RESUMO
Psoriasis is characterized by keratinocyte (KC) hyperproliferation and inflammatory cell infiltration, but the mechanisms remain unclear. In an imiquimod-induced mouse psoriasiform model, p38 activity is significantly elevated in KCs and p38α specific deletion in KCs ameliorates skin inflammation. p38α signaling promotes KC proliferation and psoriasis-related proinflammatory gene expression during psoriasis development. Mechanistically, p38α enhances KC proliferation and production of inflammatory cytokines and chemokines by activating STAT3. While p38α signaling in KCs does not affect the expression of IL-23 and IL-17, it substantially amplifies the IL-23/IL-17 pathogenic axis in psoriasis. The therapeutic effect of IL-17 neutralization is associated with decreased p38 and STAT3 activities in KCs and targeting the p38α-STAT3 axis in KCs ameliorates the severity of psoriasis. As IL-17 also highly activates p38 and STAT3 in KCs, our findings reveal a sustained signaling circuit important for psoriasis development, highlighting p38α-STAT3 axis as an important target for psoriasis treatment.
Assuntos
Proliferação de Células , Citocinas , Queratinócitos , Proteína Quinase 14 Ativada por Mitógeno , Psoríase , Fator de Transcrição STAT3 , Psoríase/metabolismo , Psoríase/genética , Psoríase/patologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Queratinócitos/metabolismo , Animais , Camundongos , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Proteína Quinase 14 Ativada por Mitógeno/genética , Citocinas/metabolismo , Regulação para Baixo , Camundongos Knockout , Interleucina-17/metabolismo , Interleucina-17/genética , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Transdução de Sinais , Humanos , ImiquimodeRESUMO
Compared to conventional nucleic acid detection methods, label-free single nucleotide polymorphism (SNP) detection presents challenging due to the necessity of discerning single base mismatches, especially in the field of enzyme-free detection. In this study, we introduce a novel bulged-type DNA duplex probe designed to significantly amplify single-base differences. This probe is integrated with programmable DNA-based nanostructures to develop a sensitive, label-free biosensor for nonenzymatic SNP detection. The duplex probe with one bulge could selectively identify wild-typed DNA (WT) and mutant-type DNA (MT) based on a competitive strand displacement reaction mechanism. The hyperbranched HCR (HHCR) by incorporating of hairpin DNA into the DNA tetrahedron and surface-tethering on the portable screen printing electrode (SPCE) significantly favor the formation of negatively charged DNA nanostructure. We harnessed strong repulsion of DNA nanostructure towards the electroactive [Fe(CN)6]³â»/4â» in combination with electrochemical technique to create a label-free biosensor. This simple, enzyme-free and label-free biosensor could detect MT with a detection limit of 56 aM, even in multiple sequence backgrounds. The study served as the proof-of-concept for the integration of enzyme-free competitive mechanism and label-free strategy, which can be extended as a powerful tool to various fields.
Assuntos
Técnicas Biossensoriais , DNA , Técnicas Eletroquímicas , Polimorfismo de Nucleotídeo Único , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , DNA/genética , DNA/química , Limite de Detecção , Nanoestruturas/química , Humanos , Sondas de DNA/química , Sondas de DNA/genéticaRESUMO
Flexible pressure sensors have garnered significant attention in the field of wearable healthcare due to their scalability and shape variability. However, a crucial challenge in their practical application for various healthcare scenarios is striking a balance between the sensitivity and sensing range. This limitation arises from the reduced compressibility of the microstructures on the surface of pressure-sensitive materials under high pressure, resulting in progressive saturation of the sensor's response and leading to a restricted and nonlinear pressure sensing range. In this study, we present a novel approach utilizing multi-level pyramidal microstructures in flexible pressure sensors to achieve both high sensitivity (8775 kPa-1) and linear response (R2 = 0.997) over a wide pressure range (up to 1000 kPa). The effectiveness of the proposed design stems from the compensatory behavior of the lower pyramidal microstructures, which counteracts the declining sensitivity associated with the gradual hardening of the higher pyramidal microstructures. Furthermore, the sensor demonstrates a fast response time of 11.6 ms and a fast relaxation time of 3.8 ms and can reliably detect pressures as low as 30.2 Pa. Our findings highlight the applicability of this flexible pressure sensor in diverse human body health detection tasks, ranging from weak pulses to finger flexion and plantar pressure distribution. Notably, the proposed sensor design eliminates the need for replacing flexible pressure sensors with varying ranges, thereby enhancing their practical utility.
RESUMO
Organized two-dimensional polystyrene bead arrays perform ion etching, and protruding nanostructures are created on polystyrene beads due to the shadow effects from the ring beads, leading to nucleus selection and growth in Au nanostructure deposition. Ag nanostructures are prepared via plasmon-mediated chemical reactions (PMCRs), leading to the Ag nanocavity geometry of the honeycomb pattern when the etching time and Ag growth time are tuned. Due to the strong electromagnetic coupling, the Ag honeycomb-shaped nanocavity array works as the SERS substrate with high sensitivity and good repeatability, which is used to detect thiram pesticide residues with a concentration down to 10-9 M.
RESUMO
Ag nanoparticles sputtered on silicon wafer are used as masks for the fabrication of silicon columns by ion etching, which induces the growth of the inclined Ag nanorod by inclined Ag sputtering. V-shaped and Z-shaped Ag nanorods can be obtained by varying incline angles and deposition times. SERS detection and FDTD simulation are used to compare and investigate the enhanced electromagnetic coupling of incline nanorod arrays with different shapes in three-dimensional space, which indicates that Z-shaped nanorods show good SERS properties. The Z-shaped Ag nanorod array is used as a SERS substrate for the detection of thiabendazole with a concentration down to 10-11 M.
RESUMO
It is very important to build uniform large-area dense hotspots to improve the surface-enhanced Raman scattering (SERS) detection limit. In our research, we designed and prepared a new flexibile SERS substrate with ultradense hot spots that has the advantages of high sensitivity, good repeatability, easy fabrication, and low cost. Due to the special dense hot spot structure, the substrate reaches a SERS enhancement factor of 2.1 × 1011. Because of the excellent physical stability of polydimethylsiloxane, the substrate can be bent at will, and the SERS performance will not change with bending. This is very important to extract effective detection objects on complex surfaces. The substrate has good light transmittance and softness and can be directly attached to the detected agricultural products to realize real-time and rapid SERS monitoring. This structure exhibits extraordinary performance for thiram detection in the ultralow concentration range of 10-13 M.
Assuntos
Nanopartículas Metálicas , Tiram , Prata/química , Dióxido de Silício , Nanopartículas Metálicas/química , Análise Espectral RamanRESUMO
Based on etched PS sphere arrays, the different growths of Ag nanoparticles with tunable LSPR are designed when SiO2-25 nm/Ag-30 nm/SiO2-100 nm sandwich nanocavity structures are annealed at 500 °C, including the hexagonal silver nanoparticle rings, circular silver nanoparticle rings, and aggregated silver nanoparticles. The uniformity of particle size and regularity of position generate enhanced electromagnetic field and good surface-enhanced Raman spectroscopy signals as confirmed by UV-vis observation and finite difference time domain method simulation. The developed nanostructures are effectively used as stable, nonreproducible, and markable anti-counterfeiting signs.
RESUMO
How to fabricate large area controllable surface-enhanced Raman scattering (SERS) active nanostructure substrates has always been one of the important issues in the development of nanostructure devices. In this paper, nano-etching technology and magnetron sputtering technology are combined to prepare nanostructure substrate with evolvable structure, and Ag/TiO2/Ag composites are introduced into the evolvable composite structure. The activity of SERS is further enhanced by the combination of TiO2 and Ag and the electron transfer characteristics of TiO2 itself. Deposition, plasma etching, and transfer are carried out on self-assembled 200 nm polystyrene (PS) colloidal sphere arrays. Due to the shadow effect between colloidal spheres and the size of metal particles introduced by deposition, a series of Ag/TiO2/Ag nanostructure arrays with adjustable nanostructure substrates such as nano-cap (NC), nano cap-star (NCS), and nano particle-disk (NPD) can be obtained. These nanoarrays with rough surfaces and different evolutionary structures can uninterruptedly regulate optical plasmon resonance and reconstruct SERS hotspots over a large range, which has potential application value in surface science, chemical detection, nanometer photonics, and so on.
RESUMO
Evacuation guiders play an important role when emergency events occur in urban open public spaces. Considering the shortcomings of the existing studies, an optimization method based on the Particle Swarm Optimization (PSO) algorithm and gradual covering model for spatial allocation of evacuation guiders in urban open public spaces is proposed. This method considers the impact of obstacles on intervisibility between guiders and evacuees, and the non-linear changing characteristics of the evacuation guiding quality based on the distances between guiders and evacuees to optimize the space allocation of evacuation guiders in urban open public spaces. Based on the emergency evacuation simulation, the evacuation efficiencies before and after the optimization of evacuation guider allocation can be compared to verify the validity of the proposed method. Furthermore, in order to improve the applicability of this method, the responsibility areas of the evacuation guiders are zoned according to different time periods. A case study of Binjiang Green Space in Xuhui District, Shanghai, China was conducted to demonstrate the feasibility of the proposed method. The results showed that the spatial allocation of evacuation guiders was highly correlated with the dynamic spatial change of evacuees. The reasonable spatial allocation optimization of evacuation guiders can effectively improve the emergency evacuation quality and reduce evacuation risks. The zoning of the evacuation guiders' responsibility areas can help to clarify the responsibility area of each guider and provide a daily safety precaution scheme under a limited number of guiders. The method can provide detailed decision support for the security precaution of security staff and emergency evacuation management in urban open public spaces.
Assuntos
Meio Ambiente , Parques Recreativos , Algoritmos , China , Planejamento de Cidades , HumanosRESUMO
The growth of metal nanostructures induced by surface plasmons has attracted widespread attention and provides a wide range of applications in the development of plasmonic nanochemistry, biosensors, photoelectrochemical coupling reactions, etc. Herein, a simple method is reported for the fabrication of Ag nanoflakes induced by the surface plasma on two-dimensional periodic nanopatterned arrays with the aid of 4-MBA molecules. The light radiation, molecules, and environmental gases are selected to track the formation mechanism of Ag nanoflakes. The in situ Raman observations and theoretical analyses confirm that small aromatic molecules with carboxyl groups play important roles in Ag nanoflake formation derived by localized surface plasmon resonance (LSPR)-driven carriers, which provide profound insights into the study of LSPR-driven carriers, participating in chemical reactions and the reconstruction of dense hot spots in nanogaps.
RESUMO
The risk of coastal storm flooding is deteriorating under global warming, especially for the heavily urbanized deltaic cities, like Shanghai. The Nature-Based Flood Defense (NBFD), as an eco-friendly design alternative for hard infrastructure against coastal flooding, is gaining attention. Nevertheless, the vulnerability of saltmarsh due to the biological instability, resulting in the uncertainties on coastal protection, is considered the bottleneck challenge that hinders the broad application of the NBFD concept. We argue that except for direct wave attenuations by the above-ground vegetation during storms, the gradual sediment trapping and consolidating during the non-storm period is a more crucial function of coastal saltmarsh, which mitigates storm waves by forming a broader and higher intertidal morphology. This benefit is an important value of saltmarsh-based coastal protection but is largely neglected in many NBFD studies. Taking Chongming Dongtan Shoal (CDS) as a case study, we demonstrated that over 2/3th wave attenuation during storms is contributed by the saltmarsh morphology, and less than 1/3th is from the saltmarsh vegetation. The relative contribution of the saltmarsh morphology on wave mitigation is even enhanced under the increasing storm grades from 100 yrs. to 5000 yrs. return levels. To promote this idea for broader application, the cost-benefit analysis of three artificial NBFD solutions (e.g., submerged breakwater, timber piles, and sand nourishment) are compared. We identified an optimal measure of the submerged breakwater for CDS, which minimizes the ecological impact and maximizes the cost-benefit. Moreover, the wave-free zone behind the breakwater increases the chance of vegetation establishment, helps suspended sediment trapping, hence fostering a beneficent cycle for saltmarsh restoration. In summary, ignoring the contribution of saltmarsh morphology on wave attenuation largely underestimated the benefits of vegetation-based coastal protection, which should be greatly emphasized to provide a solid basis for developing NBFD.
Assuntos
Inundações , Áreas Alagadas , China , EcossistemaRESUMO
Nanophotonics has been widely utilized in enhanced molecularspectroscopy or mediated chemical reaction, which has major applications in the field of enhancing sensing and enables opportunities in developing healthcare monitoring. This review presents an updated overview of the recent exciting advances of plasmonic biosensors in the healthcare area. Manufacturing, enhancements and applications of plasmonic biosensors are discussed, with particular focus on nanolisted main preparation methods of various nanostructures, such as chemical synthesis, lithography, nanosphere lithography, nanoimprint lithography, etc., and describing their respective advances and challenges from practical applications of plasmon biosensors. Based on these sensing structures, different types of plasmonic biosensors are summarized regarding detecting cancer biomarkers, body fluid, temperature, gas and COVID-19. Last, the existing challenges and prospects of plasmonic biosensors combined with machine learning, mega data analysis and prediction are surveyed.
Assuntos
Técnicas Biossensoriais , COVID-19 , Nanosferas , Nanoestruturas , Humanos , COVID-19/diagnóstico , Técnicas Biossensoriais/métodos , Nanosferas/química , Atenção à Saúde , Teste para COVID-19RESUMO
The signal molecule surfactin in biofilm formation has been extensively studied in B. subtilis, but there is rare reports in other Bacillus species. In this study, we compared the surfactin-Spo0A-SinI-SinR/SlrR signalling in regulating biofilm formation amongst four Bacillus species including B. subtilis, B. amyloliquefaciens, B. velezensis, and B. licheniformis. The role of surfactin in biofilm formation was dependent on Bacillus species and strains, and the importance of surfactin was as following: B. velezensis R9 = B. amyloliquefaciens WH1 > B. licheniformis 285-3 > B. subtilis CYY. The global regulator Spo0A was essential and very conservative for biofilm formation in all four Bacillus species. The regulators SinI and SinR played different roles to regulate biofilm formation in different Bacillus species. SinI had no obvious roles in B. velezensis, B. amyloliquefaciens and B. subtilis but had a positive role in B. licheniformis. SinR had no obvious roles in B. subtilis, but played a positive role in B. velezensis, B. amyloliquefaciens and B. licheniformis. The regulator SlrR played a positive role in the biofilm formation of all four Bacillus species. Collectively, surfactin, Spo0A and SlrR are essential for the biofilm formation in all four Bacillus species, and SinR and SinI plays different roles in different Bacillus species.
Assuntos
Bacillus , Biofilmes , Transdução de Sinais , Bacillus/genética , Lipopeptídeos/metabolismo , Peptídeos Cíclicos/metabolismo , Especificidade da EspécieRESUMO
Microorganisms including Bacillus can produce signal molecules such as surfactin, resulting in the variation of membrane potential to trigger quorum sensing such as biofilm formation and sporulation in response to the environment stresses. However, biosynthesis of surfactin requires multiple resources such as huge enzyme complex, amino acids, fatty acids, and energy. Insufficient resources in the natural soil environment restrain biosynthesis of surfactin. When surfactin is inadequate, cations in soil might serve as substitutes to regulate quorum sensing. Our results showed that both surfactin and cations could lead to the variation of membrane potential, thus providing signals to trigger the quorum sensing such as growth, biofilm formation, and sporulation in Bacillus amyloliquefaciens. Neither KinC nor Abh was essential for surfactin or cations to trigger quorum sensing. The cation signaling pathway is only partially dependent on Spo0A, but the surfactin signaling pathway is fully dependent on this global regulator. Compared to surfactin, cations are less effective in promoting biofilm formation, but more effective to trigger sporulation in B. amyloliquefaciens. This study reveals a pathway through which cations regulate the quorum sensing in B. amyloliquefaciens in the case of insufficient surfactin in environment.
Assuntos
Bacillus amyloliquefaciens , Bacillus , Proteínas de Bactérias , Cátions , Percepção de Quorum , Transdução de SinaisRESUMO
Surfactin, a quorum sensing signal molecule, is correlated with carbon metabolism in Bacillus amyloliquefaciens. In the present work, we found that mutation of srfA (ΔsrfA) led to an obviously changed carbon metabolism in B. amyloliquefaciens. Firstly, the PTS-glucose system was significantly increased as a feedback to glucose exhaustion. Secondly, the basic carbon metabolism such as glycolysis and TCA cycle was obviously weakened in ΔsrfA. Thirdly, the global regulator of CcpA (carbon catabolite protein A) and P ~ Ser46-HPr (seryl-phosphorylated form of histidine-containing protein) to mediate the CcpA-dependent CCR (carbon catabolite repression) were not increased, but the ability to use extracellular non- and less-preferred carbon sources was down-regulated in ΔsrfA. Fourthly, the carbon overflow metabolism such as biosynthesis of acetate was enhanced while biosynthesis of acetoin/2,3-butanediol and branched-chain amino acids were weakened in ΔsrfA. Finally, ΔsrfA could use most of non- and less-preferred carbon sources except for fatty acids, branched chain amino acids, and some organic acids (e.g. pyruvate, citrate and glutamate) after glucose exhaustion. Collectively, surfactin showed a global influence on carbon metabolism in B. amyloliquefaciens. Our studies highlighted a way to correlate quorum sensing with carbon metabolism via surfactin in Bacillus species.
RESUMO
The synthesis of nanostructured surfaces and thin films has potential applications in the field of plasmonics, including plasmon sensors, plasmon-enhanced molecular spectroscopy (PEMS), plasmon-mediated chemical reactions (PMCRs), and so on. In this article, we review various nanostructured surfaces and thin films obtained by the combination of nanosphere lithography (NSL) and physical vapor deposition. Plasmonic nanostructured surfaces and thin films can be fabricated by controlling the deposition process, etching time, transfer, fabrication routes, and their combination steps, which manipulate the formation, distribution, and evolution of hotspots. Based on these hotspots, PEMS and PMCRs can be achieved. This is especially significant for the early diagnosis of hepatocellular carcinoma (HCC) based on surface-enhanced Raman scattering (SERS) and controlling the growth locations of Ag nanoparticles (AgNPs) in nanostructured surfaces and thin films, which is expected to enhance the optical and sensing performance.
RESUMO
Bacillus utilize preferred sugars such as glucose over other carbon sources due to carbon catabolite repression (CCR). Surfactin is a small signal molecule to regulate the quorum-sensing (QS) response such as biofilm formation and sporulation in B. subtilis. Here, the srfA operon for synthesis of surfactin was mutated for disrupting the production of surfactin in B. amyloliquefaciens. The srfA-mutant strain showed a defective biofilm and sporulation but could be restored by addition with surfactin, indicating that surfactin is a QS signal molecule in B. amyloliquefaciens. Unexpectedly, mutation of srfA also led to the cells' death although nutrients were still enough to support the bacterial growth during this period. Analysis of transcriptomes found that the srfA-mutant strain could not relieve CCR to use non-preferred carbon sources after glucose exhaustion due to deficiency of surfactin. This was further verified by the fact that addition with glucose could dramatically restore the growth, and addition with surfactin could improve the enzymes' activity (e.g., glucanase and α-amylase) to use non-preferred carbon sources in the srfA-mutant strain. After glucose exhaustion, the cells produce surfactin to relieve CCR for utilizing non-preferred sugars. As a signal molecule to regulate QS, surfactin also directly or indirectly relieves the CcpA-mediated CCR to utilize non-preferred carbon sources countering nutrient limitation (e.g., glucose deprivation) in the environment. In conclusion, our findings provide the first evidence that the QS signal molecule of surfactin is also involved in relieving the CcpA-mediated CCR in B. amyloliquefaciens.
RESUMO
The most recent extreme heat recorded in Europe re-alerts the world to the threat of heat stress. Future extreme heat events are reported to be more frequent, long-lasting, and intense. The intense exposure to hot temperatures can cause an excess of heat-related deaths, leading to an increasing risk of heat-related health. In reducing Heat Health Risk (HHR), the use of fine-scale evidence-based mapping of heat-related health risk index (HHRI) and its underlying contributors is essential for policy-making and site-specific action plans. However, its use is still considered to be at an early stage, especially in high-density cities like Hong Kong. This study conducted a spatially explicit assessment of HHR in Hong Kong and constructed a HHRI based on indicators categorized through Principle Component Analysis (PCA) into four meaningful components representing social/language, social isolation, socioeconomic, and urbanization/environmental risks. The applicability of the index was validated against heat-related mortality data at the community level. The community-level maps of HHRI and its subcomponents revealed that portions of Kowloon Peninsula had always suffered exceptionally high HHR ten years ago and after, but the hot spots and problematic communities experienced displacement and the dominant underlying factors of their HHR also varied. Results also showed that HHRI correlated fairly well with the heat-related deaths ratio (R2 = 0.60) at the community level for most of Hong Kong (62.33% of all communities that contain 81.69% of total population). Our analysis results helped generate an evidence-based index to assess HHR in high-density cities like Hong Kong and provided fine-scale maps of the index and its subcomponents, with the aim of benefiting site-specific policy making and optimizing the existing action plans.
Assuntos
Transtornos de Estresse por Calor , Europa (Continente) , Calor Extremo , Hong Kong , HumanosRESUMO
Built-up land in floodplains (BLF) is a vital indicator of the socio-hydrological system, and its dynamics are key to understanding and managing flood risk. However, previous studies have neglected the impacts of BLF growth modes (e.g., patch sizes and expansion types) on flood vulnerability. This paper fills this gap by assessing the BLF's growth modes and revealing their divergent impacts on flood vulnerability using a case study in the Yangtze River Economic Belt (YREB), China. The results show that the BLF has nearly doubled in the YREB during 1990-2014. A considerable proportion (35.43%) of the BLF growth is scattered in small patches (≤1â¯km2), which have a much stronger correlation with flood occurrence than that of the other patch sizes. In terms of expansion types, the edge-expansion type dominates 57.52% of the BLF growth, followed by the leapfrogging and infilling expansions. Both the leapfrogging and the edge-expanding BLFs are significantly associated with flood occurrence, while the infilling type is not. The patch size and expansion type can thus influence the vulnerability of BLF patches, which is also supported by real-world cases. These findings enrich a general understanding of BLF growth and its impacts on flood vulnerability. The scientific community and policymakers should pay attention to not only the quantity of BLF growth, but also its spatial arrangement.
RESUMO
The timely and secure evacuation of an urban residential community is crucial to residents' safety when emergency events happen. This is different to evacuation of office spaces or schools, emergency evacuation in residential communities must consider the pre-evacuation time. The importance of estimating evacuation time components has been recognized for approximately 40 years. However, pre-evacuation time is rarely discussed in previous community-scale emergency evacuation studies. This paper proposes a new method that estimates the pre-evacuation time, which makes the evacuation simulation in urban residential communities more realistic. This method integrates the residents' pre-evacuation behavior data obtained by surveys to explore the influencing factors of pre-evacuation time and builds a predictive model to forecast pre-evacuation times based on the Random Forest algorithm. A sensitivity analysis is also conducted to find the critical parameters in evacuation simulations. The results of evacuation simulations in different scenarios can be compared to identify potential evacuation problems. A case study in Luoshanqicun Community, Pudong New District, Shanghai, China, was conducted to demonstrate the feasibility of the proposed method. The simulation results showed that the pre-evacuation times have significant impacts on the simulation procedure, including the total evacuation time, the congestion time and the congestion degree. This study can help to gain a deeper understanding of residents' behaviors under emergencies and improve emergency managements of urban communities.