Spatiotemporal transcriptome atlas reveals the regional specification of the developing human brain.

Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6-23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.

Regulating the Electronic Structure of Metal-Organic Frameworks by Introducing Mn for Enhanced Oxygen Evolution Activity.

The construction of low-cost and highly efficient oxygen evolution electrocatalysts is paramount for clean and sustainable hydrogen energy. In recent years, metal-organic framework (MOF) OER electrocatalysts have attracted tremendous research attention. Herein, we report a simple and facile strategy to construct bimetallic MOFs (named CoMn0.01) for enhancing OER catalytic performance. Significantly, CoMn0.01 exhibited remarkable OER activity (255 mV at 10 mA cm-2) and a low Tafel slope of 66 mV dec-1, superior to those of commercial benchmark electrocatalysts (RuO2, 352 mV, 178 mV dec-1). Besides, the catalyst demonstrated outstanding longevity for 144 h at a current density of 100 mA cm -2. Mn doping can regulate the electronic structure of Co MOFs, which optimizes charge transfer capability and improves conductivity.

Metformin protects retinal pigment epithelium cells against H2O2-induced oxidative stress and inflammation via the Nrf2 signaling cascade.

PURPOSE: Dysfunctions of retinal pigment epithelium (RPE) attributed to oxidative stress and inflammation are implicated with age-related macular degeneration (AMD). A debate on the curative role of metformin in AMD has been raised, though several recent clinical studies support the lower odds by using metformin. This study aimed to determine whether metformin could exert cytoprotection against RPE oxidative damages and the potential mechanisms. METHODS: A cellular AMD model was established by treating ARPE-19 cells with hydrogen peroxide (H2O2) for 24 h. The reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and levels of pro-inflammatory cytokines were monitored under administrations with H2O2 with/without metformin. The expression and DNA-binding activity of transcription factor erythroid-related factor 2 (Nrf2) were determined by western blot, immunofluorescence, and electrophoretic mobility shift assay. Knockout of Nrf2 was conducted by CRISPR/Cas9 gene deletion system. RESULTS: Metformin pretreatment significantly improved the H2O2-induced low viability of ARPE-19 cells, reduced ROS production, and increased contents of antioxidative molecules. Concurrently, metformin also suppressed levels of pro-inflammatory cytokines caused by H2O2. The metformin-augmented nuclear translocation and DNA-binding activity of Nrf2 were further verified by the increased expression of its downstream targets. Genetic deletion of Nrf2 blocked the cytoprotective role of metformin. CONCLUSION: Metformin possesses antioxidative and anti-inflammatory properties in ARPE-19 cells by activating the Nrf2 signaling. It supports the potential use for the control and prevention of AMD.

An NTS-CeA projection modulates depression-like behaviors in a mouse model of chronic pain.

Depressive symptoms comorbid with chronic pain are a common health problem, but the underlying neural circuit mechanisms remain elusive. Here, we identify a glutamatergic projection from the nucleus of the solitary tract (NTS) to the central nucleus of the amygdala (CeA) that mediates depression-like behaviors in a chemotherapy-induced neuropathic pain model. Inhibition or ablation of the glutamatergic NTS neurons alleviates depressive but not hypersensitive behaviors in these mice. The projected neurons form excitatory synapses with somatostatin-expressing neurons in the CeA. Silencing the NTS-CeA projection alleviates depressive but not hypersensitive behaviors, whereas activating the proection promotes depressive behaviors. In addition, in naïve mice, activation of the NTS-CeA projection induces obvious depressive behaviors that can be blocked by silencing the CeA somatostatin-expressing neurons. Together, we reveal a modulatory role of the NTS and its glutamatergic projection to the CeA circuit in modulating depression-like behaviors comorbid to chronic pain.

Mild blurry vision as the initial presentation of central nervous system relapses of acute lymphoblastic leukemia: a case report.

BACKGROUND: Leukemia relapses after hematopoietic stem cell transplantation can sometimes occur from the central nervous system prior to relapse from the bone marrow, and manifestations varied. CASE REPORT: We present a case of mild blurry vision as the initial symptom of central nervous system relapse of adult acute lymphoblastic leukemia. A 30-year-old man presented with a 1 week history of painless visual loss in both eyes. At that time there were no headaches or other systemic features. The neurological examination was without positive findings except bilateral optic nerve edema. He had a history of acute lymphoblastic leukemia and hematopoietic stem cell transplantation, which had been in clinical remission post-transplant for 1 year. Lumbar puncture revealed relapsed disease within the central nervous system, confirmed with cerebrospinal fluid leukemic blasts. CONCLUSIONS: It highlights the need for ophthalmologists to be aware of the possibility of central nervous system involvement in patients with the setting of leukemia when visual symptoms as the initial manifestation.

A Combined Experimental and Computational Study on the Adsorption Sites of Zinc-Based MOFs for Efficient Ammonia Capture.

Ammonia (NH3) is a common pollutant mostly derived from pig manure composting under humid conditions, and it is absolutely necessary to develop materials for ammonia removal with high stability and efficiency. To this end, metal-organic frameworks (MOFs) have received special attention because of their high selectivity of harmful gases in the air, resulting from their large surface area and high density of active sites, which can be tailored by appropriate modifications. Herein, two synthetic metal-organic frameworks (MOFs), 2-methylimidazole zinc salt (ZIF-8) and zinc-trimesic acid (ZnBTC), were selected for ammonia removal under humid conditions during composting. The two MOFs, with different organic linkers, exhibit fairly distinctive ammonia absorption behaviors under the same conditions. For the ZnBTC framework, the ammonia intake is 11.37 mmol/g at 298 K, nine times higher than that of the ZIF-8 framework (1.26 mmol/g). In combination with theoretical calculations, powder XRD patterns, FTIR, and BET surface area tests were conducted to reveal the absorption mechanisms of ammonia for the two materials. The adsorption of ammonia on the ZnBTC framework can be attributed to both physical and chemical adsorption. A strong coordination interaction exists between the nitrogen atom from the ammonia molecule and the zinc atom in the ZnBTC framework. In contrast, the absorption of ammonia in the ZIF-8 framework is mainly physical. The weak interaction between the ammonia molecule and the ZIF-8 framework mainly results from the inherent severely steric hindrance, which is related to the coordination mode of the imidazole ligands and the zinc atom of this framework. Therefore, this study provides a method for designing promising MOFs with appropriate organic linkers for the selective capture of ammonia during manure composting.

Tunable Ammonia Adsorption within Metal-Organic Frameworks with Different Unsaturated Metal Sites.

Ammonia (NH3) emissions during agricultural production can cause serious consequences on animal and human health, and it is quite vital to develop high-efficiency adsorbents for NH3 removal from emission sources or air. Porous metal-organic frameworks (MOFs), as the most promising candidates for the capture of NH3, offer a unique solid adsorbent design platform. In this work, a series of MOFs with different metal centers, ZnBTC, FeBTC and CuBTC, were proposed for NH3 adsorption. The metal centers of the three MOFs are coordinated in a different manner and can be attacked by NH3 with different strengths, resulting in different adsorption capacities of 11.33, 9.5, and 23.88 mmol/g, respectively. In addition, theoretical calculations, powder XRD patterns, FTIR, and BET for the three materials before and after absorption of ammonia were investigated to elucidate their distinctively different ammonia absorption mechanisms. Overall, the study will absolutely provide an important step in designing promising MOFs with appropriate central metals for the capture of NH3.

Downregulation of metallothionein-2 contributes to oxaliplatin-induced neuropathic pain.

BACKGROUND: We previously reported a correlation between small doses of oxaliplatin penetrating onto the spinal cord and acute pain after chemotherapy. Here, we propose that MT2 within the spinal dorsal horns participates in the development of oxaliplatin-induced neuropathic pain and may be a pharmacological target for the prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: The rat model of CIPN was established by 5 consecutive injections of oxaliplatin (0.4 mg/100 g/day). Genetic restoration of neuron-specific metallothionein-2 was implemented 21 days before oxaliplatin treatment, and also, genetic inhibition by metallothionein-2 siRNA was performed. Mechanical allodynia and locomotor activity were assayed. Cell-specific expression of metallothionein-2, the mRNA levels of pro-inflammatory cytokines, nuclear translocation of NF-κB, the protein levels of expression of IκB-α, and interaction between IκB-α and P65 were evaluated in the spinal dorsal horns. Also, in vitro interaction of sequentially deleted IκB-α promoter with metallothionein-2 was used to assess the signal transduction mechanism. RESULTS: We found that oxaliplatin induced downregulation of metallothionein-2 in rat spinal cord neurons. By contrast, genetic restoration of metallothionein-2 in the spinal dorsal horn neuron blocked and reversed neuropathic pain in oxaliplatin-treated rats of both sexes, whereas genetic inhibition of metallothionein-2 triggered neuropathic pain in normal rats. Overall locomotor activity was not impaired after the genetic alterations of metallothionein-2. At the molecular level, metallothionein-2 modulated oxaliplatin-induced neuroinflammation, activation of NF-κB, and inactive transcriptional expression of IκB-α promoter, and these processes could be blocked by genetic restoration of metallothionein-2 in the spinal dorsal horn neurons. CONCLUSIONS: Metallothionein-2 is a potential target for the prevention and treatment of CIPN. A reduction of NF-κB activation and inflammatory responses by enhancing the transcription of IκB-α promoter is proposed in the mechanism.

Gut microbiota affect the formation of calcium oxalate renal calculi caused by high daily tea consumption.

Kidney stones are a common and frequently occurring disease worldwide. Stones can cause urinary tract obstruction, pain, haematuria, and other symptoms. In this study, the relationship between calcium oxalate renal calculi and gut microbiota was considered. The dietary habits of 30 patients with calcium oxalate kidney stones and 30 healthy people were investigated. The 16S rDNA sequences and short-chain fatty acids (SCFAs) in their stool samples were analysed. We identified 5 genera of the gut microbiota as biomarkers for calcium oxalate renal calculi, namely, Bacteroides, Phascolarctobacterium, Faecalibacterium, Akkermansia, and Lactobacillus, with a receiver operating characteristic (ROC) curve value of 0.871 (95% confidence interval (CI) 0.785-0.957). Phascolarctobacterium and Faecalibacterium showed a positive relationship with SCFA synthesis to reduce the risk of kidney stones. Meanwhile, according to the analysis, Lactobacillus spp. made the largest contribution (79%) to prevent kidney stones caused by tea consumption, since tea offers the great parts of oxalate in kidney stone formation. Three strains of Lactobacillus spp. were isolated from stools of a healthy person with a high level of tea consumption who did not suffer from kidney stones. All these strains survived in the colon with supplementation of high concentrations of tea and efficiently degraded oxalic acid (Ca. 50%) in an in vitro colonic simulation. Therefore, a suitable adjustment of the gut microbiota or SCFA concentration enhanced the degradation of oxalate from food, which can be applied to prevent the formation of calcium oxalate renal calculi caused by tea. KEY POINTS: • Five genera, including Lactobacillus, were identified as biomarkers for calcium oxalate renal calculi. • Lactobacillus is a potential gut bacterium associated with preventing kidney stone formation. • Isolated Lactobacillus strains have the ability to degrade oxalic acid in vitro.

HDAC1 and HDAC2 regulate anti-inflammatory effects of anesthetic isoflurane in human monocytes.

Pre-exposure to volatile anesthetics inhibits inflammation induced by various stimuli, including surgical procedures and ischemia. We hypothesize that volatile anesthetics may induce anti-inflammatory effects via a mechanism involving regulation of histone deacetylases (HDACs). Pre-exposure of 1.5% isoflurane for 0.5 h induced anti-inflammatory effects [measured by cytokine production of tumor necrosis factor-ɑ, interleukin-8 (IL-8) and IL-1ß] in both human THP-1 cells and primary human peripheral blood monocytes stimulated by lipopolysaccharide. In human THP-1 cells, coadministration of the HDAC inhibitor trichostatin A (TSA) blocked the isoflurane-induced anti-inflammatory effects. TSA also blocked isoflurane-upregulated HDAC1-3 expression and isoflurane-reduced nuclear translocation of p65 and p50 subunits of nuclear factor-κB (NF-κB). The ability of isoflurane to reduce NF-κB nuclear translocation and proinflammatory responses in the cell line was blocked by gene silencing of HDAC1 and HDAC2, but not by gene silencing of HDAC3. A coimmunoprecipitation assay demonstrated that the decreased interaction between HDAC1 and HDAC2 through lipopolysaccharide was restored by isoflurane pretreatment. These findings were validated in primary human peripheral blood monocytes  wherein gene silencing of HDAC1 and HDAC2 resulted in increased cytokine production and NF-κB nuclear translocation induced by isoflurane pre-exposure and lipopolysaccharide stimulation. These results indicate that anti-inflammatory effects of the volatile anesthetic isoflurane in human monocytes involve regulation of HDAC1 and HDAC2.

Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.

The mitochondrial complexes are prone to sirtuin (Sirt)3-mediated deacetylation modification, which may determine cellular response to stimuli, such as oxidative stress. In this study, we show that the cytochrome c oxidase (COX)-1, a core catalytic subunit of mitochondrial complex IV, was acetylated and deactivated both in 2,2'-azobis(2-amidinopropane) dihydrochloride-treated NIH/3T3 cells and hydrogen peroxide-treated primary neuronal cells, correlating with apoptotic cell death induction by oxidative stress. Inhibition of Sirt3 by small interfering RNA or the inhibitor nicotinamide induced accumulation of acetylation of COX-1, reduced mitochondrial membrane potential, and increased cell apoptosis. In contrast, overexpression of Sirt3 enhanced deacetylation of COX-1 and inhibited oxidative stress-induced apoptotic cell death. Significantly, rats treated with ischemia/reperfusion injury, a typical oxidative stress-related disease, presented an inhibition of Sirt3-induced hyperacetylation of COX-1 in the brain tissues. Furthermore, K13, K264, K319, and K481 were identified as the acetylation sits of COX-1 in response to oxidative stress. In conclusion, COX-1 was discovered as a new deacetylation target of Sirt3, indicating that the Sirt3/COX-1 axis is a promising therapy target of stress-related diseases.-Tu, L.-F., Cao, L.-F., Zhang, Y.-H., Guo, Y.-L., Zhou, Y.-F., Lu, W.-Q., Zhang, T.-Z., Zhang, T., Zhang, G.-X., Kurihara, H., Li, Y.-F., He, R.-R. Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.

Liquid crystalline networks based on photo-initiated thiol-ene click chemistry.

Photo-initiated thiol-ene click chemistry is used to develop shape memory liquid crystalline networks (LCNs). A biphenyl-based di-vinyl monomer is synthesized and cured with a di-thiol chain extender and a tetra-thiol crosslinker using UV light. The effects of photo-initiator concentration and UV light intensity on the curing behavior and liquid crystalline (LC) properties of the LCNs are investigated. The chemical composition is found to significantly influence the microstructure and the related thermomechanical properties of the LCNs. The structure-property relationship is further explored using molecular dynamics simulations, revealing that the introduction of the chain extender promotes the formation of an ordered smectic LC phase instead of agglomerated structures. The concentration of the chain extender affects the liquid crystallinity of the LCNs, resulting in distinct thermomechanical and shape memory properties. This class of LCNs exhibits fast curing rates, high conversion levels, and tailorable liquid crystallinity, making it a promising material system for advanced manufacturing, where complex and highly ordered structures can be produced with fast reaction kinetics and low energy consumption.

Up-regulation of P-gp via NF-κB activation confers protection against oxidative damage in the retinal pigment epithelium cells.

Dysfunction of retinal pigment epithelial (RPE) cells has been associated with the pathogenesis of age-related macular degeneration in relation to increased oxidative stress, subsequent mitochondrial dysfunction and cell death. Permeability-glycoprotein (P-gp), encoded by the multidrug resistance 1 gene (MDR1), is an active efflux pump involved in cell homeostasis and nuclear factor κB (NF-κB) shows potential involvement in P-gp regulation due to its binding to the promoter domains of MDR1 gene. This study sought to determine the role of P-gp expression regulated by NF-κB in RPE cells during oxidative stress. The human RPE D407 cells were exposed to increasing concentrations of hydrogen peroxide (H2O2) for 24 h. The small-interfering RNA (siRNA) transfection was used to down-regulate P-gp and NF-κB, and the expressions of P-gp and NF-κB p65 were determined by quantitative real-time PCR, western blot and immunofluorescence. The activity of NF-κB was detected by luciferase reporter assay. Mitochondrial membrane potential and cell death rate were detected by flow cytometry. We found that H2O2 exposure caused increasing rate of cell death and induced an elevated expression of P-gp as well as NF-κB activation and nucleus translocation in D407 cells. Inhibiting or silencing NF-κB led to a decrease in the oxidative-induced expression of P-gp. Down-regulation of P-gp by siRNA transfection further impaired the mitochondrial membrane potential and cell death rate in oxidative cells. Moreover, inhibition/knockdown of NF-κB decreased the high rate of cell death caused by H2O2. In conclusion, P-gp can provide moderate cytoprotection for the human RPE cells by ameliorating the mitochondrial dysfunction and NF-κB activation may be a potential regulator of P-gp expression response to oxidative stress.

Bis[1,8,15,22-tetrakis(3-pentyloxy)phthalocyaninato]terbium Double-Decker Single-Ion Magnets.

For the purpose of further exploring the effect of nonperipherally attached substituents on single-ion magnet (SIMs) performance, tetrasubstituted bis[1,8,15,22-tetrakis(3-pentyloxy)phthalocyaninato]terbium double-deckers, in both the reduced form TbH[Pc(α-OC5H11)4]2 (1) and the neutral form Tb[Pc(α-OC5H11)4]2 (2), were prepared. Single-crystal X-ray diffraction analysis for 2 unambiguously demonstrates the pinwheellike molecular structure with C4 symmetry. Magnetic investigations of the two bis(phthalocyaninato)terbium double-deckers reveal their characteristic SIM nature. 2 exhibits SIM performance superior to that of 1, as revealed by the larger energy barrier of 466 K for the former species and 431 K for the latter species due to the presence of organic radical-f (radical-Tb) interactions. The enhanced SIM performance of 2 in comparison to 1 actually stems from the presence of radical-f interactions and an enhanced ligand field strength. The latter positive factor is indicated by the electrostatic potential around the terbium ion on the basis of density functional theory (DFT) calculations.

Preparation and application performance study of biomass-based carbon materials with various morphologies by a hydrothermal/soft template method.

Nitrogen-doped carbon materials with controllable morphologies were prepared via a soft template method using chitosan as the carbon and nitrogen source and F127 or ionic liquid as the template. The performance of the materials as electrodes and adsorbents for carbon dioxide removal were evaluated. Carbon spheres (CSs) with developed micropore structures were obtained without a template, whereas a tubular structure (CSF) containing mesopores with long-range order was obtained using F127. Layered carbon (CSI) containing micro-/mesopores with short- and long-range order was obtained using an ionic liquid. The samples exhibited graphite-like structure and the soft template increased the graphitization degree. Nitrogen existed mainly in the form of pyridine and pyridone groups in CSs and CSF and as pyridine, pyridone, and quaternary groups in CSI. The specific capacitances of CSs, CSF, and CSI were 144, 161, and 178 F g-1, respectively, at a current density of 1.0 A g-1 in 1 M sulfuric acid. The carbon dioxide adsorption capacities of CSs, CSF, and CSI were 142, 73, and 115 mg g-1, respectively; CSs displayed the highest value because of its developed micro- and ultramicroporous structure. Our results indicated that these carbon materials with various morphologies can be used as both electrodes and adsorbents.

Mixed Phthalocyanine-Porphyrin Fused Conjugated Pentameric Nanoarrays.

The largest phthalocyanine-porphyrin-fused pentameric molecular arrays have been synthesized and spectroscopically characterized. The saddled molecular conformation revealed for the pentamer by DFT-D3 calculation in combination with the bulky peripheral substituents precludes effective face-to-face π-π intermolecular interaction. As a consequence, intermolecular C-H⋅⋅⋅π interactions together with the ubiquitous dispersion force arrays help to self-assemble the representative metal-free pentameric molecules into the three-dimensional supramolecular structures with nanorod morphology in CHCl3 and n-butanol. Powder X-ray diffraction (XRD) analysis and selected area electron diffraction (SAED) disclose the gradually increased long range of molecular ordering in the nanorods along with the increase in the substrate temperature from 30, 40, 50, to 60 °C. This in turn results in an increase in the semiconductivity of the single nanorod in the same order from 9.4×10-9 to 3.8×10-8 , 7.6×10-7 , and 6.3×10-5  S m-1 .

Liquid crystalline epoxy networks with exchangeable disulfide bonds.

A liquid crystalline epoxy network (LCEN) with exchangeable disulfide bonds is synthesized by polymerizing a biphenyl-based epoxy monomer with an aliphatic dicarboxylic acid curing agent containing a disulfide bond. The effect of disulfide bonds on curing behavior and liquid crystalline (LC) phase formation of the LCEN is investigated. The presence of the disulfide bonds results in an increase in the reaction rate, leading to a reduction in liquid crystallinity of the LCEN. In order to promote LC phase formation and stabilize the self-assembled LC domains, a similar aliphatic dicarboxylic acid without the disulfide bond is used as a co-curing agent to reduce the amount of exchangeable disulfide bonds in the system. After optimizing the molar ratio of the two curing agents, the resulting LCEN exhibits improved reprocessability and recyclability because of the disulfide exchange reactions, while preserving LC properties, such as the reversible LC phase transition and macroscopic LC orientation, for shape memory applications.

High ocular CMV copies and mismatched receipts may predict poor visual prognosis in CMV retinitis patients following allogeneic haematopoietic stem cell transplantation.

BACKGROUND: To summarize the clinical characteristics and potential factors affecting the visual outcomes in patients with cytomegalovirus retinitis following allogeneic haematopoietic stem cell transplantation (HSCT). METHODS: This retrospective study enrolled 12 patients (19 eyes) with cytomegalovirus retinitis after HSCT at Guangzhou First People's Hospital in China between January 2013 and December 2014. Demographic and clinical characteristics, ocular manifestations and visual outcomes were evaluated by reviewing medical records at the Departments of Hematology and Ophthalmology. All patients were followed up at least 6 months after stopping antiviral therapy. The visual outcome was defined as improvement, stabilization and deterioration. RESULTS: The subjects were composed of 7 human leucocyte antigen-matched and 5 mismatched receipts. All patients received combined systemic and intravitreous antiviral therapy. Eleven eyes gained improved or stabilized visual acuity, while 8 eyes suffered deterioration. Eyes with cytomegalovirus load less than 1 × 104 copies/ml in vitreous accounted for higher rate in eyes with good visual prognosis than those with cytomegalovirus copies above 1 × 104 copies/ml (52.63% vs 5.26%, P < 0.001). Human leucocyte antigen-matched receipts gained better visual prognosis than those mismatched ones (47.37% vs10.53%, P < 0.05). The virus types, cytomegalovirus peak in the blood, involved retinal zone and size had no influence on the visual outcomes (all P > 0.05). CONCLUSIONS: High ocular cytomegalovirus copies and mismatched receipts may be potential adverse factors affecting visual outcomes in cytomegalovirus retinitis patients following allogeneic HSCT.

TMPyP4-regulated cell proliferation and apoptosis through the Wnt/ß-catenin signaling pathway in SW480 cells.

BACKGROUND: The aim of this study was to investigate the potential effects of the 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of SW480 cells and the underlying mechanisms by which TMPyP4 exerted its actions. METHODS: After treated with different doses of TMPyP4, cell viability was determined by MTT method, the apoptosis was observed by flow cytometry (FCM) and the expression of Wnt, GSK-3ß, ß-catenin and cyclinD1 was measured by RT-PCR and Western blot analysis. RESULTS: The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of SW480 cells in a dose-dependent manner. In addition, the downregulation of Wnt, ß-catenin and cyclinD1 expression levels was detected in TMPyP4-treated SW480 cells. However, followed by the block of Wnt signaling pathway using siRNA methods, the effects of TMPyP4 on proliferation and apoptosis of SW480 cells were significantly reduced. CONCLUSION: It indicates that the TMPyP4-inhibited proliferation and -induced apoptosis in SW480 cells was accompanied by the suppression of Wnt/ß-catenin signaling pathway. Therefore, TMPyP4 may represent a potential therapeutic method for the treatment of colon carcinoma.

Heteroleptic Tetrapyrrole-Fused Dimeric and Trimeric Skeletons with Unusual Non-Frustrated Fluorescence.

Phthalocyanine (Pc) and porphyrin (Por) chromophores have been fused through the benzo[α]pyrazine moiety, resulting in unprecedented heteroleptic tetrapyrrole-fused dimers and trimers. The heteroleptic tetrapyrrole nature has been clearly revealed based on single-crystal X-ray diffraction analysis of the zinc dimer. Electrochemical analysis, theoretical calculations, and time-resolved spectroscopic results disclose that the two/three-tetrapyrrole-fused skeletons behave as one totally π-conjugated system as a result of the strong conjugative interaction between/among the tetrapyrrole chromophores. In particular, the effectively extended π-electron system through the fused-bridge induced strong electronic communication between the Pc and Por moieties and large transition dipole moments in the Pc-Por-fused systems, providing high fluorescence quantum yields (>0.13) and relatively long excited state lifetimes (>1.3 ns) in comparison with their homo-tetrapyrrole-fused analogues.