Lithium Niobate MEMS Antisymmetric Lamb Wave Resonators with Support Structures.

The piezoelectric thin film composed of single-crystal lithium niobate (LiNbO3) exhibits a remarkably high electromechanical coupling coefficient and minimal intrinsic losses, making it an optimal material for fabricating bulk acoustic wave resonators. However, contemporary first-order antisymmetric (A1) Lamb mode resonators based on LiNbO3 thin films face specific challenges, such as inadequate mechanical stability, limited power capacity, and the presence of multiple spurious modes, which restrict their applicability in a broader context. In this paper, we present an innovative design for A1 Lamb mode resonators that incorporates a support-pillar structure. Integration of support pillars enables the dissipation of spurious wave energy to the substrate, effectively mitigating unwanted spurious modes. Additionally, this novel approach involves anchoring the piezoelectric thin film to a supportive framework, consequently enhancing mechanical stability while simultaneously improving the heat dissipation capabilities of the core.

In Situ-Formed Fibrin Hydrogel Scaffold Loaded With Human Umbilical Cord Mesenchymal Stem Cells Promotes Skin Wound Healing.

Healing of full-thickness skin wounds remains a major challenge. Recently, human umbilical cord mesenchymal stem cells (hUC-MSCs) were shown to possess an extraordinary potential to promote skin repair in clinical settings. However, their low survival rate after transplantation limits their therapeutic efficiency in treating full-thickness skin wounds. Hydrogels are considered an ideal cell transplantation vector owing to their three-dimensional mesh structure, good biosafety, and biodegradation. The objective of this study was to investigate the skin wound healing effect of a fibrin hydrogel scaffold loaded with hUC-MSCs. We found that the fibrin hydrogel had a three-dimensional mesh structure and low cytotoxicity and could prolong the time of cell survival in the peri-wound area. The number of green fluorescent protein (GFP)-labeled hUC-MSCs was higher in the full-thickness skin wound of mice treated with hydrogel-hUC-MSCs than those of mice treated with cell monotherapy. In addition, the combination therapy between the hydrogel and hUC-MSCs speed up wound closure, its wound healing rate was significantly higher than those of phosphate-buffered saline (PBS) therapy, hydrogel monotherapy, and hUC-MSCs monotherapy. Furthermore, the results showed that the combination therapy between hydrogel and hUC-MSCs increased keratin 10 and keratin 14 immunofluorescence staining, and upregulated the relative gene expressions of epidermal growth factor (EGF), transforming growth factor-ß1 (TGF-ß1), and vascular endothelial growth factor A (VEGFA), promoting epithelial regeneration and angiogenesis. In conclusion, the fibrin hydrogel scaffold provides a relatively stable sterile environment for cell adhesion, proliferation, and migration, and prolongs cell survival at the wound site. The hydrogel-hUC-MSCs combination therapy promotes wound closure, re-epithelialization, and neovascularization. It exhibits a remarkable therapeutic effect, being more effective than the monotherapy with hUC-MSCs or hydrogel.

Metformin coordinates with mesenchymal cells to promote VEGF-mediated angiogenesis in diabetic wound healing through Akt/mTOR activation.

INTRODUCTION: Cell therapy with mesenchymal stem cells (MSCs) and biomaterials holds great potential for the treatment of diabetic ulceration; however, the underlying mechanism as well as its compatibility with the first-line anti-diabetic drug, metformin (MTF), has not been well elucidated. METHODS: MSCs derived from the umbilical cord were labeled with fluorescent proteins, followed by transplantation in a fibrin scaffold (MSCs/FG) onto the STZ-induced diabetic wound in a C57BL6/J mouse model. MTF was administered by oral gavage at a dose of 250 mg/kg/day. The wound healing rate, epithelization, angiogenesis, and underlying mechanism were evaluated in MSCs/FG- and MTF-treated diabetic wounds. Moreover, the dose-dependent effects of MTF and involvement of the Akt/mTOR pathway were analyzed in keratinocyte and fibroblast cultures. RESULTS: MSCs/FG significantly promoted angiogenesis in diabetic wound healing without signs of differentiation or integration. The recruitment of fibroblasts and keratinocytes by MSCs/FG promotes migration and vascular endothelial growth factor (VEGF) expression in an Akt/mTOR-dependent manner. MTF, which is generally considered a mTOR inhibitor, displayed dose-dependent effects on MSC-unregulated Akt/mTOR and VEGF expression. Oral administration of MTF at an anti-diabetic dosage synergistically acted with MSCs/FG to promote Akt/mTOR activation, VEGF expression, and subsequent angiogenesis in diabetic wounds; however, it reduced the survival of MSCs. CONCLUSIONS: Our study identifies that MTF coordinates with mesenchymal cells to promote Akt/mTOR activation and VEGF-mediated angiogenesis during diabetic wound healing. These findings offer new insights into MSCs engraftment in FG scaffolds for diabetic wound healing and provide support for the promotion of MSCs therapy in patients prescribed with MTF.

Artificial Intelligence Algorithms Enable Automated Characterization of the Positive and Negative Dielectrophoretic Ranges of Applied Frequency.

The present work describes the phenomenological approach to automatically determine the frequency range for positive and negative dielectrophoresis (DEP)-an electrokinetic force that can be used for massively parallel micro- and nano-assembly. An experimental setup consists of the microfabricated chip with gold microelectrode array connected to a function generator capable of digitally controlling an AC signal of 1 V (peak-to-peak) and of various frequencies in the range between 10 kHz and 1 MHz. The suspension of latex microbeads (3-µm diameter) is either attracted or repelled from the microelectrodes under the influence of DEP force as a function of the applied frequency. The video of the bead movement is captured via a digital camera attached to the microscope. The OpenCV software package is used to digitally analyze the images and identify the beads. Positions of the identified beads are compared for successive frames via Artificial Intelligence (AI) algorithm that determines the cloud behavior of the microbeads and algorithmically determines if the beads experience attraction or repulsion from the electrodes. Based on the determined behavior of the beads, algorithm will either increase or decrease the applied frequency and implement the digital command of the function generator that is controlled by the computer. Thus, the operation of the study platform is fully automated. The AI-guided platform has determined that positive DEP (pDEP) is active below 500 kHz frequency, negative DEP (nDEP) is evidenced above 1 MHz frequency and the crossover frequency is between 500 kHz and 1 MHz. These results are in line with previously published experimentally determined frequency-dependent DEP behavior of the latex microbeads. The phenomenological approach assisted by live AI-guided feedback loop described in the present study will assist the active manipulation of the system towards the desired phenomenological outcome such as, for example, collection of the particles at the electrodes, even if, due to the complexity and plurality of the interactive forces, model-based predictions are not available.

Deer antler extracts reduce amyloid-beta toxicity in a Caenorhabditis elegans model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Velvet antler extracts (VAE) are composed of a variety of active substances and growth factors, and have been reported to improve sleep quality and memory. AIM OF THE STUDY: We aimed to explore the protective effects and mechanism of action for VAE on Alzheimer's disease (AD) using a transgenic Caenorhabditis elegans model. MATERIALS AND METHODS: C. elegans were cultivated at 40% relative humidity on solid nematode growth medium (NGM) containing live E. coli (OP50) as the food source, with Strain N2 (normal) held at 20 °C and the CL4176s (transgenic) held at 16 °C. AD-like aggregation of Aß peptide in the CL4176s strain is induced by lifting the temperature to 25 °C. Nematodes were treated with three types of VAEs and Resveratrol (positive control). Analyses included qRT-PCR for quantification of gene transcripts of interest; ELISA for measuring levels of amyloid-ß protein; Thioflavin T fluorescent staining for localizing Aß depositions; assays for reactive oxygen species (ROS) and superoxide dismutase activity (SOD). RESULTS: VAEs reduced ß-amyloid peptide (Aß) toxicity in the transgenic C. elegans model. An enzymatically-digested VAE (EDVAE) was superior to both a cold-water VAE (CWVAE) and a hot-water VAE (HWVAE) from the same velvet antler. EDVAE treatment reduced the severity of the Aß-induced paralysis phenotype and decreased the amount of Aß deposits in the AD model nematodes, and these effects were found to be significantly better than that of the positive control Resveratrol. In addition, EDVAE treatment reduced production of ROS (induced by Aß), enhanced SOD activity, and elevated expression levels of antioxidant-related transcription factors, although it is not known whether these effects were achieved directly or indirectly. CONCLUSION: EDVAE had a protective role in Aß-induced toxicity in the transgenic AD nematodes, possibly through reducing accumulation of toxic Aß and enhancing the ability of nematodes to resist oxidative stress. Thus, EDVAE has potential to be an effective treatment to relieve the symptoms of AD.

Matrigel/Umbilical Cord-Derived Mesenchymal Stem Cells Promote Granulosa Cell Proliferation and Ovarian Vascularization in a Mouse Model of Premature Ovarian Failure.

In women of reproductive age, severe injuries to the ovary are often accompanied by premature ovarian failure (POF), which can result in amenorrhea or infertility. Hormone replacement therapy has been used to treat POF; however, it has limited therapeutic efficiency and may cause several side effects. In this study, we aimed to fabricate a Matrigel scaffold loaded with human umbilical cord-derived mesenchymal stem cells (MSCs) and explore its potential to restore ovarian function and repair ovarian structures in vitro and in vivo. POF mouse models were established by injecting mice with cyclophosphamide for 15 consecutive days. Then, MSC/Matrigel was transplanted into the ovaries of the mice. Five weeks later, the morphology of the ovaries and follicles was observed by hematoxylin/eosin staining, and the tissue fibrosis ratio was measured using Masson's trichrome staining. The number of blood vessels was evaluated by α-smooth muscle actin and CD31 immunofluorescence, and Ki67 expression was used to determine the proliferation of granulosa cells. The expression of vascular endothelial growth factor (VEGF)-A was assessed by western blotting. The Matrigel scaffold regulated the expression of VEGF-A in vitro. Moreover, it promoted MSC survival and proliferation and prevented MSC apoptosis in vivo. After the transplantation of the MSC/Matrigel, the number of follicles was significantly increased in the mice with POF, and the tissue fibrosis ratio was reduced. Furthermore, the MSC/Matrigel significantly improved the proliferation rate of granulosa cells, increased the number of blood vessels, and upregulated the expression of VEGF-A. These findings demonstrate that MSC/Matrigel may support follicular development and help restore ovarian structures in vivo.

Ingredients in Zijuan Pu'er Tea Extract Alleviate ß-Amyloid Peptide Toxicity in a Caenorhabditis elegans Model of Alzheimer's Disease Likely through DAF-16.

Amyloid-ß, one of the hallmarks of Alzheimer's disease (AD), is toxic to neurons and can also cause brain cell death. Oxidative stress is known to play an important role in AD, and there is strong evidence that oxidative stress is associated with amyloid-ß. In the present study we report the protective effect of Zijuan Pu'er tea water extract (ZTWE) and the mixture of main ingredients (+)-catechins, caffeine and procyanidin (MCCP) in ZTWE on ß-amyloid-induced toxicity in transgenic Caenorhabditis elegans (C. elegans) CL4176 expressing the human Aß1⁻42 gene. ZTWE, (+)-catechins, caffeine, procyanidin and MCCP delayed the ß-amyloid-induced paralysis to different degrees. The MCCP treatment did not affect the transcript abundance of amyloid-ß transgene (amy-1); however, Thioflavin T staining showed a significant decrease in Aß accumulation compared to untreated worms. Further research using transgenic worms found that MCCP promoted the translocation of DAF-16 from cytoplasm to nucleus and increased the expression of superoxide dismutase 3 (SOD-3). In addition, MCCP decreased the reactive oxygen species (ROS) content and increased the SOD activity in CL4176 worms. In conclusion, the results suggested that MCCP had a significant protective effect on ß-amyloid-induced toxicity in C. elegans by reducing ß-amyloid aggregation and inducing DAF-16 nuclear translocation that could activate the downstream signal pathway and enhance resistance to oxidative stress.

Nitrite addition to acidified sludge significantly improves digestibility, toxic metal removal, dewaterability and pathogen reduction.

Sludge management is a major issue for water utilities globally. Poor digestibility and dewaterability are the main factors determining the cost for sludge management, whereas pathogen and toxic metal concentrations limit beneficial reuse. In this study, the effects of low level nitrite addition to acidified sludge to simultaneously enhance digestibility, toxic metal removal, dewaterability and pathogen reduction were investigated. Waste activated sludge (WAS) from a full-scale waste water treatment plant was treated at pH 2 with 10 mg NO2--N/L for 5 h. Biochemical methane potential tests showed an increase in the methane production of 28%, corresponding to an improvement from 247 ± 8 L CH4/kg VS to 317 ± 1 L CH4/kg VS. The enhanced removal of toxic metals further increased the methane production by another 18% to 360 ± 6 L CH4/kg VS (a total increase of 46%). The solids content of dewatered sludge increased from 14.6 ± 1.4% in the control to 18.2 ± 0.8%. A 4-log reduction for both total coliforms and E. coli was achieved. Overall, this study highlights the potential of acidification with low level nitrite addition as an effective and simple method achieving multiple improvements in terms of sludge management.

Enhancing toxic metal removal from acidified sludge with nitrite addition.

The production of sludge (biosolids) during wastewater treatment is a major issue for water utilities. A main issue limiting its beneficial reuse on agricultural lands is the presence of toxic metals. The currently used metal reduction technologies achieve insufficient removal of metals that are bound to the organic fraction of the sludge. In this study, we propose and demonstrate a novel method that involves the addition of nitrite during sludge acidification to enhance metal removal. Using waste activated sludge collected from three full-scale wastewater treatment plants, we found that acidification to pH 2.0 achieved good Zn solubilization of around 70%, but only 3-7% of Cu was being dissolved. Nitrite addition to the acidified sludge at a concentration of 20 mg NO2(-)-N/L (equals to 19.2 mg HNO2-N/L), substantially enhanced Cu removal to 45-64%, while Zn removal was also increased to over 81%. Metal distribution analysis using sequential chemical extraction revealed that the improvement of Cu and Zn removal was mainly due to the release of the organically bound metal fraction. We hypothesize that free nitrous acid (HNO2, FNA) may assist in the (partial) disruption of extracellular polymeric substances (EPS) and the subsequent release and solubilization of fixed metals.

Microbial fuel cell as power supply for implantable medical devices: a novel configuration design for simulating colonic environment.

This study focused on providing power for implantable medical devices (IMDs) using a microbial fuel cell (MFC) implanted in human transverse colon. Considering the condition of colonic environment, a continuous-flow single-chamber MFC without membrane was set up. The performance of the MFC was investigated. The power output of 1.6 mW under the steady state was not rich enough for some high energy-consuming IMDs. Moreover, the parameters of the simulated colonic environment, such as pH and ORP value, varied along with the time. Hence, a new MFC configuration was developed. In this novel model, pH transducers were placed in cathodic and anodic areas, so as to regulate the reactor operation timely via external intervention. And two ORP transducers were inserted next to the pH transducers, for monitoring and adjusting the MFC operation efficiently. Besides, colonic haustra were designed in order to increase the difference between cathodic and anodic areas.

Continuous flowing membraneless microbial fuel cells with separated electrode chambers.

Microbial fuel cell (MFC) is an emerging technology in the energy and environment field. Its application is limited due to its high cost caused by the utilization of membranes and noble metal catalysts. In this paper, a membraneless MFC, with separated electrode chambers, was designed. The two separated chambers are connected via a channel and the continuous electrolyte flow from anode to cathode drives proton transfer. The proton mass transfer coefficiency in this MFC is 0.9086 cm/s, which is higher than reported MFCs with membranes, such as J-cloth and glass fiber. The maximum output voltage is 160.7 mV, with 1000 Ω resistor. Its peak power density is 24.33 mW/m³. SCOD removal efficiency can reach 90.45% via this MFC. If the connection between the two electrode chambers is blocked, the performance of MFC will decrease severely. All the above results prove the feasibility and advantages of this special MFC model.