A Dual-Responsive Liquid Crystal Elastomer for Multi-Level Encryption and Transient Information Display.

Information security has gained increasing attention in the past decade, leading to the development of advanced materials for anti-counterfeiting, encryption and instantaneous information display. However, it remains challenging to achieve high information security with simple encryption procedures and low-energy stimuli. Herein, a series of strain/temperature-responsive liquid crystal elastomers (LCEs) are developed to achieve dual-modal, multi-level information encryption and real-time, rewritable transient information display. The as-prepared polydomain LCEs can change from an opaque state to a transparent state under strain or temperature stimuli, with the transition strains or temperatures highly dependent on the concentration of long-chain flexible spacers. Information encrypted by different LCE inks can be decrypted under specific strains or temperatures, leading to multi-level protection of information security. Furthermore, with the combination of the phase transition of polydomain LCEs and the photothermal effect of multi-walled carbon nanotubes (MWCNTs), we achieved a repeatable transient information display by using near-infrared (NIR) light as a pen for writing. This study provides new insight into the development of advanced encryption materials with versatility and high security for broad applications.

Mussel-Inspired Two-Dimensional Halide Perovskite Facilitated Dopamine Polymerization and Self-Adhesive Photoelectric Coating.

Polydopamine (PDA) is a good adhesion agent for lots of gels inspired by the mussel, whereas hybrid organic-inorganic perovskites (HOIPs) usually exhibit extraordinary optoelectronic performance. Herein, mussel-inspired chemistry has been integrated with two-dimensional HOIPs first, leading to the preparation of new crystal (HDA)2PbBr4 (1) (DA = dopamine). The organic cation dopamine can be introduced into PDA resulting in a thin film of (HPDA)2PbBr4 (PDA-1). The dissolved inorganic components of layered perovskite in DMF solution together with H2O2 addition can facilitate DA polymerization greatly. More importantly, PDA-1 can inherit an excellent semiconductor property of HOIPs and robust adhesion of the PDA hydrogel resulting in a self-adhesive photoelectric coating on various interfaces.

A variable-stiffness and healable pneumatic actuator.

Pneumatic-powered actuators are receiving increasing attention due to their widespread applications. However, their inherent low stiffness makes them incompetent in tasks requiring high load capacity or high force output. On the other hand, soft pneumatic actuators are susceptible to damage caused by over-pressuring or punctures by sharp objects. In this work, we designed and synthesized a coordination adaptable network (PETMP-AIM-Cu) with high mechanical rigidity (Young's modulus of 1.9 GPa and elongation <2% before fracturing) as well as excellent variable stiffness property (soft-rigid switching ability σ as high as 3 268 000 when ΔT = 90 °C). Combining PETMP-AIM-Cu with a self-healing elastomer based on dynamic disulfide bonds (LP-PDMS), we fabricated a new pneumatic actuator which shows high load capacity at room temperature, but can also easily deform upon heating and thus can be actuated pneumatically. Benefiting from the excellent self-healing ability of PETMP-AIM-Cu and LP-PDMS, the entire pneumatic actuator can still be actuated after being cut and healed. Such a variable-stiffness and healable pneumatic actuator would be useful for complex environmental applications.

Toxoplasma gondii infection triggers ongoing inflammation mediated by increased intracellular Cl- concentration in airway epithelium.

Toxoplasma gondii is a widespread parasitic protozoan causing toxoplasmosis including pulmonary toxoplasmosis. As the first line of host defense, airway epithelial cells play critical roles in orchestrating pulmonary innate immunity. However, the mechanism underlying the airway inflammation induced by the T. gondii infection remains largely unclear. This study demonstrated that after infection with T. gondii, the major anion channel located in the apical membranes of airway epithelial cells, cystic fibrosis transmembrane conductance regulator (CFTR), was degraded by the parasite-secreted cysteine proteases. The intracellular Cl- concentration ([Cl-]i) was consequently elevated, leading to activation of nuclear factor-κB (NF-κB) signaling via serum/glucocorticoid regulated kinase 1. Furthermore, the heightened [Cl-]i and activated NF-κB signaling could be sustained in a positive feedback regulatory manner resulting from decreased intracellular cAMP level through NF-κB-mediated up-regulation of phosphodiesterase 4. Conversely, the sulfur-containing compound allicin conferred anti-inflammatory effects on pulmonary toxoplasmosis by decreasing [Cl-]i via activation of CFTR. These results suggest that the intracellular Cl- dynamically modulated by T. gondii mediates sustained airway inflammation, which provides a potential therapeutic target against pulmonary toxoplasmosis.

Allicin Facilitates Airway Surface Liquid Hydration by Activation of CFTR.

Airway epithelium plays critical roles in regulating airway surface liquid (ASL), the alteration of which causes mucus stasis symptoms. Allicin is a compound released from garlic and harbors the capacity of lung-protection. However, the potential regulatory effects of allicin on airway epithelium remain elusive. This study aimed to investigate the effects of allicin on ion transport across airway epithelium and evaluate its potential as an expectorant. Application of allicin induced Cl- secretion across airway epithelium in a concentration-dependent manner. Blockade of cystic fibrosis transmembrane conductance regulator (CFTR) or inhibition of adenylate cyclase-cAMP signaling pathway attenuated allicin-induced Cl- secretion in airway epithelial cells. The in vivo study showed that inhaled allicin significantly increased the ASL secretion in mice. These results suggest that allicin induces Cl- and fluid secretion across airway epithelium via activation of CFTR, which might provide therapeutic strategies for the treatment of chronic pulmonary diseases associated with ASL dehydration.

SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl- accumulation in respiratory epithelium.

SARS-CoV-2, the culprit pathogen of COVID-19, elicits prominent immune responses and cytokine storms. Intracellular Cl- is a crucial regulator of host defense, whereas the role of Cl- signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains unclear. By using human respiratory epithelial cell lines, primary cultured human airway epithelial cells, and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge, we demonstrated that SARS-CoV-2 nucleocapsid (N) protein could interact with Smad3, which downregulated cystic fibrosis transmembrane conductance regulator (CFTR) expression via microRNA-145. The intracellular Cl- concentration ([Cl-]i) was raised, resulting in phosphorylation of serum glucocorticoid regulated kinase 1 (SGK1) and robust inflammatory responses. Inhibition or knockout of SGK1 abrogated the N protein-elicited airway inflammation. Moreover, N protein promoted a sustained elevation of [Cl-]i by depleting intracellular cAMP via upregulation of phosphodiesterase 4 (PDE4). Rolipram, a selective PDE4 inhibitor, countered airway inflammation by reducing [Cl-]i. Our findings suggested that Cl- acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 infection. Targeting the Cl- signaling pathway might be a novel therapeutic strategy for COVID-19.

G protein-coupled estrogen receptor promotes acrosome reaction via regulation of Ca2+ signaling in mouse sperm†.

G protein-coupled estrogen receptor (GPER), a seven-transmembrane G protein-coupled receptor, mediates the rapid pre-genomic signaling actions of estrogen and derivatives thereof. The expression of GPER is extensive in mammal male reproductive system. However, the functional role of GPER in mouse sperm has not yet been well recognized. This study revealed that GPER was expressed at the acrosome and the mid-flagellum of the mouse sperm. The endogenous GPER ligand 17ß-estradiol and the selective GPER agonist G1 increased intracellular Ca2+ concentration ([Ca2+]i) in mouse sperm, which could be abolished by G15, an antagonist of GPER. In addition, the G1-stimulated Ca2+ response was attenuated by interference with the phospholipase C (PLC) signaling pathways or by blocking the cation channel of sperm (CatSper). Chlortetracycline staining assay showed that the activation of GPER increased the incidence of acrosome-reacted sperm. Conclusively, GPER was located at the acrosome and mid-flagellum of the mouse sperm. Activation of GPER triggered the elevation of [Ca2+]i through PLC-dependent Ca2+ mobilization and CatSper-mediated Ca2+ influx, which promoted the acrosome reaction of mouse sperm.

Genetic, environmental and other risk factors for progression of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a commonly inherited disease of the retina, which is characterized by progressive loss of visual function due to specific genetic mutations. There are many risk factors that may have effect on the progression of RP, such as inheritance patterns, genotype, gender, age, smoking, physical activity, and other demographic and environmental factors. Baseline visual field conditions, changes of ellipsoid zone, photoreceptor layer thickness, and choroidal structure are reported to be the phenotype risk factors for RP progression. Moreover, aqueous flare and high-sensitivity C-reactive protein are probable inflammation biomarkers for assessing the progression of RP. Increased oxidative stress is considered to be one of the potential factors for the existence of RP. The risk factors can be combined to form a corresponding prediction model to predict disease progression. This review is to summarize the current literature that studies the genetic, environmental, phenotypic, demographic, inflammatory and other risk factors of RP progression and discuss the most reliable risk factors that could provide predictive models.

Activation of TRPV4 stimulates transepithelial K+ secretion in rat epididymal epithelium.

The maturation of sperms is dependent on the coordinated interactions between sperm and the unique epididymal luminal milieu, which is characterized by high K+ content. This study investigated the involvement of transient receptor potential vanilloid 4 (TRPV4) in the K+ secretion of epididymal epithelium. The expression level and cellular localization of TRPV4 and Ca2+-activated K+ channels (KCa) were analyzed via RT-PCR, real-time quantitative PCR, western blot and immunofluorescence. The functional role of TRPV4 was investigated using short-circuit current (ISC) and intracellular Ca2+ imaging techniques. We found a predominant expression of TRPV4 in the corpus and cauda epididymal epithelium. Activation of TRPV4 with a selective agonist, GSK1016790A, stimulated a transient decrease in the ISC of the epididymal epithelium. The ISC response was abolished by either the TRPV4 antagonists, HC067047 and RN-1734, or the removal of basolateral K+. Simultaneously, the application of GSK1016790A triggered Ca2+ influx in epididymal epithelial cells. Our data also indicated that the big conductance KCa (BK), small conductance KCa (SK) and intermediate conductance KCa (IK) were all expressed in rat epididymis. Pharmacological studies revealed that BK, but not SK and IK, mediated TRPV4-elicited transepithelial K+ secretion. Finally, we demonstrated that TRPV4 and BK were localized in the epididymal epithelium, which showed an increased expression level from caput to cauda regions of rat epididymis. This study implicates that TRPV4 plays an important role in the formation of high K+ concentration in epididymal intraluminal fluid via promoting transepithelial K+ secretion mediated by BK.

Interaction between CD9 and PI3K­p85 activates the PI3K/AKT signaling pathway in B­lineage acute lymphoblastic leukemia.

Our previous study has shown that CD9 knockdown could suppress cell proliferation, adhesion, migration and invasion, and promote apoptosis and the cytotoxicity of chemotherapeutic drugs in the B­lineage acute lymphoblastic leukemia (B­ALL) cell line SUP­B15. In this study, we further investigated the molecular mechanism underlying the effects of CD9 on leukemic cell progression and the efficacy of chemotherapeutic agents in B­ALL cells. Using the CD9­knockdown SUP­B15 cells, we demonstrated that the silencing of the CD9 gene significantly reduced the expression of phosphorylated­phosphatidylinositol­3 kinase (p­PI3K), phosphorylated­protein kinase B (p­AKT), P­glycoprotein (P­gp), multidrug resistance­associated protein 1 (MRP1), breast cancer resistance protein (BCRP), matrix metalloproteinase 2 (MMP2) and phosphorylated­focal adhesion kinase (p­FAK). In addition, glutathione S­transferase (GST) pull­down assay showed the binding between CD9 and both PI3K­p85α and PI3K­p85ß in vitro, while co­immunoprecipitation assay showed the binding between CD9 and both PI3K­p85α and PI3K­p85ß in vivo. Furthermore, the PI3K/AKT inhibitor LY294002 mirrored the effects of CD9 knockdown in SUP­B15 cells. Taken together, these findings demonstrated that CD9 activates the PI3K/AKT signaling pathway through direct interaction with PI3K­p85 in B­ALL cells. Our data provide evidence for the inhibition of the PI3K/AKT pathway as a novel therapeutic option in CD9 antigen­positive B­ALL.

Normal Absolute Monocyte Count at the Time of Relapse is Associated with Improved Survival After First Salvage Therapy in Adult Patients with Early Relapsed B-Lineage Acute Lymphoblastic Leukemia.

BACKGROUND: Peripheral monocytes, a key cell type for innate immunity, have been shown to be associated with survival in various types of hematological malignancies. However, no previous studies regarding the prognostic impact of peripheral absolute monocyte count (AMC) in early relapsed B-lineage acute lymphoblastic leukemia (B-ALL) have been reported. METHODS: Forty-nine cases of early relapsed adult B-ALL were reviewed. The upper (0.80 × 109/L) and lower limits (0.12 × 109/L) of the normal value for AMC were used as cut-off points. Kaplan-Meier curves and Log rank test were used for comparison of overall survival (OS). The univariate and multivariate Cox proportional hazards models were used for investigating the factors associated with OS. RESULTS: More than half (59.2%) of all patients showed a normal AMC (0.12-0.80 × 109/L). The median follow-up was 5.3 months from the start of first salvage therapy. Univariate analysis revealed that normal AMC (versus low/high AMC) at the time of relapse was a prognostic factor for improved OS (P = 0.021). On multivariate analysis, normal AMC (versus low/high AMC) at the time of relapse remained an independent prognostic factor for improved OS (hazard ratio = 0.43, P = 0.030). CONCLUSION: AMC at the time of relapse, which can be easily derived from routine clinical laboratory testing of complete blood count, might be used as a prognostic marker for survival outcomes in adult patients with early relapsed B-ALL.

Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: Continuous positive airway pressure (CPAP) therapy may decrease the risk of mortality and cardiovascular events in patients with obstructive sleep apnea. However, these benefits are not completely clear. METHODS: We undertook a meta-analysis of randomized clinical trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. RESULTS: Eighteen studies (4146 patients) were included. Overall, CPAP therapy did not significantly decrease the risk of cardiovascular events compared with the control group (odds ratio (OR), 0.84; 95 % confidence intervals (CI), 0.62-1.13; p = 0.25; I (2) = 0 %). CPAP was associated with a nonsignificant trend of lower rate of death and stroke (for death: OR, 0.85; 95 % CI, 0.35-2.06; p = 0.72; I (2) = 0.0 %; for stroke: OR, 0.56; 95 % CI, 0.18-1.73; p = 0.32; I (2) = 12.0 %), a significantly lower Epworth sleepiness score (ESS) (mean difference (MD), -1.78; 95 % CI, -2.31 to -1.24; p < 0.00001; I (2) = 76 %), and a significantly lower 24 h systolic and diastolic blood pressure (BP) (for 24 h systolic BP: MD, -2.03 mmHg; 95 % CI, -3.64 to -0.42; p = 0.01; I (2) = 0 %; for diastolic BP: MD, -1.79 mmHg; 95 % CI, -2.89 to -0.68; p = 0.001; I (2) = 0 %). Daytime systolic BP and body mass index were comparable between the CPAP and control groups. Subgroup analysis did not show any significant difference between short- and mediate-to-long-term follow-up groups with regard to cardiovascular events, death, and stroke. CONCLUSIONS: CPAP therapy was associated with a trend of decreased risk of cardiovascular events. Furthermore, ESS and BP were significantly lower in the CPAP group. Larger randomized studies are needed to confirm these findings.

Transcription factors WRKY70 and WRKY11 served as regulators in rhizobacterium Bacillus cereus AR156-induced systemic resistance to Pseudomonas syringae pv. tomato DC3000 in Arabidopsis.

The activation of both the SA and JA/ETsignalling pathways may lead to more efficient general and broad resistance to Pst DC3000 by non-pathogenic rhizobacteria. However, the mechanisms that govern this simultaneous activation are unclear. Using Arabidopsis as a model system, two transcription factors, WRKY11 and WRKY70, were identified as important regulators involved in Induced Systemic Resistance (ISR) triggered by Bacillus cereus AR156. The results revealed that AR156 treatment significantly stimulated the transcription of WRKY70, but suppressed that of WRKY11 in Arabidopsis leaves. Furthermore, they were shown to be required for AR156 enhancing the activation of cellular defence responses and the transcription level of the plant defence response gene. Overexpression of the two transcription factors in Arabidopsis also showed that they were essential for AR156 to elicit ISR. AR156-triggered ISR was completely abolished in the double mutant of the two transcription factors, but still partially retained in the single mutants, indicating that the regulation of the two transcription factors depend on two different pathways. The target genes of the two transcription factors and epistasis analysis suggested that WRKY11 regulated AR156-triggered ISR through activating the JA signalling pathway, and WRKY70 regulated the ISR through activating the SA signalling pathway. In addition, both WRKY11 and WRKY70 modulated AR156-triggered ISR in a NPR1-dependent manner. In conclusion, WRKY11 and WRKY70 played an important role in regulating the signalling transduction pathways involved in AR156-triggered ISR. This study is the first to illustrate the mechanism by which a single rhizobacterium elicits ISR by simultaneously activating both the SA and JA/ET signalling pathways.

TGF-ß1 and TIMP-4 regulate atrial fibrosis in atrial fibrillation secondary to rheumatic heart disease.

To investigate the involvement of transforming growth factor-ß1 (TGF-ß1) and tissue inhibitor of metalloproteinase 4 (TIMP-4) in influencing the severity of atrial fibrosis in rheumatic heart disease (RHD) patients with atrial fibrillation (AF). The degree of myocardial fibrosis was evaluated using Masson staining. The expression levels of TGF-ß1, TIMP-4, matrix metalloproteinase-2 (MMP-2), type I collagen, and type III collagen were estimated by Western blot analysis. Additionally, TGF-ß1 and TIMP-4 mRNA levels were quantified by qRT-PCR. The effect of TGF-ß1 stimulation on TIMP-4 expression was assessed by in vitro stimulation of freshly isolated human atrial fibroblasts with recombinant human TGF-ß1, followed by Western blot analysis to detect changes in TIMP-4 levels. Masson stain revealed that the left atrial diameter and collagen volume fraction were obviously increased in AF patients, compared to sinus rhythm (SR) controls (both P < 0.05). Western blot analysis showed significantly elevated levels of the AF markers MMP-2, type I collagen, and type III collagen in the AF group, in comparison to the SR controls (all P < 0.05). In the AF group, TGF-ß1 expression was relatively higher, while TIMP-4 expression was apparently lower than the SR group (all P < 0.05). TIMP-4 expression level showed a negative association with TGF-ß1 expression level (r = -0.98, P < 0.01) and TGF-ß1 stimulation of atrial fibroblasts led to a sharp decrease in TIMP-4 protein level. Increased TGF-ß1 expression and decreased TIMP-4 expression correlated with atrial fibrosis and ECM changes in the atria of RHD patients with AF. Notably, TGF-ß1 suppressed TIMP-4 expression, suggesting that selective TGF-ß1 inhibitors may be useful therapeutic agents.

[Study on UV-Vis absorption spectra and fluorescence emission spectra of sixteen tetra-substituted metallophthalocyanine complexes].

The UV-Visible absorption spectra and the fluorescence emission spectra of sixteen tetra-substituted metallo-phthalocyanine complexes {R4 PcM, where R = 2-[4-(2-sulfonic ethyl) piperazin-1-] ethoxyl (SPEO--), 2-(piperidin-1-yl) ethoxyl (PEO--); substitution position at alpha-position and beta-position of phthalocyanine ring; M = Zn(II), Ni(II), Co(II) and Cu(II)} were measured. The influence of different central ion, substituted group and its position, as well as different solvent on the Q-band of phthalocyanine complex in its UV-Vis absorption spectra was investigated. The influence of different central ion, substituted group and its position on the fluorescence emission spectra was discussed. Some properties of the UV-Vis absorption spectra such as the maximum absorption wavelength (lamdamax ) of Q-band and its molar extinction coefficient (epsilon), and those of the fluorescence emission spectra such as fluorescence quantum yield (phiF), fluorescence lifetime (r) and excited state energy (Es) were studied. The results showed that the lamdamax of Qband of all complexes were located at 681-718 nm, which had a distinct red shift in contrast with unsubstituted metallophthalocyanines (669-671 nm). All complexes of R4 PcM possessed a very high molar extinction coefficient up to 10(5) L x mol(-1) x cm(-1). And the UV-Vis absorption spectra and the fluorescence emission spectra of all complexes exhibited mirror shape concurrently. Two beta-substituted zinc phthalocyanine complexes with formula beta-(SPEO)4PcZn and beta-(PEO)4PcZn possessed very high molar extinction coefficient, fluorescence quantum yield and fluorescence lifetime specially. Therefore, it is hoped that these two would be developing to be new photosensitizers for photodynamic therapy (PDT)and photodynamic diagnosis (PDD).