Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.

Direct Amination of α-Triaryl Alcohols via Vanadium Catalysis.

α-Triaryl amines have been used as pharmaceuticals and pharmaceutical intermediates for antifungal and anticancer applications. Current methods to synthesize such compounds require at least two steps, and no direct amination of tertiary alcohols has been reported. Herein, we disclose efficient catalytic conditions for the direct amination of α-triaryl alcohols to access α-triaryl amines. VO(OiPr)3, a commercially available reagent, has been identified as an effective catalyst for the direct amination of several α-triaryl alcohols. This process is scalable, as demonstrated by a gram-scale synthesis, and the reaction still works at as low as a 0.01 mol % catalyst loading with the turnover number reaching 3900. Moreover, commercial pharmaceuticals including clotrimazole and flutrimazole have been successfully prepared rapidly and efficiently using this newly developed method.

Quantitative evaluation of dissociated optic nerve fibre layer (DONFL) following idiopathic macular hole surgery.

OBJECTIVES: To quantitatively evaluate concentric macular dark spots (CMDS) on spectral-domain optical coherence tomography (SD-OCT) to determine the morphological characteristics of dissociated optic nerve fibre layer (DONFL) following the performance of internal limiting membrane (ILM) peeling in patients with full-thickness idiopathic macular hole (IMH) closure. METHODS: Retrospective study on patients who underwent a vitrectomy with ILM peeling procedure. BCVA, cross-sectional OCT scans, and three-dimensional reconstructions of en face OCT scans were analysed preoperatively, at 2, 6, 12 months post-operatively. A novel image analysis technique was used to automatically measure DONFL logical properties through the radius, area, the nerve fibre layer dissociation index (NFLDI), and depth of the CMDS. RESULTS: 53 eyes of 51 patients were included, and the mean follow-up was 11.53 ± 6.26 months. CMDS was found in 46 (86.79%) eyes within 2 months after ILM peeling and 50 (94.34%) eyes within 6 months after ILM peeling. CMDS concentrated on the temporal side of the macula in all 50 eyes (100%) at first detection. The area, NFLDI, and depth of CMDS in four quadrants developed significantly during the postoperative 6 months (p < 0.05), and then these changes slowed down and remained unchanged 12 months post-operatively. The morphological changes in the temporal quadrant were significantly greater than those in other quadrants at 2, 6, 12 months (all p < 0.05) post-operatively. CONCLUSIONS: CMDS mostly appeared and concentrated on the temporal side of the macula in IMHs within two months after ILM peeling and progressed within 6 months and remained unchanged after 12 months.

Study on the Application Value of Concurrent Chemoradiotherapy and Clinical Nursing Pathway for Postoperative Patients with Esophageal Cancer.

Backgrounds: To observe the value of concurrent chemoradiotherapy and clinical nursing pathway for postoperative patients with esophageal cancer (EC). Methods: A total of 88 postoperative EC patients were divided into the radiotherapy group (RG group, 44 cases) and the chemoradiotherapy group (CRG group, 44 cases). The RG group received single three-dimensional conformal radiotherapy+clinical nursing pathway, and the CRG group was combined with chemotherapy on this basis. The 5-year overall survival rate, progression-free survival rate, pathological remission and survival rate, lymph node metastasis and survival rate, quality of life analysis, tumor-related factor level, and incidence of adverse reactions were compared between the two groups. Results: The overall survival rates at 1, 3, and 5 years were 93.18%, 56.82%, and 50.0% in the CRG group and 86.36%, 52.27%, and 43.18% in the RG group, respectively. The 5-year progression-free survival rate of the CRG group was 60.87%, which was clearly higher than that of the RG group (33.33%). The 1-, 3-, and 5-year overall survival rates of pCR and NpCR patients were 90.48%, 80.95%, and 61.90% and 89.55%, 44.78%, and 38.81%, respectively. The overall 1-year, 3-year, and 5-year survival rates were 81.08%, 37.84, and 24.32% and 96.08%, 66.67%, and 62.75% in patients with lymph node metastasis and nonlymph node metastasis, respectively, with statistical significant differences. The emotional function, physical function, cough, pain, and eating difficulty in the CRG group were better than those in the RG group. After treatment, serum CEA, SCC, CYFRA21-1, and CA199 levels in the CRG group were obviously downregulated compared with those in the RG group. There was no obvious difference in the incidence of adverse reactions between the CRG group and the RG group. Conclusion: Single radiotherapy and concurrent chemoradiotherapy can be used as effective means in the treatment of EC. Moreover, the quality of life and survival time of the concurrent chemoradiotherapy group were dramatically better than those of the single radiotherapy group, and the antitumor ability of the concurrent chemoradiotherapy group was stronger.

INTERNAL LIMITING MEMBRANE PEELING DISTORTS THE RETINAL LAYERS AND INDUCES SCOTOMA FORMATION IN THE PERIFOVEAL TEMPORAL MACULA.

PURPOSE: To determine whether internal limiting membrane peeling damages retinal function in patients with an idiopathic macular hole. METHODS: Retrospective case series. Forty-five eyes of 45 idiopathic macular hole patients who underwent vitrectomy with internal limiting membrane peeling with a minimum follow-up of 6 months. Each patient received a complete ophthalmological examination. The eyes were examined by microperimetry MP-3 in the central 20° visual field and optical coherence tomography angiography in the central 6 × 6 mm area. RESULTS: Six months after the surgery, macular hole closed in each patient. Retinal sensitivity decreased significantly in the perifoveal temporal ETDRS sector (from 24.97 ± 2.67-19.98 ± 5.68 dB, P = 0.001) but not in the other sectors. Six patients (13%) developed 24 scotomas, 62.5% presented in the perifoveal temporal sector. Anatomically, bumps in the outer nuclear layer were discovered concurrent with inner retinal dimples on B-scan images, predominantly (76.8%) in the perifoveal temporal sector, which have not been previously reported. The incidence of outer nuclear layer bumps was significantly higher in patients with scotomas than in those without (83% vs. 18%, P = 0.014). CONCLUSION: Internal limiting membrane peeling induced functional changes specifically in the perifoveal temporal macula. Distortion in the retinal layers is proposed to underly scotomas pathogenesis.

Sirt1 Mediates Vitamin D Deficiency-Driven Gluconeogenesis in the Liver via mTorc2/Akt Signaling.

As an active form of vitamin D (VD), 1,25-dihydroxyvitamin D (1,25(OH)2D3) is involved in the development of many metabolic diseases, such as diabetes, autoimmune diseases, and tumours. While prospective epidemiological studies have consistently implicated VD deficiency in the regulation of glucose metabolism and insulin sensitivity, the specific mechanism remains unclear. Here, we generated 1α(OH)ase-null mice (targeted ablation of the 25-hydroxyvitamin D 1α hydroxylase enzyme) and found that these mice developed hepatic glucose overproduction, glucose intolerance, and hepatic insulin resistance accompanied by reduced Sirtuin 1 (Sirt1) expression. The chromatin immunoprecipitation (ChIP) and a luciferase reporter assay revealed that 1,25(OH)2D3-activated VD receptor (VDR) directly interacted with one VD response element (VDRE) in the Sirt1 promoter to upregulate Sirt1 transcription, triggering a cascade of serine/threonine kinase (AKT) phosphorylation at S473 and FOXO1 phosphorylation at S256. This phosphorylation cascade reduced the expression of gluconeogenic genes, eventually attenuating glucose overproduction in the liver. In addition, a signaling pathway was found to modulate gluconeogenesis involving VDR, Sirt1, Rictor (a component of mTOR complex 2 [mTorc2]), AKT, and FOXO1, and Sirt1 and FOXO1 were identified as key modulators of dysregulated gluconeogenesis due to VD deficiency.

Robust Microcapsules with Durable Superhydrophobicity and Superoleophilicity for Efficient Oil-Water Separation.

The poor ultraviolet (UV) resistance and insufficient solvent compatibility are challenges for long-term storage and service of oil-water separation materials in practical applications. Herein, a superhydrophobic/superoleophilic surface with nano- to microscale hierarchical structures was formed spontaneously on robust microcapsules (MCs) via in situ polymerization and a sol-gel surface treatment. The resultant MCs possessed superior UV-resistant and solvent-proof superhydrophobicity. The water contact angles (WCAs) of the MC coating remained above 160° and the sliding angles (SAs) were below 3° after 9 days of UV aging test or 20 days of nonpolar and polar aprotic solvent immersion tests. More interestingly, these MCs can be used to separate the oil phase from its aqueous emulsion effectively, achieving a high and reusable separation efficiency with over 90% oil purity after 10 cycles of filtrations even after 13 days of UV aging. Therefore, these novel MCs will exhibit effective oil-water separation performance, superior chemical stability, outstanding reusability, and long-term storage stability for promising practical applications.

KIT ligand protects against both light-induced and genetic photoreceptor degeneration.

Photoreceptor degeneration is a major cause of blindness and a considerable health burden during aging but effective therapeutic or preventive strategies have not so far become readily available. Here, we show in mouse models that signaling through the tyrosine kinase receptor KIT protects photoreceptor cells against both light-induced and inherited retinal degeneration. Upon light damage, photoreceptor cells upregulate Kit ligand (KITL) and activate KIT signaling, which in turn induces nuclear accumulation of the transcription factor NRF2 and stimulates the expression of the antioxidant gene Hmox1. Conversely, a viable Kit mutation promotes light-induced photoreceptor damage, which is reversed by experimental expression of Hmox1. Furthermore, overexpression of KITL from a viral AAV8 vector prevents photoreceptor cell death and partially restores retinal function after light damage or in genetic models of human retinitis pigmentosa. Hence, application of KITL may provide a novel therapeutic avenue for prevention or treatment of retinal degenerative diseases.

Effect of Thiodiphenol-Based Epoxy Resin on the Thermal Properties of an Aluminum Oxide Composite.

The effects of thiodiphenol based epoxy resin on the thermal property of the composites containing aluminum oxide were investigated. The thermal conductivities and thermal diffusivities of the composites were dependent on the polymer resin. At the same content of Al2O3, the thermal conductivity and thermal diffusivity of composites made by synthesized polymer resin exhibited higher than that of composite made by bisphenol-A resin. The obtained maximum thermal conductivity of the composite was 0.25 W/mK, which was 0.4 times as large as that of the conventional bisphenol-A epoxy resin which has an amorphous structure. It is supposed that the reason for the high heat conductivity obtained in thiodiphenol based epoxy resin is certain high packing structure.

Cause and Effect Relationship between Changes in Scleral Matrix Metallopeptidase-2 Expression and Myopia Development in Mice.

Myopia is a serious sight-compromising condition in which decreases in scleral biomechanical strength are associated with protease up-regulation resulting in thinning of its collagenous framework and changes in the extracellular matrix composition. Matrix metallopeptidase (MMP)-2 is one of the known proteases mediating these alterations. To determine whether MMP-2 up-regulation precedes myopia development, the direct effects of gain and loss in Mmp2 gene function were evaluated on refractive development and form deprivation myopia in mice. Four weeks after injecting an adeno-associated virus serotype 8 packaged Mmp2 overexpression vector (AAV8-Mmp2), scleral MMP-2 up-regulation was accompanied by significant myopia in a normal visual environment. In contrast, AAV8 packaging with shRNA targeting Mmp2 inhibited rises in MMP-2 expression induced by form deprivation by 54% and reduced myopia development by 23% compared with eyes injected with an irrelevant scrambled sequence. Because opposing changes in MMP-2 protein expression levels had corresponding effects on myopia progression, up-regulation of this protease contributes to inducing this condition. This notion of a cause-and-effect relationship between MMP-2 up-regulation and myopia development is supported by showing that form-deprived myopia development was attenuated by 27% in fibroblast-specific Mmp2 deletion (S100a4creMmp2fl/fl) mice relative to Cre-negative littermates (Mmp2fl/fl). Therefore, MMP-2 is a potential drug target for inhibiting myopia progression.

Fabrication and Release Behavior of Microcapsules with Double-Layered Shell Containing Clove Oil for Antibacterial Applications.

In this study, double-layer polyurethane/poly(urea-formaldehyde) (PU/PUF) shell microcapsules containing clove oil with antibacterial properties were successfully synthesized via in situ and interfacial polymerization reactions in an oil-in-water emulsion. The morphology, core-shell structure, and composition of the microcapsules were investigated systematically. Additionally, the release behaviors of microcapsules synthesized under different reaction parameters were studied. It was found that the release rate of clove oil can be controlled by tuning the amount of PU reactants and the length of PUF deposition time. The release profile fitted well against the Baker-Lonsdale model, which indicates diffusion as the primary release mechanism. Experimental results based on the ASTM E2315 time kill test revealed that the fabricated microcapsules have great antibacterial activities against the marine bacteria Vibrio coralliilyticus, Escherichia coli, Exiguobacterium aestuarii, and marine biofilm-forming bacteria isolated from the on-site contaminated samples, showing their great potential as an eco-friendly solution to replace existing toxic antifouling agent.

Resveratrol inhibits oral squamous cell carcinoma through induction of apoptosis and G2/M phase cell cycle arrest.

The present study was performed to investigate the effect of resveratrol (trans-3,4',5-trihydroxystilbene) present as a natural phytoalexin in grapes, peanuts, and red wine on oral squamous cancer cell lines, SCC-VII, SCC-25, and YD-38. MTS assay and flow cytometry, respectively, were used for the analysis of inhibition of cell proliferation and apoptosis. Western blot analysis was performed to examine the effect of resveratrol on the expression of proteins associated with cell cycle regulation. The results revealed a concentration- and time-dependent inhibition of proliferation in all the three tested cell lines on treatment with resveratrol. The IC50 of resveratrol for SCC-VII, SCC-25, and YD-38 cell lines was found to be 0.5, 0.7, and 1.0 µg/ml, respectively, after 48-h treatment. Examination of the cell cycle analysis showed that resveratrol treatment induced cell cycle arrest in the G2/M phase and enhanced the expression of phospho-cdc2 (Tyr 15), cyclin A2, and cyclin B1 in the oral squamous cell carcinoma (OSCC) cells. It also caused a marked increase in the percentage of apoptotic cells as revealed by the fluorescence-activated cell sorting analysis. Thus, resveratrol exhibits inhibitory effect on the proliferation of OSCC oral cancer cells through the induction of apoptosis and G2/M phase cell cycle arrest.

Impact of MDM2 single nucleotide polymorphism on oral squamous cell carcinoma risk.

Mouse Double Minute 2 (MDM2) has emerged as a pivotal cellular antagonist of p53 by destructing the suppressive function of p53 against tumorigenesis. The MDM2 309 T > G polymorphism has been studied for its association with oral squamous cell carcinoma (OSCC) susceptibility, but the evidence was confusing and inconclusive. Here, we performed a meta-analysis to estimate the effects of the 309 T > G polymorphism on the development of OSCC. The relevant studies were searched on both PubMed and Embase. We estimated the risk of OSCC using odds ratio (OR) and 95 % confidence interval (CI). In addition, between-study heterogeneity was measured by the χ (2)-based statistic test; sensitivity analysis, and the funnel plots and Egger's test were also performed in this meta-analysis. Based on five case-control studies with a total of 1,369 OSCC cases and 2,167 control subjects, the meta-analysis result showed neither increased nor decreased risk of OSCC associated with any genetic model of the 309 T > G polymorphism. Similar results were observed in the subgroup of Asians. No significant heterogeneity and publication bias were detected in the meta-analysis. The evidence provided in our study indicated that the 309 T > G polymorphism might have no significant contribution to susceptibility toward OSCC.

Platelet-like nickel hydroxide: synthesis and the transferring to nickel oxide as a gas sensor.

Free-standing Ni(OH)2 platelet-like nanostructures with average width of 124 nm and thickness of 19 nm were successfully prepared through a simple one-pot polymer assisted process. The preparation involves the assistance of poly (sodium-4-styrene sulfonate) (PSS) and is easy to perform. The influence of pH value on the structure of the Ni(OH)2 product was investigated and it was found that pH value plays an important role for the formation of free-standing Ni(OH)2 nanoplatelets. A possible formation mechanism is proposed. In addition, from the obtained Ni(OH)2 nanoplatelets, a NiO sensor was fabricated and tested, which exhibits a 5 ppm sensing sensitivity to ethanol and propanol.