Passive control of temperature distribution in cancerous tissue during photothermal therapy using optical phase change nanomaterials

Thermal therapy is a very promising alternative treatment for benign tumor, in which the temperature control is a key issue to avoid unwanted thermal damage of healthy tissue. However, the active temperature control methods usually require the assistance of real-time and accurate temperature monitoring devices. Even though, the lag of temperature control is inevitable. Therefore, in the present work, a passive control method is proposed to improve the uniformity of temperature distribution inside tumorous tissue during laser induced thermal therapy (LITT). Optical phase change nanoparticles (O-PCNPs) are utilized to replace the commonly used noble metal nanoparticles to enhance and adjust the localized light absorption in tumor. In the early stage of LITT, the O-PCNPs is used to improve the specific absorption rate in the targeted region. However, after the local temperature reaches a certain level (phase transition temperature), the O-PCNPs convert from amorphous state to crystalline state. By carefully selecting the size, shape, and laser wavelength, the absorption cross section of O-PCNPs could drop dramatically after phase transition. Therefore, in the high temperature zone the local temperature increasing rate reduces due to the reduction of local heat generation rate. On the contrary, the temperature increasing rate rises in the low temperature zone since more energy is transferred to the deeper tissue. In the present work, results show that SiO2@VO2 nanoshells can be applied as thermal contrast agents to improve the temperature uniformity in tumor during LITT

Nanoparticle manipulation using plasmonic optical tweezers based on particle sizes and refractive indices

As an effective tool for micro/nano-scale particle manipulation, plasmonic optical tweezers can be used to manipulate cells, DNA, and macromolecules. Related research is of great significance to the development of nanoscience. In this work, we investigated a sub-wavelength particle manipulation technique based on plasmonic optical tweezers. When the local plasmonic resonance is excited on the gold nanostructure arrays, the local electromagnetic field will be enhanced to generate a strong gradient force acting on nanoparticles, which could achieve particle sorting in sub-wavelength scale. On this basis, we explored the plasmonic enhancement effect of the sorting device and the corresponding optical force and optical potential well distributions. Additionally, the sorting effect of the sorting device was investigated in statistical methods, which showed that the sorting device could effectively sort particles of different diameters and refractive indices

Geological conditions of coal reservoir occurrence in the Southern Qinshui Basin and its impact on permeability

The occurrence and output of coalbed methane (CBM) are controlled by the occurrence geological conditions of coal reservoirs, such as stress, pressure, and temperature. The correct analysis of the occurrence geological conditions of coal reservoirs and their impact on permeability is a key issue of concern for an effective development of CBM. Based on the test data of 63 CBM wells in the southern part of the Qinshui Basin, the ground stress, pressure and temperature conditions of coal reservoirs in the study area are systematically analyzed, the variation law of coal reservoir stress, pressure and temperature with burial depth is revealed, and the relationship between the minimum horizontal principal stress and the vertical principal stress and the pressure of coal reservoir is established. Using the triaxial seepage test system, the experiment of CBM seepage under different stress, pressure and temperature conditions is carried out, and the variation law and control mechanism of coal sample permeability under different temperature, stress and pressure conditions are revealed. The results show that the maximum and minimum horizontal principal stresses of the coal reservoirs in the study area are 6.62−42.06 MPa and 3.30−26.40 MPa, respectively, with the gradients of 1.20−5.26 MPa/hm and 0.99−2.95 MPa/hm, respectively. The coal reservoir pressures and their gradients are 0.99−12.63 MPa and 0.23−1.18 MPa/hm; the coal reservoir temperatures and their gradients are 19.36−38.84 ℃ and 1.98 ℃/hm, respectively. The coal reservoir stress, pressure and temperature increase linearly with the increase of depth. With the increase of effective stress, the permeability of the coal reservoir decreases continuously, the permeability decreases greatly in the initial pressurization stage, but decrease slows down with the increase of effective stress. Under the same stress conditions, the permeability of coal samples and the decrease rate of permeability decrease continuously with the increase of temperature. With the increase of effective stress and temperature, the permeability of coal reservoir decreases according to the law of negative exponential function. With the decrease of pore pressure, the effective stress increases, but the permeability of coal reservoir decreases. In the initial depressurization stage, the permeability of the coal reservoir decreases sharply, and with the reduction of pore pressure, the decrease rate of permeability gradually slows down. When the pore pressure is less than 0.6 MPa, the permeability of the coal reservoir increases with the decrease of pore pressure. Under the condition of high pore pressure, the permeability decreases with the increase of temperature in a negative exponential function, while under the condition of low pore pressure, the permeability of coal reservoir decreases linearly with the increase of temperature. Based on the above results, the relationship model between coal reservoir permeability and stress, pressure and temperature is established. Also, the law and control mechanism of coal reservoir permeability decrease according to negative exponential function with the increase of stress, pressure and temperature stress are expounded

JAK3 restrains inflammatory responses and protects against periodontal disease through Wnt3a signaling

Homeostasis between pro- and anti- inflammatory responses induced by bacteria is critical for the maintenance of health. In the oral cavity, proinflammatory mechanisms induced by pathogenic bacteria are well-established; however, the anti-inflammatory responses that act to restrain innate responses remain poorly characterized. Here, we demonstrate that infection with the periodontal pathogen P. gingivalis enhances the activity of JAK3 in innate immune cells, and subsequently phospho-inactivates Nedd4-2, a ubiquitin E3 ligase. In turn, Wnt3 ubiquitination is decreased, while total protein levels are enhanced, leading to a reduction in proinflammatory cytokine levels. In contrast, JAK3 inhibition or Wnt3a robustly enhances NF-κB activity and the production of proinflammatory cytokines in P. gingivalis-stimulated innate immune cells. Moreover, using gain- and loss-of-function approaches, we demonstrate that downstream molecules of Wnt3a signaling, including Dvl3 and β-catenin, are responsible for the negative regulatory role of Wnt3a. In addition, using an in vivo P. gingivalis-mediated periodontal disease model, we show that JAK3 inhibition enhances infiltration of inflammatory cells, reduces expression of Wnt3a and Dvl3 in P. gingivalis-infected gingival tissues, and increases disease severity. Together, our results reveal a new anti-inflammatory role for JAK3 in innate immune cells and show that the underlying signaling pathway involves Nedd4-2-mediated Wnt3a ubiquitination

Oxygen-evolving photosystem II structures during S1–S2–S3 transitions

Photosystem II (PSII) catalyses the oxidation of water through a four-step cycle of Si states (i = 0–4) at the Mn4CaO5 cluster1,2,3, during which an extra oxygen (O6) is incorporated at the S3 state to form a possible dioxygen4,5,6,7. Structural changes of the metal cluster and its environment during the S-state transitions have been studied on the microsecond timescale. Here we use pump-probe serial femtosecond crystallography to reveal the structural dynamics of PSII from nanoseconds to milliseconds after illumination with one flash (1F) or two flashes (2F). YZ, a tyrosine residue that connects the reaction centre P680 and the Mn4CaO5 cluster, showed structural changes on a nanosecond timescale, as did its surrounding amino acid residues and water molecules, reflecting the fast transfer of electrons and protons after flash illumination. Notably, one water molecule emerged in the vicinity of Glu189 of the D1 subunit of PSII (D1-E189), and was bound to the Ca2+ ion on a sub-microsecond timescale after 2F illumination. This water molecule disappeared later with the concomitant increase of O6, suggesting that it is the origin of O6. We also observed concerted movements of water molecules in the O1, O4 and Cl-1 channels and their surrounding amino acid residues to complete the sequence of electron transfer, proton release and substrate water delivery. These results provide crucial insights into the structural dynamics of PSII during S-state transitions as well as O–O bond formation

Characterization of a High Hierarchical Regulator, PtrGATA12, Functioning in Differentially Regulating Secondary Wall Component Biosynthesis in Populus trichocarpa

In plants, GATA transcription factors (TFs) have been reported to play vital roles in to a wide range of biological processes. To date, there is still no report about the involvement and functions of woody plant GATA TFs in wood formation. In this study, we described the functional characterization of a Populus trichocarpa GATA TF, PtrGATA12, which encodes a nuclear-localized transcriptional activator predominantly expressing in developing xylem tissues. Overexpression of PtrGATA12 not only inhibited growths of most phenotypic traits and biomass accumulation, but also altered the expressions of some master TFs and pathway genes involved in secondary cell wall (SCW) and programmed cell death, leading to alternated SCW components and breaking forces of stems of transgenic lines. The significant changes occurred in the contents of hemicellulose and lignin and SCW thicknesses of fiber and vessel that increased by 13.5 and 10.8%, and 20.83 and 11.83%, respectively. Furthermore, PtrGATA12 bound directly to the promoters of a battery of TFs and pathway genes and activated them; the binding sites include two cis-acting elements that were specifically enriched in their promoter regions. Taken together, our results suggest PtrGATA12, as a higher hierarchical TF on the top of PtrWND6A, PtrWND6B, PtrMYB152, and PtrMYB21, exert a coordinated regulation of SCW components biosynthesis pathways through directly and indirectly controlling master TFs, middle-level TFs, and further downstream pathway genes of the currently known hierarchical transcription network that governs SCW formation

Relationship between multiscale nanopore structure and coal connectivity during coalification process

The complex nanopore structures in coal provide the space for gas adsorption and migration, which is crucial for the development of coalbed methane. However, the mechanism of the evolution of multi-scale nanopore structures during coalification is still unclear. In this work, a combined method of CO2/N2 adsorption and synchrotron radiation Nano-CT experiments were used to reveal the multi-scale pore structure characterization during coalification. The synchrotron radiation Nano-CT experiment reconstructed the 3D pore network model for different rank coal and revealed the effective diameter is less than 0.5 & mu;m, accounting for 97.4%-99.6% of the total number of macropores. The combination of these methods, including CO2/N2 adsorption and Nano-CT, accurately characterizes the multi-scale pore distribution in coal, ranging from <2 nm, 2-300 nm and 64 nm - 3.5 & mu;m. The ultra-micropores occupy the primary advantage, accounting for approximately 60.3%-95.2% of the total pore volume and the micropores, mesopores and macropores are more poorly developed than ultramicropores. During the coalification process, the proportion of porosity contributed by ultra-micropores to the total porosity gradually increases, with the contribution rising by 57.9%. The proportion of porosity contributed by micropores, mesopores and macropores to the total porosity gradually decreases, with the contribution decreasing by 81.0%, 82.8% and 93.6%, respectively. Besides, with growing coal maturity, the total permeability gradually decreases by 9.26 x 10-3 - 3.05 x 10-1 mD, which is negatively correlated with coal maturity during coalification. And the total permeability is mainly provided by macropores, which account for about 99% of the total permeability. This research provides an in-depth understanding of the storage and transport of coalbed methane in a multi-scale nanopore structure

A method for detecting two‐dimensional plane stress distribution in basin‐type insulator based on critically refracted longitudinal wave

Abstract Basin‐type insulator often has small cracks due to stress concentration. The current method cannot accurately reflect the stress condition of the insulator to find the stress concentration areas. To solve these problems, a method for detecting two‐dimensional plane stress (δ1 and δ2) within different depth ranges in a basin‐type insulator is proposed based on critically refracted longitudinal (LCR) wave. First, the acoustoelastic equation characterising the relationship between the variation of LCR wave propagation time and the plane stress was derived. Next, the propagation characteristics of LCR wave in epoxy resin samples were investigated. Then, the stress distribution within different depth ranges of the insulator subjected to hydraulic load was measured using the proposed method, including direction (θ), δ1 and δ2. The results show that the magnitude of the stress alone cannot accurately characterise the stress state. Points with equal distances to the centre have similar stress magnitudes, but their directions are not the same. With increasing depth, θ remains essentially unchanged at the same location, while δ1 and δ2 decrease, and the rate of decrease varies at different locations. Comparing the measured and simulated data, the results showed that they were in good agreement, and the maximum errors of stress value and θ were 0.69 MPa and 2.97°, respectively, which confirmed the feasibility and accuracy of the stress detection in the proposed method

Accelerating thrombolysis using a precision and clot-penetrating drug delivery strategy by nanoparticle-shelled microbubbles

Conventional thrombolytic drugs for vascular blockage such as tissue plasminogen activator (tPA) are challenged by the low bioavailability, off-target side effects and limited penetration in thrombi, leading to delayed recanalization. We hypothesize that these challenges can be addressed with the targeted and controlled delivery of thrombolytic drugs or precision drug delivery. A porous and magnetic microbubble platform is developed to formulate tPA. This system can maintain the tPA activity during circulation, be magnetically guided to the thrombi, and then remotely activated for drug release. The ultrasound stimulation also improves the drug penetration into thrombi. In a mouse model of venous thrombosis, the residual thrombus decreased by 67.5% when compared to conventional injection of tPA. The penetration of tPA by ultrasound was up to several hundred micrometers in thrombi. This strategy not only improves the therapeutic efficacy but also accelerates the lytic rate, enabling it to be promising in time-critical thrombolytic therapy.Published versio

JAK3 restrains inflammatory responses and protects against periodontal disease through Wnt3a signaling

Homeostasis between pro- and anti- inflammatory responses induced by bacteria is critical for the maintenance of health. In the oral cavity, proinflammatory mechanisms induced by pathogenic bacteria are well-established; however, the anti-inflammatory responses that act to restrain innate responses remain poorly characterized. Here, we demonstrate that infection with the periodontal pathogen P. gingivalis enhances the activity of JAK3 in innate immune cells, and subsequently phospho-inactivates Nedd4-2, a ubiquitin E3 ligase. In turn, Wnt3 ubiquitination is decreased, while total protein levels are enhanced, leading to a reduction in proinflammatory cytokine levels. In contrast, JAK3 inhibition or Wnt3a robustly enhances NF-κB activity and the production of proinflammatory cytokines in P. gingivalis-stimulated innate immune cells. Moreover, using gain- and loss-of-function approaches, we demonstrate that downstream molecules of Wnt3a signaling, including Dvl3 and β-catenin, are responsible for the negative regulatory role of Wnt3a. In addition, using an in vivo P. gingivalis-mediated periodontal disease model, we show that JAK3 inhibition enhances infiltration of inflammatory cells, reduces expression of Wnt3a and Dvl3 in P. gingivalis-infected gingival tissues, and increases disease severity. Together, our results reveal a new anti-inflammatory role for JAK3 in innate immune cells and show that the underlying signaling pathway involves Nedd4-2-mediated Wnt3a ubiquitination