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1.
Science ; 384(6695): 579-584, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38696580

RESUMO

Fractional quantum Hall (FQH) states are known for their robust topological order and possess properties that are appealing for applications in fault-tolerant quantum computing. An engineered quantum platform would provide opportunities to operate FQH states without an external magnetic field and enhance local and coherent manipulation of these exotic states. We demonstrate a lattice version of photon FQH states using a programmable on-chip platform based on photon blockade and engineering gauge fields on a two-dimensional circuit quantum electrodynamics system. We observe the effective photon Lorentz force and butterfly spectrum in the artificial gauge field, a prerequisite for FQH states. After adiabatic assembly of Laughlin FQH wave function of 1/2 filling factor from localized photons, we observe strong density correlation and chiral topological flow among the FQH photons. We then verify the unique features of FQH states in response to external fields, including the incompressibility of generating quasiparticles and the smoking-gun signature of fractional quantum Hall conductivity. Our work illustrates a route to the creation and manipulation of novel strongly correlated topological quantum matter composed of photons and opens up possibilities for fault-tolerant quantum information devices.

2.
Chin Med J (Engl) ; 134(14): 1669-1680, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34397593

RESUMO

BACKGROUND: The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer, but the effects on safety and survival are still controversial. The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery (NACS) and surgery alone (SA) for locally advanced gastric cancer. METHODS: Databases (PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar) were explored for relative studies from January 2000 to January 2021. The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale, respectively. The Review Manager software (version 5.3) was used to perform this meta-analysis. The overall survival was evaluated as the primary outcome, while perioperative indicators and post-operative complications were evaluated as the secondary outcomes. RESULTS: Twenty studies, including 1420 NACS cases and 1942 SA cases, were enrolled. The results showed that there were no significant differences in overall survival (P = 0.240), harvested lymph nodes (P = 0.200), total complications (P = 0.080), and 30-day post-operative mortality (P = 0.490) between the NACS and SA groups. However, the NACS group was associated with a longer operation time (P < 0.0001), a higher R0 resection rate (P = 0.003), less reoperation (P = 0.030), and less anastomotic leakage (P = 0.007) compared with SA group. CONCLUSIONS: Compared with SA, NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage. While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.


Assuntos
Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
3.
Biochemistry ; 60(19): 1564-1568, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33929828

RESUMO

Group A Streptococcus (GAS, or Streptococcus pyogenes) is a leading human bacterial pathogen with diverse clinical manifestations, ranging from mild to life-threatening and to severe immune sequela. These diseases, combined, account for more than half a million deaths per year, globally. To accomplish its vast pathogenic potential, GAS expresses a multitude of virulent proteins, including the pivotal virulence factor ScpC. ScpC is a narrow-range surface-exposed subtilisin-like serine protease that cleaves the last 14 C-terminal amino acids of interleukin 8 (IL-8 or CXCL8) and impairs essential IL-8 signaling processes. As a result, neutrophil migration, bacterial killing, and the formation of neutrophil extracellular traps are strongly impaired. Also, ScpC has been identified as a potential vaccine candidate. ScpC undergoes an autocatalytic cleavage between Gln244 and Ser245, resulting in two polypeptide chains that assemble together forming the active protease. Previously, we reported that the region harboring the autocatalytic cleavage site, stretching from Gln213 to Asp272, is completely disordered. Here, we show that a deletion mutant (ScpCΔ60) of this region forms a single polypeptide chain, whose crystal structure we determined at 2.9 Å resolution. Moreover, we show that ScpCΔ60 is an active protease capable of cleaving its substrate IL-8 in a manner comparable to that of the wild type. These studies improve our understanding of the proteolytic activity of ScpC.


Assuntos
Peptídeo Hidrolases/metabolismo , Streptococcus pyogenes/metabolismo , Proteínas de Bactérias/metabolismo , Catálise , Endopeptidases/metabolismo , Humanos , Peptídeo Hidrolases/ultraestrutura , Proteólise , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/patologia , Subtilisinas/metabolismo , Subtilisinas/ultraestrutura , Virulência , Fatores de Virulência/metabolismo
4.
Br J Nurs ; 29(2): S18-S23, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31972104

RESUMO

BACKGROUND: Intravenous therapy is an integral part of professional nursing practice. Nurses have a responsibility to recognise risk factors for phlebitis. AIMS: To investigate nurses' perceptions of risk factors for phlebitis in a tertiary teaching hospital in north-east Peninsular Malaysia. METHODS: A cross-sectional study of 199 randomly selected nurses were surveyed for their perceptions of risk factors for phlebitis using a self-administered questionnaire. FINDINGS: More than half of the nurses (56.8%) had a good perception levels of risk factors for phlebitis. There was a significant association between the clinical area and nurses' perceptions of risk factors for phlebitis (p=0.04). Nurses working in medical, orthopaedic, and surgical areas had slightly better perceptions than nurses working in multidisciplinary and oncology areas. CONCLUSION: These findings suggest that nurses need to continually improve their knowledge about risk factors for phlebitis to ensure safer nursing practice.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Recursos Humanos de Enfermagem Hospitalar/psicologia , Flebite/enfermagem , Adulto , Estudos Transversais , Feminino , Hospitais de Ensino , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Fatores de Risco , Inquéritos e Questionários , Centros de Atenção Terciária , Adulto Jovem
5.
Biochem Biophys Res Commun ; 502(3): 307-312, 2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-29787761

RESUMO

The Hippo tumor suppressor pathway is an important regulator of cell proliferation and apoptosis, and signal transduction occurs through phosphorylation of the effector protein TAZ by the serine/threonine kinase LATS1/2. Here, we report the biophysical and computational studies to characterize the interaction between TAZ and LATS1/2 through WW domain-PPxY motif binding. We show that the TAZ WW domain exhibits a binding preference for the second of the two PPxY motifs of LATS1 in vitro. We modelled the structure of the domain in complex with LATS1 PPxY2 peptide and, through molecular dynamics simulations, show that WW domain-PPxY2 complex is stable with some flexibility in the peptide region. Next, we predict and verify that L143 and T150 of the WW domain are important for TAZ binding with the PPxY2 peptide using mutational and isothermal titration calorimetric studies. Furthermore, we suggest that the electrostatic potential of charged residues within the binding pocket may influence the ligand affinity among otherwise highly similar WW domains.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Fenômenos Biofísicos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Modelos Moleculares , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Domínios e Motivos de Interação entre Proteínas , Proteínas Serina-Treonina Quinases/genética , Estabilidade Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Homologia Estrutural de Proteína , Transativadores , Fatores de Transcrição , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Domínios WW/genética
6.
J Lab Autom ; 18(1): 46-62, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22989771

RESUMO

Vesicles have been studied for several years in their ability to deliver drugs. Mathematical models have much potential in reducing time and resources required to engineer optimal vesicles, and this review article summarizes these models that aid in understanding the ability of targeted vesicles to bind and internalize into cancer cells, diffuse into tumors, and distribute in the body. With regard to binding and internalization, radiolabeling and surface plasmon resonance experiments can be performed to determine optimal vesicle size and the number and type of ligands conjugated. Binding and internalization properties are also inputs into a mathematical model of vesicle diffusion into tumor spheroids, which highlights the importance of the vesicle diffusion coefficient and the binding affinity of the targeting ligand. Biodistribution of vesicles in the body, along with their half-life, can be predicted with compartmental models for pharmacokinetics that include the effect of targeting ligands, and these predictions can be used in conjunction with in vivo models to aid in the design of drug carriers. Mathematical models can prove to be very useful in drug carrier design, and our hope is that this review will encourage more investigators to combine modeling with quantitative experimentation in the field of vesicle-based drug delivery.


Assuntos
Células/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Corpo Humano , Modelos Teóricos , Neoplasias/metabolismo , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Células/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico
7.
Fa Yi Xue Za Zhi ; 28(5): 379-82, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23213791

RESUMO

It is never an easy thing to diagnose heart vascular disease only depending on the unenhanced postmortem computed tomography (PMCT). This article reported a case of sudden natural death after the complaint of anterior chest pain in which coronary artery calcification (CAC) was clearly displayed using PMCT scan. The entire coronary artery system was almost reconstructed via multiplanar reformation (MPR) and volume-rendering reconstruction (VR), and the total calcium score of the coronary arteries was obtained with CaScoring automatic analysis software. The results showed that CAC was conspicuous; the total calcium score was 640.3, considerably higher than 400. The pulmonary ground-glass opacity (GGO) and small amount of fluid both in the subglottic trachea and main bronchi were also found. The imaging results confirmed those of autopsy. In addition, the results concluded that PMCT might serve as an invaluable adjunct to the classic autopsy procedure.


Assuntos
Calcinose/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Vasos Coronários/patologia , Morte Súbita/etiologia , Tomografia Computadorizada por Raios X/métodos , Autopsia , Causas de Morte , Patologia Legal , Humanos
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