Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer.

The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling1 and is altered in over 20% of cancers2,3. Here we developed a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4, called AU-15330. Androgen receptor (AR)+ forkhead box A1 (FOXA1)+ prostate cancer cells are exquisitely sensitive to dual SMARCA2 and SMARCA4 degradation relative to normal and other cancer cell lines. SWI/SNF ATPase degradation rapidly compacts cis-regulatory elements bound by transcription factors that drive prostate cancer cell proliferation, namely AR, FOXA1, ERG and MYC, which dislodges them from chromatin, disables their core enhancer circuitry, and abolishes the downstream oncogenic gene programs. SWI/SNF ATPase degradation also disrupts super-enhancer and promoter looping interactions that wire supra-physiologic expression of the AR, FOXA1 and MYC oncogenes themselves. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide, even inducing disease remission in castration-resistant prostate cancer (CRPC) models without toxicity. Thus, impeding SWI/SNF-mediated enhancer accessibility represents a promising therapeutic approach for enhancer-addicted cancers.

Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer.

ABTRACT: Forkhead box A1 (FOXA1) is a pioneer transcription factor that is essential for the normal development of several endoderm-derived organs, including the prostate gland1,2. FOXA1 is frequently mutated in hormone-receptor-driven prostate, breast, bladder and salivary-gland tumours3-8. However, it is unclear how FOXA1 alterations affect the development of cancer, and FOXA1 has previously been ascribed both tumour-suppressive9-11 and oncogenic12-14 roles. Here we assemble an aggregate cohort of 1,546 prostate cancers and show that FOXA1 alterations fall into three structural classes that diverge in clinical incidence and genetic co-alteration profiles, with a collective prevalence of 35%. Class-1 activating mutations originate in early prostate cancer without alterations in ETS or SPOP, selectively recur within the wing-2 region of the DNA-binding forkhead domain, enable enhanced chromatin mobility and binding frequency, and strongly transactivate a luminal androgen-receptor program of prostate oncogenesis. By contrast, class-2 activating mutations are acquired in metastatic prostate cancers, truncate the C-terminal domain of FOXA1, enable dominant chromatin binding by increasing DNA affinity and-through TLE3 inactivation-promote metastasis driven by the WNT pathway. Finally, class-3 genomic rearrangements are enriched in metastatic prostate cancers, consist of duplications and translocations within the FOXA1 locus, and structurally reposition a conserved regulatory element-herein denoted FOXA1 mastermind (FOXMIND)-to drive overexpression of FOXA1 or other oncogenes. Our study reaffirms the central role of FOXA1 in mediating oncogenesis driven by the androgen receptor, and provides mechanistic insights into how the classes of FOXA1 alteration promote the initiation and/or metastatic progression of prostate cancer. These results have direct implications for understanding the pathobiology of other hormone-receptor-driven cancers and rationalize the co-targeting of FOXA1 activity in therapeutic strategies.

Template-Directed Polymerization of Binary Acrylate Monomers on Surface-Activated Lignin Nanoparticles in Toughening of Bio-Latex Films.

Fabricating bio-latex colloids with core-shell nanostructure is an effective method for obtaining films with enhanced mechanical characteristics. Nano-sized lignin is rising as a class of sustainable nanomaterials that can be incorporated into latex colloids. Fundamental knowledge of the correlation between surface chemistry of lignin nanoparticles (LNPs) and integration efficiency in latex colloids and from it thermally processed latex films are scarce. Here, an approach to integrate self-assembled nanospheres of allylated lignin as the surface-activated cores in a seeded free-radical emulsion copolymerization of butyl acrylate and methyl methacrylate is proposed. The interfacial-modulating function on allylated LNPs regulates the emulsion polymerization and it successfully produces a multi-energy dissipative latex film structure containing a lignin-dominated core (16% dry weight basis). At an optimized allyl-terminated surface functionality of 1.04 mmol g-1 , the LNPs-integrated latex film exhibits extremely high toughness value above 57.7 MJ m-3 . With multiple morphological and microstructural characterizations, the well-ordered packing of latex colloids under the nanoconfinement of LNPs in the latex films is revealed. It is concluded that the surface chemistry metrics of colloidal cores in terms of the abundance of polymerization-modulating anchors and their accessibility have a delicate control over the structural evolution of core-shell latex colloids.

Photocross-Linkable and Shape-Memory Biomaterial Hydrogel Based on Methacrylated Cellulose Nanofibres.

In the context of three-dimensional (3D) cell culture and tissue engineering, 3D printing is a powerful tool for customizing in vitro 3D cell culture models that are critical for understanding the cell-matrix and cell-cell interactions. Cellulose nanofibril (CNF) hydrogels are emerging in constructing scaffolds able to imitate tissue in a microenvironment. A direct modification of the methacryloyl (MA) group onto CNF is an appealing approach to synthesize photocross-linkable building blocks in formulating CNF-based bioinks for light-assisted 3D printing; however, it faces the challenge of the low efficiency of heterogenous surface modification. Here, a multistep approach yields CNF methacrylate (CNF-MA) with a decent degree of substitution while maintaining a highly dispersible CNF hydrogel, and CNF-MA is further formulated and copolymerized with monomeric acrylamide (AA) to form a super transparent hydrogel with tuneable mechanical strength (compression modulus, approximately 5-15 kPa). The resulting photocurable hydrogel shows good printability in direct ink writing and good cytocompatibility with HeLa and human dermal fibroblast cell lines. Moreover, the hydrogel reswells in water and expands to all directions to restore its original dimension after being air-dried, with further enhanced mechanical properties, for example, Young's modulus of a 1.1% CNF-MA/1% PAA hydrogel after reswelling in water increases to 10.3 kPa from 5.5 kPa.

Aqueous Processable One-Dimensional Polypyrrole Nanostructured by Lignocellulose Nanofibril: A Conductive Interfacing Biomaterial.

One-dimensional (1D) nanomaterials of conductive polypyrrole (PPy) are competitive biomaterials for constructing bioelectronics to interface with biological systems. Synergistic synthesis using lignocellulose nanofibrils (LCNF) as a structural template in chemical oxidation of pyrrole with Fe(III) ions facilitates surface-confined polymerization of pyrrole on the nanofibril surface within a submicrometer- and micrometer-scale fibril length. It yields a core-shell nanocomposite of PPy@LCNF, wherein the surface of each individual fibril is coated with a thin nanoscale layer of PPy. A highly positive surface charge originating from protonated PPy gives this 1D nanomaterial a durable aqueous dispersity. The fibril-fibril entanglement in the PPy@LCNFs facilely supported versatile downstream processing, e.g., spray thin-coating on glass, flexible membranes with robust mechanics, or three-dimensional cryogels. A high electrical conductivity in the magnitude of several to 12 S·cm-1 was confirmed for the solid-form PPy@LCNFs. The PPy@LCNFs are electroactive and show potential cycling capacity, encompassing a large capacitance. Dynamic control of the doping/undoping process by applying an electric field combines electronic and ionic conductivity through the PPy@LCNFs. The low cytotoxicity of the material is confirmed in noncontact cell culture of human dermal fibroblasts. This study underpins the promises for this nanocomposite PPy@LCNF as a smart platform nanomaterial in constructing interfacing bioelectronics.

Facile fabrication of AgVO3/rGO/BiVO4 hetero junction for efficient degradation and detoxification of norfloxacin.

In the recent past, the development of efficient materials for degradation and detoxification of antibiotics has gained more attention in wastewater treatment process. As a visible light active material AgVO3 has attracted much concern in environmental remediation. To improve its efficiency and stability, a novel heterojunction was prepared by combining AgVO3 with rGO and BiVO4 through a hydrothermal method. The prepared AgVO3/rGO/BiVO4 composite was further utilized for effective detoxification of Norfloxacin (NFC) antibiotic. The morphological analysis revealed the clear rod shaped AgVO3 and leaf like BiVO4 that are evenly distributed on reduced graphene oxide (rGO) layers. The visible light absorbance and the catalytic activity of AgVO3/rGO/BiVO4 was dramatically improved compared to pure AgVO3 and BiVO4. From the results it showed that the degradation efficiency of AgVO3/rGO/BiVO4 (∼96.1%, k = 0.01782 min-1) was 2.5 times higher than pure AgVO3 and 3.4 times higher than the pure BiVO4 respectively towards NFC after 90 min. The higher efficiency could be attributed to the heterojunction formation and faster charge separation. The radical trapping experiments results indicated that the •OH, and O2•- are the main species responsible for degradation. The degradation products of NFC were analysed through ESI-LC/MS and pathway was proposed. Furthermore, the toxicity assessment of pure NFC and its degradation products was studied using E. coli as the model bacteria through colony forming unit assay and the results indicated the efficient detoxification was attained during the degradation process. Thus, our study provides new insight into detoxification of antibiotics using AgVO3 based composites.

Effects of rTMS combined with rPMS on stroke patients with arm paralysis after contralateral seventh cervical nerve transfer: a case-series.

OBJECTIVE: We conducted this study to evaluate the effect of rTMS combined with rPMS on stroke patients with arm paralysis after CSCNTS. METHODS: A case-series of four stroke patients with arm paralysis, ages ranging from 39 to 51 years, that underwent CSCNTS was conducted. Patients were treated with 10 HZ rTMS on the contralesional primary motor cortex combined with 20 HZ rPMS on groups of elbow and wrist muscles for 15 days. RESULTS: The muscle tone of elbow flexor muscle (EFM), elbow extensor muscle (EEM), wrist flexor muscle (WFM) and flexor digitorum (FD) reduced immediately after operation followed by increasing gradually. After rehabilitation, the muscle tone of EEM and EFM reduced by 14% and 11%, respectively. There was a 13% and 45% change ratio in WFM and FD. The numeric rating scale (mean = 5.75 ± 1.71) was significantly lower (mean = 3.25 ± 1.90, t = 8.66, p = .00). Grip and pinch strength (mean = 23.65 ± 4.91; mean = 4.9 ± 0.59) were significantly higher (mean = 34.63 ± 5.23, t = -61.07, p = .00; mean = 7.1 ± 0.73, t = -13.91, p = .00). CONCLUSIONS: The rehabilitation of stroke patients with arm paralysis after CSCNTS is a long, complicated process which includes great change of neuropathic pain, muscle tone, and muscle strength. In order to enhance the neural connection between the contralesional hemisphere and the hemiplegic limb, alleviate postoperative complications, as well as accelerate the rehabilitation process, we can consider to use rTMS combined with rPMS.

A Novel Selenium Polysaccharide Alleviates the Manganese (Mn)-Induced Toxicity in Hep G2 Cells and Caenorhabditis elegans.

Manganese (Mn) is now known to have a variety of toxicities, particularly when exposed to it in the workplace. However, there are still ineffective methods for reducing Mn's hazardous effects. In this study, a new selenium polysaccharide (Se-PCS) was developed from the shell of Camellia oleifera to reduce Mn toxicity in vitro and in vivo. The results revealed that Se-PCS may boost cell survival in Hep G2 cells exposed to Mn and activate antioxidant enzyme activity, lowering ROS and cell apoptosis. Furthermore, after being treated with Se-PCS, Caenorhabditis elegans survived longer under Mn stress. daf-16, a tolerant critical gene, was turned on. Moreover, the antioxidant system was enhanced as the increase in strong antioxidant enzyme activity and high expression of the sod-3, ctl-2, and gst-1 genes. A variety of mutations were also used to confirm that Se-PCS downregulated the insulin signaling pathway. These findings showed that Se-PCS protected Hep G2 cells and C. elegans via the insulin/IGF-1 signaling pathway and that it could be developed into a promising medication to treat Mn toxicity.

Identification of prostate cancer specific methylation biomarkers from a multi-cancer analysis.

BACKGROUND: Detecting prostate cancer at a non-aggressive stage is the main goal of prostate cancer screening. DNA methylation has been widely used as biomarkers for cancer diagnosis and prognosis, however, with low clinical translation rate. By taking advantage of multi-cancer data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we aimed to identify prostate cancer specific biomarkers which can separate between non-aggressive and aggressive prostate cancer based on DNA methylation patterns. RESULTS: We performed a comparison analysis of DNA methylation status between normal prostate tissues and prostate adenocarcinoma (PRAD) samples at different Gleason stages. The candidate biomarkers were selected by excluding the biomarkers existing in multiple cancers (pan-cancer) and requiring significant difference between PRAD and other urinary samples. By least absolute shrinkage and selection operator (LASSO) selection, 8 biomarkers (cg04633600, cg05219445, cg05796128, cg10834205, cg16736826, cg23523811, cg23881697, cg24755931) were identified and in-silico validated by model constructions. First, all 8 biomarkers could separate PRAD at different stages (Gleason 6 vs. Gleason 3 + 4: AUC = 0.63; Gleason 6 vs. Gleason 4 + 3 and 8-10: AUC = 0.87). Second, 5 biomarkers (cg04633600, cg05796128, cg23523811, cg23881697, cg24755931) effectively detected PRAD from normal prostate tissues (AUC ranged from 0.88 to 0.92). Last, 6 biomarkers (cg04633600, cg05219445, cg05796128, cg23523811, cg23881697, cg24755931) completely distinguished PRAD with other urinary samples (AUC = 1). CONCLUSIONS: Our study identified and in-silico validated a panel of prostate cancer specific DNA methylation biomarkers with diagnosis value.

Skp2 regulates DNA damage repair and apoptosis via interaction with Ku70.

PURPOSE: Skp2, an oncoprotein, regulates tumor proliferation, invasion and metastasis. Ku70 is a critical component of the non-homologous end-joining (NHEJ) process. Both Skp2 and Ku70 are positively associated in multiple cancers. However, there is no report about the relationship between Skp2 and Ku70 proteins. METHODS: In this study, we carried out Bioinformatics and molecular biological methods to investigate the relationship between Skp2 and Ku70 proteins. RESULTS: We first observed Skp2 and Ku70 mRNAs were significantly increased in cervical cancer tissues. And we identified Ku70 as a Skp2-binding protein and the binding site located in the C-terminal of Ku70 protein. We further found that Skp2 knockdown decreased the Ku70 protein level in cells, and increase the cellular apoptosis and DNA damage, suggesting Skp2 mediates the Ku70 protein stability and function via post-translational modification. CONCLUSION: The direct interaction between Skp2 and Ku70 proteins mediates the DNA damage repair and cellular apoptosis by regulating Ku70 stability and function via post-translational modification. The molecular mechanisms how Skp2 stabilize Ku70 would be clarified in our following research work.

Performance of zinc oxide quantum dots coated paper and application of fluorescent anti-counterfeiting.

Fluorescent anti-counterfeiting is one of the most widely used anti-counterfeiting technologies at present. The demand to develop new anti-counterfeiting materials and technology is more and more urgent. Zinc oxide quantum dots (ZnO QDs) have superior fluorescent properties under ultraviolet light, making them a suitable replacement for traditional phosphors for anti-counterfeiting printing, which is environmentally friendly and meets the needs of sustainable development. In this paper, water-soluble ZnO QDs with an average particle size of 5.64 nm were prepared. Paper coated by ZnO QDs was obtained after ultrasonic treatment, which could emit bright yellow fluorescence when excited by ultraviolet light. As the concentration of ultrasonic solution is increased, the loading amount of ZnO QDs on the coated paper increased gradually, reaching the maximum when the concentration is increased to 1molL-1, which then does not change with an increase in concentration. The fluorescent intensity of the coated paper was consistent with the changing trend of the loading amount. The coated paper has excellent optical stability, is easy to recycle, and provides simple identification of authenticity by ultraviolet light and anti-copy functionality. Their application in packaging and printing is of great significance to the development of complex, concealed and non-repeatable anti-counterfeiting technology.

Combination of pregabalin and transcutaneous electrical nerve stimulation for neuropathic pain in a stroke patient after contralateral C7 nerve transfer: a case report.

BACKGROUND: Contralateral C7 nerve transfer is a new surgical treatment for stroke patients with unilateral upper extremity paralysis, but neuropathic pain in the nonparalyzed side is the common complication after surgery. We report a stroke patient with neuropathic pain after C7 nerve transfer who received combination treatment of transcutaneous electrical nerve stimulation(TENS) and pregabalin. CASE SUMMARY: A 53-year old, 6 months post-stroke patient with right hemiplegia after contralateral C7 nerve transfer was admitted in our department with a significant neuropathic pain in his left upper extremity. The treatment of pregabalin and TENS were used for patient. The visual analogue scale(VAS), medical outcomes study sleep scale(MOS-SS) and hospital anxiety and depression scale(HADS) were assessed after 1 months treatment. After treatment, the pain of his nonparalyzed upper extremity was relieved, the sleeping quality and the anxiety and depression were improved in patient. CONCLUSION: This report suggests that the combination of pregabalin and TENS have prominent clinical effects on neuropathic pain of nonparalyzed side in stroke patients after contralateral C7 nerve transfer.

Discovery and biological evaluation of proteolysis targeting chimeras (PROTACs) as an EGFR degraders based on osimertinib and lenalidomide.

Epidermal growth factor receptor (EGFR) is one of the important and valuable drug targets. Overexpression of EGFR is associated with the development of many types of cancer. In this study, three PROTACs small molecules (16a-16c) were designed, synthesized and evaluated for their cytotoxicity against the growth in different NSCLC cell line and the degradation effect. The bioassay results indicated that 16c has a good inhibition in PC9 cells and H1975 cells, and the corresponding IC50 value was 0.413 µM and 0.657 µM, respectively. Western blotting results demonstrated that compound 16c could serve as an effective EGFRdel19-targeting degrader in PC9 cells.

Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer.

Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. Progression to CRPC after androgen ablation therapy is predominantly driven by deregulated androgen receptor (AR) signalling. Despite the success of recently approved therapies targeting AR signalling, such as abiraterone and second-generation anti-androgens including MDV3100 (also known as enzalutamide), durable responses are limited, presumably owing to acquired resistance. Recently, JQ1 and I-BET762 two selective small-molecule inhibitors that target the amino-terminal bromodomains of BRD4, have been shown to exhibit anti-proliferative effects in a range of malignancies. Here we show that AR-signalling-competent human CRPC cell lines are preferentially sensitive to bromodomain and extraterminal (BET) inhibition. BRD4 physically interacts with the N-terminal domain of AR and can be disrupted by JQ1 (refs 11, 13). Like the direct AR antagonist MDV3100, JQ1 disrupted AR recruitment to target gene loci. By contrast with MDV3100, JQ1 functions downstream of AR, and more potently abrogated BRD4 localization to AR target loci and AR-mediated gene transcription, including induction of the TMPRSS2-ERG gene fusion and its oncogenic activity. In vivo, BET bromodomain inhibition was more efficacious than direct AR antagonism in CRPC xenograft mouse models. Taken together, these studies provide a novel epigenetic approach for the concerted blockade of oncogenic drivers in advanced prostate cancer.

Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer.

Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. In our study, we report that EZH2 and embryonic ectoderm development (EED) indicate respective direct interaction with androgen receptor (AR). In the context of AR-positive prostate cancer, EZH2 and EED regulate AR expression levels and AR downstream targets. More importantly, we demonstrate that targeting EZH2 with the small-molecule inhibitor astemizole in cancer significantly represses the EZH2 and AR expression as well as the neoplastic capacities. These results collectively suggest that pharmacologically targeting EZH2 might be a promising strategy for advanced prostate cancer.

Gene expression profiles of HTR8-S/Vneo cells after changes in ABCA1 expression.

ABCA1 is expressed in placental trophoblasts, such that when the expression level of ABCA1 changes, the function of trophoblasts dramatically changes. However, the mechanism by which ABCA1 affects the function of trophoblast cells remains unclear. Here, we used biochemical and transcriptomic to uncover the potential mechanism of the effect of ABCA1 on trophoblast function. HTR8/SVneo cells were either treated with the agonist T0901317 or transfected with siRNA to regulate ABCA1 expression levels. A human gene expression microarray was used to analyze the expression spectrum of ABCA1. Microarray results were confirmed by Western blotting and RT-PCR. Immunofluorescence allowed detection of the cellular localization of ABCA1, CCL8, CXCL10, CXCL11, and S1PR1 in HTR8/SVneo cells. Co-immunoprecipitation was used to test interactions among these proteins. Concomitant with an increase in ABCA1 expression, S1PR1 expression increased, whereas expression of CCL8, CXCL10, and CXCL11 decreased significantly; opposite effects were observed with a decrease in ABCA1 expression. Thus, changes in ABCA1 expression may lead to changes in downstream gene expression. Whereas the interaction between ABCA1 and S1PR1 was direct, interactions among ABCA1 and CCL8, CXCL10, and CXCL11 were indirect. We propose that, in conjunction with S1PR1, ABCA1 regulates expression levels of CCL8, CXCL10, and CXCL11; this may lead to changes in the immune function of trophoblastic cells. Thus, we suspect that the effect of ABCA1 on trophoblast function may involve many biological processes, molecular function changes, and the activation of multiple signaling pathways.

Identification of miRNAs as non-invasive biomarkers for early diagnosis of lung cancers.

Current clinical diagnostic methods lack the specificity in detecting lung cancer patients. The issue is particularly critical for stage I and II patients. Considerable evidence showed microRNA plays a very important role in lung carcinogenesis. Here, we identified a panel of 41 miRNAs significantly elevated in patients with lung cancer, of which eight miRNAs were further validated in an independent sample cohort. Classification analysis using the panel of eight miRNAs generated a discriminatory power of 93.3 % sensitivity and 93.8 % specificity in separating non-small-cell lung cancer (NSCLC) patients from normal controls, indicating the miRNAs have a potential clinical utility in discriminating NSCLC. Interestingly, miR-1244 was found significantly elevated in the serum samples of lung cancer patients, and the test characteristics of the single miRNA were area under the curve (AUC) of 0.832 in NSCLC vs healthy controls, and 0.861 in NSCLC vs patients with unidentified pulmonary nodules. This is the first study showing serum miR-1244 could be a biomarker to screen lung cancer patients from the high-risk population.

MiR-1244 sensitizes the resistance of non-small cell lung cancer A549 cell to cisplatin.

BACKGROUND: Cisplatin (DDP)-based chemotherapy is the mainstay of first-line therapy for lung cancer. However, their efficacy is often limited by the existence or development of chemoresistance. The aim of this study was to find and investigate the function of miRNAs in cisplatin (DDP)-resistant non-small cell lung cancer (NSCLC) A549 cell. METHODS: Quantitative real-time PCR assay was employed to compare the differences of miRNA expression in both cisplatin-resistant A549 (A549/DDP) cell and the parental A549 cell. The dysregulated miRNAs were then corrected by transfecting oligonucleotides into A549/DDP cells. The cellular sensitivity to cisplatin, cell apoptosis and migration were conducted by MTT, flow cytometry and cell wound healing assay, respectively. RESULTS: Both miR-589 and miR-1244 were significantly down-regulated in A549/DDP cell compared to the parental A549, while the expression of miR-182 and miR-224 were increased in A549/DDP cell (P < 0.05). Importantly, transfection of the cisplatin-resistant cells with either miR-589 or miR-1244 resulted in an increased sensitivity to cisplatin, indicating that the dysregulated miRNA may play an important role in chemotherapy resistance in cancer cell. The rescued expression of miRNA also reduced cell invasion and increased apoptosis of A549/DDP cell. CONCLUSION: The study indicates a crucial role of miR-1244 in the progress of cisplatin resistance of A549. Further understanding of miR-1244-mediated signaling pathways may promote the clinical use of miR-1244 in lung cancer therapy.

Visible-Light-Driven Intermolecular [2+2] Cycloadditions between Coumarin-3-Carboxylates and Acrylamide Analogs.

This paper reports a room temperature visible-light-driven protocol for the intermolecular [2+2] cycloadditions between coumarin-3-carboxylates and acrylamides analogs by an energy-transfer process. Using an iridium complex FIrPic as a photosensitizer and a 3 W blue LED as a light source, an array of cyclobutabenzocypyranones were prepared in moderate to excellent yields.