Efficacy and Mechanisms of Natural Products as Therapeutic Interventions for Chronic Respiratory Diseases.

Chronic respiratory diseases are long-term conditions affecting the airways and other lung components that are characterized by a high prevalence, disability rate, and mortality rate. Further optimization of their treatment is required. Natural products, primarily extracted from organisms, possess specific molecular and structural formulas as well as distinct chemical and physical properties. These characteristics grant them the advantages of safety, gentleness, accessibility, and minimal side effects. The numerous advances in the use of natural products for treating chronic respiratory diseases have provided a steady source of motivation for new drug research and development. In this paper, we introduced the pathogenesis of chronic respiratory diseases and natural products. Furthermore, we classified natural products according to their mechanism for treating chronic respiratory diseases and describe the ways in which these products can alleviate the pathological symptoms. Simultaneously, we elaborate on the signal transduction pathways and biological impacts of natural products' targeting. Additionally, we present future prospects for natural products, considering their combination treatment approaches and administration methods. The significance of this review extends to both the research on preventing and treating chronic respiratory diseases, as well as the advancement of novel drug development in this field.

Hydrogel-assisted microfluidic spinning of stretchable fibers via fluidic and interfacial self-adaptations.

Stretchable polymeric fibers have enormous potential, but their production requires rigorous environmental controls and considerable resource consumption. It's also challenging for elastic polymers with high performance but poor spinnability, such as silicones like polydimethylsiloxane and Ecoflex. We present a hydrogel-assisted microfluidic spinning (HAMS) method to address these challenges by encapsulating their prepolymers within arbitrarily long, protective, and sacrificable hydrogel fibers. By designing simple apparatuses and manipulating the fluidic and interfacial self-adaptations of oil/water flows, we successfully produce fibers with widely controllable diameter (0.04 to 3.70 millimeters), notable length, high quality (e.g., smooth surface, whole-length uniformity, and rounded section), and remarkable stretchability (up to 1300%) regardless of spinnability. Uniquely, this method allows an easy, effective, and controllable reshaping production of helical fibers with exceptional stretchability and mechanical compliance. We deeply reveal the mechanisms in producing these fibers and demonstrate their potential as textile components, optoelectronic devices, and actuators. The HAMS method would be a powerful tool for mass-producing high-quality stretchable fibers.

Microcrack Arrays in Dense Graphene Films for Fast-Ion-Diffusion Supercapacitors.

Laminated graphene film has great potential in compact high-power capacitive energy storage owing to the high bulk density and opened architecture. However, the high-power capability is usually limited by tortuous cross-layer ion diffusion. Herein, microcrack arrays are fabricated in graphene films as fast ion diffusion channels, converting tortuous diffusion into straightforward diffusion while maintaining a high bulk density of 0.92 g cm-3 . Films with optimized microcrack arrays exhibit sixfold improved ion diffusion coefficient and high volumetric capacitance of 221 F cm-3 (240 F g-1 ), representing a critical breakthrough in optimizing ion diffusion toward compact energy storage. This microcrack design is also efficient for signal filtering. Microcracked graphene-based supercapacitor with 30 µg cm-2  mass loading exhibits characteristic frequency up to 200 Hz with voltage window up to 4 V, showing high promise for compact, high-capacitance alternating current (AC) filtering. Moreover, a renewable energy system is conducted using microcrack-arrayed graphene supercapacitors as filter-capacitor and energy buffer, filtering and storing the 50 Hz AC electricity from a wind generator into the constant direct current, stably powering 74 LEDs, demonstrating enormous potential in practical applications. More importantly, this microcracking approach is roll-to-roll producible, which is cost-effective and highly promising for large-scale manufacture.

REVIEW ARTICLE Engineering bio-inks for 3D bioprinting cell mechanical microenvironment.

144Three-dimensional (3D) bioprinting has become a promising approach to constructing functional biomimetic tissues for tissue engineering and regenerative medicine. In 3D bioprinting, bio-inks are essential for the construction of cell microenvironment, thus affecting the biomimetic design and regenerative efficiency. Mechanical properties are one of the essential aspects of microenvironment, which can be characterized by matrix stiffness, viscoelasticity, topography, and dynamic mechanical stimulation. With the recent advances in functional biomaterials, various engineered bio-inks have realized the possibility of engineering cell mechanical microenvironment in vivo. In this review, we summarize the critical mechanical cues of cell microenvironments, review the engineered bio-inks while focusing on the selection principles for constructing cell mechanical microenvironments, and discuss the challenges facing this field and the possible solutions for them.

Anxiety during the COVID-19 pandemic in prisoners who had high risks to suffer from mood disorders: A longitudinal study before and during the COVID-19.

We compared the anxiety levels in prisoners before and after the COVID-19 outbreak and analyzed the causes of the changes in anxiety. The first survey was conducted in October 2019 (T0), and the second was conducted in March 2020 (T1). Generalized anxiety disorder-7 (GAD-7), Patient Health Questionnaire-9, and Insomnia Severity Index scales were selected to assess the quality of emotion and sleep among prisoners (N = 803). Three subjective questions were asked to evaluate prisoners' personal feelings on the COVID-19. Paired Samples T-test, Binary, and Multivariate Logistic Stepwise Regression were used to analyze the data. GAD-7 scores decreased at T1 (p < 0.001). For the prisoners without anxiety at T0 (n = 480), GAD-7's mean value at T1 raised (p < 0.001), whereas the mean value decreased (p < 0.001) for the prisoners with anxiety at T0 (n = 323). For the prisoners without anxiety, shorter years of education (OR = 0.843), COVID-19 (OR = 4.936), severer depression at T1 (OR = 1.683), and severer insomnia at T1 (OR = 1.134) were associated with the new onset of anxiety. For the prisoners with anxiety, anxiety was alleviated in 71.2% and exacerbated in 10.5% at T1. For the alleviators, severer depression at T1 (OR = 0.667) and COVID-19 (OR = 0.258) were associated with anxiety unrelief; severer anxiety at T0 (OR = 1.343) was associated with anxiety alleviation. For the exacerbators, severer anxiety at T0 (OR = 0.517) was associated with anxiety unaggravation; severer depression at T1 (OR = 1.196), COVID-19 (OR = 22.882), and severer depression at T0 (OR = 1.181) were associated with anxiety exacerbation. At the outbreak of COVID-19, prisoners' anxiety was reduced. The main factor was the baseline anxiety levels. That may be related to prison management and the Downward Social Comparison.

Broadband Frequency Selective Rasorber Based on Spoof Surface Plasmon Polaritons.

A broadband frequency selective rasorber (FSR) based on spoofsurface plasmon polaritons (SSPP) is proposed. The FSR is composed of a multi-layer structure comprising frequency selective surface (FSS)-polyresin (PR)-indium tin oxide (ITO)-PR-FSS and placed vertically on a metal base plate. A periodic square cavity structure is formed. The transmission characteristics of the FSR are studied by full-wave simulation and equivalent circuit method. The simulation results demonstrate that under normal incidence, the absorption rate of the structure remains 95% in the 5-30 GHz band, and the absorption rate is also 80% in the 3.5-5 GHz band. As the incident angle of the electromagnetic wave increases to 40°, the absorption rate in the 15-20 GHz band decreases to 70% in the transverse electric (TE) mode, and the absorption rate in the transverse magnetic (TM) mode is almost the same as that of vertical incidence. The transmission response of the structure is measured in an anechoic chamber. The measurement results agree well with the simulation results, proving the reliability of the design and fabrication. The structure is less sensitive to the incident angle of magnetic waves and has a better broadband absorbing ability.

Phase-field numerical study on the dynamic process of thermocapillary patterning.

It is well known that surface tension is dependent on temperature, and thus a nonuniform temperature may cause thermocapillary flow which is referred to as the Marangoni effect. For a thin liquid-air film confined between a flat hot plate and a topographical cold template, it undergoes deformation due to thermocapillary flow. This phenomenon is termed as thermocapillary patterning, and has been used to fabricate micro- and nanostructure in polymer films. In most cases, the obtained structure conforms to the template; i.e., it can be considered as a replication technique. In this paper, we developed a two-phase flow numerical model based on the phase field to study the dynamic process of thermocapillary patterning. As a remeshing-free method, the phase field enables the incorporation of thermal field and multiphase flow with free surface deformation. The numerical model was employed to study the dynamic process of thermocapillary patterning. Meanwhile, the effects of some parameters, e.g., temperature, geometry parameters, and contact angle, were also investigated.

Compact 3D Metal Collectors Enabled by Roll-to-Roll Nanoimprinting for Improving Capacitive Energy Storage.

Reducing the contact resistance between active materials and current collectors is of engineering importance for improving capacitive energy storage. 3D current collectors have shown extraordinary promise for reducing the contact resistance, however, there is a major obstacle of being bulky or inefficient fabrication before they become viable in practice. Here a roll-to-roll nanoimprinting method is demonstrated to deform flat aluminum foils into 3D current collectors with hierarchical microstructures by combining soft matter-enhanced plastic deformation and template-confined local surface nanocracks. The generated 3D current collectors are inserted by and interlocked with active electrode materials such as activated carbon, decreasing the contact resistance by at least one order of magnitude and quadrupling the specific capacitance at high current density of 30 A g-1 for commercial-level mass loading of 5 mg cm-2 . The 3D current collectors are so compact that they have a low volume percentage of 7.8% in the entire electrode film, resulting in energy and power density of 29.1 Wh L-1 and 12.8 kW L-1 , respectively, for stack cells in organic electrolyte. Furthermore, roll-to-roll nanoimprinting of metal microstructures is low-cost, high-throughput, and can be extended to other systems that involve the microstructured metal interface, such as batteries and thermal management.

Fabrication and Biomedical Applications of Heart-on-a-chip.

Heart diseases have become the main killer threatening human health, and various methods have been developed to study heart disease. Among them, heart-on-a-chip has emerged in recent years as a method for constructing disease (or normal) models in vitro and is considered as a promising tool to study heart diseases. Compared with other methods, the advantages of heart-on-a-chip include the high portability, high throughput, and the capability to mimic microenvironments in vivo. It has shown a great potential in disease mechanism study and drug screening. In this paper, we review the recent advances in heart-on-a-chip, including the fabrication methods (e.g., 3D bioprinting) and biomedical applications. By analyzing the structure of the existing heart-on-a-chip, we proposed that a highly integrated heart-on-a-chip includes four elements: Microfluidic chips, cells/microtissues, microactuators to construct the microenvironment, and microsensors for results readout. Finally, the current challenges and future directions of heart-on-a-chip are discussed.

Tuning the Mechanical and Electrical Properties of Porous Electrodes for Architecting 3D Microsupercapacitors with Batteries-Level Energy.

Microsupercapacitors (MSCs) are vital power sources for internet of things (IoTs) and miniaturized electronics. The performance of MSCs is often restricted by its low areal energy density, which is due to the low areal mass loading of active materials. Constructing thick planar microelectrode with fine structure and high aspect ratio is an efficient way to increase mass loading, but limited by the breakable nature of porous electrode materials. Here, it is found that the mechanical and electrical properties of porous electrodes, as well as their surface area utilization and internal ion diffusion pathway, can be synergistically tuned by infilling gel electrolyte into internal pores of porous electrode films. The tuned thick porous electrode films are robust enough to enable laser ablation of three dimensional (3D) microelectrodes for high mass loading and high aspect ratio. The areal capacitance of 3D microelectrodes is able to increase linearly with mass loading (or thickness) up to at least 13 mg cm-2  (or 260 µm) for a value of up to 4640 mF cm-2 based on active carbon. The 3D MSCs deliver areal energy density of 1318 µWh cm-2 , which is comparable to the best of Li-ion 3D microbatteries while exhibiting superior electrochemical and mechanical stability.

Construction of cancer-on-a-chip for drug screening.

Cancer-on-a-chip has effectively contributed to the development of drug screening, holding great promise for more convenient and reliable drug development as well as personalized drug administration.

Recent Advances in 4D Bioprinting.

4D bioprinting has emerged as a powerful technique where the fourth dimension "time" is incorporated with 3D bioprinting. In this technique, the printed bioconstructs are able to change their shapes or functionalities when triggered by either internal or external stimuli. In 4D bioprinting, the materials with/without cells enable the spatial-temporal control of the shape and/or functionality of the constructs. Using this method, researchers have printed bioconstructs that can transform into rather complex structures which are difficult to obtain directly by 3D bioprinting or other methods. Although the history of 4D bioprinting is short, rapid progress in this field is witnessed recently, with focus mainly on developing novel 4D printable materials, exploring novel methods to precisely control the process, and pursuing biomedical applications. To better understand this technique, the recent advances of 4D bioprinting, including the mechanism, structure design principles, applications in biomedical engineering, and also the facing challenges are reviewed.

Microfluidic Printing of Three-Dimensional Graphene Electroactive Microfibrous Scaffolds.

Graphene materials have attracted special attention because of their electrical conductivity, mechanical properties, and favorable biocompatibility. Although various methods have been developed for fabricating micro/nano conductive fibrous scaffolds, it is still challenging to fabricate the three-dimensional (3D) graphene fibrous scaffolds. Herein, we developed a new method, termed as microfluidic 3D printing technology (M3DP), to fabricate 3D graphene oxide (GO) microfibrous scaffolds with an adjustable fiber length, fiber diameter, and scaffold structure by integrating the microfluidic spinning technology with a programmable 3D printing system. GO microfibrous scaffolds were then transformed into conductive reduced graphene oxide (rGO) microfibrous scaffolds by hydrothermal reduction. Our results demonstrated that the fabricated 3D fibrous graphene scaffolds exhibited tunable structures, maneuverable mechanical properties, and good electrical conductivity and biocompatibility, as reflected by the adhesion and proliferation of SH-SY5Y cells on the graphene microfibrous scaffolds in an obviously oriented manner. The developed M3DP would be a powerful tool for fabricating 3D graphene microfibrous scaffolds for electroactive tissue regeneration and drug-screening applications.

Deformation hysteresis of a water nano-droplet in an electric field.

Electric field is an effective method to manipulate droplets in micro/nano-scale, and various physical phenomena have been found due to the interaction of electric field and fluid flow. In this study, we developed a molecular dynamic model to investigate the deforming behavior of a nano-droplet in a uniform electric field. The nano-droplet was initially confined between two plates and then wetted on the lower plate (i.e., substrate) until an equilibrium state, after that a uniform electric field in vertical direction was imposed to the system. Due to the electrical force, the droplet started to deform until achieving a new equilibrium state and the dynamic process is recorded. By comparing the equilibrium state under different electric field strength, we found a deformation hysteresis phenomenon, i.e., different deformations were obtained when increasing and decreasing the electric field. To be specific, a large electric field (E = 0.57 V ·nm^-1) is needed to stretch the nano-droplet to touch the upper plate, while a relatively lower field (E = 0.40 V ·nm^-1) is adequate to keep it contacting with the plate. Accompanied by the deformation hysteresis, a distribution hysteresis of the average dipole orientations of water molecules in the nano-droplet is also found. Such a hysteresis phenomenon is caused by the electrohydrodynamic interactions between droplet and plates, and the findings of this study could enhance our understanding of droplet deformation in an electric field.

Exogenous melatonin delays postharvest fruit senescence and maintains the quality of sweet cherries.

We assessed the effects of postharvest exogenous melatonin (50,100 and 150 µmol L-1) on the senescence and quality of sweet cherries during storage at 0 ±â€¯0.5 °C. Melatonin treatment decreased decay incidence, respiration rate, and weight loss. It delayed the degradation of firmness, lightness, saturation, hue angle, titratable acidity, and total soluble solids content, thus maintaining better fruit quality. Melatonin treatment inhibited increases in O2-, H2O2, malondialdehyde content, and relative membrane permeability, while maintaining higher endogenous melatonin levels and increasing superoxide dismutase and catalase activity. Additionally, melatonin treatment enhanced the activity of antioxidant enzymes, increased the levels of ascorbic acid, and reduced glutathione levels, which are related to the ascorbate-glutathione cycle, as well as increasing the AsA:DHA and GSH:GSSG ratios. Delayed senescence in sweet cherries after exogenous melatonin treatment may be associated with high endogenous melatonin levels and increased antioxidant activity and content.

Analysis of Leukocyte Behaviors on Microfluidic Chips.

The orchestration of massive leukocytes in the immune system protects humans from invading pathogens and abnormal cells in the body. So far, researches focusing on leukocyte behaviors are performed based on both in vivo and in vitro models. The in vivo animal models are usually less controllable due to their extreme complexity and nonignorable species issue. Therefore, many researchers turn to in vitro models. With the advances in micro/nanofabrication, the microfluidic chip has emerged as a novel platform for model construction in multiple biomedical research fields. Specifically, the microfluidic chip is used to study leukocyte behaviors, due to its incomparable advantages in high throughput, precise control, and flexible integration. Moreover, the small size of the microstructures on the microfluidic chip can better mimic the native microenvironment of leukocytes, which contributes to a more reliable recapitulation. Herein are reviewed the recent advances in microfluidic chip-based leukocyte behavior analysis to provide an overview of this field. Detailed discussions are specifically focused on host defense against pathogens, immunodiagnosis, and immunotherapy studies on microfluidic chips. Finally, the current technical challenges are discussed, as well as possible innovations in this field to improve the related applications.

Improved Resolution and Fidelity of Droplet-Based Bioprinting by Upward Ejection.

Bioprinting has emerged as a powerful biofabrication technology with widespread applications in biomedical fields because of its superiority in high-throughput, high-precision, 3D structure fabrication. For bioprinting, two of the most important parameters are the printing precision (i.e., droplets resolution) and structural fidelity (i.e., conformity of the printed objects to the design). The major factors that hinder resolution and fidelity are gravity and impact force between printed droplets and substrate. However, existing solutions to these two issues, including decreasing droplet volume and introducing sacrificial materials, cause other problems, such as complexity or poor biocompatibility. Here, we reported a variant 3D bioprinting technique, termed as upward bioprinting, in which the nozzle of bioprinter is overturned and the ejection direction is opposite to gravitational force. Employing this technique, we fabricated discrete droplets, continuous lines, and 3D multilayer constructs using alginate and gelatin methacrylate (GelMA). The characterizations show that the upward bioprinting could improve the resolution and also fidelity as compared with the conventional downward bioprinting. Meanwhile, this method enables cell printing without affecting the viability. In addition, this method can be easily implemented without upgrading any hardware. Such an upward bioprinting technique could be an alternative to scale down microtissues and to fabricate 3D complex bioconstructs. We envision that the upward bioprinting, as a general method, could be extended to other bioprinting processes or applied to 3D bioprinting in outer space.

Microfluidic Chip for Odontoblasts in Vitro.

Odontoblast processes, which grow inside dentin tubules, are critical parts of odontoblasts, and they play an important role in dentin hypersensitivity. However, modeling the growth of odontoblast processes in vitro is difficult, which hinders the study of dentin hypersensitivity and other dental diseases. To our knowledge, no technique has yet been developed to induce the growth of odontoblast processes from a cell body in vitro. In the current study, we fabricated a microfluidic chip via soft lithography. The microchannels on the chip can mimic the microstructures of dentin tubules, and the microchambers that connect to the microchannels can be used for odontoblast culture. We successfully induced the growth of odontoblast processes from cell bodies by using this chip. In addition, we designed chips with different microchannel sizes (i.e., 2, 4, 6, and 8 µm) to investigate the relationship between the growth of odontoblast processes and the geometric constraint imposed by microchannels. Experimental results show that the growth of odontoblast processes can be successfully induced by 2 µm channels. However, odontoblasts will migrate in the 4, 6, and 8 µm channels. This finding indicates that 2 µm is the appropriate size for inducing the growth of odontoblast processes in vitro. This value is consistent with the size of dentin tubules in vivo. The fabricated microfluidic chip can serve as a powerful tool for investigating the physiology and pathology of odontoblast processes in the future and developing treatment solutions for dental diseases, such as dentin hypersensitivity.

Myeloid peroxisome proliferator-activated receptor gamma deficiency aggravates myocardial infarction in mice.

BACKGROUND AND AIMS: Agonists of peroxisome proliferator-activated receptor gamma (Pparγ) have been demonstrated to reduce the risk of myocardial infarction (MI) in clinical trials and animal experiments. However, the cellular and molecular mechanisms are not completely understood. We aimed to reveal the functions of myeloid Pparγ in MI and explore the potential mechanisms in this study. METHODS: Myeloid Pparγ knockout (MPGKO) mice (n = 12) and control mice (n = 8) underwent coronary artery ligation to induce MI. Another cohort of MPGKO mice and control mice underwent coronary artery ligation and were then treated with IgG or neutralizing antibodies against interleukin (IL)-1ß. Infarct size was determined by TTC staining and cardiac function was measured using echocardiography. Conditioned media from GW9662- or vehicle-treated macrophages were used to treat H9C2 cardiomyocyte cell line. Gene expression was analyzed using quantitative PCR. Reactive oxygen species were measured using flow cytometry. RESULTS: Myeloid Pparγ deficiency significantly increased myocardial infarct size. Cardiac hypertrophy was also exacerbated in MPGKO mice, with upregulation of ß-myosin heavy chain (Mhc) and brain natriuretic peptide (Bnp) and downregulation of α-Mhc in the non-infarcted zone. Conditioned media from GW9662-treated macrophages increased expression of ß-Mhc and Bnp in H9C2 cells. Echocardiographic measurements showed that MPGKO mice had worsen cardiac dysfunction after MI. Myeloid Pparγ deficiency increased gene expression of NADPH oxidase subunits (Nox2 and Nox4) in the non-infarcted zone after MI. Conditioned media from GW9662-treated macrophages increased reactive oxygen species in H9C2 cells. Expression of inflammatory genes such as IL-1ß and IL-6 was upregulated in the non-infarcted zone of MPGKO mice after MI. With the injection of neutralizing antibodies against IL-1ß, control mice and MPGKO mice had comparable cardiac function and expression of inflammatory genes after MI. CONCLUSIONS: Myeloid Pparγ deficiency exacerbates MI, likely through increased oxidative stress and cardiac inflammation.

In vitro diagnosis of DNA methylation biomarkers with digital PCR in breast tumors.

Liquid biopsy of cancers using DNA methylation biomarkers has received significant interest, where the quantification of multiple biomarkers is generally needed for improving the sensitivity and specificity of cancer diagnosis. However, the inefficiency of the traditional quantitative polymerase chain reaction (qPCR)-based MethyLight assay for detecting the extremely low concentration of methylated DNA fragments in body fluids limits its clinical applications. Here, we developed an ultrasensitive microwell chip digital polymerase chain reaction (dPCR)-based MethyLight assay. Using the synthesized samples, the developed MethyLight assay can achieve 103-104-fold lower limit of detection and 1-16-fold lower limit of quantification than the traditional MethyLight assay. Four hypermethylated alleles (RARß2, BRCA1, GSTP1 and RASSF1A) related to breast cancer in twenty-three clinical samples were tested using the microwell chip dPCR-based MethyLight assay. The results showed that the dPCR assay achieves ∼2 times enhancement in the cancer detection rate over the traditional quantitative PCR. Furthermore, the dPCR can detect the healthy and benign samples, which are undetectable using the traditional MethyLight assay. In multiple gene analysis, we achieved the highest detection rate of 93.3% (in the "OR" format of RARß2 and GSTP1). Lastly, the estimated cut-off values in the dPCR assay were: <1, ∼1 to 100 and >100 (copies per µL) referring to the healthy, benign and malignant breast cancers, respectively. Therefore, the developed microwell chip dPCR-based MethyLight assay could provide a powerful tool for cancer biopsy diagnosis and disease monitoring.