Fatigue Resistant Aerogel/Hydrogel Nanostructured Hybrid for Highly Sensitive and Ultrabroad Pressure Sensing.

Achieving high sensitivity over a broad pressure range remains a great challenge in designing piezoresistive pressure sensors due to the irreconcilable requirements in structural deformability against extremely high pressures and piezoresistive sensitivity to very low pressures. This work proposes a hybrid aerogel/hydrogel sensor by integrating a nanotube structured polypyrrole aerogel with a polyacrylamide (PAAm) hydrogel. The aerogel is composed of durable twined polypyrrole nanotubes fabricated through a sacrificial templating approach. Its electromechanical performance can be regulated by controlling the thickness of the tube shell. A thicker shell enhances the charge mobility between tube walls and thus expedites current responses, making it highly sensitive in detecting low pressure. Moreover, a nucleotide-doped PAAm hydrogel with a reversible noncovalent interaction network is harnessed as the flexible substrate to assemble the aerogel/hydrogel hybrid sensor and overcome sensing saturation under extreme pressures. This highly stretchable and self-healable hybrid polymer sensor exhibits linear response with high sensitivity (Smin  > 1.1 kPa-1 ), ultrabroad sensing range (0.12-≈400 kPa), and stable sensing performance over 10 000 cycles at the pressure of 150 kPa, making it an ideal sensing device to monitor pressures from human physiological signals to significant stress exerted by vehicles.

UV illumination-enhanced ultrasensitive ammonia gas sensor based on (001)TiO2/MXene heterostructure for food spoilage detection.

Ammonia has been used as an important marker to indicate the extent of food spoilage. However, current gas sensors for ammonia suffer from either insufficient sensitivity and selectivity or unsatisfactory levels of automation, impeding their practical application for on-site and real-time monitoring of food quality. To overcome these limitations, we propose here the design of a sensing material by in-situ growing (001)TiO2 onto a two-dimensional transition-metal carbide (Ti3C2Tx, MXene). In this design, TiO2 with a highly active (001) crystal plane provides efficient photogeneration under UV irradiation, while Ti3C2Tx can store holes through Schottky junction formed at the interface with TiO2, which greatly promotes the separation of electron-hole pairs, thereby enhancing ammonia sensing performance. By further introducing UV light for electron excitation, the (001)TiO2/Ti3C2Tx based sensor shows 34 times higher sensitivity for ammonia (30 ppm) than that of Ti3C2Tx. The density functional theory further revealed that the (001) plane of TiO2 and Ti3C2Tx composite configuration exhibited the highest adsorption affinity towards ammonia. Finally, an integrated circuit alarm system including near-field communication and a micro-controller system was designed to detect the decay process of fresh pork, fish, and shrimp. We believe such a sensing technology holds great promise in food quality monitoring.

Pd-Fe3O4 Janus nanozyme with rational design for ultrasensitive colorimetric detection of biothiols.

Although nanozyme-based colorimetric assays have been broadly used for biosensing, some limitations such as low catalytic activity of nanozyme, poor sensitivity to analytes and lack of understanding the structure-activity relationship remain unsolved. In this work, we developed an ultrasensitive colorimetric method for biothiols detection based on density functional theory-assisted design of janus Pd-Fe3O4 nanozyme. The Pd-Fe3O4 dumbbell-like nanoparticles (DBNPs) prepared by seed-mediated approach shows a uniform heterodimeric nanostructure. Ultrasensitive biothiols detection is achieved from two aspects. On one hand, due to the synergistic effect between Pd and Fe3O4 in the dumbbell structure, Pd-Fe3O4 DBNPs show enhanced peroxidase-mimic activity compared to the individual components. On the other hand, when the target biothiols molecule is present, its inhibition effect on the janus Pd-Fe3O4 nanozyme is also significantly enhanced. The above results are confirmed both in experiment and theoretical calculation. Based on the rational design, a simple, highly selective and urtrasensitive colorimetric and quantitative assay for biothiols is developed. The limit of detection (LOD) can reach as low as 3.1 nM in aqueous solution. This assay is also successfully applied to the detection of biothiols in real urine samples. Moreover, the Pd-Fe3O4 nanozyme is used to discriminate biothiols levels in normal and cancer cells with high sensitivity at the cell density of 15,000/mL, which demonstrates its great potential in biological and clinical analysis. This work not only shows the great promise of janus bimetallic nanozymes' excellent functionalities but also provides rational guidelines to design high-performance nanozymes for biosensing and biomedical applications.

The emerging role of microRNA-4487/6845-3p in Alzheimer's disease pathologies is induced by Aß25-35 triggered in SH-SY5Y cell.

BACKGROUND: Accumulation of amyloid ß-peptide (Aß) is implicated in the pathogenesis and development of Alzheimer's disease (AD). Neuron-enriched miRNA was aberrantly regulated and may be associated with the pathogenesis of AD. However, regarding whether miRNA is involved in the accumulation of Aß in AD, the underlying molecule mechanism remains unclear. Therefore, we conduct a systematic identification of the promising role of miRNAs in Aß deposition, and shed light on the molecular mechanism of target miRNAs underlying SH-SY5Y cells treated with Aß-induced cytotoxicity. RESULTS: Statistical analyses of microarray data revealed that 155 significantly upregulated and 50 significantly downregulated miRNAs were found on the basis of log2 | Fold Change | ≥ 0.585 and P < 0.05 filter condition through 2588 kinds of mature miRNA probe examined. PCR results show that the expression change trend of the selected six miRNAs (miR-6845-3p, miR-4487, miR-4534, miR-3622-3p, miR-1233-3p, miR-6760-5p) was consistent with the results of the gene chip. Notably, Aß25-35 downregulated hsa-miR-4487 and upregulated hsa-miR-6845-3p in SH-SY5Y cell lines associated with Aß-mediated pathophysiology. Increase of hsa-miR-4487 could inhibit cells apoptosis, and diminution of hsa-miR-6845-3p could attenuate axon damage mediated by Aß25-35 in SH-SY5Y. CONCLUSIONS: Together, these findings suggest that dysregulation of hsa-miR-4487 and hsa-miR-6845-3p contributed to the pathogenesis of AD associated with Aß25-35 mediated by triggering cell apoptosis and synaptic dysfunction. It might be beneficial to understand the pathogenesis and development of clinical diagnosis and treatment of AD. Further, our well-designed validation studies will test the miRNAs signature as a prognostication tool associated with clinical outcomes in AD.

Germline and somatic variations influence the somatic mutational signatures of esophageal squamous cell carcinomas in a Chinese population.

BACKGROUND: Esophageal squamous cell carcinomas (ESCC) is the fourth most lethal cancer in China. Previous studies reveal several highly conserved mutational processes in ESCC. However, it remains unclear what are the true regulators of the mutational processes. RESULTS: We analyzed the somatic mutational signatures in 302 paired whole-exome sequencing data of ESCC in a Chinese population for potential regulators of the mutational processes. We identified three conserved subtypes based on the mutational signatures with significantly different clinical outcomes. Our results show that patients of different subpopulations of Chinese differ significantly in the activity of the "NpCpG" signature (FDR = 0.00188). In addition, we report ZNF750 and CDC27, of which the somatic statuses and the genetic burdens consistently influence the activities of specific mutational signatures in ESCC: the somatic ZNF750 status is associated with the AID/APOBEC-related mutational process (FDR = 0.0637); the somatic CDC27 copy-number is associated with the "NpCpG" (FDR = 0.00615) and the AID/APOBEC-related mutational processes (FDR = 8.69 × 10- 4). The burdens of germline variants in the two genes also significantly influence the activities of the same somatic mutational signatures (FDR < 0.1). CONCLUSIONS: We report multiple factors that influence the mutational processes in ESCC including: the subpopulations of Chinese; the germline and somatic statuses of ZNF750 and CDC27 and exposure to alcohol and tobacco. Our findings based on the evidences from both germline and somatic levels reveal potential genetic regulators of the somatic mutational processes and provide insights into the biology of esophageal carcinogenesis.

Adsorption Mechanism of Oil by Resilient Graphene Aerogels from Oil-Water Emulsion.

A facile synthesis strategy was adopted to prepare resilient graphene aerogel (GA) with properties of high emulsified oil adsorption capacities, excellent rebounding performance, oil-water selectivity, and recycling abilities. The maximum adsorption capacity of GA for emulsified diesel oil was 2.5 × 104 mg g-1. The microscopic kinetic and thermodynamic mutual reaction models of diesel oil emulsion adsorption onto GA were investigated to describe the adsorption mechanism. The emulsified diesel oil was able to be separated efficiently from the oil-water emulsion by GA because of their high oil selectivity. Interestingly, both kinetics and thermodynamic experiments show that emulsified oil adsorption on GA is a physical adsorption and spontaneous process. Besides, GA can be reused with prominent repeatability for at least 10 cycles, demonstrating feasibility in practical applications of GA-based oily water treatment.

Dasatinib and chemotherapy in a patient with early T-cell precursor acute lymphoblastic leukemia and NUP214-ABL1 fusion: A case report.

The present study aimed to evaluate the therapeutic efficacy of dasatinib in a patient with nucleoporin 214-tyrosine protein kinase ABL1 proto-oncogene 1 (NUP214-ABL1)-positive early T-cell precursor-acute lymphoblastic leukemia (ETP-ALL), as well as that of selinexor and dasatinib for NUP214-ABL1-positive ETP-ALL in vitro. ETP leukemia is a form of T-cell ALL (T-ALL) with poor prognosis. The NUP214-ABL1 gene is present in ~6% of T-ALL cases, however the prevalence of NUP214-ABL1 gene expression in ETP-ALL in particular has not yet been verified. The current study reports the rare case of a 29-year-old man with ETP-ALL harboring the NUP214-ABL1 fusion gene, presenting with low-grade fever, stomachache and splenomegaly. The patient was successfully treated with dasatinib and vincristine, idarubicin, cyclophosphamide and prednisone (VICP) chemotherapy. The therapeutic efficacy of selinexor and dasatinib was also evaluated in vitro. Apoptosis was analyzed using Annexin V/propidium iodide staining and flow cytometry, and poly ADP-ribose polymerase (PARP) cleavage was detected using western blot analysis. The results demonstrated that the apoptotic cell population significantly increased following selinexor or dasatinib treatment compared with the control (P<0.05). Furthermore, combined selinexor and dasatinib treatment led to a significant increase in cell apoptosis compared with either treatment alone (P<0.05). The apoptosis results were confirmed by PARP cleavage. Thus, NUP214-ABL1 fusion gene expression should be tested in T-ALL, including ETP-ALL. Dasatinib used in combination with traditional induction chemotherapy may reverse the high induction failure of ETP-ALL with NUP214-ABL1 fusion gene; however, further prospective studies are required to confirm this. Therefore, selinexor with or without dasatinib may serve as a potential salvage therapy in the case of relapse and may be developed as a novel treatment for ETP-ALL with the NUP214-ABL1 fusion gene.

Piezo1 is as a novel trefoil factor family 1 binding protein that promotes gastric cancer cell mobility in vitro.

BACKGROUND: Trefoil factor family 1 (TFF1) is a member of the TFF-domain peptide family involved in epithelial restitution and cell motility. Recently, we screened Piezo1 as a candidate TFF1-binding protein. AIM: We aimed to confirm Piezo1 as a novel TFF1 binding protein and to assess the role of this interaction in mediating gastric cancer cell mobility. METHODS: This interaction was confirmed by co-immunoprecipitation and co-localisation of TFF1 and Piezo1 in GES-1 cells. We used stable RNA interference to knockdown Piezo1 protein expression and restored the expression of TFF1 in the gastric cancer cell lines SGC-7901 and BGC-823. Cell motility was evaluated using invasion assay and migration assay in vitro. The expression levels of the integrin subunits ß1, ß5, α1 as well as the expression of ß-catenin and E-cadherin were detected by Western blot. RESULTS: We demonstrate that TFF1, but not TFF2 or TFF3, bind to and co-localize with Piezo1 in the cytoplasm in vitro. TFF1 interacts with the C-terminal portion of the Piezo1 protein. Wound healing and trans-well assays demonstrated that the restored expression of TFF1 promoted cell mobility in gastric cancer cells, and this effect was attenuated by the knockdown of Piezo1. Western blots demonstrated the decreased expression of integrin ß1 in Piezo1-knockdown cells. CONCLUSIONS: Our data demonstrate that Piezo1 is a novel TFF1 binding protein that is important for TFF1-mediated cell migration and suggest that this interaction may be a therapeutic target in the invasion and metastasis of gastric cancer.

TFF3 mediated induction of VEGF via hypoxia in human gastric cancer SGC-7901 cells.

Increasing evidence indicates that in gastric epithelial cells, induction of TFF3 by hypoxia is mediated by HIF-1. Since VEGF is one of the most important angiogenic factors on cancer progression, we have started to investigate the possible link among HIF-1α, VEGF, and TFF3 in gastric cancer cells. We induced the hypoxic condition in SGC-7901cells using hypoxia-mimetic agent of CoCI2. SGC7901 cells were transfected with pcPUR + U6 plasmid carrying RNAi targeted to human TFF3 and selected puromycin-resistant pools to establish the stable knockdown of TFF3 cells. Our results showed the induction of HIF-1a via hypoxia and consequences of increased expressions of the TFF3 and VEGF in gastric cancer SGC-7901 cells. Overexpression of TFF3 upregulated the mRNA expressions of VEGF and HIF-1a induced by hypoxia, and stable knockdown of TFF3 impaired the mRNA upregulations of VEGF and HIF-1a induced by hypoxia. Furthermore, knockdown of TFF3 reduced the VEGF protein secretion: as VEGF secretion was increased time dependent manner in response to the hypoxia induction in TFF3-WT cells; however, VEGF production was significantly decreased in TFF3-KD cells (621 ± 89 vs. 264 ± 73 at 6 h and 969 ± 97 vs. 508 ± 69 at 12 h, P < 0.05). Our data demonstrated the TFF3 mediated regulation of VEGF expression induced by hypoxia, and implicated that TFF3 might be applied as a potential anti-angiogenic target for treatment of gastric cancer.

[Silk protein fiber biomaterials and tissue engineering].

OBJECTIVE: To summarize the latest developments in silk protein fiber as biomaterials and their applications in tissue engineering. METHODS: Recent original literature on silk protein fiber as biomaterials were reviewed, illustrating the properties of silk protein fiber biomaterials. RESULTS: The silk protein fiber has the same functions of supporting the cell adhesion, differentiation and growth as native collagen, and is renewed as novel biomaterials with good biocompatibility, unique mechanical properties and is degradable over a longer time. CONCLUSION: Silk protein fiber can be used as a suitable matrix for three dimensional cell culture in tissue engineering. It has a great potential applications in other fields.