Modeling autosomal dominant retinitis pigmentosa by using patient-specific retinal organoids with a class-3 RHO mutation.

Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP) causes progressive vision loss and is potentially incurable, accounting for 25% of adRP cases. Studies on RHO-adRP mechanism were at large based on the biochemical and cellular properties, especially class-3. Nonetheless, the absence of an appropriate model for class-3 RHO-adRP has impeded comprehensive exploration. Here, induced pluripotent stem cells (iPSCs) were generated from a healthy control and two sibling RP patients with the same point mutation, c.403C>T (p.R135W). The first three-dimensional (3D) retinal organoid model of a class-3 RHO point mutation from patient-derived iPSCs was generated. Significant defects were observed in rod photoreceptors in terms of localization, morphology, transcriptional profiling and single cell resolution, to better understand the human disease resulting from RHO mutations from a developmental perspective. This first human model of class-3 RHO-adRP provides a representation of patient's retina in vitro and displays features of RHO-adRP retinal organoids relevant for therapeutic development.

Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling.

Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1). Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.

Preparation of a bis-triazolyl bridged ß-cyclodextrin stationary phase and its application for enantioseparation of chiral compounds by HPLC.

A novel bis-triazolyl bridged ß-cyclodextrin was first synthesized by the Click reaction between azido-ß-cyclodextrin and 1,6-heptadiyne. Then it was bonded onto silica gel to obtain a bis-triazolyl bridged ß-cyclodextrin-based chiral stationary phase (BCDP). After structure characterization, the HPLC performance of BCDP was systematically evaluated by using different types of compounds as probes. The results showed that BCDP could well separate 18 kinds of achiral aromatic compounds (homologues, positional isomers, etc.) and 35 kinds of chiral drugs or pesticides, such as triazoles (Rs = 1.33-3.15), flavanones (Rs = 1.49-2.62), dansyl amino acids (Rs = 0.96-1.99), and ß-blocker drugs (Rs = 0.68-2.78). BCDP could separate a wider range of compounds (53 kinds); especially, some chiral substance pairs that were difficult to be resolved on the ordinary cyclodextrin CSPs, including triazoles containing two chiral carbons (triadimenol, bitertanol, metconazole, and triticonazole), strongly ionized amino acids (acidic Asp, alkalic Arg, and polar Thr) and ß-blockers with bulky groups (carvedilol, propranolol, and pindolol). Obviously, the unique synergistic inclusion effect of bridged cyclodextrin with double cavities and the bis-triazole bridging group could provide multiple action sites, such as hydrogen bonding, π-π stacking and acid-base action sites, thus improving its chiral chromatographic performance.

Gene replacement therapy restores RCBTB1 expression and cilium length in patient-derived retinal pigment epithelium.

Biallelic mutations in the RCBTB1 gene cause retinal dystrophy. Here, we characterized the effects of RCBTB1 gene deficiency in retinal pigment epithelial (RPE) cells derived from a patient with RCBTB1-associated retinopathy and restored RCBTB1 expression in these cells using adeno-associated viral (AAV) vectors. Induced pluripotent stem cells derived from a patient with compound heterozygous RCBTB1 mutations (c.170delG and c.707delA) and healthy control subjects were differentiated into RPE cells. RPE cells were treated with AAV vectors carrying a RCBTB1 transgene. Patient-derived RPE cells showed reduced expression of RCBTB1. Expression of NFE2L2 showed a non-significant reduction in patient RPE cells compared with controls, while expression of its target genes (RXRA, IDH1 and SLC25A25) was significantly reduced. Trans-epithelial electrical resistance, surface microvillus densities and primary cilium lengths were reduced in patient-derived RPE cells, compared with controls. Treatment of patient RPE with AAV vectors significantly increased RCBTB1, NFE2L2 and RXRA expression and cilium lengths. Our study provides the first report examining the phenotype of RPE cells derived from a patient with RCBTB1-associated retinopathy. Furthermore, treatment of patient-derived RPE with AAV-RCBTB1 vectors corrected deficits in gene expression and RPE ultrastructure, supporting the use of gene replacement therapy for treating this inherited retinal disease.

Elevated whole blood arsenic level is associated with type 2 diabetes in coal-burning areas in Guizhou.

The potential association between coal-burning arsenic exposure and type 2 diabetes (T2D) was examined through a case control study, conducted in coal-burning arsenic poisoning areas in the Guizhou Province. This study included patients diagnosed with type 2 diabetes. Control subjects without type 2 diabetes were recruited randomly after gender and age 1:1 matching. All subjects completed questionnaire surveys and underwent physical examination and whole blood arsenic level testing. The whole blood arsenic level was associated with a significant increase in the risk of type 2 diabetes (75th versus 25th, adjusted OR = 1.76, 95% CI: 1.03-3.01). However, a nonlinear relationship was observed between the blood arsenic level and type 2 diabetes. The risk of type 2 diabetes increased with blood arsenic levels above 3.69 µg/L (Log As ≥0.57). The subgroup analysis revealed that blood arsenic levels were associated with significantly increased risk of type 2 diabetes in people who ever smoked (P < .05), particularly those who smoked ≥15 years (adjusted OR = 3.15, 95% CI: 1.9-7.28). Therefore, prolonged arsenic exposure, even at a low level, is associated with a higher prevalence of type 2 diabetes in a nonlinear pattern. Blood arsenic levels less than 3.69 µg/L may be considered safe with respect to the risk of T2D. However, smoking, particularly smoking ≥15 years, may be associated with the development of diabetes in patients with arsenic exposure.

Mutation spectrum and genotype-phenotype correlation of inherited retinal dystrophy in Taiwan.

BACKGROUND: Inherited retinal dystrophy (IRD) is a group of irreversible retinal degenerative disorders with significant genotypic and phenotypic heterogeneity, which cause difficulty in making a precise clinical diagnosis. Furthermore, the mutation spectrum of IRD in Taiwan remains unknown. Therefore, our study focused on investigating the spectrum of mutations among Taiwanese families with IRD using targeted exome sequencing (TES) technology. METHODS: We recruited a total of 60 unrelated Taiwanese families with IRD; most of them were retinitis pigmentosa. We employed TES to investigate 284 candidate genes. Bioinformatics analysis, Sanger sequencing-based co-segregation testing, and computational assessment were performed to validate each mutation and its pathogenicity. The genotype-phenotype correlation was analysed in all patients with mutations defined in the guidelines provided by the American College of Medical Genetics. RESULTS: We successfully identified genetic causes in 32 families (detection rate of 53.3%). Among them, 16 had a sporadic inheritance (16/36, 44.4%); eight had an autosomal recessive inheritance (8/14, 57.1%); four had an autosomal dominant inheritance (4/5, 80%); four had an X-linked inheritance (4/5, 80%). Among 38 pathological mutations in 19 known genes, 20 mutations are reported here for the first time. Novel mutation spectrum and genotype-phenotype correlations were revealed as well. CONCLUSION: Here we achieved a detection rate of 53.3% and elucidated the mutation spectrum in Taiwanese families with IRD for the first time. The results indicated that CYP4V2 and USH2A might be the most common pathogenic genes in IRD patients in Taiwan.

Polarization-selective waveguide holography in the visible spectrum.

We propose and experimentally demonstrate a polarization-selective waveguide hologram at optical wavelengths, based on an all-dielectric metamaterial multilayer system. We show that two spatially separated or overlapped holographic images can be produced with two orthogonally polarized beams, incorporated into a binary computer generated hologram (CGH). These two images can be combined into a single 3D stereoscopic image observable using linearly or circularly polarized glasses. The two polarized beams can also be utilized to construct radially and azimuthally polarized "vortex" beams. The fundamental and first higher-order TM and TE modes of an optical waveguide are used to guide the two polarization states with distinct propagation constants. The two guided waves act as spatially distinct reference waves such that the integrated, on-chip hologram can distinguish the two and provide two independent images corresponding to the two polarizations. Polarization selective waveguide holograms can be used in a diverse set of applications, from chip-scale displays and augmented reality (AR) to optical trapping.

Enhanced Two-Photon Photochromism in Metasurface Perfect Absorbers.

Light switchable materials are essential to optoelectronic applications in photovoltaics, memories, sensors, and communications. Natural switchable materials suffer from weak absorption and slow response times, preventing their use in low-power, ultrafast applications. Integrating light switchable materials with metasurface perfect absorbers offers an innovative route to achieving desirable features for nanophotonic devices, such as directional emission, low-power and broadband operation, high radiative quantum efficiency, and large spontaneous emission rates. Here we show an enhanced two-photon photochromism based on a metasurface perfect absorber: film-coupled colloidal silver nanocubes. The photochromic molecules, spiropyrans, are sandwiched between the silver nanocubes and the gold substrate. With nearly 100% absorption and an accompanying large field enhancement in the molecular junction, the transformation of spiropyrans to merocyanines is observed under excitation with 792 nm laser light. Fluorescence lifetime measurements on the merocyanine form reveal that large Purcell enhancement in the film-coupled nanocubes leads to large enhancements of the spontaneous emission rate and a high quantum efficiency. An averaged incident power as low as 10 µW is enough to initiate the two-photon isomerization of spiropyran in the film-coupled nanocubes, and a power of 100nW is able to excite the merocyanines to emit fluorescence. The power consumption is orders of magnitude lower than bare spiropyran thin films on silicon and gold, which is highly desirable for the writing and reading processes relevant to optical data storage. By sweeping the plasmonic resonance of the film-coupled nanocubes, wavelength specificity is demonstrated, which opens up new possibilities for minimizing the cross talk between adjacent bits in nanophotonic devices.

Clarification of surface modes of a periodic nanopatch metasurface.

We study the angle-dependent optical reflectance spectrum of a metasurface consisting of a periodic array of film-coupled plasmonic nanopatch particles. The nanopatch metasurface exhibits a strong, angle-independent absorption resonance at a wavelength defined by the nanopatch geometry and relative density. When the nanopatches are arranged in a regular lattice, a second, sharp absorption dip is present that varies strongly as a function of the incidence angle. This second resonance is a collective effect involving the excitation of surface plasmon modes and relates to a Wood's anomaly. Using an analytical model, we compute the surface modes of the structure and confirm details about the various mechanisms that contribute to the reflection spectra. The measured reflectance spectra are in excellent agreement with both analytical calculations and full-wave numerical simulations.

MED12 mutations and NOTCH signalling in chronic lymphocytic leukaemia.

Mutations in the N-terminus of MED12 protein occur at high frequency in uterine leiomyomas and breast fibroepithelial tumours, and are frequently found in chronic lymphocytic leukaemia (CLL). MED12 mutations have been previously linked to aberrant Cyclin C-CDK8 kinase activity, but the exact oncogenic function in CLL is unknown. Here, we characterized MED12 mutations in CLL and identified recurrent mutations in 13 out of 188 CLL patients (6·9%), which clustered in the N-terminus. MED12 mutations were associated with unmutated IGHV (P = 0·024). Protein analysis of NOTCH1 in primary CLL samples revealed increased levels of NOTCH1 intracellular domain (NICD), the active form of NOTCH1, in the context of MED12 mutations. We found evidence that NICD is the target of Cyclin C-CDK8 kinase using a specific CDK8 inhibitor. In line with these findings, MED12 mutations were mutually exclusive to mutations in NOTCH1 in CLL, based on a meta-analysis of 1429 CLL patients (P = 0·011). Our results suggest that MED12 mutations may contribute to CLL pathogenesis by activating NOTCH signalling.

Improved Durability and Sensitivity of Bitterness-Sensing Membrane for Medicines.

This paper reports the improvement of a bitterness sensor based on a lipid polymer membrane consisting of phosphoric acid di-n-decyl ester (PADE) as a lipid and bis(1-butylpentyl) adipate (BBPA) and tributyl o-acetylcitrate (TBAC) as plasticizers. Although the commercialized bitterness sensor (BT0) has high sensitivity and selectivity to the bitterness of medicines, the sensor response gradually decreases to almost zero after two years at room temperature and humidity in a laboratory. To reveal the reason for the deterioration of the response, we investigated sensor membranes by measuring the membrane potential, contact angle, and adsorption amount, as well as by performing gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found that the change in the surface charge density caused by the hydrolysis of TBAC led to the deterioration of the response. The acidic environment generated by PADE promoted TBAC hydrolysis. Finally, we succeeded in fabricating a new membrane for sensing the bitterness of medicines with higher durability and sensitivity by adjusting the proportions of the lipid and plasticizers.

In silico SNP analysis of the breast cancer antigen NY-BR-1.

BACKGROUND: Breast cancer is one of the most common malignancies with increasing incidences every year and a leading cause of death among women. Although early stage breast cancer can be effectively treated, there are limited numbers of treatment options available for patients with advanced and metastatic disease. The novel breast cancer associated antigen NY-BR-1 was identified by SEREX analysis and is expressed in the majority (>70%) of breast tumors as well as metastases, in normal breast tissue, in testis and occasionally in prostate tissue. The biological function and regulation of NY-BR-1 is up to date unknown. METHODS: We performed an in silico analysis on the genetic variations of the NY-BR-1 gene using data available in public SNP databases and the tools SIFT, Polyphen and Provean to find possible functional SNPs. Additionally, we considered the allele frequency of the found damaging SNPs and also analyzed data from an in-house sequencing project of 55 breast cancer samples for recurring SNPs, recorded in dbSNP. RESULTS: Over 2800 SNPs are recorded in the dbSNP and NHLBI ESP databases for the NY-BR-1 gene. Of these, 65 (2.07%) are synonymous SNPs, 191 (6.09%) are non-synoymous SNPs, and 2430 (77.48%) are noncoding intronic SNPs. As a result, 69 non-synoymous SNPs were predicted to be damaging by at least two, and 16 SNPs were predicted as damaging by all three of the used tools. The SNPs rs200639888, rs367841401 and rs377750885 were categorized as highly damaging by all three tools. Eight damaging SNPs are located in the ankyrin repeat domain (ANK), a domain known for its frequent involvement in protein-protein interactions. No distinctive features could be observed in the allele frequency of the analyzed SNPs. CONCLUSION: Considering these results we expect to gain more insights into the variations of the NY-BR-1 gene and their possible impact on giving rise to splice variants and therefore influence the function of NY-BR-1 in healthy tissue as well as in breast cancer.

Optical bistability with film-coupled metasurfaces.

Metasurfaces comprising arrays of film-coupled, nanopatch antennas are a promising platform for low-energy, all-optical switches. The large field enhancements that can be achieved in the dielectric spacer region between the nanopatch and the metallic substrate can substantially enhance optical nonlinear processes. Here we consider a dielectric material that exhibits an optical Kerr effect as the spacer layer and numerically calculate the optical bistability of a metasurface using the finite element method (FEM). We expect the proposed method to be highly accurate compared with other numerical approaches, such as those based on graphical post-processing techniques, because it self-consistently solves for both the spatial field distribution and the intensity-dependent refractive index distribution of the spacer layer. This method offers an alternative approach to finite-difference time-domain (FDTD) modeling. We use this numerical tool to design a metasurface optical switch and our optimized design exhibits exceptionally low switching intensity of 33 kW/cm2, corresponding to switching energy on the order of tens of attojoules per resonator, a value much smaller than those found for most devices reported in the literature. We propose our method as a tool for designing all-optical switches and modulators.

Bilateral optic atrophy in Wilson disease: A case report and literature review.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The clinical manifestations of WD are complex and variable, with Kayser-Fleischer ring (K-F ring) and the sunflower cataract being the most common ocular findings. Visual impairment is rare in patients with WD. We report the case of a 17-year-old female with bilateral optic atrophy associated with WD and summarize the clinical features of previously reported cases of optic neuropathy in WD, Clinicians should be aware that WD is a rare cause of optic neuropathy and that optic neuropathy in patients with WD may need to be recognized and screened.

Elevated serum trimethylamine oxide levels as potential biomarker for diabetic kidney disease.

Background: Diabetic kidney disease (DKD) has become a major cause of chronic kidney disease. However, early diagnosis of DKD is challenging. Trimethylamine oxide (TMAO) is an intestinal microbial metabolite which might be associated with diabetes complications. The aim of this study was to investigate the correlation between TMAO and DKD. Methods: A cross-sectional study was conducted. A total of 108 T2DM patients and 33 healthy subjects were enrolled in this study. Multiple logistic regression analyses and area under receiver operating characteristic curves (AUROC) were performed to evaluate the correlation between serum TMAO and DKD. Results: Serum TMAO levels were significantly higher in DKD patients than healthy control group and the NDKD (T2DM without combined DKD) group (P < 0.05). TMAO levels were negatively correlated with eGFR and positively correlated with urea nitrogen, ACR and DKD (P < 0.05). Logistic regression analysis indicated that serum TMAO was one of the independent risk factors for DKD patients (P < 0.05). In the diagnostic model, the AUROC of TMAO for the diagnosis of DKD was 0.691. Conclusion: Elevated levels of serum TMAO levels were positively associated with the risk of DKD in T2DM patients, which might be a potential biomarker for DKD.

Mitochondrial Dysfunction and Impaired Antioxidant Responses in Retinal Pigment Epithelial Cells Derived from a Patient with RCBTB1-Associated Retinopathy.

Mutations in the RCBTB1 gene cause inherited retinal disease; however, the pathogenic mechanisms associated with RCBTB1 deficiency remain poorly understood. Here, we investigated the effect of RCBTB1 deficiency on mitochondria and oxidative stress responses in induced pluripotent stem cell (iPSC)-derived retinal pigment epithelial (RPE) cells from control subjects and a patient with RCBTB1-associated retinopathy. Oxidative stress was induced with tert-butyl hydroperoxide (tBHP). RPE cells were characterized by immunostaining, transmission electron microscopy (TEM), CellROX assay, MitoTracker assay, quantitative PCR and immunoprecipitation assay. Patient-derived RPE cells displayed abnormal mitochondrial ultrastructure and reduced MitoTracker fluorescence compared with controls. Patient RPE cells displayed increased levels of reactive oxygen species (ROS) and were more sensitive to tBHP-induced ROS generation than control RPE. Control RPE upregulated RCBTB1 and NFE2L2 expression in response to tBHP treatment; however, this response was highly attenuated in patient RPE. RCBTB1 was co-immunoprecipitated from control RPE protein lysates by antibodies for either UBE2E3 or CUL3. Together, these results demonstrate that RCBTB1 deficiency in patient-derived RPE cells is associated with mitochondrial damage, increased oxidative stress and an attenuated oxidative stress response.

Foveal hypoplasia in a Chinese adolescent with 48, XXYY syndrome.

BACKGROUND: 48, XXYY syndrome is a rare sex chromosome aneuploidy with severe systemic features. Ophthalmic manifestation of 48, XXYY syndrome include hypertelorism, epicanthic folds, hooded eye lids, strabismus, retinitis pigmentosa and Duane's syndrome. CASE: We present mild foveal hypoplasia in a 12-year-old boy with 48, XXYY syndrome using swept-source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The boy was referred for assessment of strabismus and poor visual acuity. OCT revealed persistence of inner retinal layers, and thinning of the outer nuclear layer in the perifoveal region with thickening of the outer plexiform layer. OCTA revealed increased vessel density with reduced foveal avascular zone. CONCLUSION: We described novel OCT and OCTA features of bilateral foveal hypoplasia and reduction of FAZ in a case of 48, XXYY syndrome based on detailed clinical observation and thorough genetic testing. This case expanded the current literature of this rare sex chromosome abnormality and suggest the importance of retinal examinations in 48, XXYY syndrome.

Preparation and evaluation of a perylenediimide bridged bis(ß-cyclodextrin) chiral stationary phase for HPLC.

A large π-conjugated perylenediimide bridged bis(ß-cyclodextrin)-bonded stationary phase (PBCDP) was first prepared and characterized. The chiral HPLC performance was systematically evaluated using a series of chiral probes. The results showed that PBCDP could resolve 36 kinds of chiral compounds in reversed-phase and polar organic modes with high resolutions (Rs) 1.48-3.28 for profens, 1.25-2.85 for triazoles, 1.34-5.29 for flavanones, 1.66-4.58 for amino acids and 1.22-1.97 for ß-blockers. Especially, PBCDP could completely resolve acidic non-steroidal chiral drugs (profens) and simultaneously resolve basic five triazole pesticides, which were difficult to separate by ordinary CDCSP. Compared with CDCSP (15 kinds), the new stationary phase has a wider resolution range (36 kinds). Obviously, the synergistic inclusion of the two cavities of bridged cyclodextrin, as well as the large π-π stacking, hydrogen bond, dipole-dipole and basic primary amine site (-NH-) provided by the perylenediimide bridging group contributed together to the improvement of the above chiral separations. PBCDP was a new type of versatile chiral separation material without port derivatization.

One-Pot Synthesis of Amphiphilic Biopolymers from Oxidized Alginate and Self-Assembly as a Carrier for Sustained Release of Hydrophobic Drugs.

In this paper, we developed an organic solvent-free, eco-friendly, simple and efficient one-pot approach for the preparation of amphiphilic conjugates (Ugi-OSAOcT) by grafting octylamine (OCA) to oxidized sodium alginate (OSA). The optimum reaction parameters that were obtained based on the degree of substitution (DS) of Ugi-OSAOcT were a reaction time of 12 h, a reaction temperature of 25 °C and a molar ratio of 1:2.4:3:3.3 (OSA:OCA:HAc:TOSMIC), respectively. The chemical structure and composition were characterized by Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (1H NMR), X-ray diffraction (XRD), thermogravimetry analyser (TGA), gel permeation chromatography (GPC) and elemental analysis (EA). It was found that the Ugi-OSAOcT conjugates with a CMC value in the range of 0.30-0.085 mg/mL could self-assemble into stable and spherical micelles with a particle size of 135.7 ± 2.4-196.5 ± 3.8 nm and negative surface potentials of -32.8 ± 0.4--38.2 ± 0.8 mV. Furthermore, ibuprofen (IBU), which served as a model poorly water-soluble drug, was successfully incorporated into the Ugi-OSAOcT micelles by dialysis method. The drug loading capacity (%DL) and encapsulation efficiency (%EE) of the IBU-loaded Ugi-OSAOcT micelles (IBU/Ugi-OSAOcT = 3:10) reached as much as 10.9 ± 0.4-14.6 ± 0.3% and 40.8 ± 1.6-57.2 ± 1.3%, respectively. The in vitro release study demonstrated that the IBU-loaded micelles had a sustained and pH-responsive drug release behavior. In addition, the DS of the hydrophobic segment on an OSA backbone was demonstrated to have an important effect on IBU loading and drug release behavior. Finally, the in vitro cytotoxicity assay demonstrated that the Ugi-OSAOcT conjugates exhibited no significant cytotoxicity against RAW 264.7 cells up to 1000 µg/mL. Therefore, the amphiphilic Ugi-OSAOcT conjugates synthesized by the green method exhibited great potential to load hydrophobic drugs, acting as a promising nanocarrier capable of responding to pH for sustained release of hydrophobic drugs.

High-directionality spin-selective routing of photons in plasmonic nanocircuits.

Efficient on-chip manipulation of photon spin is of crucial importance in developing future integrated nanophotonics as is electron spin in spintronics. The unidirectionality induced by the interaction between spin and orbital angular momenta suffers low efficiency in classical macroscopic optics, while it can be highly enhanced on subwavelength scales with suitable architectures. Here we propose and demonstrate a spin-sorting achiral split-ring coupler to unidirectionally excite dielectric-loaded plasmonic modes in two independent waveguides. We found experimentally that the impinging light with different spin can be selectively directed into one of two branching plasmonic waveguides with a directionality contrast up to 15.1 dB. A circular-helicity-independent compact beam splitter is also realized demonstrating great potential in designing complex interconnect nanocircuits. The illustrated approach is believed to open new avenues for developing advanced optical functionalities with a flexible degree of freedom in manipulation of on-chip chirality within chiral optics.