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Developing a tumor model with vessels has been a challenge in microfluidics. This difficulty is because cancer cells can overgrow in a co-culture system. The up-regulation of anti-angiogenic factors during the initial tumor development can hinder neovascularization. The standard method is to develop a quiescent vessel network before loading a tumor construct in an adjacent chamber, which simulates the interaction between a tumor and its surrounding vessels. Here, we present a new method that allows a vessel network and a tumor to develop simultaneously in two linked chambers. The physiological environment of these two chambers is controlled by a microfluidic resistive circuit using two symmetric long microchannels. Applying the resistive circuit, a diffusion-dominated environment with a small 2-D pressure gradient is created across the two chambers with velocity <10.9 nm s−1 and Péclet number <6.3 × 10−5. This 2-D pressure gradient creates a V-shaped velocity clamp to confine the tumor-associated angiogenic factors at pores between the two chambers, and it has two functions. At the early stage, vasculogenesis is stimulated to grow a vessel network in the vessel chamber with minimal influence from the tumor that is still developed in the adjacent chamber. At the post-tumor-development stage, the induced steep concentration gradient at pores mimics vessel–tumor interactions to stimulate angiogenesis to grow vessels toward the tumor. Applying this method, we demonstrate that vasculogenic vessels can grow first, followed by stimulating angiogenesis. Angiogenic vessels can grow into stroma tissue up to 1.3 mm long, and vessels can also grow into or wrap around a 625 μm tumor spheroid or a tumor tissue developed from a cell suspension. In summary, our study suggests that the interactions between a developing vasculature and a growing tumor must be controlled differently throughout the tissue development process, including at the early stage when vessels are still forming and at the later stage when the tumor needs to interact with the vessels. [ABSTRACT FROM AUTHOR]

Baseflow is among the most important components of streamflow. It is the main source of streamflow from groundwater systems in the dry season and also plays an important role as a water resource in the ecological environment and for human activities. In recent years, because of climate change, the number of dry season days in Taiwan has increased, and the wet season has been delayed, resulting in fewer rainy days and increased precipitation intensity. In addition, the spatial distribution of rainfall is uneven, and rivers are short and fast-flowing. Taiwan has become a country with abundant rainfall but insufficient water resources; therefore, the assessment of baseflow is important. This study selected eight basins with distinct wet and dry seasons in southern Taiwan as the study area. The baseflow characteristics and their relationships with climate features were assessed using time series analysis, baseflow attribution analysis, and wavelet analysis. The results showed that baseflow has an increasing trend; both precipitation and evapotranspiration have a significant positive correlation with baseflow, and the impact of precipitation is greater than that of evaporation. Sensitivity analysis showed that baseflow increases with increasing evaporation and precipitation; this behavior is related to the concentration of precipitation and evaporation in the wet season. Baseflow attribution analysis showed that the contribution of climate change to baseflow (75.0%) was larger than that of human activities (−2.9%), indicating that climate change was the main factor in the increase in baseflow. Wavelet analysis showed that both the El Niño–Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) are correlated with baseflow, where the PDO is more strongly correlated than the ENSO. The main timescales of the ENSO and PDO are a 4–8-year band and an 8-year band, respectively. The ENSO may have a timescale above the 8-year band, and the PDO exhibits periodic correlation changes at a 1-year band. [ABSTRACT FROM AUTHOR]

Obesity and its associated complications are global public health concerns. Metabolic disturbances and immune dysregulation cause adipose tissue stress and dysfunction in obese individuals. Immune cell accumulation in the adipose microenvironment is the main cause of insulin resistance and metabolic dysfunction. Infiltrated immune cells, adipocytes, and stromal cells are all involved in the production of proinflammatory cytokines and chemokines in adipose tissues and affect systemic homeostasis. Interferons (IFNs) are a large family of pleiotropic cytokines that play a pivotal role in host antiviral defenses. IFNs are critical immune modulators in response to pathogens, dead cells, and several inflammation-mediated diseases. Several studies have indicated that IFNs are involved in the pathogenesis of obesity. In this review, we discuss the roles of IFN family cytokines in the development of obesity-induced inflammation and insulin resistance. [ABSTRACT FROM AUTHOR]

A new design concept for a distributed sensor, which was developed based on the principle that the strain distribution of an arbitrary finite plate structure can be expressed as the superposition of even and odd strain functions, is presented. The distributed sensors adopt a symmetric weighting electrode to match the symmetric distribution of the even parts of the strain in order to introduce a no-phase delay low-pass filter to tailor the sensor transfer function. Both the design concept and the experimental results are detailed herein.

The relentless scaling of semiconductor devices pushes the doping level far above the equilibrium solubility, yet the doped material must be sufficiently stable for subsequent device fabrication and operation. For example, in epitaxial silicon doped above the solubility of phosphorus, most phosphorus dopants are compensated by vacancies, and some of the phosphorus-vacancy clusters can become mobile around 700 °C to further cluster with isolated phosphorus ions. For efficient and stable doping, we use microwave annealing to selectively activate metastable phosphorus-vacancy clusters by interacting with their dipole moments, while keeping lattice heating below 700 °C. In a 30-nm-thick Si nanosheet doped with 3 × 1021 cm−3 phosphorus, a microwave power of 12 kW at 2.45 GHz for 6 min resulted in a free-electron concentration of 4 × 1020 cm−3 and a junction more abrupt than 4 decades/nm. The doping profile is stable with less than 4% variation upon thermal annealing around 700 °C for 5 min. Thus, microwave annealing can result in not only efficient activation and abrupt profile in epitaxial silicon but also thermal stability. In comparison, conventional rapid thermal annealing can generate a junction as abrupt as microwave annealing but 25% higher sheet resistance and six times higher instability at 700 °C. [ABSTRACT FROM AUTHOR]

Structural changes known as airway remodeling characterize chronic/severe asthma and contribute to lung dysfunction. We previously reported that neonatal SSEA-1+ pulmonary stem/progenitor cells (PSCs) ameliorated airway inflammation in asthmatic mice. However, the molecular mechanisms by which endogenous SSEA-1+ PSC of adult mice afford beneficial effects in alveolar homeostasis and lung repair after allergen challenge remain incompletely understood. To analyze the expression profile and clarify the biological significance of endogenous adult lung SSEA-1+ cells in asthmatic mice. Lung SSEA-1+ cells and circulating SSEA-1+ cells in peripheral blood were determined by confocal microscopy and cytometric analysis. GFP chimeric mice were used to trace cell lineage in vivo. The roles of circulating SSEA-1+ cells were verified in ovalbumin-induced and house dust mite-induced allergic asthmatic models. In asthmatic mice, endogenous lung SSEA-1+ cells almost disappeared; however, a unique population of circulating SSEA-1+ cells was enriched after the challenge phase. In asthmatic mice, adoptive transfer of circulating SSEA-1+ cells had a specific homing preference for the lung in response to inhaled antigen through upregulating CXCR7–CXCL11 chemokine axis. Circulating SSEA-1+ cells can transdifferentiate in the alveolar space and ameliorate lung inflammation and structural damage through inhibiting the infiltration of inflammatory cells into peribronchovascular and goblet cell hyperplasia areas, reducing the thickened smooth muscle layers and PAS-positive mucus-containing goblet cells. Reinforcing bone marrow-derived circulating SSEA-1+ cells from peripheral blood into lung tissue which create a rescue mechanism in maintaining alveolar homeostasis and tissue repair to mediate lung protection for emergency responses after allergen challenge in asthmatic conditions. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology that can affect nearly every organ system in the body. Besides genetic and environmental factors, unbalanced pro‐inflammatory and anti‐inflammatory cytokines contribute to immune dysregulation, trigger an inflammatory response, and induce tissue and organ damage. Inflammatory responses in SLE can be promoted and/or maintained by the availability of cytokines that are overproduced systemically and/or in local tissues. Several key cytokines have been considered potential targets for the reduction of chronic inflammation in SLE. Recent studies indicated that dysregulated production of several cytokines, including those of the IL‐1 family and IL‐10 family, orchestrate immune activation and self‐tolerance, play critical roles in the pathogenesis of SLE. Among IL‐1 family cytokines, IL‐1, IL‐18, IL‐33, IL‐36, IL‐37, and IL‐38 had been the most thoroughly investigated in SLE. Additionally, IL‐10 family cytokines, IL‐10, IL‐20, IL‐22, IL‐26, IL‐28, and IL‐29 are dysregulated in SLE. Therefore, a better understanding of the initiation and progression of SLE may provide suitable novel targets for therapeutic intervention. In this review, we discuss the involvement of inflammation in the pathogenesis of SLE, with a focus on IL‐1 family and IL‐10 family cytokines, and highlight pathophysiological approaches and therapeutic potential for treating SLE. [ABSTRACT FROM AUTHOR]

IL‐20 is a proinflammatory cytokine of the IL‐10 family and involved in several diseases. However, the regulatory role of IL‐20 in obesity is not well understood. We explored the function of IL‐20 in the pathogenesis of obesity‐induced insulin resistance by ELISA, Western blotting and flow cytometry. The therapeutic potential of IL‐20 monoclonal antibody 7E for ameliorating diet‐induced obesity was analysed in murine models. Higher serum IL‐20 levels were detected in obese patients. It was upregulated in leptin‐deficient (ob/ob), leptin‐resistant (db/db) and high‐fat diet (HFD)‐induced murine obesity models. In vitro, IL‐20 regulated the adipocyte differentiation and the polarization of bone marrow‐derived macrophages into proinflammatory M1 type. It also caused inflammation and macrophage retention in adipose tissues by upregulating TNF‐α, monocyte chemotactic protein 1 (MCP‐1), netrin 1 and unc5b (netrin receptor) expression in macrophages and netrin 1, leptin and MCP‐1 in adipocytes. IL‐20 promoted insulin resistance by inhibiting glucose uptake in mature adipocytes through the SOCS‐3 pathway. In HFD‐induced obesity in mice, 7E treatment reduced body weight and improved glucose tolerance and insulin sensitivity; it also reduced local inflammation and the number of M1‐like macrophages in adipose tissues. We have identified a critical role of IL‐20 in obesity‐induced inflammation and insulin resistance, and we conclude that IL‐20 may be a novel target for treating obesity and insulin resistance in patients with metabolic disorders. [ABSTRACT FROM AUTHOR]

In this article, we present a new method to control the direction of traveling waves in either an x -direction or y -direction on a two-dimensional square plate. The core structure was composed of a piezoelectric serial bimorph with four electrodes. Each electrode was spatially designed to activate one of the bending modes and which included the ability to reduce adjacent modes and minimize interference. Our new method differs from other reported methods in that the four electrodes were driven at designated resonant frequencies. In our wave generator, different driving amplitudes and phases were applied to induce the traveling waves to propagate in a specific direction. To design the directional movement and to better understand the pattern of induced traveling waves, an analytical solution was derived to assist in the design of the four driving electrodes. Using our newly developed analytical method, traveling waves can be controlled to travel in either the x -direction or y -direction using two different sets of electrodes, where each electrode can be driven at a specific but different bending mode. We found that both the voltage ratio and phase difference between the two driving electrodes are important factors for optimization. [ABSTRACT FROM AUTHOR]

In this paper, a cardiac-and-piezoelectric hybrid system is developed for drug screening. The core structure is a polyvinylidene-fluoride piezoelectric membrane that serves as a flexible structure to interact with hiPSC cardiomyocytes and that measures the contraction profile of cardiomyocytes. This design enables the capability of electrically monitoring cardiomyocytes without the aid of an optical system. To guide cardiomyocytes aligning on this circular piezoelectric membrane, concentric rings of polydimethylsiloxane microgrooves are bonded to its surface. Experimental results demonstrate that seeded cardiomyocytes can align and elongate along the circular microgrooves to form a concentric pattern. To promote cardiomyocyte maturation, bipolar stimulation is conducted using a pin and a ring electrode made of a 304 stainless steel sheet. Furthermore, to maintain body temperature and minimize environmental noise, a 304 stainless steel box is constructed to enclose the cardiac-and-piezoelectric hybrid platform. It serves as an incubator and is electrically grounded for electromagnetic interference shielding. Using this system, continuous and repeated contractions of cardiomyocytes can be developed and monitored electrically. The system performance is verified using two commercial drugs: isoproterenol and metoprolol. It is experimentally demonstrated that this system can monitor the dosage effect of both drugs. Our results also show that the measured EC50 and IC50 values of contraction frequency and amplitude are in the same range. These findings suggest that both drugs can influence the beat frequency and contraction force simultaneously. In summary, taking advantage of the electro-mechanical coupling effect of the piezoelectric membrane, this system could be scaled up to perform automatic and parallel screenings for drug discoveries. [ABSTRACT FROM AUTHOR]

In this paper, a new type of lab-on-a-chip system, called vacuum pouch microfluidic (VPM) system, is reported. The core of this technology is a thin-film vacuum pouch that provides negative pumping pressure once it is activated. It is a degassed plastic bag that encloses a microfluidic chip. To demonstrate its performance, a passive thin-film micromixer is developed to integrate with the vacuum pouch. Since both the vacuum pouch and the thin-film micromixer are made of plastic film, they can be laminated together to construct a multi-layered microfluidic system. Excluding the storage reservoir, the overall thickness is 0.4 mm and the total weight is 0.3 g. This system provides a simple and straightforward strategy to construct a standalone, portable, flexible and low cost microfluidic system. The thin-film micromixer uses a serpentine channel to perform the mixing process, and it is found to have distinct mixing mechanisms under different Reynolds (Re) numbers, where lateral diffusion dominates for Re < 1 and chaotic mixing starts to contribute for Re > 10. Integrating this thin-film micromixer with the vacuum pouch, it is demonstrated that the negative pumping pressure can be adjusted by different storage reservoirs being placed at the channel exit. Reynolds numbers ranging from 0.0064 to 45.2 can be achieved. It also is verified that the VPM micromixer can be stored for 4 weeks to provide a sufficient flow rate for mixing applications. Finally, to demonstrate the feasibility of applying this VPM-based thin-film micromixer for on-site detection, this system is integrated with the colorimetric method. It is verified that a 10 μl ferrous ion solution and a 10 μl potassium ferricyanide solution can be mixed in 12 seconds, and concentrations of 10 ppm to 1000 ppm can be quantified by analyzing the colorimetric signal in hue values. [ABSTRACT FROM AUTHOR]

Chronic kidney disease and its complications are a major public health problem worldwide. Diabetic nephropathy has become the main contributing cause of terminal renal failure. There are now evidences that different inflammatory molecules, including proinflammatory cytokines, play a critical role in the development of microvascular diabetic complications, including nephropathy. IL‐20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory disorders likes psoriasis, atherosclerosis, and renal failure. This review discusses the role of IL‐20 as a pathogenic factor in renal injury, focusing on chronic kidney disease and diabetic nephropathy, and describes potential treatment strategies based on modulation of IL‐20's function. IL‐20 is a crucial mediator for regulating tubular cell apoptosis, promoting renal fibrosis, and enhancing podocyte dysfunction. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive destruction of articular cartilage. Interleukin (IL)-20 is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis. We investigated the role of IL-20 in OA and evaluated whether anti-IL-20 antibody (7E) treatment attenuates disease severity in murine models of surgery-induced OA. Immunohistochemical staining was used to detect IL-20 and its receptors expression in synovial tissue and cartilage from OA patients, and in OA synovial fibroblasts (OASFs) and chondrocytes (OACCs) from rodents with surgery-induced OA. RTQ-PCR and western blotting were used to determine IL-20-regulated OA-associated gene expression in OASFs and OACCs. OA rats and OA mice were treated with 7E. Arthritis severity was determined based on the degree of cartilage damage and the arthritis severity score. We found that IL-20 and its receptors were expressed in OASFs and OACCs. IL-20 induced TNF-α, IL-1β, MMP-1, and MMP-13 expression by activating ERK-1/2 and JNK signals in OASFs. IL-20 not only upregulated MCP-1, IL-6, MMP-1, and MMP-13 expression, but also downregulated aggrecan, type 2 collagen, TGF-β, and BMP-2 expression in OACCs. Arthritis severity was significantly lower in 7E-treated OA rats, and 7E- or MSC-treated OA mice. Therefore, we concluded that IL-20 was involved in the progression and development of OA through inducing proinflammatory cytokines and OA-associated gene expression in OASFs and OACCs. 7E reduced the severity of arthritis in murine models of surgery-induced OA. Our findings provide evidence that IL-20 is a novel target and that 7E is a potential therapeutic agent for OA. [ABSTRACT FROM AUTHOR]

This paper proposes a leader–follower-based model of mobile molecular communication networks for target detection applications. The proposed model divides the application functionalities of molecular communication networks into two types of mobile bio-nanomachine: leader and follower bio-nanomachines. Leader bio-nanomachines distribute in the environment to detect a target and create an attractant gradient around the target. Follower bio-nanomachines move according to the attractant gradient established by leader bio-nanomachines; they approach the target and perform necessary functionalities, such as releasing drug molecules. This paper develops mathematical expressions for the proposed model, describes wet laboratory experiments designed to estimate model parameters, and performs biologically realistic computer simulation experiments to evaluate the performance of the proposed model. The main contributions of this paper are to demonstrate the functional division of molecular communication networks, which will facilitate the design and development of molecular communication networks. Furthermore, insight into the application-level performance of molecular communication networks will be provided based on the proposed model. [ABSTRACT FROM PUBLISHER]