A highly conductive, robust, self-healable, and thermally responsive liquid metal-based hydrogel for reversible electrical switches.

This study introduces a thermally responsive smart hydrogel with enhanced electrical properties achieved through volume switching. This advancement was realized by incorporating multiscale liquid metal particles (LMPs) into the PNIPAM hydrogel during polymerization, using their inherent elasticity and conductivity when deswelled. Unlike traditional conductive additives, LMPs endow the PNIPAM hydrogel with a remarkably consistent volume switching ratio, significantly enhancing electrical switching. This is attributed to the minimal nucleation effect of LMPs during polymerization and their liquid-like behavior, like vacancies in the polymeric hydrogel under compression. The PNIPAM/LMP hydrogel exhibits the highest electrical switching, with an unprecedented switch of 6.1 orders of magnitude. Even after repeated swelling/deswelling cycles that merge some LMPs and increase the conductivity when swelled, the hydrogel consistently maintains an electrical switch exceeding 4.5 orders of magnitude, which is still the highest record to date. Comprehensive measurements reveal that the hydrogel possesses robust mechanical properties, a tissue-like compression modulus, biocompatibility, and self-healing capabilities. These features make the PNIPAM/LMP hydrogel an ideal candidate for long-term implantable bioelectronics, offering a solution to the mechanical mismatch with dynamic human tissues.

Antioxidative 0-dimensional nanodrugs overcome obstacles in AKI antioxidant therapy.

Acute kidney injury (AKI) is a commonly encountered syndrome associated with various aetiologies and pathophysiological processes leading to enormous health risks and economic losses. In the absence of specific drugs to treat AKI, hemodialysis remains the primary clinical treatment for AKI patients. The revelation of the pathology opens new horizons for antioxidant therapy in the treatment of AKI. However, small molecule antioxidant drugs and common nanozymes have failed to challenge AKI due to their unsatisfactory drug properties and renal physiological barriers. 0-Dimensional (0D) antioxidant nanodrugs stand out at this time thanks to their small size and high performance. Recently, a number of research studies have been carried out around 0D nanodrugs for alleviating AKI, and their multi-antioxidant enzyme mimetic activities, smooth glomerular filtration barrier permeability and excellent biocompatibility have been investigated. Here, we comprehensively summarize recent advances in 0D nanodrugs for AKI antioxidant therapy. We classify these representative studies into three categories according to the characteristics of 0D nanomaterials, namely ultra-small metal nanodots, inorganic non-metallic quantum dots and polymer nanodots. We focus on the antioxidant mechanisms and their distribution in vivo in each inspiring work, and the purpose and ingenuity of each design are rigorously captured and described. Finally, we provide our reflections and prospects for 0D antioxidant nanodrugs in AKI treatment. This mini review provides unique insights and valuable clues in the design of 0D nanodrugs and other kidney absorbable drugs.

Polyphyllin I induces apoptosis and autophagy in temozolomide-resistant glioma via modulation of NRF2 and MAPK-signaling activation.

Glioma is the most prevailing main malignant neoplasm of the central nervous system with a miserable prognosis. Temozolomide is the first-line chemotherapy drug for glioma, but its drug resistance reduces temozolomide's clinical efficacy and becomes the principal cause of the failure of glioma chemotherapy. Polyphyllin I (PPI), an active component in Rhizoma Paridis, demonstrates favorable therapeutic actions in diverse malignant neoplasms. Its effect on temozolomide-resistant glioma, however, has not yet been characterized. Here, we demonstrated that polyphyllin I inhibited the proliferation of temozolomide-resistant glioma cell in a concentration-dependent manner. Further, we found that polyphyllin I had a direct effect on temozolomide-resistant glioma tumor cells and promote reactive oxygen species (ROS)-dependent apoptosis and autophagy via mitogen-activated protein kinase (MAPK)-signaling (p38-JNK) pathway. Mechanistically, we showed that polyphyllin I downregulate the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, indicating that polyphyllin I may be an expected therapeutic strategy for patients with temozolomide-resistant gliomas.

Ultra-small molybdenum-based nanodots as an antioxidant platform for effective treatment of periodontal disease.

Periodontal disease (PD) is a local inflammatory disease with high morbidity, manifesting tissue destruction results from inflammation of the host immune response to bacterial antigens and irritants. The supportive function of connective tissue and skeletal tissue can be jeopardized without prompt and effective intervention, representing the major cause of tooth loss. However, traditional treatments exhibited great limitations, such as low efficacies, causing serious side effects and recurrent inflammatory episodes. As a major defense mechanism, reactive oxygen species (ROS) play important roles in the pathological progression of PD. Antioxidant therapy is widely believed to be an effective strategy for ROS-triggered diseases, including oxidative stress-induced PD. Most antioxidants can only scavenge one or a few limited kinds of ROS and cannot handle all kinds. In addition, current antioxidant nanomaterials present limitations associated with toxicity, low stability, and poor biocompatibility. To this end, we develop ultra-small molybdenum-based nanodots (MoNDs) with strong ROS in oxidative stress-induced PD. To the best of our knowledge, this is the first time that MoNDs have been used for PD. In the present study, MoNDs have shown extremely good therapeutic effects as ROS scavengers. Spectroscopic and in vitro experiments provided strong evidence for the roles of MoNDs in eliminating multiple ROS and inhibiting ROS-induced inflammatory responses. In addition, the mouse model of PD was established and demonstrated the feasibility of MoNDs as powerful antioxidants. It can alleviate periodontal inflammation by scavenging multiple ROS without obvious side effects and exhibit good biocompatibility. Thus, this newly developed nanomedicine is effective in scavenging ROS and inhibiting M1 phenotypic polarization, which provides promising candidates for the treatment of PD.

Corrigendum: Ultra-small molybdenum-based nanodots as an antioxidant platform for effective treatment of periodontal disease.

[This corrects the article DOI: 10.3389/fbioe.2022.1042010.].

Highly conductive thermoresponsive silver nanowire PNIPAM nanocomposite for reversible electrical switch.

Highly conductive nanocomposite hydrogels have been challenging to produce due to their high water volumes inhibiting the incorporation of an essential amount of conductive nanofillers. Furthermore, the most common fillers used, typically for easy integration, display small aspect ratios. Thus, the formation of interparticle pathways for electronic travel is limited, resulting in low conductivities. Here, we introduce ultralong silver nanowires (ULAgNWs) into a thermoresponsive, volume changing PNIPAM gel to form a nanocomposite that shows switchable electronic performance. The produced nanocomposite surpasses other PNIPAM nanocomposites by expressing the largest electrical switch ratio and the highest peak conductivity. The PNIPAM matrix possesses an interconnected microporous structure that offers a spacious network for the dispersion of nanowires while still maintaining a high volume switch ratio and excellent elastic behavior under extreme compression cycles (98% compression). The ULAgNWs significantly enhance the probability of more numerous connections forming during shrinking cycles. The high swellability displayed by the PNIPAM gel provides the ability to separate the embedded nanowires by many lengths. Together, they form a nanocomposite that can thermo-modulate its electrical properties. Moreover, the conductive PNIPAM maintains the electrical switch of 4.3-4.4 orders of magnitude with thermo-responsive cycles. Because of their high electrical conductivity and outstanding elastic behavior, these stimuli-responsive nanocomposite hydrogels may expand the prospects for conductive hydrogel applications and provide greater performance in their applications.

Modulation of autophagy as a therapeutic strategy for Toxoplasma gondii infection.

Toxoplasma gondii infection is a severe health threat that endangers billions of people worldwide. T. gondii utilizes the host cell membrane to form a parasitophorous vacuole (PV), thereby fully isolating itself from the host cell cytoplasm and making intracellular clearance difficult. PV can be targeted and destroyed by autophagy. Autophagic targeting results in T. gondii killing via the fusion of autophagosomes and lysosomes. However, T. gondii has developed many strategies to suppress autophagic targeting. Accordingly, the interplay between host cell autophagy and T. gondii is an emerging area with important practical implications. By promoting the canonical autophagy pathway or attenuating the suppression of autophagic targeting, autophagy can be effectively utilized in the development of novel therapeutic strategies against T gondii. Here, we have illustrated the complex interplay between host cell mediated autophagy and T. gondii. Different strategies to promote autophagy in order to target the parasite have been elucidated. Besides, we have analyzed some potential new drug molecules from the DrugBank database using bioinformatics tools, which can modulate autophagy. Various challenges and opportunities focusing autophagy mediated T. gondii clearance have been discussed, which will provide new insights for the development of novel drugs against the parasite.

Chemical Analysis of the Gallium Surface in a Physiologic Buffer.

Gallium and its alloys have been regarded as one of the promising materials for flexible bioelectronics due to their liquid-like mechanical properties, excellent electrical property, and low toxicity. Although many studies have fabricated bioelectronics from gallium-based liquid metals, gallium surface chemistry in physiologic conditions is rarely investigated. Here, we investigated the chemical change of the gallium surface in a physiologic buffer at 37 °C over 45 days. The gallium ion concentration and pH measurement indicated that the oxidation and corrosion progressed more rapidly in the physiological buffer than in air. Also, the release of gallium ions and protons followed a square root of time growth. Various spectroscopic techniques were used to measure the chemical composition change on the gallium surface. The FT-IR study indicated that the GaOOH-rich gallium surface produced Ga3+ and OH- ions. The XPS study indicated the oxide layer formation within 5 days, and then the contamination layer was deposited over time, which includes different ions and organic materials derived from the physiologic buffer. This study provides a detailed chemical analysis of the gallium surface in a physiological buffer. These fundamental studies would be a cornerstone for understanding the complex interaction between the gallium surface and the biological environment.

Conductive Polymer Enabled Biostable Liquid Metal Electrodes for Bioelectronic Applications.

Gallium (Ga)-based liquid metal materials have emerged as a promising material platform for soft bioelectronics. Unfortunately, Ga has limited biostability and electrochemical performance under physiological conditions, which can hinder the implementation of its use in bioelectronic devices. Here, an effective conductive polymer deposition strategy on the liquid metal surface to improve the biostability and electrochemical performance of Ga-based liquid metals for use under physiological conditions is demonstrated. The conductive polymer [poly(3,4-ethylene dioxythiophene):tetrafluoroborate]-modified liquid metal surface significantly outperforms the liquid metal.based electrode in mechanical, biological, and electrochemical studies. In vivo action potential recordings in behaving nonhuman primate and invertebrate models demonstrate the feasibility of using liquid metal electrodes for high-performance neural recording applications. This is the first demonstration of single-unit neural recording using Ga-based liquid metal bioelectronic devices to date. The results determine that the electrochemical deposition of conductive polymer over liquid metal can improve the material properties of liquid metal electrodes for use under physiological conditions and open numerous design opportunities for next-generation liquid metal-based bioelectronics.

Camelina sativa Oil Treatment Alleviates Castor Oil-Induced Diarrhea in ICR Mice by Regulating Intestinal Flora Composition.

Diarrhea, occurring due to intestinal flora disturbance, is potentially lethal, and its current treatments have adverse effects such as constipation and vomiting. Camelina sativa oil (CSO) is a cooking ingredient and natural remedy used in several countries; however, its pharmacological effects on intestinal health remain unknown. Here, we explored the CSO treatment effects on intestinal flora in male ICR mice with castor oil-induced diarrhea. The rate and degree of loose stools, the diarrhea index, serum inflammatory indices, fecal short-chain fatty acids (SCFAs), and the diversity and abundance of intestinal flora were measured. Castor oil-administered mice experienced diarrhea, reduced intestinal flora diversity and fecal SCFAs concentrations, altered intestinal flora composition, and increased serum proinflammatory indices. In contrast, CSO treatment relieved diarrhea, improved intestinal flora composition, and increased the relative abundance of Lactobacillus and Lachnospiraceae. Additionally, CSO significantly increased the concentrations of fecal propionic acid, valeric acid, isovaleric acid, and serum sIgA, while it reduced those of serum interleukin-17. These findings suggest that CSO could be a promising preventive agent against diarrhea.

Thermally tunable hydrogel crosslinking mediated by temperature sensitive liposome.

Hydrogel crosslinking by external stimuli is a versatile strategy to control and modulate hydrogel properties. Besides photonic energy, thermal energy is one of the most accessible external stimuli and widely applicable for many biomedical applications. However, conventional thermal crosslinking systems require a relatively high temperature (over 100 °C) to initiate covalent bond formation. To our knowledge, there has not been a thermally tunable hydrogel crosslinking system suitable for biological applications. This work demonstrates a unique approach to utilize temperature sensitive liposomes to control and modulate hydrogel crosslinking over mild temperature range (below 50 °C). Temperature sensitive liposomes were used to control the release of chemical crosslinkers by moderate temperature changes. The thermally controlled crosslinker release resulted in tunable mechanical and transport properties of the hydrogel. No significant inflammable response observed in the histology results ensured the biocompatibility of the liposome-mediated crosslinkable hydrogel. This work opens new opportunities to implement thermal energy system for control and modulate hydrogel properties.

lncRNA LINC00473 promotes proliferation, migration, invasion and inhibition of apoptosis of non-small cell lung cancer cells by acting as a sponge of miR-497-5p.

Lung cancer is the leading cause of cancer-associated death worldwide and exhibits a poor prognosis. The present study aimed to determine the effect of long non-coding (lnc)RNA-LINC00473 on the development of non-small cell lung cancer (NSCLC) cells by regulating the expression of microRNA (miR)-497-5p. Reverse transcription-quantitative PCR was conducted to detect the level of LINC00473 and miR-497-5p. An MTT assay, flow cytometry and Transwell tests were performed to evaluate the proliferation, apoptosis, migration and invasion of NSCLC cells. Western blotting was performed to detect the expression of apoptosis- and migration-related proteins. RNA immunoprecipitation and a luciferase reporter assay were performed to verify the regulatory relationship between lncRNA-LINC00473 and miR-497-5p. LINC00473 expression was upregulated in lung cancer tissues and NSCLC cells (A549 and H1299) when compared with adjacent tissues or human bronchial epithelial cell lines and the 5-year survival rate was lower in patients with high LINC00473 expression compared with in patients with low LINC00473 expression. A negative correlation between LINC00473 and miR-497-5p was observed in lung cancer tissues. Proliferation, migration and invasion as well as the related protein levels were increased in A549 and H1299 transfected with pcDNA3.1-LINC00473, while the opposite results were obtained in A549 and H1299 transfected with small interfering (si)-LINC00473. Notably, it was demonstrated that LINC00473 could bind directly with miR-497-5p and inhibit its expression. miR-497-5p inhibitors reversed the effect of si-LINC00473. Furthermore, the present study demonstrated that LINC00473 promoted the malignant behaviour of NSCLC cells via regulating the ERK/p38 and MAPK signalling pathways and the expression of miR-497-5p.

Simultaneous measurement of neurite and neural body mass accumulation via quantitative phase imaging.

Measurement of neuron behavior is crucial for studying neural development and evaluating the impact of potential therapies on neural regeneration. Conventional approaches to imaging neuronal behavior require labeling and do not separately quantify the growth processes that underlie neural regeneration. In this paper we demonstrate the use of quantitative phase imaging (QPI) as a label-free, quantitative measurement of neuron behavior in vitro. By combining QPI with image processing, our method separately measures the mass accumulation rates of soma and neurites. Additionally, the data provided by QPI can be used to separately measure the processes of maturation and formation of neurites. Overall, our approach has the potential to greatly simplify conventional neurite outgrowth measurements, while providing key data on the resources used to produce neurites during neural development.

Level of mesothelin expression can indicate the prognosis of malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal, treatment-resistant tumor. The median survival of MPM is 9-12 months and its early prognostic markers remains uncertain. The objective of this study was to determine that the level of mesothelin expression can be as a predictor of prognosis in MPM patients. METHODS: Level of mesothelin expression was detected in 38 MPM tissue specimens by immunohistochemistry analysis. The relationship of MPM prognosis and mesothelin expression was evaluated by univariate and multivariate Cox regression, Kaplan-Meier survival curves. RESULTS: High level of mesothelin expression was significantly associated with non-epithelioid type of MPM and smoking. Meanwhile, higher level of mesothelin expression indicated a shorter total survival. CONCLUSIONS: The present study suggested that mesothelin is a dependent prognostic factor in MPM patients and might be a novel potential target for immunotherapy in MPM.

Tanshinone IIA attenuates silica-induced pulmonary fibrosis via inhibition of TGF-ß1-Smad signaling pathway.

Transforming growth factor-ß 1 (TGF-ß1) is a key mediator in fibrogenesis, and is upregulated and activated in fibrotic diseases. The exact role of TGF-ß1-Smad signaling in the progression of silicosis fibrosis is yet to be conclusively determined. Using a Wistar rat silicosis model, we examined whether tanshinone IIA (Tan IIA) could meliorate silicosis fibrosis. The pulmonary fibroblasts of rats from the normal control group and silicosis-induced model group were extracted and examined so as to further explore the disruption of TGF-ß1-Smad signaling pathway in silicosis pathogenesis and the intervention of Tan IIA in this pathway. Using RT-PCR, immunohistochemical staining, and immunofluorescence analysis, we determined that Tan IIA could ameliorate silicosis fibrosis, downregulate collagen I, collagen III, and α-SMA expression both, in vivo and in vitro. In silicosis fibroblasts, TGF-ß1 induced phosphorylation of Smad2, Smad3, and negative feedback Smad7 inhibition in a dose dependent manner, and the phosphorylation of Smad3 persisted when the upstream signal was blocked. Tan IIA treatment effectively inhibited the TGF-ß1-induced phosphorylation of Smads, especially the persistent phosphorylation of Smad3 in the nucleus, and upregulated the expression of Smad7 in silicosis fibroblasts, leading to a reduction in ECM deposition. Our findings indicate that dysregulation of the TGF-ß1-Smad signaling pathway may play an important role in the pathological process of silicosis. Tan IIA thus ameliorates silicosis fibrosis partially by suppressing activation of TGF-ß1-Smad signaling pathway, which may turn out to be a potential therapeutic approach to prevent silicosis fibrosis.

Inhibitory effects of astragaloside IV on silica-induced pulmonary fibrosis via inactivating TGF-ß1/Smad3 signaling.

PURPOSE: To observe the effect of astragaloside ASV (ASV) on silicosis fibroblasts, and further investigate its regulatory mechanism on TGF-ß1/Smad3 signaling pathway. METHODS: Silica-induced rats model was established in this study. RT-qPCR was performed to detect α-SMA, Collagen I, Collagen III, Smad2, Smad3 and Smad7 expression. Immunofluorescence was conducted to detect α-SMA, Collagen I, Collagen III and p-Smad3 protein and the nucleoplasmic distribution of p-Smad3.Western-blotting was performed to detect the protein of Smad2, p-Smad2, Smad3, p-Smad3 and Smad7. RESULTS: 20 µg/mL ASV could effectively reduce the expression of α-SMA, Collagen I, Collagen III. TGF-ß1 stimulated the proliferation of fibroblasts, promoted phosphorylation of Smad2 and Smad3, and down-regulated Smad7 expression. Among them, continuous phosphorylation of Smad3 is a major factor in causing fibrosis. Besides, ASV can inhibit silica-induced lung fibroblast fibrosis through TGF-ß1/Smad3 signaling pathway, thereby inhibiting the formation of silicosis. CONCLUSION: ASV could inhibit the expression of collagen in fibroblasts and the transformation to myofibroblasts, and has an anti-silicosis fibrosis effect, which may be related to the continuous phosphorylation of Smad3 in the TGF-ß1/Smad signaling pathway.

An improved procedure to implement NSGA-III in coordinate waste management for urban agglomeration.

With the growth of urbanization in countries globally, large cities have often formed clusters of urban agglomerations in metropolitan areas. The coordinated management of regional solid waste produced by such urban agglomeration poses a typical high-dimensional, multi-objective optimization issue. This paper aims to introduce a procedure to implement the third-generation genetic algorithm (NSGA-III), an established multi-objective genetic algorithm based on non-dominated sorting mechanisms, for the purpose of evaluating environmental and economic benefits simultaneously while seeking the optimal solutions for coordinated management among multiple recycling centres. In this study, two series of scenarios were abstracted from scrap tire recycling, representing linear calculation and nonlinear calculation cases separately. Several improvements were made to the originally published NSGA-III procedure that solve the problem of non-convergence for hypervolumes of the output. Through comparisons of calculation results, an improved procedure is suggested and shown to have improved performance.

The Protective Role of Tanshinone IIA in Silicosis Rat Model via TGF-ß1/Smad Signaling Suppression, NOX4 Inhibition and Nrf2/ARE Signaling Activation.

PURPOSE: Silicosis is an occupational disease caused by inhalation of silica and there are no effective drugs to treat this disease. Tanshinone IIA (Tan IIA), a traditional natural component, has been reported to possess anti-inflammatory, antioxidant, and anti-fibrotic properties. The current study's purpose was to examine Tan IIA's protective effects against silica-induced pulmonary fibrosis and to explore the underlying mechanisms. METHODS: 48 male SD rats were randomly divided into four groups (n=12): i) Control group; ii) Silicosis group; iii) Tan IIA group; iv) Silicosis +Tan IIA group. Two days after modeling, the rats of Tan IIA group and Silicosis +Tan IIA group were given intraperitoneal administration 25 mg/kg/d Tan IIA for 40 days. Then, the four groups of rats were sacrificed and the lung inflammatory responses were measured by ELISA, lung damage and fibrosis were analyzed by hematoxylin and eosin (H&E) staining and Masson staining, the expression levels of collagen I, fibronectin and α-smooth muscle actin (α-SMA) were measured by immunohistochemistry. The markers of oxidative stress were measured by commercial kits, and the activity of the TGF-ß1/Smad and NOX4, Nrf2/ARE signaling pathways were measured by RT-PCR and Western blotting. RESULTS: The silica-induced pulmonary inflammtory responses, structural damage and fibrosis were significantly attenuated by Tan IIA treatment. In addition, treatment with Tan IIA decreased collagen I, fibronectin and α-SMA expression, and inhibited TGF-ß1/Smad signaling in the lung tissue. The upregulated levels of oxidative stress markers in silicosis rats were also markedly restored following Tan IIA treatment. Furthermore, treatment with Tan IIA reduced NOX4 expression and enhanced activation of the Nrf2/ARE pathway in the lung tissue of silicosis rats. CONCLUSION: These findings suggest that Tan IIA may protect lung from silica damage via the suppression of TGF-ß1/Smad signaling, inhibition of NOX4 expression and activation of the Nrf2/ARE pathway.

Silicon Nanoribbon pH Sensors Protected by a Barrier Membrane with Carbon Nanotube Porins.

Limited biocompatibility and fouling propensity can restrict real-world applications of a large variety of biosensors. Biological systems are adept at protecting and separating vital components of biological machinery with semipermeable membranes that often contain defined pores and gates to restrict transmembrane transport only to specific species. Here we use a similar approach for creating fouling-resistant pH sensors. We integrate silicon nanoribbon transistor sensors with an antifouling lipid bilayer coating that contains proton-permeable carbon nanotube porin (CNTP) channels and demonstrate robust pH detection in a variety of complex biological fluids.

Detecting Population-Differentiation Copy Number Variants in Human Population Tree by Sparse Group Selection.

Copy-number variants (CNVs) account for a substantial proportion of human genetic variations. Understanding the CNV diversities across populations is a computational challenge because CNV patterns are often present in several related populations and only occur in a subgroup of individuals within each of the population. This paper introduces a tree-guided sparse group selection algorithm (treeSGS) to detect population-differentiation CNV markers of subgroups across populations organized by a phylogenetic tree of human populations. The treeSGS algorithm detects CNV markers of populations associated with nodes from all levels of the tree such that the evolutionary relations among the populations are incorporated for more accurate detection of population-differentiation CNVs. We applied treeSGS algorithm to study the 1,179 samples from the 11 populations in Hapmap3 CNV data. The treeSGS algorithm accurately identifies CNV markers of each population and the collection of populations organized under the branches of the human population tree, validated by consistency among family trios and SNP characterizations of the CNV regions. Further comparison between the detected CNV markers and other population-differentiation CNVs reported in 1,000 genome data and other recent studies also shows that treeSGS can significantly improve the current annotations of population-differentiation CNV markers. TreeSGS package is available at https://github.com/kuanglab/treeSGS.