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Hybrid lenses are created by combining metasurface optics with refractive optics, where refractive elements contribute optical power, while metasurfaces correct optical aberrations. We present an algorithm for optimizing metasurface nanostructures within a hybrid lens, allowing flexible interleaving of metasurface and refractive optics in the optical train. To efficiently optimize metasurface nanostructures, we develop a scalar field, ray-wave hybrid propagation method. This method facilitates the propagation of incident and derived adjoint fields through optical elements, enabling effective metasurface optimization within the framework of adjoint gradient optimization. Numerical examples of various lens configurations are presented to illustrate the versatility of the algorithm and showcase the benefits offered by the proposed approach, allowing metasurfaces to be positioned beyond the image space of a lens. Taking a F/2, 40° field-of-view, midwave infrared lens as an example, the lens exhibits an average focusing efficiency of 38% before the integration of metasurfaces. Utilizing the new algorithm to design two metasurfaces-one in the object space and one in the image space-results in significant enhancement of the average focusing efficiency to over 90%. In contrast, a counterpart design with both metasurfaces limited to the image space yields a lower average focusing efficiency of 73%.

Background: Gap junction protein beta 2 ( GJB2 ) p.V37I mutations are the most important hereditary cause of sensorineural hearing loss (SNHL) in Taiwan. Hearing outcomes are associated with hearing levels at baseline and the duration of follow-up. However, the audiological features of GJB2 p.V37I mutations in the adult population are unknown. The objectives of the present study were to investigate the audiological features, progression rate, and allele frequency of GJB2 p.V37I mutations among an adult Taiwanese population., Methods: Subjects of this case-control study were chosen from 13,580 participants of the Taiwan Precision Medicine Initiative. The genetic variations of GJB2 p.V37I were determined by polymerase chain reaction. We analyzed existing pure-tone threshold data from 38 individuals who were homozygous or compound heterozygotes for GJB2 p.V37I, 129 who were heterozygotes, and 602 individuals who were wild-type. Phenome-wide association studies (PheWAS) analysis was also performed to identify phenotypes associated with GJB2 p.V37I., Results: The minor allele frequency of GJB2 p.V37I was 0.92% in our study population. The mean hearing level of participants with a p.V37I mutation indicated moderate to severe hearing loss with 38.2% ± 22.3% binaural hearing impairment. GJB2 p.V37I was associated with an increased risk of hearing disability (odds ratio: 21.46, 95% confidence interval: 8.62 to 53.44, p < 0.001) in an autosomal recessive pattern. In addition, PheWAS discovered a significant association between GJB2 p.V37I and fracture of the humerus. GJB2 p.V37I is a pathogenic and prevalent variant of SNHL among the adult population., Conclusions: The present study recommends patients with known GJB2 p.V37I mutations receive regular audiometric evaluation and genetic counseling. Early assistive listening device intervention is suggested to improve the quality of hearing., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: In this study, we investigated the effect of functional endoscopic sinus surgery (FESS) on gustatory function in patients with chronic rhinosinusitis (CRS)., Methods: Forty-three patients with CRS who underwent FESS were included in this study. Prior to FESS and 3 months after surgery, the severity of rhinosinusitis was assessed using the Taiwanese version of the 22-item SNOT (SNOT-22), endoscopic examination, and acoustic rhinometry. The olfactory function was evaluated using the phenylethyl alcohol odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test, and the gustatory function was evaluated using the whole mouth suprathreshold taste test (WMTT) and the taste quad test (TQT). Subgroup analyses were performed based on CRS phenotypes and endotypes., Results: The SNOT-22 significantly improved 3 months after FESS for all patients with CRS. The endoscopic score and olfactory function significantly improved in patients with eosinophilic CRS and in patients with nasal polyps (CRSwNP). The WMTT sweet and bitter scores were significantly lower after FESS in CRSwNP, but the TQT sweet score was significantly higher in patients without nasal polyps. In addition, patients with noneosinophilic CRS had significantly decreased WMTT and salty scores 3 months after FESS., Conclusion: Our results showed that the effect of FESS on gustatory function of patients with CRS was different with the different testing procedures, the association with nasal polyps, and the underlying inflammatory patterns.

Background: A 23-gene classifier has been developed based on gene expression profiles of Taiwanese luminal-like breast cancer. We aim to stratify risk of relapse and identify patients who may benefit from adjuvant chemotherapy based on genetic model among distinct clinical risk groups. Methods: There were 248 luminal (hormone receptor-positive and human epidermal growth factor receptor II-negative) breast cancer patients with 23-gene classifier results. Using the modified Adjuvant! Online definition, clinical high/low-risk groups were tabulated with the genetic model. The primary endpoint was a recurrence-free interval (RFI) at 5 years. Results: There was a significant difference between the high/low-risk groups defined by the 23-gene classifier for the 5-year prognosis of recurrence (16 recurrences in high-risk and 3 recurrences in low-risk; log-rank test: p < 0.0001). Among the clinically high-risk group, the 5-year RFI of high risk defined by the 23-gene classifier was significantly higher than that of the low-risk group (15 recurrences in high-risk and 2 recurrences in low-risk; log-rank test: p < 0.0001). Conclusion: This study showed that 23-gene classifier can be used to stratify clinically high-risk patients into distinct survival patterns based on genomic risks and displays the potentiality to guide adjuvant chemotherapy. The 23-gene classifier can provide a better estimation of breast cancer prognosis which can help physicians make a better treatment decision.

Although hot-carrier-based photodetection using plasmonic effects has been widely investigated, photodetectors of this type with an external quantum efficiency (EQE) > 1 % and an active area of < 1 mm 2 remain out of reach even in the visible frequencies. In this work, a novel hot-electron-based, non-trench-type photodetector exploiting pure photoexcitation in a thin aluminum (Al) film and leaky plasmonic modes at and between its heterojunctions is proposed, analyzed, and experimentally demonstrated. Combining diffracted-order-resolved analytical analysis and numerical computations unravels the optical absorption mechanism of the innovative design. Leaky surface plasmon resonance (with leakage radiation into the air) produced by a propagating diffracted order and quasibound supermodes (with power leakage via coupled gap plasmon polariton and bound surface plasmon polariton modes) excited by evanescent diffracted orders are shown to significantly contribute to the absorptance in the preferred thin Al film where hot electrons are generated. At 638.9 nm and electric bias -0.9951 V, the measured per-unit-area responsivity, detectivity, and the external quantum efficiency reach 298.1444 μA/mW/mm 2 , 4.3809 × 10 9 cm Hz 1/2 /W, and 2.6878%, respectively, from an active area of 4.6457 × 10 -2 mm 2 . The performance is among the best of those previously reported operating at similar wavelengths and biases. The RC time constant is estimated to be about 1.673 μs from the current-voltage measurements. The physical insight into the innovative, experimentally demonstrated device could lay the groundwork for the practical use of low-voltage, metal-based photodetection., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

This publisher's note contains corrections to [Opt. Express30, 28438 (2022)10.1364/OE.460941].

A method for designing multi-metasurface layouts for optical aberration correction is presented. All-dielectric metasurfaces are combined with conventional refractive optics to form a hybrid lens. The optical power of a hybrid lens is primarily provided by refractive optics, and metasurfaces are optimized to control optical aberrations. This approach greatly reduces the magnitude of phase gradient required for a largescale metasurface and hence its diffraction loss. An inverse design technique is incorporated to optimize all physical parameters on a metasurface to minimize image spots across all sampling field angles and wavelengths. This approach is put to test by designing a hybrid lens composed of a midwave infrared refractive lens followed by a pair of metasurfaces. Moreover, we demonstrate the working bandwidth of the hybrid lens can be further extended by reducing phase dispersion introduced by a metasurface using holey meta-atoms instead of pillar meta-atoms.

Breast cancer is the most common cancer and the leading cause of cancer-related deaths in women. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are the important biomarkers in the prognosis of breast cancer, and their expression is used to categorize breast cancer into subtypes. We aimed to analyze the concordance among ER, PR, and HER2 expression levels and breast cancer subtyping results obtained by immunohistochemistry (IHC, for protein) and reverse transcriptase-polymerase chain reaction (RT-PCR, for mRNA) and to assess the recurrence-free survival (RFS) of the different subtypes as determined by the two methods. We compared biomarker expression by IHC and RT-PCR in 397 operable breast cancer patients and categorized all patients into luminal, HER2, and triple-negative (TN) subtypes. The concordance of biomarker expression between the two methods was 81.6% (κ = 0.4075) for ER, 87.2% (κ = 0.5647) for PR, and 79.1% (κ = 0.2767) for HER2. The κ-statistic was 0.3624 for the resulting luminal, HER2, and TN subtypes. The probability of 5-year RFS was 0.78 for the luminal subtype versus 0.77 for HER2 and 0.51 for TN, when determined by IHC (P=0.007); and 0.80, 0.71, and 0.61, respectively, when determined by the RT-PCR method (P=0.008). Based on the current evidence, subtyping by RT-PCR performs similar to conventional IHC with regard to the 5-year prognosis. The PCR method may thus provide a complementary means of subtyping when IHC results are ambiguous., (© 2022 The Author(s).)

Objective: To evaluate the validity and test-retest reliability of the novel 'TIB' Olfactory Test Device (TIB) and to determine its normative values., Methods: The study stratified the study subjects into normosmic, hyposmic and anosmic groups according to their olfactory function. The olfactory function of the subjects was evaluated using both the traditional Chinese version of the University of Pennsylvania of Smell Identification Test (UPSIT-TC) and the TIB. The normosmic group was used to retest with the UPSIT-TC and TIB at an inter-test interval of at least 7 days. The cut-off scores of TIB among the three different groups were determined by receiver operating characteristic curve analysis., Results: This study enrolled 180 subjects: 60 in each group. The mean scores of TIB were 44.1 for the normosmic group, 27.5 for the hyposmic group and 10.9 for the anosmic group. The TIB scores were significantly different across the three groups. There was a significant correlation between the first and second TIB tests ( r  = 0.506). The cut-off scores were 41 for normosmic subjects and 24 for hyposmic subjects., Conclusion: The validity and test-retest reliability results suggest that the TIB is an appropriate olfactory test for the Taiwanese population.

Clinical presentation is heterogeneous for autosomal dominant nonsyndromic hearing loss (ADNSHL). Variants of KCNQ4 gene is a common genetic factor of ADNSHL. Few studies have investigated the association between hearing impairment and the variant c.546C>G of KCNQ4 . Here, we investigated the phenotype and clinical manifestations of the KCNQ4 variant. Study subjects were selected from the participants of the Taiwan Precision Medicine Initiative. In total, we enrolled 12 individuals with KCNQ4 c.546C>G carriers and 107 non-carriers, and performed pure tone audiometry (PTA) test and phenome-wide association (PheWAS) analysis for the patients. We found that c.546C>G variant was related to an increased risk of hearing loss. All patients with c.546C>G variant were aged >65 years and had sensorineural and high frequency hearing loss. Of these patients, a third (66.7%) showed moderate and progressive hearing loss, 41.7% complained of tinnitus and 16.7% complained of vertigo. Additionally, we found a significant association between KCNQ4 c.546C>G variant, aortic aneurysm, fracture of lower limb and polyneuropathy in diabetes. KCNQ4 c.546C>G is likely a potentially pathogenic variant of ADNSHL in the elderly population. Genetic counseling, annual audiogram and early assistive listening device intervention are highly recommended to prevent profound hearing impairment in this patient group.

Background: Several prognostic factors affect the recurrence of breast cancer in patients who undergo mastectomy. Assays of the expression profiles of multiple genes increase the probability of overexpression of certain genes and thus can potentially characterize the risk of metastasis., Methods: We propose a 20-gene classifier for predicting patients with high/low risk of recurrence within 5 years. Gene expression levels from a quantitative PCR assay were used to screen 473 luminal breast cancer patients treated at Taiwan Hospital (positive for estrogen and progesterone receptors, negative for human epidermal growth factor receptor 2). Gene expression scores, along with clinical information (age, tumor stage, and nodal stage), were evaluated for risk prediction. The classifier could correctly predict patients with and without relapse (logistic regression, P<0.05)., Results: A Cox proportional hazards regression analysis showed that the 20-gene panel was prognostic with hazard ratios of 5.63 (95% confidence interval 2.77-11.5, univariate) and 5.56 (2.62-11.8, multivariate) for the "genetic" model, and of 8.02 (3.52-18.3, univariate) and 19.8 (5.96-65.87, multivariate) for the "clinicogenetic" model during a 5-year follow-up., Conclusions: The proposed 20-gene classifier can successfully separate the patients into two risk groups, and the two risk group had significantly different relapse rate and prognosis. This 20-gene classifier can provide better estimation of prognosis, which can help physicians to make better personalized treatment plans., Competing Interests: Amwise holds the patent related to the content of this manuscript (Taiwan patent application number: 109132402; China patent application number: 202011103766.4). T-HC, JW, JL, JYC, and K-HS are the employees of Amwise Diagnostics Pte. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Amwise Diagnostics Pte. Ltd. The funder had the following involvement in the study: provision of the study materials and patients, experimental support, computing resources, data management, data analysis, data interpretation and decision to submit it for publication., (Copyright © 2021 Chen, Wei, Lei, Chiu and Shih.)

A new metric for imaging systems, the volumetric imaging efficiency (VIE), is introduced. It compares the compactness and capacity of an imager against fundamental limits imposed by diffraction. Two models are proposed for this fundamental limit based on an idealized thin-lens and the optical volume required to form diffraction-limited images. The VIE is computed for 2,871 lens designs and plotted as a function of FOV; this quantifies the challenge of creating compact, wide FOV lenses. We identify an empirical limit to the VIE given by VIE < 0.920 × 10 -0.582×FOV when using conventional bulk optics imaging onto a flat sensor. We evaluate VIE for lenses employing curved image surfaces and planar, monochromatic metasurfaces to show that these new optical technologies can surpass the limit of conventional lenses and yield >100x increase in VIE.

We report a 23- gene-classifier profiled from Asian women, with the primary purpose of assessing its clinical utility towards improved risk stratification for relapse for breast cancer patients from Asian cohorts within 10 years' following mastectomy. Four hundred and twenty-two breast cancer patients underwent mastectomy and were used to train the classifier on a logistic regression model. A subset of 197 patients were chosen to be entered into the follow-up studies post mastectomy who were examined to determine the patterns of recurrence and survival analysis based on gene expression of the gene classifier, age at diagnosis, tumor stage and lymph node status, over a 5 and 10 years follow-up period. Metastasis to lymph node (N2-N3) with N0 as the reference (N2 vs. N0 hazard ratio: 2.02 (1.05-8.70), N3 vs. N0 hazard ratio: 4.32 (1.41-13.22) for 5 years) and gene expression of the 23-gene panel (P=0.06, 5 years and 0.02, 10 years, log-rank test) were found to have significant discriminatory effects on the risk of relapse (HR (95%CI):2.50 (0.95-6.50)). Furthermore, survival curves for subgroup analysis with N0-N1 and T1-T2 predicted patients with higher risk scores. The study provides robust evidence of the effectiveness of the 23-gene-classifier and could be used to determine the risk of relapse event (locoregional and distant recurrence) in Asian patients, leading to a meaningful reduction in chemotherapy recommendations., (© 2020 The Author(s).)

Plasmon-enhanced sensitive photodetection using plasmonic noble metals has been widely investigated; however, aluminum (Al)-based photoelectric conversion concurrently utilizing photonic and plasmonic approaches is less explored. Here, photodetection driven by quasi-localized plasmon resonance (QLPR) is investigated. Concurrent photonic and plasmonic contributions to strong absorption in the active region require delocalized, slow-propagating resonant electric field to occur around the peripheries of Al nano-structures and depend on the spatial distribution of diffraction efficiencies of all space harmonics. Efficiency limits are shown to be largely determined by the spatial degrees of freedom and the associated traveling distances of hot electrons during carrier transport. With strong absorption and relatively high reaching-emission probabilities structured in the same region, the measured responsivity and the external quantum efficiency of the fabricated device at 638.9 nm are 4.1889 μA/mW and 0.8129% at -0.485 V, respectively. Our results provide physical insights into related problems and may offer a route to more efficient, hot-carrier based photoelectric conversion devices.

In recent years, object detection became more and more important following the successful results from studies in deep learning. Two types of neural network architectures are used for object detection: one-stage and two-stage. In this paper, we analyze a widely used two-stage architecture called Faster R-CNN to improve the inference time and achieve real-time object detection without compromising on accuracy. To increase the computation efficiency, pruning is first adopted to reduce the weights in convolutional and fully connected (FC) layers. However, this reduces the accuracy of detection. To address this loss in accuracy, we propose a reduced region proposal network (RRPN) with dilated convolution and concatenation of multi-scale features. In the assisted multi-feature concatenation, we propose the intra-layer concatenation and proposal refinement to efficiently integrate the feature maps from different convolutional layers; this is then provided as an input to the RRPN. Using the proposed method, the network can find object bounding boxes more accurately, thus compensating for the loss arising from compression. Finally, we test the proposed architecture using ZF-Net and VGG16 as a backbone network on the image sets in PASCAL VOC 2007 or VOC 2012. The results show that we can compress the parameters of the ZF-Net-based network by 81.2% and save 66% of computation. The parameters of VGG16-based network are compressed by 73% and save 77% of computation. Consequently, the inference speed is improved from 27 to 40 frames/s for ZF-Net and 9 to 27 frames/s for VGG16. Despite significant compression rates, the accuracy of ZF-Net is increased from 2.2% to 60.2% mean average precision (mAP) and that of VGG16 is increased from 2.6% to 69.1% mAP.

Background: The information of Oncotype DX applied in Asian breast cancer patients is limited. A recurrence index for distant recurrence (RI-DR) has been developed for early-stage breast cancer (EBC) from tumor samples in Chinese patients. In this study, we compared the prognostic performance of the Oncotype DX (ODx) recurrence score (RS) with the RI-DR for any recurrence risk type., Materials and Methods: One hundred thirty-eight (138) patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative EBC who were previously tested with ODx were included for testing with the RI-DR. The cutoff score to partition the low- and high-risk patients was 26 for RS and 36 for RI-DR. The primary endpoint was recurrence-free survival (RFS)., Results: The concordance between the RI-DR and RS was 83% in N0 patients and 81% in node-positive patients when the RS score cutoff was set at 26. With a median follow-up interval of 36.8 months, the 4-year RFS for the high- and low-risk groups categorized by the RS were 61.9% and 95.0%, respectively (hazard ratio: 10.6, 95.0% confidence interval [CI]: 1.8-62.9). The 4-year RFS in the high- and low-risk groups categorized by the RI-DR were 72.6% and 98.5%, respectively (hazard ratio: 18.9, 95% CI: 1.8-138.8)., Conclusion: This paper illustrated the performance of RI-DR and ODx RS in breast cancer women in Taiwan. There was high concordance between the RI-DR and RS. The RI-DR is not inferior to the RS in predicting RFS in EBC patients. This study will fill the gap between the current and best practice in Chinese patients., (© The Author(s) 2019. Published by Oxford University Press.)

The application of optical absorption spectra in prognostic prediction has hardly been investigated. We developed and evaluated a novel two dimensional absorption spectrum measurement system (TDAS) for use in early diagnosis, evaluating response to chemoradiation, and making prognostic prediction. The absorption spectra of 120 sets of normal and tumor tissues from esophageal cancer patients were analyzed with TDAS ex-vivo. We demonstrated the cancerous tissue, the tissue from patients with a poor concurrent chemoradiotherapy (CCRT) response, and the tissue from patients with an early disease progression each had a readily identifiable common spectral signature. Principal component analysis (PCA) classified tissue spectra into distinct groups, demonstrating the feasibility of using absorption spectra in differentiating normal and tumor tissues, and in predicting CCRT response, poor survival and tumor recurrence (efficiencies of 75%, 100% and 85.7% respectively). Multivariate analysis revealed that patients identified as having poor-response, poor-survival and recurrence spectral signatures were correlated with increased risk of poor response to CCRT (P = 0.012), increased risk of death (P = 0.111) and increased risk of recurrence (P = 0.030) respectively. Our findings suggest that optical absorption microscopy has great potential to be a useful tool for pre-operative diagnosis and prognostic prediction of esophageal cancer.

Microtubule inhibitors have been shown to inhibit hypoxia-inducible factor-1α (HIF-1α) expression through inhibition translation or enhancing protein degradation. Little is known of the effect of microtubule inhibitors on the stability of HIF-1α mRNA. We recently discovered a novel indoline-sulfonamide compound, 7-aryl-indoline-1-benzene-sulfonamide (MPT0B098), as a potent microtubule inhibitor through binding to the colchicine-binding site of tubulin. MPT0B098 is active against the growth of various human cancer cells, including chemoresistant cells with IC50 values ranging from 70 to 150 nmol/L. However, normal cells, such as human umbilical vein endothelial cells (HUVEC), exhibit less susceptibility to the inhibitory effect of MPT0B098 with IC50 of 510 nmol/L. Similar to typical microtubule inhibitors, MPT0B098 arrests cells in the G2-M phase and subsequently induces cell apoptosis. In addition, MPT0B098 effectively suppresses VEGF-induced cell migration and capillary-like tube formation of HUVECs. Distinguished from other microtubule inhibitors, MPT0B098 not only inhibited the expression levels of HIF-1α protein but also destabilized HIF-1α mRNA. The mechanism of causing unstable of HIF-1α mRNA by MPT0B098 is through decreasing RNA-binding protein, HuR, translocation from the nucleus to the cytoplasm. Notably, MPT0B098 effectively suppresses tumor growth and microvessel density of tumor specimens in vivo. Taken together, our results provide a novel mechanism of inhibiting HIF-1α of a microtubule inhibitor MPT0B098. MPT0B098 is a promising anticancer drug candidate with potential for the treatment of human malignancies.

A variety of studies on the modification of combretastatin A-4 triggered our interest in the impact of the linkers between the 3,4,5-trimethoxyphenyl ring and 5-amino-6-methoxyquinoline on biological activity. The replacement of the carbonyl group with bond, amine, ether, sulfide, and sulfone groups was evaluated in this study. The results showed that compounds 14 and 15 containing sulfide and sulfone groups between the 3,4,5-trimethoxyphenyl ring (A-ring) and 5-amino-6-methoxyquinoline exhibited substantial antiproliferative activity against KB, HT29, and MKN45 cells with mean IC50 values of 42 and 12 nM, respectively. 15 inhibited the tubulin polymerization with an IC50 value of 2.0 μM, similar to that with CA4. The continued work on the C-5 substituents of 3',4',5'-trimethoxybenzoyl-6-methoxyquinoline derivatives demonstrated that compound 7 possessing OH at C-5 exhibited excellent antiproliferative activity with mean IC50 values of 3.4 nM and microtubule destabilizing potency with an IC50 of 1.5 μM, comparable to that of CA4 (IC50=1.9 μM). It also exhibited substantial vascular disrupting effects. Compounds 7 and 15 exhibited significant efficacy against MDR/MRP-related drug-resistant cell lines (KB-vin10, KB-S15, and KB-7D) with mean IC50 values of 6.7 and 2.6 nM, respectively.

In an attempt to mimic the 3,4,5-trimethoxyphenyl-Z-stilbene moiety of combretastatin A-4, a series of N-aryl-5,6,7-trimethoxyindoles were synthesized via copper-catalyzed Ullmann-type N-arylation through the corresponding 5,6,7-trimethoxyindole and aryl halides. These synthesized compounds demonstrated potent antiproliferative activity providing a novel skeleton for potent tubulin polymerization inhibitors.

This study analyzes the varying electrophoretic mobility and zeta potential of bone marrow stromal cells (BMSCs) during their differentiation towards neurons. Electrophoresis of primary BMSCs and neuron growth factor (NGF)-induced neuron-like cells with the uptake of heparin-functionalized poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) are also investigated. Immunofluorescent images revealed that a high concentration of NGF accelerated the differentiation of BMSCs into neurons. When the concentration of NGF increased, the absolute values of electrophoretic mobility and zeta potential of the differentiating BMSCs increased. In addition, a longer inductive period yielded higher charge of the differentiating BMSCs and a smaller uptake amount of heparin-functionalized PLGA NPs. However, an increase in the loading efficiency of heparin on PLGA NPs enhanced the uptake and reduced the electrical characteristics of the primary and differentiating BMSCs. Hence, a general rule is drawn that an increase in the uptake of heparin-functionalized PLGA NPs decreased the electrophoretic mobility and zeta potential of BMSCs during differentiation towards neurons.

Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) with surface modification of heparin were fabricated by microemulsion-diffusion method. These novel colloidal particles were stabilized by lecithin and Tween 80. The effects of lecithin on the loading of heparin onto PLGA NPs and on the surface conductance were analyzed. The electronic micrographs revealed that spherical colloids were prepared and the incorporation of heparin caused a slight coalescence of the particles. In addition, the average diameter of heparin-modified PLGA NPs was between 70 and 220 nm. An increase in the weight percentage of lecithin or in the concentration of heparin enlarged the average diameter. Based on constant amount of surfactants, the loading efficiency of heparin on the particle surfaces reached a maximum when the weight percentage of lecithin was 50%. Moreover, the surface conductance of heparin-modified PLGA NPs was improved by an increased weight percentage of lecithin. A high concentration of heparin in microemulsion also promoted the loading efficiency and surface conductance of heparin-modified PLGA NPs.

Background: Schizophrenia is a complex disease with multiple factors contributing to its pathogenesis. In addition to environmental factors, genetic factors may also increase susceptibility. In other words, schizophrenia is a highly heritable disease. Some candidate genes have been deduced on the basis of their known function with others found on the basis of chromosomal location. Individuals with multiple candidate genes may have increased risk. However it is not clear what kind of gene combinations may produce the disease phenotype. Their collective effect remains to be studied., Results: Most pathways except metabolic pathways are rich in protein-protein interactions (PPIs). Thus, the PPI network contains pathway information, even though the upstream-downstream relation of PPI is yet to be explored. Here we have constructed a PPI sub-network by extracting the nearest neighbour of the 36 reported candidate genes described in the literature. Although these candidate genes were discovered by different approaches, most of the proteins formed a cluster. Two major protein interaction modules were identified on the basis of the pairwise distance among the proteins in this sub-network. The large and small clusters might play roles in synaptic transmission and signal transduction, respectively, based on gene ontology annotation. The protein interactions in the synaptic transmission cluster were used to explain the interaction between the NRG1 and CACNG2 genes, which was found by both linkage and association studies. This working hypothesis is supported by the co-expression analysis based on public microarray gene expression., Conclusion: On the basis of the protein interaction network, it appears that the NRG1-triggered NMDAR protein internalization and the CACNG2 mediated AMPA receptor recruiting may act together in the glutamatergic signalling process. Since both the NMDA and AMPA receptors are calcium channels, this process may regulate the influx of Ca2+. Reducing the cation influx might be one of the disease mechanisms for schizophrenia. This PPI network analysis approach combined with the support from co-expression analysis may provide an efficient way to propose pathogenetic mechanisms for various highly heritable diseases.