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1.
Phys Rev Lett ; 131(8): 080401, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37683167

RESUMO

Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-André-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.

2.
Environ Res ; 222: 115328, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36693463

RESUMO

Soil heavy metals (HMs) contamination stemming from smelting and mining activities is becoming a global concern due to its devastating impacts on the environment and human health. In this study, 128 soil samples were investigated to assess the spatial distribution, contamination characteristics, ecological and human health risk of HMs in soils near a smelting area by using BP artificial neural network (BP-ANN) and Monte Carlo simulation. The results showed that the concentrations of all five HMs in the soil greatly exceeded the background value of study area with a basic trend: Pb > As > Cr > Cd > Hg, indicating a high pollution level. Arsenic and lead were the major pollutants in the study area with an exceedance rate of 78.95% and 28.95%, respectively. The toxic fume and dust emitted during the smelting process were identified as the major sources of HMs pollution in soil, while Cd pollution was mainly caused by agricultural activities near the study area. The probabilistic risk assessment suggested that the average HQ values of five HMs for children and adults exceeded the acceptable threshold with a trend: As > Pb > Cr > Cd > Hg. The average CR values of As, Cr and Pb for all population were greatly larger than the acceptable threshold (CR ≥ 1), indicating a high cancer risk. However, the CR values of Cd for adults and children were within the acceptable threshold (CR < 1), implying no cancer risk. The results of the present study can provide some insight into the contamination characteristics, ecological and human health risk of HMs in contaminated soils by mining and smelting activities, which can help prevent and control soil pollution and environmental risk.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Adulto , Criança , Humanos , Solo , Cádmio , Chumbo , Poluentes do Solo/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Medição de Risco , China
3.
Nano Lett ; 22(19): 7882-7891, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36169350

RESUMO

Sepsis is a life-threatening disease caused by systemic bacterial infections, with high morbidity and mortality worldwide. As the standard treatment for sepsis, antibiotic therapy faces the challenge of impaired macrophages and drug-resistant bacteria. In this study, we developed a membrane-camouflaged metal-organic framework (MOF) system for plasmid DNA (pDNA) delivery to combat sepsis. The antimicrobial gene LL37 was efficiently encapsulated in the pH-sensitive MOF, and the nanoparticles were decorated with macrophage membranes in a compatible manner. Macrophage membrane coating allows targeted delivery of LL37 to macrophages and creates macrophage factories for the continuous generation of antimicrobial peptides. Compared to naked nanoparticles, primary bone marrow mesenchymal macrophage membrane-modified nanoparticles greatly improved the survival rate of immunodeficient septic mice through the synergistic effect of efficient gene therapy and inflammatory cytokine sequestration. This study demonstrates an effective membrane biomimetic strategy for efficiently delivering pDNA, offering an excellent option for overcoming sepsis.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Sepse , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Citocinas , DNA/genética , DNA/uso terapêutico , Macrófagos , Camundongos , Sepse/genética , Sepse/terapia
4.
Gut ; 68(3): 414-422, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29150489

RESUMO

OBJECTIVE: Ulcerative colitis (UC) is a dynamic disease with its severity continuously changing over time. We hypothesised that the risk of colorectal neoplasia (CRN) in UC closely follows an actuarial accumulative inflammatory burden, which is inadequately represented by current risk stratification strategies. DESIGN: This was a retrospective single-centre study. Patients with extensive UC who were under colonoscopic surveillance between 2003 and 2012 were studied. Each surveillance episode was scored for a severity of microscopic inflammation (0=no activity; 1=mild; 2=moderate; 3=severe activity). The cumulative inflammatory burden (CIB) was defined as sum of: average score between each pair of surveillance episodes multiplied by the surveillance interval in years. Potential predictors were correlated with CRN outcome using time-dependent Cox regression. RESULTS: A total of 987 patients were followed for a median of 13 years (IQR, 9-18), 97 (9.8%) of whom developed CRN. Multivariate analysis showed that the CIB was significantly associated with CRN development (HR, 2.1 per 10-unit increase in CIB (equivalent of 10, 5 or 3.3 years of continuous mild, moderate or severe active microscopic inflammation); 95% CI 1.4 to 3.0; P<0.001). Reflecting this, while inflammation severity based on the most recent colonoscopy alone was not significant (HR, 0.9 per-1-unit increase in severity; 95% CI 0.7 to 1.2; P=0.5), a mean severity score calculated from all colonoscopies performed in preceding 5 years was significantly associated with CRN risk (HR, 2.2 per-1-unit increase; 95% CI 1.6 to 3.1; P<0.001). CONCLUSION: The risk of CRN in UC is significantly associated with accumulative inflammatory burden. An accurate CRN risk stratification should involve assessment of multiple surveillance episodes to take this into account.


Assuntos
Colite Ulcerativa/complicações , Neoplasias Colorretais/etiologia , Adulto , Colite Ulcerativa/patologia , Colonoscopia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Vigilância da População , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
5.
Soft Matter ; 13(12): 2309-2314, 2017 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-28255586

RESUMO

The Marangoni flow of room temperature liquid metal has recently attracted significant attention in developing advanced flexible drivers. However, most of its induction methods are limited to an external electric field. This study disclosed a new Marangoni flow phenomenon of liquid gallium induced by the gallium-copper galvanic corrosion couple. To better understand this effect, the flow field distribution of liquid gallium was modeled and quantitatively calculated. Then, the intrinsic mechanism of this flow phenomenon was interpreted, during which natural convection and temperature gradient were both excluded and the galvanic corrosion couple was identified as the main reason. In addition, this conclusion was further confirmed by combining the experimental measurement of liquid gallium surface potential and the thermocapillary effect. Moreover, the temperature condition was found to be an indirect factor to the Marangoni flow. This finding broadens the classical understanding of liquid metal surface flow, which also suggests a new way for the application of soft machines.

6.
Gut ; 65(2): 256-70, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25666191

RESUMO

OBJECTIVE: Dendritic cells (DC) mediate intestinal immune tolerance. Despite striking differences between the colon and the ileum both in function and bacterial load, few studies distinguish between properties of immune cells in these compartments. Furthermore, information of gut DC in humans is scarce. We aimed to characterise human colonic versus ileal DC. DESIGN: Human DC from paired colonic and ileal samples were characterised by flow cytometry, electron microscopy or used to stimulate T cell responses in a mixed leucocyte reaction. RESULTS: A lower proportion of colonic DC produced pro-inflammatory cytokines (tumour necrosis factor-α and interleukin (IL)-1ß) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4(+)FoxP3(+)IL-10(+) (regulatory) T cells. There were enhanced proportions of CD103(+)Sirpα(-) DC in the colon, with increased proportions of CD103(+)Sirpα(+) DC in the ileum. A greater proportion of colonic DC subsets analysed expressed the lymph-node-homing marker CCR7, alongside enhanced endocytic capacity, which was most striking in CD103(+)Sirpα(+) DC. Expression of the inhibitory receptor ILT3 was enhanced on colonic DC. Interestingly, endocytic capacity was associated with CD103(+) DC, in particular CD103(+)Sirpα(+) DC. However, expression of ILT3 was associated with CD103(-) DC. Colonic and ileal DC differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, and this corresponded to their ability to imprint these homing markers on T cells. CONCLUSIONS: The regulatory properties of colonic DC may represent an evolutionary adaptation to the greater bacterial load in the colon. The colon and the ileum should be regarded as separate entities, each comprising DC with distinct roles in mucosal immunity and imprinting.


Assuntos
Colo/imunologia , Células Dendríticas/imunologia , Íleo/imunologia , Antígenos CD/análise , Colo/ultraestrutura , Citocinas/metabolismo , Células Dendríticas/citologia , Citometria de Fluxo , Humanos , Íleo/ultraestrutura , Cadeias alfa de Integrinas/análise , Teste de Cultura Mista de Linfócitos , Glicoproteínas de Membrana , Microscopia Eletrônica , Impressão Molecular , Receptores CCR/análise , Receptores CCR4/análise , Receptores CCR7/análise , Receptores de Superfície Celular/análise , Receptores Imunológicos , Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia
7.
Tumour Biol ; 37(8): 11359-64, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26960692

RESUMO

Dendritic cells (DCs) are antigen-presenting cells that can acquire tumour antigens and initiate cytotoxic T cell reactions. Obesity has been proposed as a cause for tumours escaping immune surveillance, but few studies investigate the impact of other body composition parameters. We examined the relationship of DC phenotype with computer tomography (CT)-defined parameters in patients with colorectal cancer (CRC). DCs were identified within peripheral blood mononuclear cells by flow cytometry as HLA-DR positive and negative for markers of other cell lineages in 21 patients. Analysis of CT scans was used to calculate lumbar skeletal muscle index (LSMI) and mean muscle attenuation (MA). Positive correlation between the LSMI and expression of CD40 in all DCs (r = 0.45; p = 0.04) was demonstrated. The MA was positively correlated with scavenger receptor CD36 [all DCs (r = 0.60; p = 0.01) and myeloid DCs (r = 0.63; p < 0.01)]. However, the MA was negatively correlated with CCR7 expression in all DCs (r = -0.46, p = 0.03.) and with CD83 [all DCs (r = -0.63; p = 0.01) and myeloid DCs (r = -0.75; p < 0.01)]. There were no relationships between the fat indexes and the DC phenotype. These results highlight a direct relationship between muscle depletion and changes in stimulatory, migratory and fatty acid-processing potential of DC in patients with CRC.


Assuntos
Composição Corporal/imunologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Células Dendríticas/imunologia , Adulto , Idoso , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Tomografia Computadorizada por Raios X
8.
Am J Gastroenterol ; 110(7): 1022-34, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25823771

RESUMO

OBJECTIVES: This study provides an overview of the largest and longest-running colonoscopic surveillance program for colorectal cancer (CRC) in patients with long-standing ulcerative colitis (UC). METHODS: Data were obtained from medical records, endoscopy, and histology reports. Primary end points were defined as death, colectomy, withdrawal from surveillance, or censor date (1 January 2013). RESULTS: A total of 1,375 UC patients were followed up for 15,234 patient-years (median, 11 years per patient). CRC was detected in 72 patients (incidence rate (IR), 4.7 per 1,000 patient-years). Time-trend analysis revealed that although there was significant decrease in incidence of colectomy performed for dysplasia (linear regression, R=-0.43; P=0.007), IR of advanced CRC and interval CRC have steadily decreased over past four decades (Pearson's correlation, -0.99; P=0.01 for both trends). The IR of early CRC has increased 2.5-fold in the current decade compared with past decade (χ(2), P=0.045); however, its 10-year survival rate was high (79.6%). The IR of dysplasia has similarly increased (χ(2), P=0.01), potentially attributable to the recent use of chromoendoscopy that was twice more effective at detecting dysplasia compared with white-light endoscopy (χ(2), P<0.001). CRCs were frequently accompanied by synchronous CRC or spatially distinct dysplasia (37.5%). Finally, the risk of CRC was not significantly different between "indefinite" or low-grade dysplasia (log-rank, P=0.78). CONCLUSIONS: Colonoscopic surveillance may have a significant role in reducing the risk of advanced and interval CRC while allowing more patients to retain their colon for longer. Given the ongoing risk of early CRC, patients with any grade of dysplasia who are managed endoscopically should be monitored closely with advanced techniques.


Assuntos
Transformação Celular Neoplásica/patologia , Colite Ulcerativa/complicações , Colo/patologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etiologia , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Vigilância da População/métodos , Adulto , Colite Ulcerativa/patologia , Colonoscopia/métodos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Corantes , Progressão da Doença , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Reino Unido/epidemiologia
9.
Am J Gastroenterol ; 110(10): 1461-71; quiz 1472, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26416190

RESUMO

OBJECTIVES: The aim of this study was to identify risk factors associated with development of high-grade dysplasia (HGD) or colorectal cancer (CRC) in ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD). METHODS: Patients with histologically confirmed extensive UC, who were diagnosed with LGD between 1993 and 2012 at St Mark's Hospital, were identified and followed up to 1 July 2013. Demographic, endoscopic, and histological data were collected and correlated with the development of HGD or CRC. RESULTS: A total of 172 patients were followed for a median of 48 months from the date of initial LGD diagnosis (interquartile range (IQR), 15-87 months). Overall, 33 patients developed HGD or CRC (19.1% of study population; 20 CRCs) during study period. Multivariate Cox proportional hazard analysis revealed that macroscopically non-polypoid (hazard ratio (HR), 8.6; 95% confidence interval (CI), 3.0-24.8; P<0.001) or invisible (HR, 4.1; 95% CI, 1.3-13.4; P=0.02) dysplasia, dysplastic lesions ≥1 cm in size (HR, 3.8; 95% CI, 1.5-13.4; P=0.01), and a previous history of "indefinite for dysplasia" (HR, 2.8; 95% CI, 1.2-6.5; P=0.01) were significant contributory factors for HGD or CRC development. Multifocal dysplasia (HR, 3.9; 95% CI, 1.9-7.8; P<0.001), metachronous dysplasia (HR, 3.5; 95% CI, 1.6-7.5; P=0.001), or a colonic stricture (HR, 7.4; 95% CI, 2.5-22.1; P<0.001) showed only univariate correlation to development of HGD or CRC. CONCLUSIONS: Lesions that are non-polypoid or endoscopically invisible, large (≥1 cm), or preceded by indefinite dysplasia are independent risk factors for developing HGD or CRC in UC patients diagnosed with LGD.


Assuntos
Colite Ulcerativa/patologia , Colo/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Constrição Patológica/patologia , Idoso , Doenças do Colo/patologia , Colonoscopia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
10.
J Surg Oncol ; 112(1): 86-92, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26179425

RESUMO

BACKGROUND AND OBJECTIVES: The host local immune response (LIR) to cancer is a determinant of cancer outcome. Regulation of this local response is largely achieved through chemokine synthesis from the tumor microenvironment such as C-Chemokine-Receptor-7 (CCR7). We examined the LIR measured as CCR7 expression, in colorectal cancers (CRC) and explored relationships with body composition (BC) and survival. METHODS: A study of paraffin-embedded tissue specimens was carried out in 116 patients with non-metastatic CRC. CCR7 expression was determined by immunohistochemistry. Analysis of computer tomography scans was used to calculate BC parameters. Survival analyses and multivariate regression models were used. RESULTS: High CCR7(+) cell density within the tumor stroma and at the margin was significantly associated with increased age, the presence of lymphovascular invasion, higher tumor stage, lymph node metastasis, high Klintrup-Makinen immune score, and myosteatosis. High CCR7(+) cell density in the tumor margin was significantly associated with shorter disease-free (DFS) and overall survival (OS) (P < 0.001). This was also significantly associated with shorter survival in multivariate analysis (HR = 8.87; 95%CI [2.51-31.3]; P < 0.01 for OS and HR = 4.72; 95%CI (1.24-12.9); P = 0.02 for DFS). CONCLUSIONS: Our results suggest that a specific immune microenvironment may be associated with altered host's BC and tumor behavior, and that CCR7 may serve as a novel prognostic biomarker.


Assuntos
Biomarcadores Tumorais/metabolismo , Composição Corporal , Neoplasias Colorretais/patologia , Receptores CCR7/metabolismo , Idoso , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
11.
ACS Appl Bio Mater ; 7(6): 4116-4132, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38772009

RESUMO

The management of multibacterial infections remains clinically challenging in the care and treatment of chronic diabetic wounds. Photodynamic therapy (PDT) offers a promising approach to addressing bacterial infections. However, the limited target specificity and internalization properties of traditional photosensitizers (PSs) toward Gram-negative bacteria pose significant challenges to their antibacterial efficacy. In this study, we designed an iron heme-mimetic PS (MnO2@Fe-TCPP(Zn)) based on the iron dependence of bacteria that can be assimilated by bacteria and retained in different bacteria strains (Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus) and which shows high PDT antibacterial efficacy. For accelerated wound healing after antibacterial treatment, MnO2@Fe-TCPP(Zn) was loaded into a zwitterionic hydrogel with biocompatibility and antifouling properties to form a nanocomposite antibacterial hydrogel (PSB-MnO2@Fe-TCPP(Zn)). In the multibacterial infectious diabetic mouse wound model, the PSB-MnO2@Fe-TCPP(Zn) hydrogel dressing rapidly promoted skin regeneration by effectively inhibiting bacterial infections, eliminating inflammation, and promoting angiogenesis. This study provides an avenue for developing broad-spectrum antibacterial nanomaterials for combating the antibiotic resistance crisis and promoting the healing of complex bacterially infected wounds.


Assuntos
Antibacterianos , Materiais Biocompatíveis , Testes de Sensibilidade Microbiana , Fotoquimioterapia , Fármacos Fotossensibilizantes , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Heme/química , Teste de Materiais , Ferro/química , Escherichia coli/efeitos dos fármacos , Tamanho da Partícula , Diabetes Mellitus Experimental/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Compostos de Manganês/química , Compostos de Manganês/farmacologia
12.
Mediators Inflamm ; 2013: 573576, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23970814

RESUMO

BACKGROUND: Dendritic cells regulate immune responses to microbial products and play a key role in ulcerative colitis (UC) pathology. We determined the immunomodulatory effects of probiotic strain Lactobacillus casei Shirota (LcS) on human DC from healthy controls and active UC patients. METHODS: Human blood DC from healthy controls (control-DC) and UC patients (UC-DC) were conditioned with heat-killed LcS and used to stimulate allogeneic T cells in a 5-day mixed leucocyte reaction. RESULTS: UC-DC displayed a reduced stimulatory capacity for T cells (P < 0.05) and enhanced expression of skin-homing markers CLA and CCR4 on stimulated T cells (P < 0.05) that were negative for gut-homing marker ß7. LcS treatment restored the stimulatory capacity of UC-DC, reflecting that of control-DC. LcS treatment conditioned control-DC to induce CLA on T cells in conjunction with ß7, generating a multihoming profile, but had no effects on UC-DC. Finally, LcS treatment enhanced DC ability to induce TGFß production by T cells in controls but not UC patients. CONCLUSIONS: We demonstrate a systemic, dysregulated DC function in UC that may account for the propensity of UC patients to develop cutaneous manifestations. LcS has multifunctional immunoregulatory activities depending on the inflammatory state; therapeutic effects reported in UC may be due to promotion of homeostasis.


Assuntos
Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Células Dendríticas/citologia , Lacticaseibacillus casei/imunologia , Probióticos/farmacologia , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Células Dendríticas/imunologia , Citometria de Fluxo , Homeostase , Humanos , Inflamação/imunologia , Ativação Linfocitária , Linfócitos T/citologia , Linfócitos T/imunologia , Fator de Crescimento Transformador beta/metabolismo
13.
Surgeon ; 11(3): 130-3, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23153766

RESUMO

INTRODUCTION: Since the introduction of Endoscopic Thoracic Sympathectomy ( ETS ) by Kux in 1951, the procedure has been performed for treatment of primary hyperhidrosis (PH) of the upper limb. Despite its initial success and minimally invasive nature, the long-term results are yet to be established. The aim of this study is to evaluate the outcome of patients after ETS with particular emphasis on patient satisfaction and its effectiveness over a 16-year period. METHODS: A patient survey of fifty-one (n = 51) patients who had ETS for PH of palms from 1995 to 2011 was conducted. The data on age, sex, site of the PH, family history, trigger, hospital stay, relief from symptoms, complications, refractory sweating and overall satisfaction with the procedure was analysed with SAS software version 9.1.3. CONCLUSION: The mean follow-up was 77 months (range, 6-189 months) with equal gender distribution (n = 24 males Vs n = 27 females) and mean age of 19 (range, 13-64 years). The hereditary prevalence was 55%. Forty-six patients (90.2%) reported an immediate (≤24 h) and four patients (7.8%) reported a delay (>24 h) in relief of symptoms. To the best of our knowledge this is longest duration of follow-up reported in the literature.


Assuntos
Previsões , Hiperidrose/cirurgia , Simpatectomia/métodos , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Hiperidrose/fisiopatologia , Incidência , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Sudorese , Reino Unido/epidemiologia , Adulto Jovem
14.
Adv Healthc Mater ; 12(27): e2301083, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37300544

RESUMO

Radiotherapy (RT) can produce a vaccine effect and remodel a tumor microenvironment (TME) by inducing immunogenic cell death (ICD) and inflammation in tumors. However, RT alone is insufficient to elicit a systemic antitumor immune response owing to limited antigen presentation, immunosuppressive microenvironment, and chronic inflammation within the tumor. Here, a novel strategy is reported for the generation of in situ peptide-based nanovaccines via enzyme-induced self-assembly (EISA) in tandem with ICD. As ICD progresses, the peptide Fbp-GD FD FD pY (Fbp-pY), dephosphorylated by alkaline phosphatase (ALP) forms a fibrous nanostructure around the tumor cells, resulting in the capture and encapsulation of the autologous antigens produced by radiation. Utilizing the adjuvant and controlled-release advantages of self-assembling peptides, this nanofiber vaccine effectively increases antigen accumulation in the lymph nodes and cross-presentation by antigen-presenting cells (APCs). In addition, the inhibition of cyclooxygenase 2 (COX-2) expression by the nanofibers promotes the repolarization of M2-macrophages into M1 and reduces the number of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) required for TME remodeling. As a result, the combination of nanovaccines and RT significantly enhances the therapeutic effect on 4T1 tumors compared with RT alone, suggesting a promising treatment strategy for tumor radioimmunotherapy.


Assuntos
Nanofibras , Neoplasias , Vacinas , Humanos , Radioimunoterapia , Morte Celular Imunogênica , Imunoterapia/métodos , Neoplasias/radioterapia , Peptídeos , Inflamação , Microambiente Tumoral , Linhagem Celular Tumoral
15.
Nat Commun ; 14(1): 5433, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37669968

RESUMO

The quantum Hall effect, fundamental in modern condensed matter physics, continuously inspires new theories and predicts emergent phases of matter. Here we experimentally demonstrate three types of Chern insulators with synthetic dimensions on a programable 30-qubit-ladder superconducting processor. We directly measure the band structures of the 2D Chern insulator along synthetic dimensions with various configurations of Aubry-André-Harper chains and observe dynamical localisation of edge excitations. With these two signatures of topology, our experiments implement the bulk-edge correspondence in the synthetic 2D Chern insulator. Moreover, we simulate two different bilayer Chern insulators on the ladder-type superconducting processor. With the same and opposite periodically modulated on-site potentials for two coupled chains, we simulate topologically nontrivial edge states with zero Hall conductivity and a Chern insulator with higher Chern numbers, respectively. Our work shows the potential of using superconducting qubits for investigating different intriguing topological phases of quantum matter.

16.
Adv Sci (Weinh) ; 9(24): e2200681, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35751467

RESUMO

The high locoregional recurrence rate and potential wound infection in breast cancer after surgery pose enormous risks to patient survival. In this study, a polyethylene glycol acrylate (PEGDA)-alginate double-network nanocomposite hydrogel (GPA) embedded with 125 I-labeled RGDY peptide-modified gold nanorods (125 I-GNR-RGDY) is fabricated. The double-network hydrogel is formed by injection of GPA precursor solutions into the cavity of resected cancerous breasts of mice where gelation occurred rapidly. The enhanced temperature-induced PEGDA polymerization driven by near-infrared light irradiation, and then, the second polymer network is crosslinked between alginate and endogenous Ca2+ around the tumor. The double-network hydrogel possesses a dense polymer network and tightly fixes 125 I-GNR-RGDY, which exhibit superior persistent photothermal and radioactive effects. Hyperthermia induced by photothermal therapy can inhibit self-repair of damaged DNA and promote blood circulation to improve the hypoxic microenvironment, which can synergistically enhance the therapeutic efficacy of brachytherapy and simultaneously eliminate pathogenic bacteria. Notably, this nanocomposite hydrogel facilitates antibacterial activity to prevent potential wound infection and is tracked by single-photon emission computerized tomography imaging owing to isotope labeling of loaded 125 I-GNR-RGDY. The combination of photothermal therapy and brachytherapy has enabled the possibility of proposing a novel postoperative adjuvant strategy for preventing tumor recurrence and wound infection.


Assuntos
Braquiterapia , Hipertermia Induzida , Infecção dos Ferimentos , Alginatos , Animais , Hidrogéis/farmacologia , Camundongos , Nanogéis , Recidiva Local de Neoplasia/prevenção & controle , Polietilenoglicóis , Microambiente Tumoral
17.
Macromol Biosci ; 22(12): e2200359, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36208072

RESUMO

Photodynamic therapy (PDT) has attracted much attention in cancer treatment due to its tumor selectivity and noninvasive nature. Recent studies have demonstrated that PDT mediated reactive oxygen species (ROS) generation in tumor microenvironment (TME) synergistically improves the efficacy of immune checkpoint blockade (ICB) therapy. However, the instability and short half-life of the ROS generated by PDT limit its clinical applications. Herein, a coassembled peptide hydrogel comprising two short peptides that contained the same assembly unit, Ce6-KKFKFEFEF (KEF-Ce6) and RRRRRRRR-KFKFEFEF (KEF-R8) is developed. When exposed to 635 nm laser irradiation, KEF-Ce6 released ROS, while KEF-R8 plays as nitric oxide (NO) donor. Subsequently, ROS reacts with NO to produce reactive nitrogen species (RNS). Both in vitro and in vivo experiments prove that converting ROS into more cytotoxic RNS caused intense cell death. Importantly, it is observed that tumor-associated macrophages (TAMs) are polarized to proinflammatory types (M1-type) by the RNS-based PDT. The increase of M1 macrophages relieves the immunosuppressive situation in TME. Thus, when combined with αPD-L1 treatment, the survival time of tumor-bearing mice is prolonged. Overall, a simple yet efficient coassembled hydrogel that can cascade release ROS/NO/RNS and strengthen antitumor T cell responses to boost cancer immunotherapy by reprogramming TAMs is provided.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Camundongos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Hidrogéis/farmacologia , Linhagem Celular Tumoral , Peptídeos/farmacologia , Nanopartículas/química , Microambiente Tumoral , Porfirinas/química
18.
Opt Express ; 19(16): 15047-61, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-21934866

RESUMO

Interaction between micrometer-long nanoantennas within an array considerably modifies the plasmonic resonant behaviour; for fundamental resonances in the infrared already at micrometer distances. In order to get systematic knowledge on the relationship between infrared plasmonic resonances and separation distances dx and dy in longitudinal and transverse direction, respectively, we experimentally studied the optical extinction spectra for rectangularly ordered lithographic gold nanorod arrays on silicon wafers. For small dy, strong broadening of resonances and strongly decreased values of far-field extinction are detected which come along with a decreased near-field intensity, as indicated by near-field amplitude maps of the interacting nanoantennas. In contrast, near-field interaction over small dx does only marginally broaden the resonance. Our findings set a path for optimum design of rectangular nanorod lattices for surface enhanced infrared spectroscopy.


Assuntos
Nanotecnologia/instrumentação , Simulação por Computador , Eletrônica , Ouro/química , Nanopartículas Metálicas/química , Metais/química , Microscopia Eletrônica de Varredura/métodos , Modelos Teóricos , Nanotecnologia/métodos , Óptica e Fotônica , Ondas de Rádio , Espectrofotometria Infravermelho/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Ressonância de Plasmônio de Superfície
19.
RSC Adv ; 8(14): 7514-7517, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35539109

RESUMO

We have developed hybridization-sensitive fluorescent oligonucleotide probes that, in the presence of quencher strands, undergo efficient fluorescence quenching through the formation of partial DNA/DNA duplexes. In the presence of target RNA, rapid displacement of the quencher strands results in highly enhanced fluorescence.

20.
Artigo em Chinês | WPRIM | ID: wpr-985958

RESUMO

Objective: To evaluate the clinical value of dynamic volumetric CT perfusion combined with energy spectrum imaging in bronchial arterial chemoembolization (BACE) in patients with lung cancer. Methods: The data of 31 patients with lung cancer confirmed by pathology and treated with BACE in Lishui Central Hospital from January 2018 to February 2022 were retrospectively collected, including 23 men and 8 women, aged 31-84 (67) years. All patients received perfusion scans of lesion sites within 1 week before surgery and 1 month after surgery. We collected and compared the changes in preoperative and postoperative perfusion parameters such as blood flow (BF), blood volume (BV), mean through time (MTT), permeability surface (PS) and energy spectrum parameters including arterial phase CT value (CTA), venous phase CT value (CTV), arterial phase iodine concentration (ICA), venous phase of iodine concentration (ICV), arterial standardization iodine concentration (NICA), and intravenous standardized iodine concentration (NICV) to confirm the significance of these parameters in evaluating the short-term efficacy of BACE in the treatment of advanced lung cancer. Data normality was tested using the Kolmogorov-Smirnov test and normally distributed measurement data are expressed here as mean ± standard deviation; the independent-samples t-test was used for comparisons between two groups. The measurement data that were not normally distributed are expressed as median (interquartile interval) [M (Q1, Q3)], and the comparison between the two groups used the Kruskal-Wallis test. Count data are expressed as cases (%), and comparisons between groups used the χ2 test. Results: The objective response rate (ORR) and disease control rate (DCR) at 1 month after BACE were 54.8% (17/31) and 96.8% (30/31), respectively. CT perfusion parameters and energy spectrum parameters of patients before and after BACE treatment were compared. The results showed that BF, BV, MTT, ICA, ICV and NICV were significantly decreased after BACE treatment compared with before treatment, and the differences were statistically significant[58.06 (40.47,87.22) vs.23.57(10.92, 36.24) ml·min-1·100g-1,3.33(2.86,6.09) vs.2.12(1.96,3.61)ml/100g,2.70(2.19,3.88) vs.1.53 (1.12,2.25)s, 3.51 (3.11,4.14)vs.1.74 (1.26,2.50)mg/ml,2.00 (1.30,2.45) vs.1.32(0.92,1.76)mg/ml,0.51(0.42,0.57) vs.0.33(0.23,0.39)](all P<0.05). At the same time, compared with the non-remission group, the study results showed that the difference of parameters in remission group before and after BACE was more obvious, including ΔBF, ΔBV, ΔMTT, ΔPS, ΔCTA, ΔCTV, ΔICA, ΔICV, ΔNICA, ΔNICV were significantly increased, and the difference was statistically significant [36.82(32.38, 45.34) vs.9.50(-1.43, 12.34) ml·min-1·100g-1,4.46(2.52, 5.79) vs.0.22(-0.76, 4.09) ml/100g,4.22(2.25, 6.77) vs.0.43(-2.53, 1.88) s,10.07 (2.89, 13.13) vs.-2.01(-6.77, 4.28) ml·min-1·100g-1,14.22(11.88, 20.57) vs.4.18(-5.25, 6.37) HU, 34.6(14.88, 43.15) vs.11.60(0.26, 25.05) HU,0.95(0.54, 1.47) vs.0.11(0.20, 0.59) mg/ml,1.57(1.10, 2.38) vs. 0.26(-0.21, 0.63) mg/ml,0.05(0.03, 0.08) vs.-0.02(-0.04, 0.01),0.18(0.13, 0.21)vs. 0.11(-0.06, 0.16)](all P<0.05). Conclusions: CT perfusion combined with spectral imaging could effectively evaluate the changes in tumor vascular perfusion in patients with advanced lung cancer before and after BACE treatment, which has important value in judging the short-term efficacy after treatment.


Assuntos
Masculino , Humanos , Feminino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares , Iodo , Perfusão
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