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PurposeTo explore the inter-regional health index at the city level to contribute to the reduction of health inequalities.MethodsEmployed the health determinant model to select indicators for the urban health index of Shenzhen City. Utilized principal component analysis, the weights of these indicators are determined to construct the said health index. Subsequently, the global Moran’s index and local Moran’s index are utilized to investigate the geographical spatial distribution of the urban health index across various administrative districts within Shenzhen.ResultsThe level of urban health index in Shenzhen exhibits spatial clustering and demonstrates a positive spatial correlation (2017, Moran’s I = 0.237; 2019, Moran’s I = 0.226; 2021, Moran’s I = 0.217). However, it is noted that this clustering displays a relatively low probability (90% confidence interval). Over the period from 2017 to 2019, this spatial clustering gradually diminishes, suggesting a narrowing of health inequality within economically developed urban areas.ConclusionOur study reveals the urban health index in a relatively high-income (Shenzhen) in a developing country. Certain spatially correlated areas in Shenzhen present opportunities for the government to address health disparities through regional connectivity.

The excessive application of pesticides increases the pollution potential, which leads to groundwater contamination and spreading of toxic substances in the environment by leaching or in runoff. In this study, new herbicide ionic liquids (HILs) based on fomesafen with multifunctions were prepared to improve the herbicidal activity and reduce the risk to the aquatic organisms. The octanol–water partition coefficient (Kow), surface activity, soil adsorption and herbicidal activity of HILs were tested and a comparative analysis with fomesafen was made. The results show that HILs have low water solubility, excellent Kow, low surface tension, and good adsorption ability, and these properties can be regulated and optimized by selecting different counter cations. The physico-chemical properties of HILs were related to the carbon chain length of the cation. Compared with fomesafen sodium, ionic liquids N-1 showed a higher and faster herbicidal activity because of its good lipophilicity and low surface tension. HILs with lower water solubility and greater adsorption capacity in soil have less risk to algae, snail and other aquatic organisms than fomesafen sodium. The HILs will be a candidate in fomesafen applications in the future. [ABSTRACT FROM AUTHOR]

The use of bilberry ( Vaccinium myrtillus L.) as a food and medicine for improving human vision has a long history all over the world. However, there is lack of convincing evidence from rigorous clinical trials or scientific research. This study investigated the effects of different concentrations of bilberry extracts on the cell viability, cell cycle and the expression of hyaluronic acid and glycosaminoglycans of cultured human corneal limbal epithelial cells. The data showed that bilberry extracts had no cytotoxicity to the corneal limbal epithelial cells at a wide range of concentrations (10−9-10−4 M, equalized to the content of cyanidin-3-O-glucoside). Bilberry extract (10−6, 10−5 and 10−4 M) increased cell viability after 48 h incubation. The number of cells decreased in G0/G1 phase and increased prominently in S and G2/M phases after treatment with bilberry extracts at a high concentration (10−4 M). The expression of glycosaminoglycans increased prominently after incubation with bilberry extracts (10−7 and 10−4 M) for 48 h while no significant changes were observed for the expression of hyaluronic acid. The results indicated that bilberry extract may be beneficial for the physiological renewal and homeostasis of corneal epithelial cells. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: Pathologic myopia described as myopia accompanied by severe deformation of the eye besides excessive elongation of eye, is usually a genetic heterogeneous disorder characterized by extreme, familial, early-onset vision loss. However, the exact pathogenesis of pathologic myopia remains unclear. In this study, we screened a Han Chinese family with pathologic myopia to identify the causative mutation and explore the possible pathogenic mechanism based on evaluation of the biological functions of the mutation., Methods: We identified the mutations in a family with pathologic myopia by single nucleotide polymorphism array combined with short tandem repeat microsatellite marker analysis and exome sequencing. Mutations were validated among family members by direct Sanger sequencing. The subcellular localization of the protein variant was investigated by immunofluorescence, and the stability of the mutant protein was determined by immunoblotting. Intracellular levels of adenosine triphosphate and reactive oxygen species and complex I activity were measured by traditional biochemical methods to determine the functional role of the disease-associated mutation., Results: The novel missense mutation: c.798C>G (p.Asp266Glu) in NDUFAF7, cosegregated with the disease and the resulting amino acid substitution affected a highly conserved residue in its protein. The mutation D266E in NDUFAF7 impaired complex I activity, which resulted in decreased ATP levels in cultured cells., Conclusions: We propose that the heterozygous mutation (c.798C>G) in NDUFAF7 may contribute to the pathogenesis of pathologic myopia, possibly by interfering with the phototransduction cascade. Mitochondrial dysfunction during eye development may lead to pathologic myopia.

X-linked intellectual disability (XLID) has been associated with various genes. Diagnosis of XLID, especially for non-syndromic ones (NS-XLID), is often hampered by the heterogeneity of this disease. Here we report the case of a Chinese family in which three males suffer from intellectual disability (ID). The three patients shared the same phenotype: no typical clinical manifestation other than IQ score ≤ 70. For a genetic diagnosis for this family we carried out whole exome sequencing on the proband, and validated 16 variants of interest in the genomic DNA of all the family members. A missense mutation (c.710G > T), which mapped to exon 6 of the Rab GDP-Dissociation Inhibitor 1 (GDI1) gene, was found segregating with the ID phenotype, and this mutation changes the 237th position in the guanosine diphosphate dissociation inhibitor (GDI) protein from glycine to valine (p. Gly237Val). Through molecular dynamics simulations we found that this substitution results in a conformational change of GDI, possibly affecting the Rab-binding capacity of this protein. In conclusion, our study identified a novel GDI1 mutation that is possibly NS-XLID causative, and showed that whole exome sequencing provides advantages for detecting novel ID-associated variants and can greatly facilitate the genetic diagnosis of the disease.

The controlled and targeted release of pesticides with high water solubility has been a challenge for integrated pest management. In this paper, kasugamycin, an antibiotic broadly used in plant disease control, was covalently conjugated to pectin to form a kasugamycin-pectin conjugate by an amide bond. The conjugate was structurally characterized by Fourier transform infrared spectroscopy, ultraviolet spectrophotometry, and thermal gravimetric analysis. The results showed that the conjugate was stable over a wide range of pH and temperatures, as well as under UV irradiation. When incubated with Pseudomonas syringae pv. lachrymans, the conjugate could be activated, releasing the kasugamycin, which made it a promising controlled-release formulation of pesticide.

Biologically active low-molecular-mass thiols, mainly including glutathione (GSH), cysteine (Cys), homocysteine (Hcy), and cysteinylglycine (Cys-Gly), are important physiological components in biological fluids, and their analytical methods have gained continuous attention over recent years. We developed and validated a novel HPLC method for the quantification of GSH, Cys, Hcy, and Cys-Gly in human plasma, urine, and saliva using 4-chloro-3,5-dinitrobenzotrifluoride as the derivatization reagent. Analyses were linear from 0.15 to 500 μM with the coefficient regression range of 0.9987-0.9994. Detection limits ranged from 0.04 to 0.08 μM (S/N=3). The developed method was applied to quantification of four thiols in human biological fluids collected from five donors with the concentration range of 2.50-124.25 μM, 0-72.81 μM, and 0-4.25 μM for plasma, urine, and saliva, respectively. The present method seemed to be an attractive choice for the determination of thiols in plasma, urine, and saliva.

Purpose: The present study investigated dynamic alteration of low-density lipoprotein receptor and its binding and uptake of low-density lipoprotein (LDL) after exposure to transforming growth factor-beta(2) (TGF-beta(2)) in human Tenon's capsule fibroblasts., Methods: Tenon's capsule fibroblasts obtained from elective cataract surgery patients were cultured and stimulated with different concentrations (0.1-10 ng/mL) of TGF-beta(2) for 24, 48, and 72 h. The LDLr mRNA and protein levels were analyzed by relative quantification real-time RT-PCR and Western blot analysis, respectively. The binding and uptake of DiO (3,3'-dioctadecyloxacarbocyanine)-labeled LDL was assessed by confocal microscopy., Results: Real-time RT-PCR and Western blot analyses showed similar results revealing that after exposure to TGF-beta(2), the expression of protein and mRNA of LDLr occurred in a concentration-dependent and time-dependent manner with a peak at a concentration of 1.0 ng/mL at 72 h in Tenon's capsule fibroblasts. Confocal microscopy showed that DiO-LDL binding and uptake were time-dependent, reaching saturation at approximately 6 h., Conclusions: This study shows that LDLrs were overexpressed in the activated Tenon's capsule fibroblasts in a concentration-dependent and time-dependent manner after exposure to TGF-beta(2). The results suggest that LDLr in the activated Tenon's capsule fibroblasts may become a novel focus as a target receptor for controlled drug delivery, particularly in anti-scarring therapy during excessive conjunctival wound healing.

Purpose: Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide, and its pathogenesis is still unknown. The purpose of this study was to determine molecular changes in membrane proteins in trabecular meshwork (TM) cells from POAG patients compared to those of age-matched normal controls., Methods: Two-dimensional (2-D) gel electrophoresis profiles of membrane extracts from normal and glaucomatous TM cells were compared. The desired spots were identified after trypsin digestion and mass spectrometric analysis. Based on the results, a calcium-dependant membrane-binding protein, copine1, was further approached for a possible role in glaucomatous TM cells. The intracellular calcium concentration ([Ca(2+)]i) of TM cells was increased by incubating with calcium ionophore, A23187. Relative quantification real-time polymerase chain reaction (PCR) and western blot analysis measured copine1 expression and localization both in untreated and A23187-treated TM cells., Results: Real-time PCR and western blot analysis confirmed that copine1 mRNA and protein expression were upregulated in glaucomatous TM cells when compared to normal ones. The cell distribution studies further showed that copine1 existed both in the membrane and cytoplasm fractions of glaucomatous TM cells but existed exclusively in cytoplasm fractions of their normal counterparts. More importantly, an influx of Ca(2+) markedly promoted the translocation of copine1 from the cytoplasm to membranes in glaucomatous TM cells., Conclusions: Copine1 is upregulated in plasma membranes of TM cells in individuals with POAG, which may be partly explained by its Ca(2+)-dependent translocation from the cytoplasm to the membranes. Investigation of the role and functions of copine1 in TM cells should offer new insight into the abnormal intracellular Ca(2+)-signaling pathway in glaucomatous TM and help to clarify the molecular mechanism of POAG.

Purpose: To synthesize a ternary cationic copolymer called CS-g-(PEI-b-mPEG) and characterize its features as a non-viral siRNA carrier; in turn, to investigate the influence of small interfering RNA (siRNA) targeting IkappaB kinase subunit beta (IKKbeta) on the proliferation of human Tenon's capsule fibroblasts (HTFs) in vitro., Methods: First, a novel cationic copolymer composed of low molecular weight, linear poly(ethyleneimine) [PEI] blocked with polyethylene glycol (PEG) and grafted onto a chitosan (CS) molecule was synthesized. CS-g-(PEI-b-mPEG) was then compacted with 21nt siRNA at various copolymer/siRNA charge (N/P) ratios, and the resulting complexes were characterized by dynamic light scattering, gel electrophoresis, and serum incubation. Cell Titer 96 AQ(ueous) One Solution cell proliferation assay was used to investigate the cytotoxicity of this cationic copolymer. Second, siRNAs targeting IKKbeta (IKKBeta-siRNAs) were delivered into the HTFs using CS-g-(PEI-b-mPEG) as the vehicle. Real-time reverse transcription polymerase chain reaction (RT-PCR) subsequently assessed the mRNA level of IKKbeta, and western blot assay was used to determine protein expression. After IKKB-siRNA transfection, Cell Titer 96 AQ(ueous) One Solution cell proliferation assay was used to evaluate the proliferation of HTFs., Results: The diameter of the CS-g-(PEI-b-mPEG)/siRNA complexes tended to decrease whereas their zeta potential tended to increase as the N/P ratio increased. The CS-g-(PEI-b-mPEG) copolymer showed good siRNA binding ability and high siRNA protection capacity. Furthermore, the copolymer presented remarkable transfection efficiency and showed much less cytotoxicity than 25 kDa PEI. IKKB-siRNAs were successfully delivered into HTFs using CS-g-(PEI-b-mPEG) as a vector. As a result, the expression of IKKbeta was downregulated at both the mRNA and protein levels, and the activation of nuclear factor-kappaB (NF-kappaB) in the HTFs was subsequently inhibited. Most impressively, the proliferation of HTFs was also effectively suppressed through the blocking of the NF-kappaB pathway., Conclusions: All the results demonstrate that CS-g-(PEI-b-mPEG) is a promising candidate for siRNA delivery, featuring excellent biocompatibility, biodegradability, and transfection efficiency. The RNA interference (RNAi) strategy using cationic copolymers as siRNA carriers will be a safe and efficient anti-scarring method following glaucoma filtration surgery.