Highly conductive and tough polyacrylamide/sodium alginate hydrogel with uniformly distributed polypyrrole nanospheres for wearable strain sensors.

Conductive hydrogels have attracted widespread attention because of their integrated characteristics of being stretchable, deformable, adhesive, self-healable, and conductive. Herein, we report a highly conductive and tough double-network hydrogel based on a double cross-linked polyacrylamide (PAAM) and sodium alginate (SA) network with conducting polypyrrole nanospheres (PPy NSs) uniformly distributed in the network (PAAM-SA-PPy NSs). SA was employed as a soft template for synthesis of PPy NSs and distribution of PPy NSs uniformly in the hydrogel matrix to construct SA-PPy conductive network. The PAAM-SA-PPy NS hydrogel exhibited both high electrical conductivity (6.44 S/m) and excellent mechanical properties (tensile strength of 560 kPa at 870 %), as along as high toughness, high biocompatibility, good self-healing and adhesion properties. The assembled strain sensors showed high sensitivity and a wide sensing range (a gauge factor of 1.89 for 0-400 % strain and 4.53 for 400-800 % strain, respectively), as well as fast responsiveness and reliable stability. When used as a wearable strain sensor, it was able to monitor a series of physical signals from human large-scale joint motions and subtle muscle movements. This work provides a new strategy for the development of electronic skins and flexible strain sensors.

Sensitive amplified luminescent proximity homogeneous assay for the quantitative detection of CA242.

We here developed a sensitive and stable amplified luminescent proximity homogeneous assay (AlphaLISA) method for fast quantification of CA242 in human serum. Donor and acceptor beads modified with carboxyl groups could be coupled with CA242 antibodies after activation in the AlphaLISA method. CA242 was rapidly detected by the double antibody sandwich immunoassay. The method yielded good linearity (>0.996) and detection range (0.16-400 U/mL). The intra-assay precisions of CA242-AlphaLISA were between 3.43% and 6.81% (< 10%), and the inter-assay precisions were between 4.06% and 9.56% (< 15%). The relative recoveries ranged from 89.61% to 107.29%. Detection time for the CA242-AlphaLISA method was only 20 min. Moreover, results of CA242-AlphaLISA and time-resolved fluorescence immunoassay had satisfactory correlation and consistency (ρ = 0.9852). The method was successfully applied to the analysis of human serum samples. Meanwhile, serum CA242 has a good detection value in the identification and diagnosis of pancreatic cancer and the monitoring of disease degree. Furthermore, the proposed AlphaLISA method is expected to be an alternative to traditional detection methods, laying a good foundation for the further development of kits to detect other biomarkers in future studies.

An overview of biochemical technologies for the cancer biomarker miR-21 detection.

In recent years, the incidence of cancer has continuously increased, in which various miRNAs have been proposed as biomarkers for the early screening of cancer patients. As a consequence, the development of accurate methods for miRNA quantification has become a major research challenge worldwide. As one of the first discovered oncogenic miRNAs, microRNA-21 (miR-21) has been highlighted for its critical role in cancers. This review describes the main techniques currently available for miR-21 detection, compares the differences of the methods and the amplification strategies, and provides an overview of the state of knowledge in the field.

A2AR limits IL-15-induced generation of CD39+ NK cells with high cytotoxicity.

CD39-mediated inhibition of natural killer (NK) cell activity has been demonstrated, but the characteristics of CD39+ NK cells in humans are not known. We investigated the characteristics of human circulating CD39+ NK cells. In healthy donors, the proportion of circulating CD39+ NK cells in total NK cells was relatively low compared with that of CD39- NK cells. Nonetheless, a higher proportion of CD39+ NK cells expressed CD107a. Similarly, a higher proportion of CD39+ NK cells expressed CD107a in patients with hepatitis B virus or patients with hepatocellular carcinoma. Stimulation with NK-sensitive K562 cells or interleukin (IL)-12/IL-18 activated CD39+ NK cells to express higher levels of CD107a, IFN-γ and TNF-α, relative to CD39- NK cells. Importantly, IL-15 induced the generation of CD39+ NK cells. In contrast, A2A adenosine receptor (A2AR) ligation suppressed the generation of CD39+ NK cells by inhibiting IL-15 signaling. These data for the first time demonstrated that A2AR counteracts IL-15-induced generation of human CD39+ NK cells, which have a stronger cytotoxicity than CD39- NK cells. IL-15-induced human CD39+ NK cells might be better choice for immunotherapy based on adoptive transfer of NK cells.

Development of amplified luminescent proximity homogeneous assay for quantitation of gastrin-17.

A highly sensitive and convenient amplified luminescent proximity homogeneous assay (AlphaLISA) method with high throughput and automation potential was developed for quantitation of serum Gastrin-17 (G-17) levels, which can facilitate the early diagnosis of atrophic gastritis in people at high risk of gastric cancer using a non-invasive approach. In this study, donor and acceptor beads with modified carboxyl groups on the surface were directly coupled to anti-G-17 antibodies through activation was proposed for application in the development of the new AlphaLISA, which can effectively simplify the steps and shorten the reaction time to achieve faster detection. Therefore, the G-17-AlphaLISA only needs to react for 15 min to obtain good analysis results. The proposed method has a wider detection range than commercial enzyme-linked immunosorbent assay (ELISA) kits (0.12-112.8 pmol/L > 0.5-40 pmol/L). In addition, results of G-17-AlphaLISA and ELISA had good correlation and agreement (ρ = 0.936). Importantly, the developed method may be more suitable for the large-scale screening of people at high risk for gastric cancer than traditional ELISA and provides a novel solution for other biomarkers that require accurate, highly sensitive, and high throughput detection.

The circular RNA circ_0099630/miR-940/receptor-associated factor 6 regulation cascade modulates the pathogenesis of periodontitis.

Background/purpose: Periodontitis is one of the highly prevalent chronic inflammatory conditions in adults. The importance of circular RNAs (circRNAs) in the regulation of inflammation has been gradually reported in recent years, but the role of circRNA circ_0099630 in periodontitis has not been reported. Materials and methods: The contents of circ_0099630, microRNA-940 (miR-940) and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Inflammatory factor secretion, cell proliferation, and apoptosis were analyzed under the application of Enzyme-linked immunosorbent assay (ELISA), Cell Counting Kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and flow cytometry, respectively. The Western blot also analyzed the phosphorylation levels of RELA proto-oncogene (P65) and IkappaBalpha (IκBα), key molecules of the nuclear factor kappa-B (NF-κB) pathway. The relationship between miR-940 and circ_0099630 or TRAF6 was verified by luciferase reporter system and RNA immunoprecipitation (RIP) assay. Results: Higher abundance of circ_0099630 and TRAF6 and lower miR-940 expression were observed in periodontitis, and circ_0099630 knockdown attenuated the damage of human PDL cells (PDLCs) induced by lipopolysaccharides (LPS). The relationship between miR-940 and circ_0099630 or TRAF6 was evidenced, while miR-940 downregulation diminished the repair effect of si-circ_0099630 on overexpression LPS-induced damage in PDLCs. Similarly, TRAF6 upregulation impaired the mitigating effect of miR-940 overexpression on LPS-induced injury in PDLCs. Circ_0099630 silencing evidently curbed the phosphorylation levels of P65 and IκBα and thus attenuating the inflammatory response by acting on the miR-940/TRAF6 axis. Conclusion: Silencing circ_0099630 alleviates LPS-induced periodontal ligament cell injury via targeting miR-940/TRAF6/NF-κB in periodontitis.

A core/shell nanogenerator achieving pH-responsive nitric oxide release for treatment of infected diabetic wounds.

Nitric oxide is critical for eliminating infection and promoting regeneration in diabetic wounds. However, clinical uses of nitric oxide are limited by its high activity and lack of specificity in targeting infections. Herein, we develop an intelligent nitric oxide nanogenerator comprising isosorbide dinitrate (ISDN)-coated copper sulfide (CuS)/calcium carbonate (CaCO3) core/shell nanoparticles (CuS@CaCO3-ISDN) to target the acidic microenvironment of the infected diabetic wounds. Meaningfully, triggered by acid decomposition of CaCO3, this nanogenerator can achieve a responsive and accelerated release of nitric oxide from ISDN through enzyme-mimicking redox processes that involve CuS nanoparticles and then inactivate biofilm bacteria through the pathways of oxidative stress and disruption of adenosine triphosphate (ATP)-related energy metabolism. Moreover, after eliminating the infection, the pH-responsive release of nitric oxide can promote the proliferation of blood vessels and tissue regeneration and accelerate diabetic wound closure. This study expands the use of nitric oxide donors in wound treatment by developing the enzyme-mimicking release strategy, and the pH-responsive core/shell nanogenerator is promising for a variety of anti-infection therapeutic applications.

Antimicrobial peptide MPX attenuates LPS-induced inflammatory response and blood-testis barrier dysfunction in Sertoli cells.

Orchitis accounts for a high proportion of male animal reproductive disorders. Hence, it is urgent to identify drugs for the prevention and treatment of orchitis. Antimicrobial peptides (AMPs) are currently recognized as one of the most promising alternatives to antibiotics. However, the protective effects of AMPs on lipopolysaccharide (LPS)-induced orchitis have not been reported. In this study, we developed an LPS-induced orchitis model in which primary bovine Sertoli cells were used as model cells. MPX was indicated to effectively reduce the inflammatory response of Sertoli cells. MPX attenuated the gene expression of the proinflammatory cytokines TNF-α, IL-6 and IL-1ß by suppressing the MAPK pathway, especially the phosphorylation of p38 and ERK. MPX also decreased the oxidative stress response caused by LPS and upregulated Occludin and Claudin-1 expression, thereby maintaining the integrity of the blood-testis barrier. Moreover, we found that MPX inhibited apoptosis in Sertoli cells. In a mouse model, we found that MPX significantly inhibited the disruptive effects of LPS, reducing seminiferous epithelium damage, vacuolations, hyperplasia, and apoptosis in spermatogenic cells and rescuing spermatogenesis. In addition, the expression of inflammatory factors such as IL-1ß, IL-18, IL-6 and TNF-α was decreased after MPX treatment in the mouse testes. MPX had no effect on other organs in mice, indicating its safety. This study was undertaken to investigate how MPX regulates the inflammatory response in Sertoli cells and provide a reference for the clinical prevention and treatment of male animal orchitis.

Exosomes Regulate the Epithelial-Mesenchymal Transition in Cancer.

Exosomes are important mediators of intercellular communication and participate in complex biological processes by transferring a variety of bioactive molecules between cells. Epithelial-mesenchymal transition (EMT) is a process in which the cell phenotype changes from epithelioid to mesenchymal-like. EMT is also an important process for cancer cells by which they acquire invasive and metastatic capabilities, which aggravates the degree of tumor malignancy. Numerous studies have demonstrated that exosomes encapsulate various components, such as microRNAs and proteins, and transfer information between tumor cells or between tumor cells and the tumor microenvironment, thereby regulating the EMT process. Exosomes can also be used for cancer diagnosis and treatment or as a drug delivery platform. Thus, they can be used as a therapeutic tool to control the occurrence of EMT and affect cancer progression. In this review, we summarize the latest research advancements in the regulation of the EMT process in tumor cells by the contents of exosomes. Furthermore, we discuss the potential and challenges of using exosomes as a tool for cancer treatment.

The Antimicrobial Peptide Mastoparan X Protects Against Enterohemorrhagic Escherichia coli O157:H7 Infection, Inhibits Inflammation, and Enhances the Intestinal Epithelial Barrier.

Escherichia coli can cause intestinal diseases in humans and livestock, destroy the intestinal barrier, exacerbate systemic inflammation, and seriously threaten human health and animal husbandry development. The aim of this study was to investigate whether the antimicrobial peptide mastoparan X (MPX) was effective against E. coli infection. BALB/c mice infected with E. coli by intraperitoneal injection, which represents a sepsis model. In this study, MPX exhibited no toxicity in IPEC-J2 cells and notably suppressed the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) released by E. coli. In addition, MPX improved the expression of ZO-1, occludin, and claudin and enhanced the wound healing of IPEC-J2 cells. The therapeutic effect of MPX was evaluated in a murine model, revealing that it protected mice from lethal E. coli infection. Furthermore, MPX increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum. SEM and TEM analyses showed that MPX effectively ameliorated the jejunum damage caused by E. coli and increased the number and length of microvilli. In addition, MPX decreased the expression of IL-2, IL-6, TNF-α, p-p38, and p-p65 in the jejunum and colon. Moreover, MPX increased the expression of ZO-1, occludin, and MUC2 in the jejunum and colon, improved the function of the intestinal barrier, and promoted the absorption of nutrients. This study suggests that MPX is an effective therapeutic agent for E. coli infection and other intestinal diseases, laying the foundation for the development of new drugs for bacterial infections.