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Uncontrolled traumatic hemorrhage is a leading cause of preventable death. As two main forms of hemostatic materials, however, both sponges and hydrogel adhesives usually fail to control massive hemorrhage due to their respective shortcomings. Hemostatic sponge shows weak tissue adhesion, while the gelation process of hydrogel makes it difficult to seal high‐pressure bleeding wounds. There is an urgent need to develop next‐generation hemostats combining the advantages of sponges and hydrogel adhesives. Herein, a general methodology to prepare novel Fe3+‐laden porous material (Fe3+@GCS) for rapid hemostasis of the high‐pressure and ‌severe hemorrhages is proposed, which is fabricated by loading ferric chloride with ethanol into the catechol‐modified carboxylated gelatin sponge (GCS). Notably, porous Fe3+@GCS can undergo water‐triggered rapid transformation‌ to robust‐adhesive hydrogels. The sealing strength of Fe3+@GCS on wet tissues reaches an astonishing ≈600 mm Hg. Rapid water uptake of Fe3+@GCS around wound not only concentrates blood components but also excludes interfacial water, facilitating blood clotting and wound sealing with the in situ formed sticky hydrogel. Fe3+@GCS can efficiently stop the high‐pressure hemorrhaging from traumatic injuries of arteries and hearts in rats and pigs, respectively, via a simple and short‐time pressing. Furthermore, the wound sealing by Fe3+@GCS promotes wound repair and healing. [ABSTRACT FROM AUTHOR]

Summary: A novel hybrid‐multiplexed fifteen‐switch converter (HM‐15SC) topology, which can simultaneously output a set of three‐phase AC and three sets of DC, is proposed to address the problems of a single type of power electronic converter and the complexity of coordinated control of AC/DC hybrid systems for smart grid. In this paper, we conduct a detailed analysis of the topology and operating principles of HM‐15SC. This includes an examination of the converter's effective switching states in relation to output voltage, current paths, and maximum voltage stress. In addition, a modulation strategy combining single‐leg independent model prediction current control (SL‐MPCC) and time‐sharing cooperative (TSC) ideas is proposed to establish a single‐leg AC current prediction model, which effectively reduces the prediction arithmetic under the premise of realizing three‐leg independent prediction control and optimal control of AC/DC hybrid outputs. Finally, we verify the feasibility and superiority of the proposed HM‐15SC topology and its modulation strategy using the Typhoon HIL 402 platform. [ABSTRACT FROM AUTHOR]

With their unique electrical, mechanical, and surface properties, gold nanoparticles (AuNPs) open up new possibilities for sensor technology. In particular, conductive thin films constructed from ligand‐stabilized AuNPs are considered an ideal sensing platform due to their high surface area, excellent conductivity, and biocompatibility. However, most methods for making conductive AuNPs thin‐film sensors with excellent sensitivity require expensive equipment. In this work, an innovative resistive strain sensor consisting of AuNPs and poly (allylamine hydrochloride) (PAH) based on the mutual adsorption of positive and negative charges using a low‐cost layer‐by‐layer self‐assembly (LBL‐SA) approach on a flexible polyester substrate is developed. The conductance changes at low temperatures of the AuNPs/PAH agree with the Arrhenius‐type activation of charge transport. Additionally, the maximum gauge factor of the sensor is shown experimentally to be ≈656 when 1% strain is applied to the sensor film. This work demonstrates that the sensor detects body motions, eyeball movements, and facial micro‐expressions. For detecting eyeball movements and facial micro‐expressions, the macro‐recall can reach 91.5% and 98.8%. Simultaneously, the sensor can control the virtual avatar's eye movements and human facial micro‐expressions in VR. Therefore, nanoparticle‐based sensors can be extensively used in future applications related to healthcare and human‐computer interaction. [ABSTRACT FROM AUTHOR]

Motion recognition (MR)‐based somatosensory interaction technology, which interprets user movements as input instructions, presents a natural approach for promoting human‐computer interaction, a critical element for advancing metaverse applications. Herein, this work introduces a non‐intrusive muscle‐sensing wearable device, that in conjunction with machine learning, enables motion‐control‐based somatosensory interaction with metaverse avatars. To facilitate MR, the proposed device simultaneously detects muscle mechanical activities, including dynamic muscle shape changes and vibrational mechanomyogram signals, utilizing a flexible 16‐channel pressure sensor array (weighing ≈0.38 g). Leveraging the rich information from multiple channels, a recognition accuracy of ≈96.06% is achieved by classifying ten lower‐limb motions executed by ten human subjects. In addition, this work demonstrates the practical application of muscle‐sensing‐based somatosensory interaction, using the proposed wearable device, for enabling the real‐time control of avatars in a virtual space. This study provides an alternative approach to traditional rigid inertial measurement units and electromyography‐based methods for achieving accurate human motion capture, which can further broaden the applications of motion‐interactive wearable devices for the coming metaverse age. [ABSTRACT FROM AUTHOR]

Background: Necroptosis induced by receptor‐interacting protein kinase 3 (RIPK3) is engaged in intracerebral hemorrhage (ICH) pathology. In this study, we explored the impact of RIPK3 activation on neuronal necroptosis and the mechanism of the death domain‐associated protein (DAXX)‐mediated nuclear necroptosis pathway after ICH. Methods: Potential molecules linked to the progression of ICH were discovered using RNA sequencing. The level of DAXX was assessed by quantitative real‐time PCR, ELISA, and western blotting. DAXX localization was determined by immunofluorescence and immunoprecipitation assays. The RIPK3 inhibitor GSK872 and DAXX knockdown with shRNA‐DAXX were used to examine the nuclear necroptosis pathway associated with ICH. Neurobehavioral deficit assessments were performed. Results: DAXX was increased in patients and mice after ICH. In an ICH mouse model, shRNA‐DAXX reduced brain water content and alleviated neurologic impairments. GSK872 administration reduced the expression of DAXX. shRNA‐DAXX inhibited the expression of p‐MLKL. Immunofluorescence and immunoprecipitation assays showed that RIPK3 and AIF translocated into the nucleus and then bound with nuclear DAXX. Conclusions: RIPK3 revitalization promoted neuronal necroptosis in ICH mice, partially through the DAXX signaling pathway. RIPK3 and AIF interacted with nuclear DAXX to aggravate ICH injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is currently an increase in the use of new types of fertilizers in modern agriculture. Studies have shown that amino acid fertilizers can improve crop yield and quality. However, their effects on crop rhizosphere ecology and their ecological impacts on crop yield are largely unknown. This study evaluated the effects of a water‐soluble amino acid fertilizer (WAAF) on tomatoes and its ecological effects on rhizosphere bacterial communities using greenhouse pot experiments. RESULTS: The results showed that WAAF could promote the growth of tomatoes and improve the quality of fruits more effectively than water‐soluble chemical fertilizer controls. Interestingly, WAAF showed a different regulating pattern on root exudates and increased the secretion of 17 major water‐soluble root exudates, including hexadecanoic acid and 3‐hydroxy‐γ‐butyrolactone. Water‐soluble amino acid fertilizer also affected noticeably the composition, abundance, and beta‐diversity of rhizosphere bacterial communities, and strengthened the potential relationships between community members. Water‐soluble amino acid fertilizer showed a significant selective enrichment ability and recruited some members of the genera such as Cupriavidus, Ralstonia, Chitinophaga, Gemmatimonas, Mitsuaria, Mucilaginibacter, Paracoccus, Sphingopyxis, and Variovorax. Network analysis and functional prediction implied that, besides fertilizer effects, the recruiting of beneficial microbes involved in chemotaxis and biofilm formation was also a considerable factor in tomato yield and quality improvement. CONCLUSION: Our study revealed ecological and recruiting effects of WAAF on rhizosphere microbes and potentially beneficial microbiota, and provided a basis for the amino acid fertilizer regulation of rhizosphere ecology to improve soil health and further improve crop yield and quality. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Parametric optimization always plays important roles in bioengineering systems to obtain a high product yield under the proper conditions. The parametric conditions of lactic acid production by homologous batch fermentation of Lactobacillus pentosus cells was optimized by the Box–Behnken design. The highest l‐lactic acid yield was obtained as 0.836 ± 0.003 g/g glucose with the productivity of 0.906 ± 0.003 g/(L × H) under the optimum conditions of 34.7 °C, pH 6.2, 148 rpm agitation speed, and 9.3 g/L nitrogen source concentration determined by quadratic response surface with high accuracy. The adequate kinetic models of cell growth rate, lactic production rate, and glucose consumption rate were also established to describe the fermentation behavior of L. pentosus cells with the correlation coefficients of 09985, 0.9990, and 0.9989, respectively. [ABSTRACT FROM AUTHOR]

Hazardous rock refers to an unstable rock block that is cut by weak structural planes and gradually separates from the slope. Hazardous rock generally collapses rapidly, and at present, it is challenging to effectively identify the separation degree of the rock and accurately predict its sudden failure. In this study, focusing on a hazardous rock with tilt behavior, a microelectromechanical system (MEMS) acceleration sensor is used in combination with the calculation principle of the included angle of the space vector to establish a microtilt angle monitoring method. A physical model test is designed, in which a thermally sensitive material (with heat-sensitive strength) is adopted as the weak structural plane of the hazardous block, and the change in the tilt angle during the process of block instability is monitored at a sampling frequency of 1000 Hz. The test results show that the accelerated evolution of the tilt angle is a precursor to hazardous rock failure. In the rapid acceleration stage, the reciprocal of the tilt angle rate is approximately linear with time, and a correlation equation is obtained. Assuming that the change rate of the tilt angle is approximately infinite, the failure time of hazardous rock can be predicted using the correlation equation. In addition, the effectiveness of the instability prediction method based on microtilt angle monitoring is verified by analyzing the long-term monitoring data of hazardous rock. [ABSTRACT FROM AUTHOR]

Most natural sedimentary clay contains organic matter, and even a small amount of organic matter will have a great impact on the physical and mechanical properties of clay. In order to clarify the influence of organic matter content on clay soil, the illite-quartz mixture was mixed with natural amorphous peat soil (organic matter content is 50%) in different proportions for studying the influence of different organic matter contents on the physical properties (specific gravity, Gs; moisture content, w ; void ratio, e; liquid limit, w L ; plastic limit, w p ; plasticity index, Ip) and shear characteristics (cohesion, c; friction angle, φ) of clay soil. The experimental results found that, with the change of organic matter content, the specific gravity and void ratio of clay changed linearly, while the water content, Atterberg limit, shear strength, cohesion, and friction angle changed nonlinearly with the increase of organic matter content. Moisture content and Atterberg limit have a turning point when OC = 7.5%. Shear strength, cohesion, and friction angle all have obvious turning points when OC = 7.5% and OC = 37.5%. The variation of moisture content and Atterberg limit with organic matter content indicates that OC = 7.5% may be the limit value for the different forms of organic matter in the clay. When OC ≤ 7.5%, the organic matter in clay is in the bound state; when OC > 7.5%, the bound organic matter reaches saturation; and the free organic matter gradually increases. The change law of shear strength characteristics with organic matter content shows that the interaction between minerals and organic matter exhibits different shear characteristics under different organic matter content. When OC ≤ 7.5%, clay shows mineral properties, when 7.5% < OC ≤ 37.5%, clay shows mineral-free organic matter properties, and when OC > 37.5%, clay shows free organic matter properties. [ABSTRACT FROM AUTHOR]

Based on a long-term comprehensive instrumentation program, the performance of an excavation pit constructed by the top-down method in downtown Kunming was extensively examined. The measured excavation responses included the deflections of diaphragm wall, vertical column movement, slab axial force, building settlement caused by ground deformation, and the influence of pit excavation on the adjacent subway tunnel. This paper analyses the monitoring data of the existing construction stage. Based on the analyses on the data of field and numerical simulation, the following major findings were obtained: (1) the relationship between the measured maximum wall deflection, δ h m , and excavation depth, H , in this study is δ h m = 0.06 % H ∼ 0.27 % H , which is quite different compared with the relationship of soft-soil pit δ h m = 0.02 % H ∼ 1.2 % H , but closer to the normalized curve of rock-socketed pile δ h m = 0.01 % H ∼ 0.45 % H and rock-socketed diaphragm wall δ h m = 0.031 % H ∼ 0.129 % H. (2) The relationship between the maximum settlement of column ( δ p ) and excavation depth (H) is δ p = − 0.09 % ∼ 0.04 % H. The maximum distortion between the diaphragm wall and the column is less than 1/500 of the limit range proposed by Bjerrum. (3) The impact range caused by excavation is about 3.8 times the maximum excavation depth. The ground settlement around the foundation pit is groove type, and the maximum settlement point is located at 2.7 times the maximum excavation depth. (4) The excavation of the foundation pit leads to the maximum vertical settlement of 2 mm and maximum horizontal displacement of 5.2 mm in the subway tunnel; the maximum change of axial force and bending moment are 8.8 kN (the vertical direction) and 6.4 kN·m/m (the horizontal direction), respectively. [ABSTRACT FROM AUTHOR]

A highway project of up to 100 km/h is currently being constructed between Colombo and Katunayake International Airport across a Sri Lankan muskeg area. At this site, peat deposit was initially 0.8∼15.3 m thick and was underlain by sand, clay, or gneiss. The ground improvement methods adopted in the project were combined drainage consolidation-preloading methods, pipe pile foundation, and geogrids. This paper provides a detailed insight into the implementation of combined drainage consolidation-preloading methods used in the project, including sand pile, gravel pile, and plastic drainage plate as the prefabricated vertical drains. Periodical field-level observations were taken during the ten years, including the construction and postconstruction periods. The results show that peat soils' consolidation coefficient has been increased several times to tens of times due to ground improvement. After removing the temporary surcharge, the highway embankments did not heave and was followed by long-term settlements totaling 1.3∼7.4 cm over the following seven years of observations. Analysis of the settlement records shows that combined drainage consolidation-preloading methods have helped accelerate drainage consolidation and reduce postconstruction settlement. [ABSTRACT FROM AUTHOR]

The effects of ultrasonic waves, microwaves, thermal stress, thermal stress combined with ultrasonic waves and thermal stress combined with microwaves on the germination of Tartary buckwheat seeds from Ningxia and Sichuan were compared. On the seventh d of germination, the highest germination rate of Tartary buckwheat from Ningxia treated with ultrasonic waves was 87.33%, which was 4.66% higher than that of the control (p <.05). The highest germination rate of the microwaves treatment of Tartary buckwheat from Sichuan was 86.67%, which was 4.67% (p <.05) higher than that of the control. The ultrasonic waves and microwaves treatments increased the content of flavonoids and reducing sugars and enhanced the DPPH and ABTS radical scavenging activities. In addition, the ultrasonic waves and microwaves treatments had positive effects on the activities of catalase and phenylalanine ammonia lyase. Practical Applications: Tartary buckwheat is highly valued as food and for its nutritional and health benefits. The germination of Tartary buckwheat seeds can improve its food quality and nutritional value. Germinated buckwheat has higher contents of phenolics and flavonoids. Two such high‐speed, high efficiency and low energy consumption of heating methods, microwaves and ultrasonic waves processing technologies, are highly significant for the seed germination. In this study, two types of Tartary buckwheat seeds were treated with ultrasonic waves, microwaves, and thermal stress. In addition, the present study reflected the relationship between the germination characteristics and various physiological and biochemical indices. We found that these results are important for the seed germination of Tartary buckwheat and provide the best means of expanding the use of Tartary buckwheat and related products. [ABSTRACT FROM AUTHOR]

Ammonia oxidizers (ammonia‐oxidizing archaea (AOA) and bacteria (AOB)), nitrite oxidizers (e.g., Nitrobacter and Nitrospira) and comammox Nitrospira play important roles in the nitrogen cycle in agroecosystems, yet their activities and abundance in soil microhabitats under environmental disturbances remain unclear. In this study, we collected samples from treatment plots in a field experiment established in 2010 in a lime concretion black soil in central China to investigate the effects of varying inorganic and organic fertilizer managements in a wheat–maize crop rotation, in order to investigate the impacts on the abundance and activities of ammonia and nitrite oxidizers inhabiting different microenvironments in soil, represented by three soil aggregate size fractions. The treatments were: control without fertilizer (CK), chemical fertilization (NPK), NPK and straw (NPKS), NPKS and pig manure (NPKSP) or cow manure (NPKSC). The potential nitrite oxidation activity (PNO) and soil nutrients (soil carbon, nitrogen and phosphorus content) were the highest in the microaggregates, followed by those in the macroaggregates and silt+clay fractions in all the plots. Both the ammonia and nitrite oxidizers were more abundant in the macroaggregates and microaggregates than in the silt+clay fractions. A two‐way analysis of variance (ANOVA) indicated that the soil aggregate size had a significant influence on the abundance of ammonia and nitrite oxidizers and the soil nutrients. We also found a significant positive correlation between PNO and the nitrite oxidizer and AOA abundance. In addition, the abundances of the ammonia oxidizers (AOA and AOB) and nitrite oxidizers (Nitrobacter and Nitrospira) were positively correlated with each other. Overall, the soil aggregates with a higher inorganic nutrient and organic carbon content may provide a better protective microenvironment to guard against environmental disturbances and facilitate the inhabitation of ammonia and nitrite oxidizers, which cooperate in the nitrogen cycling process. Highlights: Nitrifying guilds and their activities were investigated under soil aggregates in a Vertisol.Soil aggregates of different sizes provide spatially heterogeneous habitats for nitrifying guilds.Ammonia‐ and nitrite‐oxidizer abundances and their activities are controlled by soil aggregate size.Soil aggregates with higher nutrients may provide a better protective habitat for nitrifying guilds. [ABSTRACT FROM AUTHOR]

This paper is devoted to characterizing the boundedness of the Riemann-Stieltjes operators from analytic Morrey spaces to Bloch-type spaces. Moreover, the boundedness of the superposition operator and weighted composition operator on analytic Morrey spaces is discussed, respectively. [ABSTRACT FROM AUTHOR]

Contemporary general-purpose graphic processing units (GPGPUs) successfully parallelize an application into thousands of concurrent threads with remarkably improved performance. Such massive threads will compete for the small-sized first-level data (L1D) cache, leading to an exaggerated cache-thrashing problem, which may degrade the overall performance significantly. In this paper, we propose a selective victim cache design to enable better data locality and higher performance. Instead of a small fully associative structure, we first redesign the victim cache as a set associative structure that is equivalent to the original L1D cache to suit the GPGPU applications with massive concurrent threads. To keep the mostly used data in L1D for better operand service, we apply a simple prediction scheme to avoid costly block interchanges and evictions. To further save the area for data storage, we propose to leverage the unallocated registers and shared memory entries to hold the victim cache data. The experiments demonstrate that our proposed approach can increase the on-chip data cache hit rate considerably and deliver a better performance with negligible changes to the baseline GPGPU architecture. For example, our selective victim cache design can improve the performance by 41.3% on average, achieving 54.7% increase in data cache hit rate and 21.8% reduction in block interchanges and evictions. [ABSTRACT FROM AUTHOR]

As outlined below, this paper is devoted to a Carleson-type-measure-based study of the holomorphic Campanato 2-space on the open unit ball [ABSTRACT FROM AUTHOR]

Hypertrophic scar (HTS), a fibroproliferative disorder (FPD), complicates burn wound healing. Although the pathogenesis is not understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune/inflammatory responses through toll-like receptor 4 (TLR4) activated by lipopolysaccharide (LPS) through adaptor molecules, leading to nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinases activation, cytokine gene transcription and co-stimulatory molecule expression resulting in inflammation. This study explored the possible role of TLR4 in HTS formation. Paired normal and HTS tissue from burn patients was collected and dermal fibroblasts isolated and cultured. Immunohistochemical analysis of tissues demonstrated increased TLR4 staining in HTS tissue. Quantitative RT-PCR of three pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 (MyD88) in HTS fibroblasts were increased significantly compared with normal fibroblasts. Flow cytometry showed increased TLR4 expression in HTS fibroblasts compared with normal. ELISA demonstrated protein levels for prostaglandin E2, interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in HTS fibroblasts compared to normal. When paired normal and HTS fibroblasts were stimulated with LPS, significant increases in mRNA and protein levels for MyD88, IL-6, IL-8, and MCP-1 were detected. However, when transfected with MyD88 small interfering RNA (siRNA), then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS-stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore, controlling inflammation and manipulating TLR signaling in skin cells may result in novel treatment strategies for HTS and other FPD. J. Cell. Physiol. 226: 1265-1273, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Hypertrophic scar (HTS) following thermal injury and other forms of trauma is a dermal fibroproliferative disorder that leads to considerable morbidity. Because of the lack of an ideal animal model, research is difficult. We have established an HTS model that involves transplanting human split-thickness skin graft (STSG) or full-thickness skin graft (FTSG) onto the backs of nude mice. The animals developed raised, firm, and reddish scars 2 months following transplantation. Histology and micromeasurement indicate raised, thickened engrafted skin with STSG and FTSG. In contrast, thickening was not observed with full-thickness rat skin grafts used as controls. Masson's trichrome staining demonstrates increased accumulations of collagen fibrils in the dermis in both scars grafted with STSG and FTSG. Staining cells with toludine blue and an antibody for F4/80 showed an increase in the infiltration of mast cells and macrophages. Quantification of fibrocytes reveals increased fibrocytes. Moreover, STSG grafted skin had significantly more macrophages, mast cells, and fibrocytes than FTSG. Real-time polymerase chain reaction analysis showed significantly elevated mRNA levels for type I collagen, transforming growth factor-β, connective tissue growth factor and heat shock protein 47 in both types of engrafted skin. These data demonstrate that human skin grafted onto nude mice develops red raised and thickened scars having intrinsic properties that closely resemble HTS formation as seen in humans. Interestingly, STSG developed more scar than FTSG. Furthermore, inflammatory cells and bone marrow-derived fibrocytes may play a critical role in HTS development in this animal model. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the progression of urodynamic changes, as well as histological and biochemical outcomes over a prolonged period of partial bladder outlet obstruction (pBOO) in an animal model with physiologically relevant pBOO. MATERIALS AND METHODS Healthy, adult, female Fischer rats underwent surgical creation of a pBOO for either 2, 4, 8, or 13 weeks and were compared with sham-operated rats. Urodynamic measurements were used to compare bladder volumes and pressure. Tissue was grossly analysed with light microscopy and bladder weights and thicknesses were compared. Reverse transcription-polymerase chain reaction for collagen, transforming growth factor β (TGF-β ), connective tissue growth factor (CTGF), hypoxia inducible factor 1α (HIF-1α ), and platelet-derived growth factor (PDGF-A) was performed on all samples, as well as immunohistochemistry (IHC) for α-smooth muscle actin ( α-SMA). Finally, mass spectrometry was used to quantify the collagen content of the bladders as a measure of fibrosis. RESULTS After induction of pBOO, all rats remained healthy. Initial urodynamics showed an increase in capacity while maintaining normal pressures, but then deteriorated into small capacity, high-pressure bladders. Haematoxylin and eosin (H&E) staining showed an initial inflammatory response, and this was confirmed with significantly increased mRNA levels of TGF-β, CTGF, HIF- 1α, and PDGF. The progression to smooth muscle hypertrophy was evident on H&E and confirmed with increased bladder mass and thickness. IHC for α-SMA showed a progressive increase associated with the elevated bladder pressures. Masson's trichrome and mass spectrometry showed a progressive increase in collagen to 13 weeks. CONCLUSION With this model, we have effectively replicated the clinical scenario, with significant pathophysiological changes occurring insidiously in otherwise healthy rats. We believe that our observed changes represent distinct phases of bladder decompensation; with an initial inflammatory response to the stress of the pBOO, smooth muscle hypertrophy to overcome the increased urethral resistance, and eventual decompensation to fibrosis. The time course of the inflammatory markers implies the need for early intervention to prevent this cascade. Novel strategies targeting these observed physiological responses could lead to improved preventative strategies, with respect to biochemical pathways and the time course of their initiation. [ABSTRACT FROM AUTHOR]

This study examined the mechanism of nanocrystalline silver antiinflammatory activity, and tested nanocrystalline silver for systemic antiinflammatory effects. Secondary ion mass spectroscopy of skin treated directly with nanocrystalline silver for 24 hours showed that at skin surfaces there were significant deposits at weights corresponding to Ag, AgO, AgCl, AgNO3, Ag2O, and silver clusters Ag2-6, but silver penetration was minimal. To test for translocation of the effect, a porcine contact dermatitis model in which wounds were induced on one side of the back and then treated with nanocrystalline silver on the opposite side of the back was used. Visual and histological data showed improvement relative to animals treated with saline only. Significantly increased induction of apoptosis in the inflammatory cells present in the dermis was observed with remote nanocrystalline silver treatments. In addition, immunohistochemical analysis showed decreased levels of proinflammatory cytokines tumor necrosis factor-α and interleukin-8, and increased levels of antiinflammatory cytokine interleukin-4, epidermal growth factor, keratinocyte growth factor, and keratinocyte growth factor-2. Thus, the antiinflammatory effects of nanocrystalline silver appear to be induced by interactions with cells in the top layers of the skin, which then release biological signals resulting in widespread antiinflammatory activity. [ABSTRACT FROM AUTHOR]

The development of hypertrophic scar involves a complex interplay between cells and cytokines. Although the mechanism underlying its pathogenesis is not well understood, a polarized T-helper type 2 immune response has been reported, indicating a role for CD4+ T lymphocytes in hypertrophic scarring. Here, we report an increased frequency of CD4+/transforming growth factor-β (TGF-β)-producing T cells in the peripheral blood and hypertrophic scar tissue of burn patients. These cells may play an indirect regulatory role in hypertrophic scar by affecting the functions of dermal fibroblasts. Our results show an increase in cell proliferation and collagen synthesis by dermal fibroblasts treated with medium derived from burn patient CD4+ T lymphocytes but not from the CD4+ T cells of normal subjects. Using confocal microscopy and immunoblotting, we found the level of α-smooth muscle actin to be elevated in these treated dermal fibroblasts, which also showed an enhanced ability to contract collagen lattices. TGF-β levels in medium conditioned by the culture of CD4+ T lymphocytes from burn patients were significantly higher than in the conditioned medium from CD4+ T lymphocytes of normal subjects. In addition, the application of a TGF-β–neutralizing antibody significantly reduced the effect of burn patient CD4+ T lymphocyte medium on dermal fibroblast proliferation and collagen lattice contraction. Our study suggests that CD4+/TGF-β–producing T lymphocytes may play an important role in postburn hypertrophic scarring. [ABSTRACT FROM AUTHOR]

Optimum healing of a cutaneous wound requires a well-orchestrated integration of the complex biological and molecular events of cell migration and proliferation, and of extracellular matrix deposition and remodeling. Several studies in recent years suggest that bone marrow derived stem cells such as mesenchymal stem cells, progenitor cells such as endothelial progenitor cells and fibrocytes may be involved in these processes, contributing to skin cells or releasing regulatory cytokines. Stem/progenitor cells may be mobilized to leave the bone marrow, home to injured tissues and participate in the repair and regeneration. Direct injection of bone marrow derived mesenchymal stem cells or endothelial progenitor cells into injured tissues shows improved repair through mechanisms of differentiation and/or release of paracrine factors. Enhanced understanding of these cells may help develop novel therapies for difficult cutaneous conditions such as non-healing chronic wounds and hypertrophic scarring as well as engineering cutaneous substitutes. [ABSTRACT FROM AUTHOR]