Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus.

Genome-wide association studies (GWAS) have identified rs11672691 at 19q13 associated with aggressive prostate cancer (PCa). Here, we independently confirmed the finding in a cohort of 2,738 PCa patients and discovered the biological mechanism underlying this association. We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated transcript levels of two biologically plausible candidate genes, PCAT19 and CEACAM21, implicated in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Remarkably, CRISPR/Cas9-mediated single-nucleotide editing showed the direct effect of rs11672691 on PCAT19 and CEACAM21 expression and PCa cellular aggressive phenotype. Clinical data demonstrated synergistic effects of rs11672691 genotype and PCAT19/CEACAM21 gene expression on PCa prognosis. These results provide a plausible mechanism for rs11672691 associated with aggressive PCa and thus lay the ground work for translating this finding to the clinic.

Discriminative Analysis of NOx Gases by Two-Dimensional Violet Phosphorus Field-Effect Transistors.

Two-dimensional violet phosphorus (VP) has emerged as a new sensing material in various sensing applications due to its unique electrical properties and high stability among allotropes of phosphorus. Currently, the research of the VP-based analysis method is at the early stage. In this work, a VP nanosheet-based field-effect transistor (FET) sensor is reported for the detection of NO2 and N2O gases with extraordinary sensing performance. This sensor can achieve excellent sensitivity of up to ∼50% current change/ppm and a low detection limit of 5.9 ppb and enables the NO2 analysis in various mixed gases. Moreover, this sensor can effectively distinguish between NO2 and N2O gases, which is a big challenge for current FET or chemiresistor gas sensors. The different sensing behaviors of the VP sensor to NO2 and N2O gases have been investigated, and the mechanism study shows that the adsorption energy, bond length of the gas molecule on the VP surface, and the decomposition of N2O led to the differential responses. This work is one of the pioneer studies of VP gas sensors and presents a new sensing method for the discriminative analysis of NO2 and N2O for greenhouse gas emission monitoring and air quality control.

NudCL2 is an Hsp90 cochaperone to regulate sister chromatid cohesion by stabilizing cohesin subunits.

Sister chromatid cohesion plays a key role in ensuring precise chromosome segregation during mitosis, which is mediated by the multisubunit cohesin complex. However, the molecular regulation of cohesin subunits stability remains unclear. Here, we show that NudCL2 (NudC-like protein 2) is essential for the stability of cohesin subunits by regulating Hsp90 ATPase activity in mammalian cells. Depletion of NudCL2 induces mitotic defects and premature sister chromatid separation and destabilizes cohesin subunits that interact with NudCL2. Similar defects are also observed upon inhibition of Hsp90 ATPase activity. Interestingly, ectopic expression of Hsp90 efficiently rescues the protein instability and functional deficiency of cohesin induced by NudCL2 depletion, but not vice versa. Moreover, NudCL2 not only binds to Hsp90, but also significantly modulates Hsp90 ATPase activity and promotes the chaperone function of Hsp90. Taken together, these data suggest that NudCL2 is a previously undescribed Hsp90 cochaperone to modulate sister chromatid cohesion by stabilizing cohesin subunits, providing a hitherto unrecognized mechanism that is crucial for faithful chromosome segregation during mitosis.

High-Performance Ni3(HHTP)2 Film-Based Flexible Field-Effect Transistor Gas Sensors.

Conductive metal-organic frameworks (MOFs) have received increasing attention in recent years and present high application potential as sensing elements in electronic sensors. In this study, flexible field-effect transistor (FET) sensors based on conductive MOF, i.e., Ni3(HHTP)2, have been constructed. This Ni3(HHTP)2 sensor has high sensitivity (detection limit of 56 ppb) as well as superior selectivity for NO2 detection at room temperature, which is demonstrated by accurate gas detection in a mixed gas atmosphere. Moreover, by employing six flexible substrates, i.e., polyimide (PI), tape (PET), facemask, paper cup, tablecloth, and take-out bag (textile), we successfully demonstrate the universality of the flexible sensor construction with conductive MOF as sensing film on various substrates. This study of conductive MOF-based flexible electronic sensors offers a new opportunity for a wide range of sensing applications with wearable and portable electronic devices.

An Inherited Allele Confers Prostate Cancer Progression and Drug Resistance via RFX6/HOXA10-Orchestrated TGFß Signaling.

Genetic and epigenetic alterations are cancer hallmark characteristics. However, the role of inherited cancer predisposition alleles in co-opting lineage factor epigenetic reprogramming and tumor progression remains elusive. Here the FinnGen cohort phenome-wide analysis, along with multiple genome-wide association studies, has consistently identified the rs339331-RFX6/6q22 locus associated with prostate cancer (PCa) risk across diverse populations. It is uncovered that rs339331 resides in a reprogrammed androgen receptor (AR) binding site in PCa tumors, with the T risk allele enhancing AR chromatin occupancy. RFX6, an AR-regulated gene linked to rs339331, exhibits synergistic prognostic value for PCa recurrence and metastasis. This comprehensive in vitro and in vivo studies demonstrate the oncogenic functions of RFX6 in promoting PCa cell proliferation and metastasis. Mechanistically, RFX6 upregulates HOXA10 that profoundly correlates with adverse PCa outcomes and is pivotal in RFX6-mediated PCa progression, facilitating the epithelial-mesenchymal transition (EMT) and modulating the TGFß/SMAD signaling axis. Clinically, HOXA10 elevation is associated with increased EMT scores, tumor advancement and PCa recurrence. Remarkably, reducing RFX6 expression restores enzalutamide sensitivity in resistant PCa cells and tumors. This findings reveal a complex interplay of genetic and epigenetic mechanisms in PCa pathogenesis and drug resistance, centered around disrupted prostate lineage AR signaling and abnormal RFX6 expression.

A trace amine associated receptor mediates antimicrobial immune response in the oyster Crassostrea gigas.

Trace amine-associated receptors (TAARs) are a class of G protein-coupled receptors, playing an immunomodulatory function in the neuroinflammatory responses. In the present study, a TAAR homologue with a 7tm_classA_rhodopsin-like domain (designated as CgTAAR1L) was identified in oyster Crassostrea gigas. The abundant CgTAAR1L transcripts were detected in visceral ganglia and haemocytes compared to other tissues, which were 55.35-fold and 32.95-fold (p < 0.01) of those in adductor muscle, respectively. The mRNA expression level of CgTAAR1L in haemocytes significantly increased and reached the peak level at 3 h after LPS or Poly (I:C) stimulation, which was 4.55-fold and 12.35-fold of that in control group, respectively (p < 0.01). After the expression of CgTAAR1L was inhibited by the injection of its targeted siRNA, the mRNA expression levels of interleukin17s (CgIL17-1, CgIL17-5 and CgIL17-6), and defensin (Cgdefh1) significantly decreased at 3 h after LPS stimulation, which was 0.51-fold (p < 0.001), 0.39-fold (p < 0.01), 0.48-fold (p < 0.05) and 0.41-fold (p < 0.05) of that in the control group, respectively. The nuclear translocation of Cgp65 protein was suppressed in the CgTAAR1L-RNAi oysters. Furthermore, the number of Vibrio splendidus in the haemolymph of CgTAAR1L-RNAi oysters significantly increased (4.11-fold, p < 0.001) compared with that in the control group. In contrast, there was no significant difference in phagocytic rate of haemocytes to V. splendidus in the CgTAAR1L-RNAi oysters. These results indicated that CgTAAR1L played an important role in the immune defense against bacterial infection by inducing the expressions of interleukin and defensin.

NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody.

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for successful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mammalian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinucleation and midbody disorganization. Using iTRAQ-based quantitative proteomic analysis, we find that RCC2 levels are decreased in NudCL2 knockout (KO) cells. Moreover, Hsp90 forms a complex with NudCL2 to stabilize RCC2, which is essential for cytokinesis. RCC2 depletion mirrors phenotypes observed in NudCL2-downregulated cells. Importantly, ectopic expression of RCC2 rescues the cytokinesis defects induced by NudCL2 deletion, but not vice versa. Together, our data reveal the significance of the NudCL2/Hsp90/RCC2 pathway in cytokinesis at the midbody.

Altered diurnal variation and localization of clock proteins in the remnant kidney of 5/6 nephrectomy rats.

AIM: To investigate the localization and diurnal variation of clock proteins (BMAL1, PER2) and clock output protein (DBP) in the remnant kidney of 5/6 nephrectomy rats (STNx). METHODS: Male wistar rats were randomly divided into sham STNx group (Control) and STNx group. Rats were synchronized 12 weeks to the light: dark cycle 12:12 with light on from 07.00 hours (Zeitgeber time ZT 0). Kidneys were collected to detect the localization and expression rhythm of clock proteins (BMAL1, PER2 and DBP) every 4 h throughout the day by immunohistochemistry and Western blotting. RESULTS: Clock proteins showed diurnal rhythm in the kidney of the control. But diurnal rhythm of clock proteins changed in the STNx rats. Acrophase of BMAL1, DBP and PER2 advanced 4 h, respectively; mesor of clock proteins increased in the STNx rats. BMAL1 was located in endothelial cells of glomerulus and tubular interstitial vasculars, and it was also expressed in nucleus of tubular cells in cortex and medulla. PER2 was mainly expressed in proximal tubular cells at the juncture of cortex and medulla. DBP was widely expressed in the kidney. The localization of BMAL1 and PER2 were changed in remnant kidneys of the STNx group. CONCLUSION: The localization and diurnal variation of BMAL1, DBP and PER2 are changed in remnant kidney of 5/6 nephrectomy rats and are involved in diurnal rhythm of renal function.

NudC-like protein 2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90.

The type I lissencephaly gene product LIS1, a key regulator of cytoplasmic dynein, is critical for cell proliferation, survival, and neuronal migration. However, little is known about the regulation of LIS1. Here, we identify a previously uncharacterized mammalian homolog of Aspergillus NudC, NudCL2 (NudC-like protein 2), as a regulator of LIS1. NudCL2 is localized to the centrosome in interphase, and spindle poles and kinetochores during mitosis, a pattern similar to the localization of LIS1 and cytoplasmic dynein. Depletion of NudCL2 destabilized LIS1 and led to phenotypes resembling those of either dynein or LIS1 deficiency. NudCL2 complexed with and enhanced the interaction between LIS1 and Hsp90. Either disruption of the LIS1-Hsp90 interaction with the C terminus of NudCL2 or inhibition of Hsp90 chaperone function by geldanamycin decreased LIS1 stability. Thus, our results suggest that NudCL2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone. This represents a hitherto undescribed mechanism of the LIS1/dynein regulation in mammalian cells.

GATA2 co-opts TGFß1/SMAD4 oncogenic signaling and inherited variants at 6q22 to modulate prostate cancer progression.

BACKGROUND: Aberrant somatic genomic alteration including copy number amplification is a hallmark of cancer genomes. We previously profiled genomic landscapes of prostate cancer (PCa), yet the underlying causal genes with prognostic potential has not been defined. It remains unclear how a somatic genomic event cooperates with inherited germline variants contribute to cancer predisposition and progression. METHODS: We applied integrated genomic and clinical data, experimental models and bioinformatic analysis to identify GATA2 as a highly prevalent metastasis-associated genomic amplification in PCa. Biological roles of GATA2 in PCa metastasis was determined in vitro and in vivo. Global chromatin co-occupancy and co-regulation of GATA2 and SMAD4 was investigated by coimmunoprecipitation, ChIP-seq and RNA-seq assays. Tumor cellular assays, qRT-PCR, western blot, ChIP, luciferase assays and CRISPR-Cas9 editing methods were performed to mechanistically understand the cooperation of GATA2 with SMAD4 in promoting TGFß1 and AR signaling and mediating inherited PCa risk and progression. RESULTS: In this study, by integrated genomics and experimental analysis, we identified GATA2 as a prevalent metastasis-associated genomic amplification to transcriptionally augment its own expression in PCa. Functional experiments demonstrated that GATA2 physically interacted and cooperated with SMAD4 for genome-wide chromatin co-occupancy and co-regulation of PCa genes and metastasis pathways like TGFß signaling. Mechanistically, GATA2 was cooperative with SMAD4 to enhance TGFß and AR signaling pathways, and activated the expression of TGFß1 via directly binding to a distal enhancer of TGFß1. Strinkingly, GATA2 and SMAD4 globally mediated inherited PCa risk and formed a transcriptional complex with HOXB13 at the PCa risk-associated rs339331/6q22 enhancer, leading to increased expression of the PCa susceptibility gene RFX6. CONCLUSIONS: Our study prioritizes causal genomic amplification genes with prognostic values in PCa and reveals the pivotal roles of GATA2 in transcriptionally activating the expression of its own and TGFß1, thereby co-opting to TGFß1/SMAD4 signaling and RFX6 at 6q22 to modulate PCa predisposition and progression.

Corrigendum: NudC L279P mutation destabilizes filamin a by inhibiting the Hsp90 chaperoning pathway and suppresses cell migration.

[This corrects the article DOI: 10.3389/fcell.2021.671233.].

Extensive germline-somatic interplay contributes to prostate cancer progression through HNF1B co-option of TMPRSS2-ERG.

Genome-wide association studies have identified 270 loci conferring risk for prostate cancer (PCa), yet the underlying biology and clinical impact remain to be investigated. Here we observe an enrichment of transcription factor genes including HNF1B within PCa risk-associated regions. While focused on the 17q12/HNF1B locus, we find a strong eQTL for HNF1B and multiple potential causal variants involved in the regulation of HNF1B expression in PCa. An unbiased genome-wide co-expression analysis reveals PCa-specific somatic TMPRSS2-ERG fusion as a transcriptional mediator of this locus and the HNF1B eQTL signal is ERG fusion status dependent. We investigate the role of HNF1B and find its involvement in several pathways related to cell cycle progression and PCa severity. Furthermore, HNF1B interacts with TMPRSS2-ERG to co-occupy large proportion of genomic regions with a remarkable enrichment of additional PCa risk alleles. We finally show that HNF1B co-opts ERG fusion to mediate mechanistic and biological effects of the PCa risk-associated locus 17p13.3/VPS53/FAM57A/GEMIN4. Taken together, we report an extensive germline-somatic interaction between TMPRSS2-ERG fusion and genetic variations underpinning PCa risk association and progression.

ALKBH3-dependent m1A demethylation of Aurora A mRNA inhibits ciliogenesis.

Primary cilia are antenna-like subcellular structures to act as signaling platforms to regulate many cellular processes and embryonic development. m1A RNA modification plays key roles in RNA metabolism and gene expression; however, the physiological function of m1A modification remains largely unknown. Here we find that the m1A demethylase ALKBH3 significantly inhibits ciliogenesis in mammalian cells by its demethylation activity. Mechanistically, ALKBH3 removes m1A sites on mRNA of Aurora A, a master suppressor of ciliogenesis. Depletion of ALKBH3 enhances Aurora A mRNA decay and inhibits its translation. Moreover, alkbh3 morphants exhibit ciliary defects, including curved body, pericardial edema, abnormal otoliths, and dilation in pronephric ducts in zebrafish embryos, which are significantly rescued by wild-type alkbh3, but not by its catalytically inactive mutant. The ciliary defects caused by ALKBH3 depletion in both vertebrate cells and embryos are also significantly reversed by ectopic expression of Aurora A mRNA. Together, our data indicate that ALKBH3-dependent m1A demethylation has a crucial role in the regulation of Aurora A mRNA, which is essential for ciliogenesis and cilia-associated developmental events in vertebrates.

The L279P mutation of nuclear distribution gene C (NudC) influences its chaperone activity and lissencephaly protein 1 (LIS1) stability.

LIS1, a gene mutated in classical lissencephaly, plays essential roles in cytoplasmic dynein regulation, mitosis and cell migration. However, the regulation of LIS1 (lissencephaly protein 1) protein remains largely unknown. Genetic studies in Aspergillus nidulans have uncovered that the Nud (nuclear distribution) pathway is involved in the regulation of cytoplasmic dynein complex and a temperature-sensitive mutation in the nudC gene (L146P) greatly reduces the protein levels of NudF, an Aspergillus ortholog of LIS1. Here, we showed that L146 in Aspergillus NudC and its flanking region were highly conservative during evolution. The similar mutation in human NudC (L279P) obviously led to reduced LIS1 and cellular phenotypes similar to those of LIS1 down-regulation. To explore the underlying mechanism, we found that the p23 domain-containing protein NudC bound to the molecular chaperone Hsp90, which is also associated with LIS1. Inhibition of Hsp90 chaperone function by either geldanamycin or radicicol resulted in a decrease in LIS1 levels. Ectopic expression of Hsp90 partially reversed the degradation of LIS1 caused by overexpression of NudC-L279P. Furthermore, NudC was found to regulate the ATPase activity of Hsp90, which was repressed by the mutation of L279P. Interestingly, NudC itself was shown to possess a chaperone function, which also was suppressed by the L279P mutation. Together, these data suggest that NudC may be involved in the regulation of LIS1 stability by its chaperone function.

Impaired activation of phosphatidylinositol 3-kinase by leptin is a novel mechanism of hepatic leptin resistance in NAFLD.

BACKGROUND/AIMS: The aim of this study was to detect the levels of leptin in serum and the expression of leptin, obesity receptor (OB-R), phosphatidylinositol 3-Kinase (p85) (PI3-K p85) and phospho-Akt-kinase (Akt) in non-alcoholic fatty liver disease (NAFLD). METHODOLOGY: The expressions of leptin, OB-R and PI3-K/ Akt kinase pathway were examined by immunohistochemistry. The level of leptin in serum was measured by radioimmunoassay. RESULTS: In agreement with significantly elevated serum leptin levels in NAFLD patients (p<0.05), expression of leptin, OB-R and PI3-K (p85) was significant higher in NAFLD patients (p<0.05) compared with the control patients. In contrast, expression of Akt was significantly down-regulated in the NAFLD patients (p<0.05). Moreover, PI3-K (p85) expression was significantly, positively correlated with leptin (r= 0.365, p<0.05) but negatively correlated with Akt (r=-0.854, p<0.01). CONCLUSIONS: Leptin may be involved in NAFLD pathogenesis by activating the PI3-K/Akt kinase pathway via OB-R and the defective leptin activation of PI3-K is a novel mechanism of leptin resistance in NAFLD.

An N-Port Universal Multimode Optical Router Supporting Mode-Division Multiplexing.

Optical network-on-chip (ONoC) is based on optical interconnects and optical routers (ORs), which have obvious advantages in bandwidth and power consumption. Transmission capacity is a significant performance in ONoC architecture, which has to be fully considered during the design process. Relying on mode-division multiplexing (MDM) technology, the system capacity of optical interconnection is greatly improved compared to the traditional multiplexing technology. With the explosion in MDM technology, the optical router supporting MDM came into being. In this paper, we design a multimode optical router (MDM-OR) model and analyze its indicators. Above all, we propose a novel multimode switching element and design an N-port universal multimode optical router (MDM-OR) model. Secondly, we analyze the insertion loss model of different optical devices and the crosstalk noise model of N-port MDM-OR. On this basis, a multimode router structure of a single-mode five-port optical router is proposed. At the same time, we analyze the transmission loss, crosstalk noise, signal-to-noise radio (OSNR), and bit error rate (BER) of different input-output pairs by inputting the 1550 nm TE0, TE1, and TE2 modes to the router.

NudCL2 is an autophagy receptor that mediates selective autophagic degradation of CP110 at mother centrioles to promote ciliogenesis.

Primary cilia extending from mother centrioles are essential for vertebrate development and homeostasis maintenance. Centriolar coiled-coil protein 110 (CP110) has been reported to suppress ciliogenesis initiation by capping the distal ends of mother centrioles. However, the mechanism underlying the specific degradation of mother centriole-capping CP110 to promote cilia initiation remains unknown. Here, we find that autophagy is crucial for CP110 degradation at mother centrioles after serum starvation in MEF cells. We further identify NudC-like protein 2 (NudCL2) as a novel selective autophagy receptor at mother centrioles, which contains an LC3-interacting region (LIR) motif mediating the association of CP110 and the autophagosome marker LC3. Knockout of NudCL2 induces defects in the removal of CP110 from mother centrioles and ciliogenesis, which are rescued by wild-type NudCL2 but not its LIR motif mutant. Knockdown of CP110 significantly attenuates ciliogenesis defects in NudCL2-deficient cells. In addition, NudCL2 morphants exhibit ciliation-related phenotypes in zebrafish, which are reversed by wild-type NudCL2, but not its LIR motif mutant. Importantly, CP110 depletion significantly reverses these ciliary phenotypes in NudCL2 morphants. Taken together, our data suggest that NudCL2 functions as an autophagy receptor mediating the selective degradation of mother centriole-capping CP110 to promote ciliogenesis, which is indispensable for embryo development in vertebrates.

NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration.

Filamin A, the first discovered non-muscle actin filament cross-linking protein, plays a crucial role in regulating cell migration that participates in diverse cellular and developmental processes. However, the regulatory mechanism of filamin A stability remains unclear. Here, we find that nuclear distribution gene C (NudC), a cochaperone of heat shock protein 90 (Hsp90), is required to stabilize filamin A in mammalian cells. Immunoprecipitation-mass spectrometry and western blotting analyses reveal that NudC interacts with filamin A. Overexpression of human NudC-L279P (an evolutionarily conserved mutation in NudC that impairs its chaperone activity) not only decreases the protein level of filamin A but also results in actin disorganization and the suppression of cell migration. Ectopic expression of filamin A is able to reverse these defects induced by the overexpression of NudC-L279P. Furthermore, Hsp90 forms a complex with filamin A. The inhibition of Hsp90 ATPase activity by either geldanamycin or radicicol decreases the protein stability of filamin A. In addition, ectopic expression of Hsp90 efficiently restores NudC-L279P overexpression-induced protein stability and functional defects of filamin A. Taken together, these data suggest NudC L279P mutation destabilizes filamin A by inhibiting the Hsp90 chaperoning pathway and suppresses cell migration.

NudCL2 regulates cell migration by stabilizing both myosin-9 and LIS1 with Hsp90.

Cell migration plays pivotal roles in many biological processes; however, its underlying mechanism remains unclear. Here, we find that NudC-like protein 2 (NudCL2), a cochaperone of heat shock protein 90 (Hsp90), modulates cell migration by stabilizing both myosin-9 and lissencephaly protein 1 (LIS1). Either knockdown or knockout of NudCL2 significantly increases single-cell migration, but has no significant effect on collective cell migration. Immunoprecipitation-mass spectrometry and western blotting analyses reveal that NudCL2 binds to myosin-9 in mammalian cells. Depletion of NudCL2 not only decreases myosin-9 protein levels, but also results in actin disorganization. Ectopic expression of myosin-9 efficiently reverses defects in actin disorganization and single-cell migration in cells depleted of NudCL2. Interestingly, knockdown of myosin-9 increases both single and collective cell migration. Depletion of LIS1, a NudCL2 client protein, suppresses both single and collective cell migration, which exhibits the opposite effect compared with myosin-9 depletion. Co-depletion of myosin-9 and LIS1 promotes single-cell migration, resembling the phenotype caused by NudCL2 depletion. Furthermore, inhibition of Hsp90 ATPase activity also reduces the Hsp90-interacting protein myosin-9 stability and increases single-cell migration. Forced expression of Hsp90 efficiently reverses myosin-9 protein instability and the defects induced by NudCL2 depletion, but not vice versa. Taken together, these data suggest that NudCL2 plays an important role in the precise regulation of cell migration by stabilizing both myosin-9 and LIS1 via Hsp90 pathway.

A photoresponsive molecularly imprinted polymer with rapid visible-light-induced photoswitching for 4-ethylphenol in red wine.

The trans to cis isomerization of the azobenzene chromophore in most azobenzene-based photoresponsive molecularly imprinted polymers (MIPs) is initiated by UV irradiation. This limits the application of these materials in cases where UV light toxicity is an issue, such as in biological systems, food monitoring, and drug delivery. Herein we report a tetra-ortho-methyl substituted azobenzene, (4-[(4-methacryloyloxy)-2,6-dimethyl phenylazo]-3,5-dimethyl benzenesulfonic acid (MADPADSA). The photoswitching of MADPADSA could be induced by visible-light irradiation (550 nm for trans to cis and 475 nm for cis to trans) in 4-hydroxyethylpiperazineethanesulfonic acid (HEPES) buffer-ethanol (4:1, v/v) at pH 7.0, however, the photoisomerization was slow. With the use of MADPADSA as a functional monomer, NaYF4:Yb3+,Er3+ as a substrate, 4-ethylphenol (4-EP) as a template, a novel photoresponsive surface molecularly imprinted polymer NaYF4:Yb3+,Er3+@MIP was obtained. The NaYF4:Yb3+,Er3+@MIP displayed rapid visible-light-induced photoswitching. The NaYF4:Yb3+,Er3+ substrate could efficiently increase the trans to cis isomerization rate of the photoresponsive MIP on its surface, which was faster than that of the corresponding azobenzene monomer MADPADSA. Possible reasons for this effect were investigated by fluorescence spectroscopy. NaYF4:Yb3+,Er3+@MIP displayed good specificity toward 4-EP with a specific binding constant (Kd) of 3.67 × 10-6 mol L-1 and an apparent maximum adsorption capacity (Qmax) of 10.73 µmol g-1, respectively. NaYF4:Yb3+,Er3+@MIP was applied to determine the concentration of 4-EP in red wine with good efficiency and a limit of detection lower than the value that could cause an unpleasant off-flavor.