72 h and 2.78 µM in 96 h of treatment. Neferine at a concentration of 3 µM could significantly inhibit the migration and invasion abilities of the HepG2 cells in vitro. We also explored the mechanism of action of Neferine via Western blot. We showed that Neferine could reduce RhoA expression by effectively inhibiting the phosphorylation of MYPT1, thereby effectively exerting anti-metastasis activity against HepG2 cells. Thus, we have optimized the isolation procedures for highly pure Neferine by response surface methodology (RSM) in this study, and purified Neferine is shown to play an essential role in the anti-metastasis process of liver cancer cells. The Neferine purification procedure may make a wide contribution to the follow-up development of other anti-metastasis lead compounds.
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Benzilisoquinolinas , Neoplasias Hepáticas , Humanos , Células Hep G2 , Benzilisoquinolinas/farmacologia , Neoplasias Hepáticas/patologia , Linhagem CelularRESUMO
Afterglow, an intrinsic phenomenon of persistent luminescence emitted from chemical defects after light irradiation, has shown tremendous promise for applications in bioimaging with an ultra-high signal-to-background ratio (SBR) in vivo. In contrast to inorganic phosphor materials, organic afterglow substrates possess high biocompatibility and structural diversity for the construction of molecular afterglow imaging probes with an ideal intensity, wavelength, and duration for in vivo imaging. In this tutorial review, we aim to introduce the recent advances in molecular afterglow imaging with a comprehensive summary of the reported afterglow substrates and mechanisms. Molecular designs of multicomponent afterglow imaging probes are also introduced with their biomedical applications in disease diagnosis and treatment. Lastly, future perspectives and potential challenges of molecular afterglow imaging in preclinical uses and clinical translations are discussed.
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Nanopartículas , Nanopartículas/química , Luminescência , Imagem MolecularRESUMO
Background: We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. Methods: Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. Results: Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805-1336), and normal CD4/CD8 ratio (median 1.8, range 1.2-1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4-14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). Conclusions: Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation.