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The past several decades have witnessed great progress in high‐performance field effect transistors (FET) as one of the most important electronic components. At the same time, due to their intrinsic advantages, such as multiparameter accessibility, excellent electric signal amplification function, and ease of large‐scale manufacturing, FET as tactile sensors for flexible wearable devices, artificial intelligence, Internet of Things, and other fields to perceive external stimuli has also attracted great attention and become a significant field of general concern. More importantly, FET has a unique three‐terminal structure, which enables its different components to detect external mechanics through different sensing mechanisms. On one hand, it provides an important platform to shed deep insights into the underlying mechanisms of the tactile sensors. On the other hand, these properties could in turn endow excellent components for the construction of tactile matrix sensor arrays with high quality. With special emphasis on the configuration of FETs, this review classified and summarized structure‐optimized FET tactile sensors with gate, dielectric layer, semiconductor layer, and source/drain electrodes as sensing active components, respectively. The working principles and the state‐of‐the‐art protocols in terms of high‐performance tactile sensors are detail discussed and highlighted, the innovative pixel distribution and integration analysis of the transistor sensor matrix array concerning flexible electronics are also introduced. We hope that the introduction of this review can provide some inspiration for future researchers to design and fabricate high‐performance FET‐based tactile sensor chips for flexible electronics and other fields. This review focuses on FET‐based tactile pressure sensors. The working principles of this kind of tactile sensors are discussed in detail, the state‐of‐the‐art protocols for high‐performance tactile sensing are highlighted, and the major advances in large‐scale tactile sensor arrays and their applications in robotics, health care, and smart manufacturing in terms of transistor matrix are also introduced.

Osteoimmunomodulation was identified as a new and important strategy to enhance osteogenic differentiation together with other osteogenic approaches. However, approaches regulating osteogenic differentiation and macrophage polarization to remodel an osteoinductive microenvironment are separate and complicated. Therefore, the design and synthesis of one biomaterial that couples the osteogenic performance and immunomodulatory ability is a major challenge for efficient bone repair. In this study, self-assembled iron-catechin nanoparticles (Fe-cat NPs) were designed based on the coordinated reaction between iron ions and catechin and synthesized via a facile one-pot strategy. Interestingly, Fe-cat NPs show intracellular pH-responsive disassembly and release catechin molecules under the low pH of lysosomes after endocytosis. This strategy delivers catechin intracellularly and then enhances the osteogenic differentiation while inhibits the adipogenic differentiation of human adipose-derived stem cells (hADSCs). More importantly, Fe-cat NPs remodel the osteogenic immune microenvironment by resisting inflammation and promoting M2 polarization of macrophages. As a promising metal-organic nanodrug, the intracellular pH-responsive Fe-cat NPs significantly enhance the therapeutic effect of bone regneration by orchestrating osteogenic differentiation and immunomodulation, which may have great potential in bone tissue engineering.

Background Phasmatodea (stick and leaf insects) play a central role on the debate regarding wing reduction and loss, and its wings are putative reacquisition from secondarily wingless ancestors based solely on extant species. A pivotal taxon in this respect is the species-poor Timematodea, consisting of approximately 21 wingless extant species, which form the sister group of all remaining winged or wingless stick and leaf insects, the Euphasmatodea. Results Herein, the new fossils of Timematodea from mid-Cretaceous Kachin amber are reported, with winged and wingless species co-occurring. The palaeogeographic distributions of all fossils of Holophasmatodea are summarized, showing their wide paleo-distributions. The phylogenetic analysis based on morphological characters confirms the earliest-diverging lineage of winged Breviala cretacea gen. et sp. nov. in Timematodea, and the possible relationships among all families of Holophasmatodea. These are critical for the reconstruction of patterns of wing evolution in early Phasmatodea. Conclusions The new fossils suggest that Timematodea once had wings, at least during the mid-Cretaceous. The palaeogeographic occurrences imply that Timematodea probably have been widely distributed since at least the Jurassic. The phylogenetic analysis with the ancestral-state reconstruction of wings indicates that the common ancestors of Holophasmatodea were winged, the reductions and losses of wings among Timematodea and Euphasmatodea have occurred independently since at least the Cretaceous, and the reduction or loss of the forewing earlier than the hind wings.

Spinal cord injury (SCI) damages signal connections and conductions, with the result that neuronal circuits are disrupted leading to neural dysfunctions. Such injuries represent a serious and relatively common central nervous system condition and current treatments have limited success in the reconstruction of nerve connections in injured areas, especially where sizeable gaps are present. Biomaterial scaffolds have become an effective alternative to nerve transplantation in filling these gaps and provide the foundation for simulating the 3D structure of solid organs. However, there remain some limitations with the application of 3D bioprinting for preparation of biomaterial scaffolds. Here, the approach in constructing and testing mini‐tissue building blocks and self‐assembly, solid 3D gelatin microsphere (GM) scaffolds with multiple voids as based on the convenient preparation of gelatin microspheres by microfluidic devices is described. These 3D GM scaffolds demonstrate suitable biocompatibility, biodegradation, porosity, low preparation costs, and relative ease of production. Moreover, 3D GM scaffolds can effectively bridge injury gaps, establish nerve connections and signal transductions, mitigate inflammatory microenvironments, and reduce glial scar formation. Accordingly, these 3D GM scaffolds can serve as a novel and effective bridging method to promote nerve regeneration and reconstruction and thus recovery of nerve function after SCI. 3D gelatin microsphere scaffolds with suitable void size, biocompatibility, porosity, and degradability are fabricated by a microfluidic device with low cost and facile process. It is used to bridge injury gaps in rats. After spinal cord injury, its unique porous structure improves the microenvironment, promotes the survival and regeneration of neurons and axons, promoting functional recovery after spinal cord injury.

Curcumin (CUR), as a traditional Chinese medicine monomer extracted from the rhizomes of some plants in Ginkgo and Araceae, has shown a wide range of therapeutic and pharmacological activities such as anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, anti-liver fibrosis, anti-atherosclerosis, and anti-Alzheimer's disease. However, some issues significantly affect its biological activity, such as low aqueous solubility, physico-chemical instability, poor bioavailability, and low targeting efficacy. In order to further improve its curative effect, numerous efficient drug delivery systems have been carried out. Among them, physicochemical targeting preparations could improve the properties, targeting ability, and biological activity of CUR. Therefore, in this review, CUR carrier systems are discussed that are driven by physicochemical characteristics of the microenvironment (eg, pH variation of tumorous tissues), affected by external influences like magnetic fields and vehicles formulated with thermo-sensitive materials.

BackgroundFamotidine was reported to potentially provide benefits to Coronavirus Disease 2019 (COVID-19) patients. However, it remains controversial whether it is effective in treating COVID-19.AimsThis study aimed to explore whether famotidine use is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.MethodsThis study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42020213536). A comprehensive search was performed to identify relevant studies up to October 2020. I-squared statistic and Q-test were utilized to assess the heterogeneity. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated through the random effects or fixed effects model according to the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also conducted.ResultsFive studies including 36,635 subjects were included. We found that famotidine use was associated with a statistically non-significant reduced risk of progression to severe disease, death, and intubation for Coronavirus Disease 2019 (COVID-19) patients (pooled RR was 0.82, 95% CI = 0.52–1.30, P = 0.40).ConclusionFamotidine has no significant protective effect in reducing the risk of developing serious illness, death, and intubation for COVID-19 patients. More original studies are needed to further clarify whether it is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) might be involved in the activation of important pathways related to tumor immune escape, along with programmed death-ligand 1 (PD-L1). Here, we aimed to investigate the correlation between the expression of Siglec-15 and PD-L1 in nasopharyngeal carcinoma (NPC) patients. We determined the expression of PD-L1 via immunohistochemical staining and that of Siglec-15 via immunofluorescence staining in 182 NPC tissue samples. A significant correlation was identified between the PD-L1 and Siglec-15 expression (P = 0.000). Moreover, Kaplan–Meier survival curves showed that PD-L1 expression was associated with improved overall survival (OS) (P = 0.025) and Siglec-15 expression was associated with improved distant failure-free survival (D-FFS) (P = 0.048). Moreover, multivariate Cox analysis showed that PD-L1 and Siglec-15 were independent predictors of OS (P = 0.020) and D-FFS (P = 0.047), respectively. The results of the log-rank test and Cox regression analyses showed that patients exhibiting no PD-L1/Siglec-15 expression had significant advantages regarding OS, compared to other groups (P = 0.037). PD-L1 and Siglec-15 may represent novel biomarkers for predicting the prognosis of NPC patients. Siglec-15 may be considered as a potential target for the development of therapeutics for NPC treatment in the future.

Although adipose‐derived mesenchymal stem cells (ADMSCs) isolated from patients’ fat are considered as the most important autologous stem cells for tissue repair, significant difficulties in the neural differentiation of ADMSCs still impede stem cell therapy for neurodegenerative diseases. Herein, a wireless‐electrical stimulation method is proposed to direct the neural differentiation of ADMSCs based on the electromagnetic effect using a graphene film as a conductive scaffold. By placing a rotating magnet on the top of a culture system without any inducer, the ADMSCs cultured on graphene differentiate into functional neurons within 15 days. As a conductive biodegradable nanomaterial, graphene film acts as a wireless electrical signal generator driven by the electromagnetic induction, and millivolt‐level voltage generated in situ provokes ADMSCs to differentiate into neurons, proved by morphological variation, extremely high levels of neuron‐specific genes, and proteins. Most importantly, Ca2+ intracellular influx is observed in these ADMSC‐derived neurons once exposure to neurotransmitters, indicating that these cells are functional neurons. This research enhances stem cell therapy for neurodegenerative diseases using autologous ADMSCs and overcomes the lack of neural stem cells. This nanostructure‐mediated physical‐signal simulation method is inexpensive, safe, and localized, and has a significant impact on neural regeneration. This novel stimulation method does not rely on the function of neural‐inducing biological factors, but only utilizes the conducting properties of a scaffold material (graphene) to convert external magnetic fields into electrical fields based on electromagnetic induction. The resultant wireless electric stimulation inspires the adipose‐derived mesenchymal stem cells to differentiate into functional neurons to transmit nerve impulses.

The present study aims to develop a kind of novel nanoliposomes for the lung-targeting delivery system of baicalin as a Chinese medicine monomer. Baicalin-loaded nanoliposomes were prepared by the effervescent dispersion and lyophilized techniques. Baicalin-loaded nanoliposomes had an average particle size of 131.7±11.7 nm with 0.19±0.02 polydispersity index, 82.8%±1.24% entrapment efficiency and 90.47%±0.93% of yield and sustaining drug release effect over 24 h and were stable for 12 months at least. In vitro no hemolytic activity was observed for the experimental drug concentration. After intravenous administration of baicalin-loaded nanoliposomes to rabbits, drug concentration in the lungs was the highest among the tested organs at all time points and was significantly higher than that of its solution. For the targeting parameters, the relative intake rate and the ratio of peak concentration of lung were 4.837 and 2.789, respectively. Compared with plasma, liver, spleen, and kidney, the ratios of targeting efficacy (T ) to (T ) of lung were increased by a factor of 14.131, 1.893, 3.357, and 3.470, respectively. Furthermore, the results showed that the baicalin-loaded nanoliposomes did not induce lung injury. Importantly, baicalin-loaded nanoliposomes showed better antitumor therapeutic efficacy in the nude mice bearing orthotopic human lung cancer with the median survival time of blank liposomes (11.40±0.16 days), baicalin solution (17.30±0.47 days), and baicalin-loaded nanoliposomes (25.90±0.53 days). Therefore, the liposome is a promising drug carrier with an excellent lung-targeting property and therapeutic effect for the treatment of lung disease, such as lung cancer.

Colorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed. Graphical Abstract