MXene-Based Skin-Like Hydrogel Sensor and Machine Learning-Assisted Handwriting Recognition.

Conductive hydrogels are widely used in flexible sensors owing to their adjustable structure, good conductivity, and flexibility. The performance of excellent mechanical properties, high sensitivity, and elastic modulus compatible with human tissues is of great interest in the field of flexible sensors. In this paper, the functional groups of trisodium citrate dihydrate (SC) and MXene form multiple hydrogen bonds in the polymer network to prepare a hydrogel with mechanical properties (Young's modulus (23.5-92 kPa) of similar human tissue (0-100 kPa)), sensitivity (stretched GF is 4.41 and compressed S1 is 5.15 MPa-1), and durability (1000 cycles). The hydrogel is able to sensitively detect deformations caused by strain and stress and can be used in flexible sensors to detect human movement in real time such as fingers, wrists, and walking. In addition, the combination of matrix sensing and machine learning was successfully used for handwriting recognition with an accuracy of 0.9744. The combination of machine learning and flexible sensors shows great potential in areas such as healthcare, information security, and smart homes.

A gas-pressure-assisted ratiometric atomic flame assay for the point-of-care testing of tumor-cell-derived exosomes.

The multicolor-based point-of-care testing (POCT) of tumor cell-derived exosomes is of vital importance for understanding tumor growth and metastasis. Multicolor-based ratiometric signals most often rely on molecular optics, such as fluorescence resonance energy transfer (FRET)-dependent molecular fluorescence and localized surface plasmon resonance (LSPR)-related molecular colorimetry. However, finding acceptable FRET donor-acceptor fluorophore pairs and the kinetically slow color responses during size-related molecular colorimetry have greatly impeded POCT applications. Herein, an atomic flame was used to develop a visual sensing platform for the POCT of tumor-cell-derived exosomes. In comparison with common molecular optics, the atomic flame possessed the advantages of providing both a variety of ratiometric flame signals and fast response sensitivity. The integration of a gas-pressure-assisted flame reaction and dual-aptamer recognition guaranteed the sensitive and selective analysis of exosomes with a low limit of detection (LOD) of 7.6 × 102 particles per mL. Such a novel optical signal will inspire the development of more user-friendly POCT approaches.

MiR-330-3p functions as a tumor suppressor that regulates glioma cell proliferation and migration by targeting CELF1.

INTRODUCTION: Glioma is a common type of neoplasm that occurs in the central nervous system. miRNAs have been demonstrated to act as critical regulators of carcinogenesis and tumor progression in multiple cancers, but the molecular mechanism of miR-330-3p in glioma remained unclear. The purpose of the study was to explore the role of miR-330-3p in glioma cell reproduction and migration. MATERIAL AND METHODS: The expression levels of miR-330-3p and CELF1 in 27 glioma tissue specimens and human glioma cell lines were examined by qRT-PCR and western blot. The TargetScan database was used to predict the relationship between miR-330-3p and CELF1. Then the target relationship was verified using dual-luciferase reporter assay. The effects of miR-330-3p/CELF1 on glioma cell proliferation were evaluated by MTT and colony formation assay. Wound healing assay was employed to measure the migration ability of glioma cells. RESULTS: MiR-330-3p was found lowly expressed in glioma tissues and cells compared with adjacent tissues and normal astrocytes, while CELF1 expression was relatively high in the glioma tissues and cells. Dual-luciferase reporter assay confirmed that miR-330-3p could directly target CELF1. Furthermore, miR-330-3p could down-regulate the expression of CELF1, therefore suppressing glioma cell reproduction and migration. CONCLUSIONS: MiR-330-3p inhibited the propagation and migration of glioma cells by repressing CELF1 expression.

Diethylenetriamine directed the assembly of Co0.85Se nanosheets layer by layer on N-doped carbon nanosheets for high performance lithium ion batteries.

Co0.85Se nanosheets assembled layer by layer on N-doped carbon nanosheets (NC@Co0.85Se) are designed and fabricated through a facile solvothermal process. The hexamethylenetetramine as the solvent and complexing agent promotes the accumulation of Co0.85Se layer by layer. The long chain diethylenetriamine between the Co0.85Se nanosheets provides buffer space and nanochannels for accelerating the Li+ transportation. The N-doped carbon nansheets in NC@Co0.85Se provide effective conductive network during charge-discharge process. As an anode material for lithium-ion batteries, the NC@Co0.85Se nanocomposites deliver a high specific capacity of 636 mAh g-1 after 100 cycles at current density of 200 mA g-1, and 399 mAh g-1 for 500 cycles at high current density of 5000 mA g-1.

Metal-organic framework derived 3D graphene decorated NaTi2(PO4)3 for fast Na-ion storage.

NASCION-type materials featuring super ionic conductivity are of considerable interest for energy storage in sodium ion batteries. However, the issue of inherent poor electronic conductivity of these materials represents a fundamental limitation in their utilization as battery electrodes. Here, for the first time, we develop a facile strategy for the synthesis of NASICON-type NaTi2(PO4)3/reduced graphene oxide (NTP-rGO) Na-ion anode materials from three-dimensional (3D) metal-organic frameworks (MOFs). The selected MOF serves as an in situ etching template for the titanium resource, and importantly, endows the materials with structure-directing properties for the self-assembly of graphene oxide (GO) through a one-step solvothermal process. Through the subsequent carbonization, an rGO decorated NTP architecture is obtained, which offers fast electron transfer and improved Na+ ion accessibility to active sites. Benefiting from its unique structural merits, the NTP-rGO exhibits improved sodium storage properties in terms of high capacity, excellent rate performance and good cycling life. We believe that the findings of this work provide new opportunities to design high performance NASICON-type materials for energy storage.

Purifying the Phase of NaTi2(PO4)3 for Enhanced Na+ Storage Properties.

Sodium-ion batteries (SIBs) are increasingly on demand owning to their prospect as an inexpensive alternative to Li-ion batteries. However, designing electrode materials with satisfactory rate capacity performance requires high electron transport and Na+ conductivity, which is extremely challenging. Herein, we report a hexadecylamine (HDA)-mediated synthesis of NaTi2(PO4)3 (NTP) electrodes via one-step solvothermal process. The addition of HDA material (1) enables the formation of a carbon coating that improves the electron conductivity and (2) importantly serves as a structure-directing agent reducing the NTP-impurity phases in which the transport of Na+ ions are sluggish. As a result, the synthesized NTP anode delivers superior rate of capacity retention of 77.8% under the 100-fold increase in current densities. Moreover, outstanding specific capacity of 117.9 mAh g-1 at 0.5 C and capacity retention of 88.6% after 1500 cycles at 1 C can be obtained. The findings of this work provide new opportunity to design SIBs electrodes with superior electrical and ionic conductivity.

LncRNA UCA1 promotes renal cell carcinoma proliferation through epigenetically repressing p21 expression and negatively regulating miR-495.

Long non-coding RNAs have recently emerged as important regulators in the pathogenesis and progression of cancers. The long non-coding RNA urothelial carcinoma-associated 1 is reportedly upregulated and functions as an oncogene in some tumors. However, the role of urothelial carcinoma-associated 1 in renal cell carcinoma is not well elucidated so far. In this study, we found that urothelial carcinoma-associated 1 was overexpressed in renal cell carcinoma tissues compared with the adjacent normal tissues, and higher urothelial carcinoma-associated 1 expression levels were positively associated with advanced tumor stage and poor survival time in renal cell carcinoma patients. Further studies showed that knockdown of urothelial carcinoma-associated 1 suppressed renal cell carcinoma cell proliferation and S-phase cell number in vitro. Moreover, urothelial carcinoma-associated 1 was found to be associated with enhancer of zeste homolog 2, which suppressed p21 expression through histone methylation (H3K27me3) on p21 promoter. We also showed that knockdown of urothelial carcinoma-associated 1 increased the p21 protein expression through regulating enhancer of zeste homolog 2. In addition, bioinformatics analysis and dual-luciferase reporter assays confirmed that miR-495 was a target of urothelial carcinoma-associated 1 in renal cell carcinoma, and urothelial carcinoma-associated 1 promoted cell proliferation by negatively regulating miR-495. These findings illuminated that urothelial carcinoma-associated 1 promoted renal cell carcinoma progression through enhancer of zeste homolog 2 and interacted with miR-495. Overall, overexpression of urothelial carcinoma-associated 1 functions as an oncogene in renal cell carcinoma that may offer a novel therapeutic target for renal cell carcinoma patients.

Pin1 in cardiovascular dysfunction: A potential double-edge role.

BACKGROUNDS: Our lab focused on the structural and functional properties of Pin1, which is the only known cis-trans isomerase regulating pSer/pThr-Pro motifs in proteins and facilitates various signaling pathways. We are lucky enough to read the article, contributed by Costantino et al. in your esteemed journal, on the role of Pin1 in diabetes-induced vascular dysfunction. Pin1 regulates the production of nitric oxide (NO), which is a key physiological stimulator of blood vessels and promotes vascular relaxation responses significantly. However, the regulation of cardiovascular diseases by Pin1 is somewhat controversial. METHODS AND RESULTS: We compared the recent studies that support the down-regulation, as well as up-regulation, of NO production by Pin1 and tried to explore the underlying molecular mechanisms. We especially compared the different regulations of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) by Pin1, which is potentially the major reason leading to the controversial role of Pin1. Interestingly, the regulation of both eNOS and iNOS by Pin1 involves a double-edge effect, positively and negatively, contributing to paradoxical Pin1 functions in different animal models and cell lines. The extremely complex Pin1-regulated signaling networks might further exacerbate distinct cellular responses in vivo and influence NO production. CONCLUSIONS: Pin1 plays a dual role, both positive and negative, in regulating NO production and in mediating the pathogenesis of cardiovascular diseases. Pin1 functions may vary a lot under different circumstances. Future investigations should focus on eNOS as well as iNOS in order to increase authenticity and accuracy of results.

Expression of RKIP, E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma and their correlations.

To detect the expression of RKIP, E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma (ESCC) and study their correlations. Steptavidin-peroxidase (S-P) method was employed to detect the expressions of RKIP, E-cadherin and NF-kB p65 in ESCC tissues from 77 cases and paracancerous tissues from 77 cases. The correlations between their expressions and clinicopathological indices and between the expressions of these proteins themselves were analyzed. The expressions of RKIP and E-cadherin in ESCC tissues were obviously lower than those in the paracancerous tissues (P<0.01); the expressions in ESCC tissues from cases with lymph node metastasis were lower than those from cases without lymph node metastasis (P<0.01); the expression of RKIP was positively correlated with the expression of E-cadherin in ESCC tissues (P<0.01). The expression of NF-kB p65 in ESCC tissues was correlated with clinical staging, lymph node metastasis and tumor differentiation (P<0.01); the expression of RKIP was negatively correlated with the expression of NF-kB p65 in ESCC tissues (P<0.05). Downregulation or depletion of RKIP was related to the onset and progression of ESCC, and facilitated the invasion and metastasis of ESCC by downregulating E-cadherin and upregulating NF-kB p65.

Reduction behavior induced by HL010183, a metformin derivative against the growth of cutaneous squamous cell carcinoma.

Metformin is a biguanide widely prescribed as a first-line antidiabetic drug in type 2 diabetes mellitus patients. Animal and cellular studies support that metformin has a strong anti-proliferative effect on various cancers. Herein, we report that metformin derivative, HL010183 significantly inhibited human epidermoid A431 tumor xenograft growth in nu/nu mice, which in turn is associated with a significant reduction in proliferative biomarkers PCNA and cyclins D1/B1. Enhanced apoptotic cell death and an increase in Bax: Bcl2 ratio supported the tumor growth reduction. The mechanism of the drug effects appears to be dependent on the inhibition of nuclear factor kappa B (NFkB) and mTOR signaling pathways. Reduced enhancement of NFkB transcriptional target proteins, iNOS/COX-2 together with decreased phosphorylation of NFkB inhibitory protein IKBa were also observed. Further, AKT signaling activation was evaluated by the reduced phosphorylation at Ser473. In addition, a concomitant decrease in mTOR signaling pathway was also estimated from the reduced phosphorylation at mTOR regulatory proteins p70S6K and 4E-BP-1. Along with this, decreased phosphorylation of GSK3b, which is carried out by AKT kinases was also observed. Overall results suggested that HL010183 interrupt SCC growth via NFkB and mTOR signaling pathways.

Gremlin aggravates hyperglycemia-induced podocyte injury by a TGFß/smad dependent signaling pathway.

Gremlin is a bone morphogenic protein (BMP) antagonist and is elevated in diabetic kidney tissues. In the early course of diabetic nephropathy (DN), podocyte are injured. We studied the protein and gene expression of gremlin in mice podocytes cultured in hyperglycemia ambient. The role of gremlin on podocyte injury and the likely signaling pathways involved were determined. Expression of gremlin was visualized by confocal microscopy. Recombinant mouse gremlin and small interfering RNA (siRNA) targeting to gremlin1 identified the role played by gremlin on podocytes. Study of canonical (smad2/3) and non-canonical (p38MAPK and JNK1/2) transforming growth factor beta (TGFß)/smad mediated signaling revealed the putative signaling mechanisms involved. Smad2/3 siRNA and TGFß receptor inhibition (SB431542) were used to probe canonical TGFß/smad signaling in gremlin-induced podocyte injury. Apoptosis of podocytes was measured by TUNEL assay. Gremlin expression was enhanced in high glucose cultured mouse podocytes, and was localized predominantly in the cytoplasm and negligibly on the cell membrane. Not only expression of nephrin and synaptopodin were decreased on treatment with gremlin, but also synaptopodin rearrangement and nephrin relocalization were evident. Knockdown gremlin1 or smad2/3 by siRNA, and inhibition of TGFßR (SB431542) attenuated podocyte injury. Inhibition of canonical TGF-ß signal blocked the injury of gremlin on podocytes. In conclusion, gremlin was clearly elevated in high glucose cultured mouse podocytes, and likely employed endogenous canonical TGFß1/Smad signaling to induce podocyte injury. Knockdown gremlin1 by siRNA may be clinically useful in the attenuation of podocyte injury.

The highly efficient delivery of exogenous proteins into cells mediated by biodegradable chimaeric polymersomes.

Biodegradable chimaeric polymersomes based on asymmetric PEG-PCL-PDEA triblock copolymers were prepared and investigated for delivery of exogenous proteins into cells. PEG-PCL-PDEA copolymers with M(n)(PEG) = 5 kg/mol, M(n)(PCL) = 18.2 kg/mol, and short PDEA blocks ranging from 1.1, 2.7 to 4.1 kg/mol (denoted as copolymer 1, 2 and 3, respectively) were obtained by controlled reversible addition-fragmentation chain transfer (RAFT) polymerization. The direct hydration of copolymer thin films in MES buffer (pH 5.3) yielded uniform polymersomes with sizes of 130-175 nm. These polymersomes had close to neutral zeta potentials (-2 approximately +2.7 mV) at pH 7.4. The polymersomal structures were confirmed by confocal laser scanning microscopy (CLSM), transmission electron microscopy (TEM), and catalytic activity experiment on 3,3',3''-phosphinidyne(trisbenzenesulfonic acid)-loaded polymersomes. MTT assays showed that these polymersomes were non-toxic up to a concentration of 0.5mg/mL. These chimaeric polymersomes, in particular polymersome 2, showed remarkably high protein loading efficiencies and loading contents for bovine serum albumin (BSA), cytochrome C (CC), lysozyme (Lys), ovalbumin (OVA) and immunoglobulin G (IgG). The encapsulation of proteins did not significantly alter the polymersome size distributions and zeta potentials. The protein release studies showed that both BSA and CC were released in a controlled manner. Importantly, the released CC fully maintained its activity. Notably, CLSM studies showed that FITC-CC loaded polymersomes efficiently delivered and released proteins into the cytoplasm of RAW 264.7 cells. Moreover, these chimaeric polymersomes were able to simultaneously load and transport proteins and doxorubicin into the cytoplasm as well as the cell nucleus. We are convinced that these biodegradable chimaeric polymersomes have great potentials in protein therapy.