Hypoxia Reversion by Low-Immunogenic Ultra-Acid-Sensitive Comicelles of Protein-Polymer Conjugates Sensitizes Tumors to Photodynamic Therapy.

Hypoxia is characteristic of the tumor microenvironment, which is correlated with resistance to photodynamic therapy (PDT), radiotherapy, chemotherapy, and immunotherapy. Catalase is potentially useful to catalyze the conversion of endogenous H2O2 to O2 for hypoxia reversion. However, the efficient delivery of catalase into the hypoxia regions of tumors is a huge challenge. Here, we report the self-assembly of ultra-acid-sensitive polymer conjugates of catalase and albumin into nanomicelles that are responsive to the acidic tumor microenvironment. The immunogenicity of catalase is mitigated by the presence of albumin, which reduces the cross-linking of catalase with B cell receptors, resulting in improved pharmacokinetics. The ultra acid sensitivity of the nanomicelles makes it possible to efficiently escape the lysosomal degradation after endocytosis and permeate into the interior of tumors to reverse hypoxia in vitro and in vivo. In mice bearing triple-negative breast cancer, the nanomicelles loaded with a photosensitizer effectively accumulate and penetrate into the whole tumors to generate a sufficient amount of O2 to reverse hypoxia, leading to enhanced efficacy of PDT without detectable side effects. These findings provide a general strategy of self-assembly to design low-immunogenic ultra-acid-sensitive comicelles of protein-polymer conjugates to reverse tumor hypoxia, which sensitizes tumors to PDT.

Electroacupuncture regulates the P2X7R-NLRP3 inflammatory cascade to relieve decreased sensation on ocular surface of type 2 diabetic rats with dry eye.

Dry eye (DE) is a prevalent ocular surface disease in patients with type 2 diabetes (T2DM). However, current medications are ineffective against decreased sensation on the ocular surface. While electroacupuncture (EA) effectively alleviates decreased sensation on ocular surface of DE in patients with T2DM, the neuroprotective mechanism remains unclear. This study explored the pathogenesis and therapeutic targets of T2DM-associated DE through bioinformatics analysis. It further investigated the underlying mechanism by which EA improves decreased sensation on the ocular surface of DE in rats with T2DM. Bioinformatic analysis was applied to annotate the potential pathogenesis of T2DM DE. T2DM and DE was induced in male rats. Following treatment with EA and fluorometholone, comprehensive metrics were assessed. Additionally, the expression patterns of key markers were studied. Key targets such as NLRP3, Caspase-1, and NOD-like receptor signaling may be involved in the pathogenesis of T2DM DE. EA treatment improved ocular measures. Furthermore, EA potently downregulated P2X7R, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 expression within the trigeminal ganglion and spinal trigeminal nucleus caudalis. Targeted P2X7R antagonist (A-438079) and agonist (BzATP) employed as controls to decipher the biochemistry of the therapeutic effects of EA showed an anti-inflammatory effect with A-438079, while BzATP blocked the anti-inflammatory effect of EA. EA relieved DE symptoms and attenuated inflammatory damage to sensory nerve pathways in T2DM rats with DE. These findings suggest a crucial role of EA inhibition of the P2X7R-NLRP3 inflammatory cascade to provide these benefits.

Electroacupuncture modulates the TLR4-NF-κB inflammatory signaling pathway to attenuate ocular surface inflammation in dry eyes of type 2 diabetic rats.

Bioinformatics analysis was performed to reveal the underlying pathogenesis of type 2 diabetes (T2DM) dry eye(DE) and to predict the core targets and potential pathways for electroacupuncture (EA) treatment of T2DM DE, in which key targets such as Toll-likereceptor4 (TLR4), NF-κB and Tumor necrosis factor-α (TNF-α) may be involved. Next, streptozotocin and a high-fat diet were used to generate T2DM-DE rats. Randomly picked EA, fluorometholone, model, and sham EA groups were created from successfully modelled T2DM DE rats. Six more rats were chosen as the blank group from among the normal rats. The results of DE index showed that EA improved the ocular surface symptoms.HE staining showed that EA attenuated the pathological changes in the cornea, conjunctiva and lacrimal gland of T2DM DE rats. EA decreased the expression of TLR4, MyD88, P-NF-κB P65, and TNF-α in the cornea, conjunctiva, and lacrimal gland, in accordance with immunofluorescence and Western blot data. Thus, EA reduced ocular surface symptoms and improved pathological changes of cornea, conjunctiva, and lacrimal gland induced by T2DM DE inT2DM DE rats, and the mechanism may be related to the inhibition of overactivation of the TLR4/NF-κB signaling pathway by EA and thus attenuating ocular surface inflammation.

[Morphological study of sexual reproductive disorders in Ligusticum chuanxiong].

Chuanxiong Rhizoma is a well-known Sichuan-specific herbal medicine. Its original plant, Ligusticum chuanxiong, has been cultivated asexually for a long time. L. chuanxiong has sexual reproductive disorders, which restricts its germplasm innovation. However, there is little research on the reproductive system of L. chuanxiong. This study is based on a comparative anatomical research approach, using morphological dissection, paraffin sectioning, staining and compression, and combined with scanning electron microscopy technology, to observe and compare the flowers, fruits, and seeds at various stages of reproductive growth of L. chuanxiong and its wild relative L. sinense. The results showed that the meiosis of pollen mother cells is abnormal in L. chuanxiong anthers, and the size and number of microspores are uneven and inconsistent in the tetrad stage. tapetum cells are not completely degenerated during anther development. During the pollen ripening stage, there are fine cracks in the anther wall, while most anthers could not release pollen normally. The surface of mature pollen grains is concave and partially deformed, and the pollens are all inactive and cannot germinate in vitro. The starch, polysaccharides, and lipids in the pollen were insufficient. The filaments of L. chuanxiong are short at the flowering stage and recurved downward. Double-hanging fruits were observed in the fruiting stage, being wrinkled; with shriveled seeds. Compared with L. sinense at the same stage, the anthers of L. sinense developed normally, and the pollen grains are vigorous and can germinate in vitro. The double-hanging fruits of L. sinense are full and normal; at the flowering period, the filaments are long and erect, significantly higher than the stigma. Mature blastocysts are visible in the ovary of both L. chuanxiong and L. sinense, and there is no significant difference in stigmas. The conclusion is that during the development of L. chuanxiong stamens, the meiosis of pollen mother cells is abnormal, and tetrad, tapetum, filament and other pollen structures develop abnormally. L. chuanxiong has the characteristic of male infertility, which is an important reason for its sexual reproductive disorders.

Hypoxia-Triggered Bioreduction of Poly(N-oxide)-Drug Conjugates Enhances Tumor Penetration and Antitumor Efficacy.

PEGylation prolongs the blood circulation time of drugs; however, it simultaneously reduces the tumor penetration of drugs due to the nonfouling function and bulky hydrodynamic volume of PEG, leading to unsatisfactory outcomes in the treatment of solid tumors. Herein, we report the in situ growth of a bioreducible polymer of poly(N-oxide) from an important protein drug of interferon alpha (IFN) to generate site-specific IFN-poly(N-oxide) conjugates with higher bioactivity than a clinically used PEGylated IFN of PEGASYS. An IFN-poly(N-oxide) conjugate is screened out to have a circulating half-life as long as 51 h, which is similar to that of PEGASYS but 96-fold greater than that of IFN. However, the conjugate greatly outperforms PEGASYS and IFN in tumor penetration and antitumor efficacy in mice bearing melanoma. This enhanced tumor penetration is ascribed to the adsorption-mediated transcytosis of the conjugate whose poly(N-oxide) is biologically reduced into poly(tertiary amine), under hypoxia, which can be further protonated in the acidic tumor microenvironment. These novel findings demonstrate that poly(N-oxide)s are not only long-circulating but also bioreducible under hypoxia and are of great promise as next-generation carriers to deliver drugs into the interior of solid tumors to enhance their antitumor efficacy.

Imaging quality characterization and optimization of segmented planar imaging system based on honeycomb dense azimuth sampling lens array.

Segmented planar photoelectric imaging is an advanced computational imaging technology that utilizes photonic integrated circuits (PICs) to achieve the miniaturization of imaging systems. The original radial-spoke lens array has dense radial sampling and coarse azimuthal sampling. The sparsity and inhomogeneity of spatial frequency sampling lead to the loss of spatial frequency information and blurred reconstructed images. In this paper, a honeycomb dense azimuth sampling lens array is proposed, and three baseline pairing methods are designed, which can realize dense azimuth sampling, effectively increase spatial frequency sampling and improve the imaging quality. The signal transmission model of the segmented planar imaging system is established and the imaging process is simulated and analyzed. The simulation results show that the honeycomb lens array improves the azimuth sampling density and spatial frequency coverage, and its imaging quality is significantly improved compared with the hexagonal lens array and the radial-spoke lens array. Furthermore, the optimal choice of the baseline pairing method and the error range of the fill factor and are also given in this paper. The results indicate that the mixed pairing method first ensures low and medium-frequency dense sampling, and then increases high-frequency sampling, which makes the imaging results better than those of the other two baseline pairing methods in terms of image contour, contrast and image detail information. The sampling density of the spatial frequency and the imaging quality can be improved by increasing the fill factor. In the actual manufacturing process, the allowable error range of the fill factor of the lens array is within 5%. The research results will provide theoretical support for the design and development of segmented planar imaging system.

N-Terminal Lysozyme Conjugation to a Cationic Polymer Enhances Antimicrobial Activity and Overcomes Antimicrobial Resistance.

Microbial resistance to antibiotics is one of the greatest global healthcare challenges. There is an urgent need to develop effective strategies to overcome antimicrobial resistance. We, herein, report photoinduced in situ growth of a cationic polymer from the N-terminus of lysozyme. The attachment of the cationic polymer improves the proteolytic and thermal stability of lysozyme. Notably, the conjugate can efficiently overcome lysozyme resistance in Gram-positive bacteria and antibiotics-resistance in Gram-negative bacteria, which may be ascribed to the synergistic interactions of lysozyme and the cationic polymer with the bacteria to disrupt their cell membranes. In a rat periodontitis model, the lysozyme-polymer conjugate not only greatly outperforms lysozyme in therapeutic efficacy but also is superior to minocycline hydrochloride, which is the gold standard for periodontitis therapy. These findings may provide an efficient strategy to dramatically enhance the antimicrobial activities of lysozyme and pave a way to overcome antimicrobial resistance.

Thermosensitive Polymer Conjugated Prodrug-Activating Enzyme with Enhanced Tumor Retention and Antitumor Efficacy.

Enzyme-activated prodrug therapy has emerged as an effective strategy for cancer therapy. However, the inefficient delivery of prodrug-activating enzymes into tumor tissues leads to unsatisfactory antitumor efficacy and undesirable toxicity to normal tissues. Herein, we report in situ growth of a thermosensitive polymer of poly(diethylene glycol) methyl ether methacrylate (PDEGMA) from horseradish peroxidase (HRP) to yield a HRP-PDEGMA conjugate with well-retained activity as compared to HRP. The conjugate shows a sharp phase transition behavior with a lower critical solution temperature of 23 °C. The conjugate catalyzes the conversion of non-cytotoxic indole-3-acetic acid (IAA) into cytotoxic species for killing tumor cells. Notably, the PDEGMA conjugation not only increases the stability and cellular uptake of HRP but also prolongs the tumor retention time of HRP upon intratumoral injection. As a result, in mice bearing melanoma, the conjugate inhibits the growth of melanoma much more efficiently than HRP. These results demonstrate that the thermosensitive polymer conjugation of an enzyme is an effective strategy that can enhance the antitumor efficacy of an enzyme-activated prodrug.

OsNRAMP5 Is a Major Transporter for Lead Uptake in Rice.

Lead (Pb) is one of the most toxic metals affecting human health globally. Food is an important source of chronic Pb exposure in humans. How Pb is taken up by rice, a staple food for over half of the global population, remains unknown. In the present study, we investigated the role of OsNRAMP5, a member of the NRAMP (Natural Resistance-Associated Macrophage Protein) transporter family, in Pb uptake by rice roots. Heterologous expression of OsNRAMP5 in yeast increased Pb uptake and sensitivity toward Pb. Knockout of OsNRAMP5 in rice by CRISPR/Cas9 gene editing resulted in significant decreases in root uptake of Pb and accumulation in rice shoots. The maximum influx velocity (Vmax) for Pb uptake of the knockout mutants was 70% lower than that of wild-type plants. When grown in Pb-contaminated paddy soil, OsNRAMP5 knockout mutants accumulated approximately 50 and 70% lower Pb concentrations in the grain and straw, respectively, than the wild type. OsNRAMP5 expression in rice roots was not affected by Pb exposure. These results indicate that OsNRAMP5 is a major transporter for Pb uptake in rice, in addition to its role in the uptake of manganese and cadmium. This study provides a mechanistic understanding of Pb uptake in rice plants and a potential strategy to limit Pb accumulation in rice grains.

Plasma Level of Apelin as a Promising Factor for Retinopathy of Prematurity.

INTRODUCTION: To investigate the relevance of plasma levels of apelin and other risk factors in infants with retinopathy of prematurity (ROP). METHODS: This was a single-center cross-sectional study. Fifty preterm infants with ROP and 50 preterm infants without ROP were enrolled. The analysis included evaluation of gestational age, birth weight, and measurement of plasma concentrations of apelin, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and insulin-like growth factor (IGF-1) using enzyme-linked immunosorbent assay. RESULTS: The mean BW and GA of babies with ROP were considerably lower than those without ROP (P < 0.001, P = 0.003, respectively). Plasma levels of VEGF, EPO, and IGF-1 were all lower in babies with ROP (all P < 0.001), while plasma apelin levels were greater (P < 0.001). We compared the sensitivity and selected the best cut-offs while keeping the specificity constant (80.0%). Among all the criteria, plasma apelin levels had the best sensitivity (72%), with a 21.08 pg/mL cut-off. Multivariable logistic regression analyses showed that the plasma level of apelin was the only parameter associated with ROP (P = 0.02, OR = 16, CI = 95%: 1.54-166.53). The AUC of the multivariable regression model that comprised GA, BW alone was 0.67, while the model that included apelin was 0.90. CONCLUSIONS: Plasma apelin level demonstrated good sensitivity and specificity with regard to the association of ROP, the inclusion of apelin may be a promising factor to include in screening criteria.

Quantitative analysis and optimization design of the segmented planar integrated optical imaging system based on an inhomogeneous multistage sampling lens array.

The non-uniformity of the lens array in the segmented planar integrated optical imaging system has not been studied. We design an inhomogeneous multistage sampling lens array based on a hierarchical multistage sampling lens array of the segmented planar integrated optical imaging system by changing the radius of the lenslet for frequency-selective sampling to optimize the design of the UV spatial frequency distribution. The signal transfer model of the proposed imaging system was established considering the radius of the lenslet and key waveguide parameters. Simulation results show that the proposed system produces better imaging quality owing to the selective sampling of frequency. Compared with the homogeneous multistage sampling lens array (radius of 1.8 mm), the optimal radius parameters of the inhomogeneous multistage sampling lens array are given for the same longest lens array length. Detailed calculations of the parameters of the waveguide connected to the lens array were performed. Our results provide a theoretical basis for the optimal design and process of a new segmented planar integrated optical imaging system.

Puerarin protects against human retinal endothelial cells injury induced by high glucose via regulating miR-16-5p/CASP1 axis.

We aimed to investigate the effects of puerarin on high glucose (HG)-induced human retinal endothelial cells (HRECs) injury. Cells were exposed to puerarin in the presence or absence of HG challenge. Cell viability was determined using a CCK-8 assay. Then, the levels of the oxidative stress-related factors were evaluated using corresponding kits. Pyroptosis was assessed by measurement of gasdermin-N domain (GSDMD-N) and caspase-1 (CASP1) expression. Subsequently, miR-16-5p expression was detected using RT-qPCR. The levels of oxidative stress and pyroptosis were examined after miR-16-5p silencing. The Starbase database predicted that CASP1 is a potential target of miR-16-5p, which was verified through a luciferase reporter assay. Moreover, CASP1 expression was determined after miR-16-5p silencing in HG-stimulated HRECs with puerarin exposure. Results revealed that puerarin significantly enhanced cell viability and inhibited oxidative stress. Furthermore, puerarin markedly downregulated GSDMD-N and CASP1 expression, and miR-16-5p level was notably inhibited in HG-stimulated HRECs, which was reversed after puerarin intervention. Following transfection with miR-16-5p inhibitor, the effects of puerarin on cell viability, oxidative stress and pyroptosis were attenuated in HG-induced HRECs. CASP1 was confirmed as a direct target gene of miR-16-5p. Taken together, puerarin alleviates oxidative stress and pyroptosis in HG-stimulated HRECs through regulating the miR- 16-5p/CASP1 axis.

Polymerization-Induced Coassembly of Enzyme-Polymer Conjugates into Comicelles with Tunable and Enhanced Cascade Activity.

Living organisms utilize spatially organized enzyme complexes to carry out signal transduction and metabolic pathways in an efficient and specific way. Herein, inspired by natural enzyme complexes, we report the polymerization-induced coassembly (PICA) of enzyme-polymer conjugates into comicelles with tunable and enhanced cascade activity by using the cascade reaction implemented by glucose oxidase (GOX) and horseradish peroxidase (HRP) as a model system. Notably, the cascade activity of GOX/HRP-polymer comicelles monotonically increases with the GOX/HRP ratio. The cascade activity of GOX/HRP-polymer comicelles is up to 4.9 times higher than that of free GOX and HRP mixtures at the same GOX/HRP ratio. We further demonstrate that our system can quickly detect glucose in contrast with a commercially available glucose assay kit. These findings provide a new and general method of PICA for the controlled construction of artificial enzyme complexes with tunable and enhanced activity in enzyme cascades for advanced biomedical applications.

Precision Conjugation: An Emerging Tool for Generating Protein-Polymer Conjugates.

Protein-polymer conjugates are increasingly being applied in biomedicine because of the unique combination of the biological activity of the proteins and the multifunctionality and flexibility of the polymers. However, traditional protein-polymer conjugation techniques suffer from some unavoidable drawbacks, including nonspecificity and low efficiency. In this Minireview, we discuss a new approach based on "precision conjugation" for the construction of the next-generation protein-polymer conjugates in a more controlled, more efficient, and tailorable fashion for a broad range of advanced applications. In illustrating the concept, we highlight two general methods: site-specific in situ growth and intrinsically disordered polypeptide fusion, with a focus on the in situ, efficient, and controllable formation of protein-polymer conjugates. At the end, the challenges associated with this emerging concept are further discussed.

Effects of long-distance transportation on blood constituents and composition of the nasal microbiota in healthy donkeys.

BACKGROUND: This study aims to determine the effects of transportation on the nasal microbiota of healthy donkeys using 16S rRNA sequencing. RESULTS: Deep nasal swabs and blood were sampled from 14 donkeys before and after 21 hours' long-distance transportation. The values of the plasma hormone (cortisol (Cor), adrenocorticotrophic hormone (ACTH)), biochemical indicators (total protein (TP), albumin (ALB), creatinine (CREA), lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), blood urea (UREA), plasma glucose (GLU)) and blood routine indices (white blood cell (WBC), lymphocyte (LYM), neutrophil (NEU), red blood cell (RBC), hemoglobin (HGB)) were measured. 16S rRNA sequencing was used to assess the nasal microbiota, including alpha diversity, beta diversity, and phylogenetic structures. Results showed that levels of Cor, ACTH, and heat-shock protein 90 (HSP90) were significantly increased (p < 0.05) after long-distance transportation. Several biochemical indicators (AST, CK) and blood routine indices (Neu, RBC, and HGB) increased markedly (p < 0.05), but the LYM decreased significantly (p < 0.05). Nine families and eight genera had a mean relative abundance over 1%. The predominant phyla in nasal microbiota after and before transportation were Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. Transportation stress induced significant changes in terms of nasal microbiota structure compared with those before transportation based on principal coordinate analysis (PCoA) coupled with analysis of similarities (ANOSIM) (p < 0.05). Among these changes, a notably gain in Proteobacteria and loss in Firmicutes at the phylum level was observed. CONCLUSIONS: These results suggest transportation can cause stress to donkeys and change the richness and diversity of nasal microbiota. Further studies are required to understand the potential effect of these microbiota changes on the development of donkey respiratory diseases.

Polymerization Induced Self-Assembly of a Site-Specific Interferon α-Block Copolymer Conjugate into Micelles with Remarkably Enhanced Pharmacology.

Conjugating a hydrophilic and protein-resistant polymer to a protein is a widely used strategy to extend the in vivo half-life of the protein; however, the benefit of the half-life extension is usually limited by the bioactivity decrease. Herein we report a supramolecular self-assembly strategy of site-specific in situ polymerization induced self-assembly (SI-PISA) to address the dilemma. An amphiphilic block copolymer (POEGMA-PHPMA) was directly grown from the C-terminus of an important therapeutic protein interferon-α (IFN) to in situ form IFN-POEGMA-PHPMA conjugate micelles. Notably, the in vitro bioactivity of the micelles was 21.5-fold higher than that of the FDA-approved PEGylated interferon-α PEGASYS. Particularly, the in vivo half-life of the micelles (83.8 h) was 1.7- and 100-fold longer than those of PEGASYS (49.5 h) and IFN (0.8 h), respectively. In a tumor-bearing mouse model, the micelles completely suppressed tumor growth with 100% animal survival, whereas at the same dose, PEGASYS and IFN were much less effective. These findings suggest that SI-PISA is promising as a next-generation technology to remarkably enhance the pharmacological performance of therapeutic proteins with short circulation half-lives.

Site-Selective in Situ Growth-Induced Self-Assembly of Protein-Polymer Conjugates into pH-Responsive Micelles for Tumor Microenvironment Triggered Fluorescence Imaging.

Self-assembly of site-selective protein-polymer conjugates into stimuli-responsive micelles is interesting owing to their potential biomedical applications, ranging from molecular imaging to drug delivery, but remains a significant challenge. Herein we report a method of site-selective in situ growth-induced self-assembly (SIGS) to synthesize site-specific human serum albumin-poly(2-(diisopropylamino)ethyl methacrylate) (HSA-PDPA) conjugates that can in situ self-assemble into pH-responsive micelles with tunable morphologies. Indocyanine green (ICG) was selectively loaded into the core of sphere-like HSA-PDPA micelles to form pH-responsive fluorescence nanoprobes. The nanoprobes rapidly dissociated into protonated individual unimers at a transition pH of around 6.5, that is the extracellular pH of tumors, which resulted in a sharp fluorescence increase and markedly enhanced cellular uptake. In a tumor-bearing mouse model, they exhibited greatly enhanced tumor fluorescence imaging as compared to ICG alone and pH-nonresponsive nanoprobes. These findings suggest that pH-responsive and site-selective protein-polymer conjugate micelles synthesized by SIGS are promising as a new class of tumor microenvironment-responsive nanocarriers for enhanced tumor imaging and therapy.

A Fast and Efficient Replacement of CTAB with MUA on the Surface of Gold Nanorods Assisted by a Water-Immiscible Ionic Liquid.

The synthesis and surface modification of gold nanorods (GNRs) is one of the most important and basic issues in nanoscience. Most of the widely investigated GNRs are coated with a cetyltrimethylammonium bromide(CTAB) bilayer. Here, a highly efficient method is proposed to replace CTAB from the surface of GNRs with a bifunctional 11-mercaptoundecanoic acid in order to decrease the possible toxicity caused by CTAB. This ligand exchange is achieved in a biphasic mixture of an aqueous solution and a water-immiscible ionic liquid (IL), [BMIM][Tf2 N]. That is, by mixing IL, mercaptoundecanoic acid (MUA)/IL (200 × 10-3 m) and a concentrated aqueous solution of GNRs together, followed by vortex stirring for 90 s, CTAB-capped GNRs with varying aspect ratios can be turned into corresponding MUA-capped GNRs with the same aspect ratio. Furthermore, the formed MUA-capped GNRs can be obtained in a large quantity and stored as powders for easy use. The MUA-capped GNRs with improved biocompatibility and colloidal stability are well suited for further biological functionalization and potential applications. This IL-assisted ligand exchange can reverse the surface charge, enhance the stability of GNRs, and suppress its cytotoxicity.

SET and MYND Domain-Containing Protein 3 (SMYD3) Polymorphism as a Risk Factor for Susceptibility and Poor Prognosis in Ovarian Cancer.

BACKGROUND We investigated the relationship of the polymorphisms of SET and MYND domain-containing protein 3 (SMYD3) with risk and prognosis of ovarian cancer. MATERIAL AND METHODS The polymerase chain reaction (PCR) amplification method was applied to detect the polymorphisms of variable number of tandem repeats (VNTR) in the SMYD3 gene promoter region for 156 patients with ovarian cancer (case group) and 174 healthy people (control group). Quantitative reverse transcription polymerase chain reaction and Western blot were applied to detect SMYD3 mRNA and protein expressions. RESULTS The frequencies of VNTR genotype 3/3 and allele genotype 3 in the case group were significantly higher than those in the control group, while the frequency of genotype 2/2 in the control group was significantly higher than that in case group (all P<0.05). The proportion of poorly differentiated patients carrying VNTR genotype 3/3 was significantly higher than the proportion of poorly differentiated patients carrying VNTR genotype 2/2+2/3, while the proportion of patients carrying genotype 3/3 with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV disease was significantly higher than the proportion of patients carrying genotype 2/2 +2/3 with FIGO stage III-IV disease (all P<0.05). SMYD3 mRNA and protein expressions were higher in the patients carrying genotype 3/3 than they were in the patients with the 2/2+2/3 genotype (all P<0.05). The 5-year survival rate for patients carrying VNTR genotype 3/3 was significantly lower than that of patients carrying genotype 2/2+2/3, and Cox regression analysis showed that VNTR genotype 3/3 was an independent risk factor for ovarian cancer prognosis (all P<0.05). CONCLUSIONS VNTR genotype 3/3 of the SMYD3 gene was associated with the risk of ovarian cancer. The polymorphism of VNTR genotype could be recognized as an indicator for the poor prognosis of patients with ovarian cancer.

[Finite element analysis of temperature field of retina by electrical stimulation with microelectrode array].

We studied the influence of electrode array parameters on temperature distribution to the retina during the use of retinal prosthesis in order to avoid thermal damage to retina caused by long-term electrical stimulation. Based on real epiretinal prosthesis, a three-dimensional model of electrical stimulation for retina with 4 X 4 microelectrode array had been established using the finite element software (COMSOL Multiphysics). The steady-state temperature field of electrical stimulation of the retina was calculated, and the effects of the electrode parameters such as the distance between the electrode contacts, the materials and area of the electrode contact on temperature field were considered. The maximum increase in the retina steady temperature was about 0. 004 degrees C with practical stimulation current. When the distance between the electrode contacts was changed from 130 microm to 520 microm, the temperature was reduced by about 0.006 microC. When the contact radius was doubled from 130 microm to 260 microm, the temperature decrease was about 0.005 degrees C. It was shown that there were little temperature changes in the retina with a 4 x 4 epiretinal microelectrode array, reflecting the safety of electrical stimulation. It was also shown that the maximum temperature in the retina decreased with increasing the distance between the electrode contacts, as well as increasing the area of electrode contact. However, the change of the maximum temperature was very small when the distance became larger than the diameter of electrode contact. There was no significant difference in the effects of temperature increase among the different electrode materials. Rational selection of the distance between the electrode contacts and their area in electrode design can reduce the temperature rise induced by electrical stimulation.