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The mechanism driving dysthyroid optic neuropathy (DON) is unclear. Diffusion-tensor imaging (DTI) allows for noninvasively assessing the microstructure of the entire visual pathway and may facilitate a better understanding of the mechanism of DON.To assess microstructural changes of the whole visual pathway and to investigate the potential mechanism of trans-synaptic damage（TSD） pathogenesis in DON with DTI.Cross-sectional.Sixty-four patients with bilateral thyroid-associated ophthalmopathy (TAO), 30 with and 34 without DON, and 30 age- and sex-matched healthy controls (HCs).3 T/DTI (A single-shot diffusion-weighted echo-planar imaging sequence).Differences in DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in each segment (optic nerve, tract, and radiation) of the entire visual pathway among the groups were compared. The parameters of visual evoked potentials (VEPs), visual field tests, and mean retinal nerve fiber layer (mRNFL) thickness on optical coherence tomography were also compared across patients.Student's t-test, chi-square test; ANOVA with post-hoc testing, interclass correlation coefficient, and correlation analysis. Significance level: P 0.05.TAO patients with DON showed significantly reduced mRNFL thickness and abnormal VEPs. There was a tendency for gradually reduced FA and AD, and increased RD and MD from HCs, with non-DON to with DON in optic nerve and tract, statistically. For radiation, the RD and MD showed statistical increase, the AD and FA just showed numerical decrease (P = 0.119 and 0.059, respectively). For DON, the FA and MD of visual pathway segments showed correlations with abnormal VEPs.DTI may be a useful tool for detecting microstructural changes in the entire visual pathway in DON. The changes in RNFL thickness and DTI parameters suggested TSD as a potential pathogenic mechanism of DON.4 Technical Efficacy: Stage 5.

In this article, a novel vertical wire-bonding interconnect structure is intelligently modeled and optimized with general artificial neural network (GRNN) and genetic algorithm (GA) for multilayered system in package. A compensation structure is constructed with a hybrid inductive and capacitive technique, while a capacitive stripline with series inductive short-end via is designed underneath the 50-Ω transmission line. The GRNN algorithm is employed to build the electromagnetic model databases during the procedure of GA optimization. In comparison with the conventional optimization algorithm, the output performances can be directly achieved with collaboratively combined methods, which can significantly reduce the calculation time. From the measurement results, the return loss is improved significantly while the parasitic inductive behavior of the bonding wire is eliminated with the presented design. Moreover, compared with the traditional compensation techniques, no additional area is occupied on the surface plane of the wire-bonding interconnection, which is more suitable for the high-integrated circuit system.

The hydrogel wound dressings are mostly sheet-like and do not possess adhesive properties, so it is often difficult for them to adhere well to the skin tissues and fit completely with the irregularly shaped wounds or deep wounds, thereby affecting their therapeutic effects. Herein, the chitosan derivative-based mussel-inspired hydrogels have been developed to overcome these obstacles. Specifically, the principle of adhesion of marine mussel was imitated to synthesize catechol-modified chitosan (CMC), which was potentially used as the raw material to prepare the mussel-inspired hydrogels, that can contribute to the excellent adhesive property and make the hydrogels adhere well to the wound sites. The o-diphenyl groups in CMC could be easily oxidized to form o-diquinone to further form a covalent binding with amino groups (–NH2), or can directly form coordination binding with Fe3+.This strong covalent and coordination binding causes the hydrogels to possess a complex spatial structure, which facilitates the hydrogels to display good swelling properties, drug loading and release properties. Furthermore, the total saponins of Panax notoginseng were loaded in the hydrogels and the therapeutic effects of drug-loaded hydrogel were investigated in the model of full-thickness skin injury in mice. The wound healing rate was observed to be as high as 92.5% without exhibiting any scarring. Overall, our findings provided a novel strategy for the preparation of hydrogels for therapeutic applications.

Purpose Fast-track surgery is a developing trend in medical care. It is a core challenge for clinical anesthesia to reasonably reduce the dosage of opioids and relieve postoperative pain. Serratus anterior plane block (SAPB) is a novel analgesic technique with such advantages as easy operation, good safety, and few side effects. Patients and methods In total, 60 patients aged 18 to 65 years who were diagnosed with lung cancer and scheduled for thoracoscopic resection were randomly assigned to receive SABP or local infiltration anesthesia. We analyzed the time within 48 hrs after operation to visual analogue scale (VAS) pain score of 4 or higher and the number of patients requiring additional analgesics at 6 hrs and 12 hrs after operation. Results The estimated median time to VAS ≥4 was 4 hrs (1.32 to 6.68) in the control group and 11 hrs (6.71 to 15.29) in the SAPB group (log-rank test: P=0.008). The number of patients requiring additional analgesics at 6- and 12 hrs after operation was significantly lower in the SAPB group than that in the control group (P Conclusion Compared with local infiltration, SAPB provided extended postoperative analgesia after thoracoscopic surgery with reduced consumption of additional analgesics in the early postoperative stage.

A fluorescent Zn(II)-based coordination polymer, {[Zn(Hssa)(1,4-bib)(H2O)](H2O)}n (1), has been successfully constructed from 5-sulfosalicylic acid (H3ssa) and 1,4-bis(1H-imidazol-1-yl)benzene (1,4-bib) with zinc acetate by solvothermal conditions, which was further characterized by elemental analysis, IR spectra, and thermogravimetric analysis. Single crystal X-ray structure analysis reveals that 1 crystallizes in a 1D zigzag chain. Of particular interest is that the alternating 1D zigzag chains have been orderly staggered in a 2D parallel arrangement in the crystal structure. These neighboring chains are further connected through π⋯π stacking interactions and O H⋯O hydrogen bonds, resulting in the formation of a 3D supramolecular structure. Furthermore, the photoluminescent properties for metal cations were studied at room temperature. 1 shows intense fluorescence in the solid state and exhibits a highly sensitive and selectivity for Fe3+ through fluorescence quenching effect in aqueous solutions at room temperature.

Soil nitrogen (N) is critical to ecosystem services and environmental quality. Hotspots of soil N in areas with high soil moisture have been widely studied, however, their spatial distribution and their linkage with soil N variation have seldom been examined at a catchment scale in areas with low soil water content. We investigated the spatial variation of soil N and its hotspots in a mixed land cover catchment on the Chinese Loess Plateau and used multiple statistical methods to evaluate the effects of the critical environmental factors on soil N variation and potential hotspots. The results demonstrated that land cover, soil moisture, elevation, plan curvature and flow accumulation were the dominant factors affecting the spatial variation of soil nitrate (NN), while land cover and slope aspect were the most important factors impacting the spatial distribution of soil ammonium (AN) and total nitrogen (TN). In the studied catchment, the forestland, gully land and grassland were found to be the potential hotspots of soil NN, AN and TN accumulation, respectively. We concluded that land cover and slope aspect could be proxies to determine the potential hotspots of soil N at the catchment scale. Overall, land cover was the most important factor that resulted in the spatial variations of soil N. The findings may help us to better understand the environmental factors affecting soil N hotspots and their spatial variation at the catchment scale in terrestrial ecosystems.

Nowadays, although the exploration of proton conductive materials has ranged from traditional sulfonated polymers to novel crystalline solid materials such as MOFs, COFs, and HOFs, research on crystalline cluster-based organic framework materials is very limited. Here, a pair of homologues Cu(i)-based organic framework containing a Cu12S6 cluster, [Cu12(MES)6(H2O)3]n (1) and {[Cu12(MPS)6(H2O)4]·6H2O}n (2) (H2MES = 2-mercaptoethanesulfonate acid and H2MPS = 2-mercaptoethanesulfonate acid), were hydrothermally synthesized under the same conditions and fully investigated for their proton conduction. Their structures were characterized by means of single-crystal X-ray diffraction, elemental analysis, thermogravimetric analyses, and PXRD measurements. The two MOFs show significant structural differences in the topological fashions. MOF 1 has a three-dimensional network and can be simplified into two topology types: a 10-connected gpu structure with a Schläfli symbol (312·426·57) and a 3,12-connected new topology with a point symbol {3·42}2{310·418·519·614·74·9}. MOF 2 also has a three-dimensional framework and topology as a 6-connected pcu primitive cubic network with a Schläfli symbol {412·63}. The two MOFs show different proton conduction parameters, but both indicate temperature-dependent proton conductive features. Intriguingly, the two MOFs exhibit high water stability and their proton conductivities are 3.63 × 10-5 and 2.75 × 10-5 S cm-1 under 333 K and 98% RH, respectively. The suggested mechanism for the synthesis for 1 and 2, and their proton conductivity performance comparison has been discussed in detail. In addition, Hirshfeld surface and fingerprint analysis on the two MOFs were computed to compare contacts between the molecules, which is essential for analyzing the relationships between their hydrogen bonds and proton conductivity properties.

The paper shows the determination of the transmission of one dimensional metal-dielectric photonic band gap materials (1D-MD PBG) theoretically and experimentally. It has been found that the location and bandwidth of transmission can be tailored by initiatively adopting a suitable structure. We proposed a special 1D-MD PBG obtained by magnetron sputtering, in which each layer of metal film is not continuous. These structures have a number of advantages such as high transmittance (55% or better), broad bandwidth (the full width at half of maximum ranges from 400 nm to 780 nm) and high electrical conductivity (the sheet resistance can be lower than 0.98 Ω /square). Meanwhile, it has been also theoretically and experimental indicated that both the light transmittance and electrical conductivity could be improved effectively by using the (pqp)N structure.

Purpose Hyperuricemia is an important potential pathogenic factor for hypertension, cardiovascular disease and stroke. The current study aimed to investigate the prevalence of hyperuricemia and its relationship to lifestyle characteristics and dietary habits in centenarians and near-centenarians. Patients and methods In total, 966 centenarians and 788 near-centenarians were included. Community-based surveys were conducted to collect information about lifestyle. Blood examinations were performed using enzymatic assays. T-tests and χ2 tests were used to investigate significant indicators of hyperuricemia, and multivariate logistic regression was used to analyze the related risk factors. A comprehensive analysis of nineteen modifiable factors, including lifestyle characteristics, dietary habits, general characteristics and blood test indexes, was conducted. Results The prevalence of hyperuricemia was 29.02%. The percentage of men, waist circumference (WC), waist-hip ratio, estimated glomerular filtration rate (eGFR), levels of total protein (TP), alanine aminotransferase, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol, serum homocysteine, serum uric acid, serum urea and serum creatinine, passive smoking, alcohol consumption, snoring, preference for fried flavors, and meat, seafood and vegetable consumption were significantly different between the hyperuricemia group and the normouricemia group (p

In this study, a one-dimensional steady-state mathematical model of radon transport in fragmented uranium ore was established according to Fick's law and radon transfer theory in an air-water interface. The model was utilized to obtain an analytical solution for radon concentration in the air-water, two-phase system under steady state conditions, as well as a corresponding radon exhalation rate calculation formula. We also designed a one-dimensional experimental apparatus for simulating radon diffusion migration in the uranium ore with various water levels to verify the mathematical model. The predicted results were in close agreement with the measured results, suggesting that the proposed model can be readily used to determine radon concentrations and exhalation rates in fragmented uranium ore with varying water levels.

The radon diffusion coefficient and the free radon production rate are important parameters for describing radon migration in the fragmented uranium ore. In order to determine the two parameters, the pure diffusion migration equation for radon was firstly established and its analytic solution with the two parameters to be determined was derived. Then, a self manufactured experimental column was used to simulate the pure diffusion of the radon, the improved scintillation cell method was used to measure the pore radon concentrations at different depths of the column loaded with the fragmented uranium ore, and the nonlinear least square algorithm was used to inversely determine the radon diffusion coefficient and the free radon production rate. Finally, the solution with the two inversely determined parameters was used to predict the pore radon concentrations at some depths of the column, and the predicted results were compared with the measured results. The results show that the predicted results are in good agreement with the measured results and the numerical inverse method is applicable to the determination of the radon diffusion coefficient and the free radon production rate for the fragmented uranium ore.

Objective: Newborn hearing screening has been widely adopted and made an achievement to some degree. Current screening protocols rely solely on detecting existing auditory disorders at the time of screening and are unable to identify individuals susceptible to auditory disorders in later life. Even if the hearing loss newborn is referred, most cases could not be diagnosed until 6–12 months old with no etiology being elucidated. This study reports the first effort to combine traditional hearing screening with genetic screening to improve the efficacy of newborn hearing screening. Methods: This study was undertaken in 12 regional hospitals located in 11 provinces of China. 14,913 newborn babies received hearing concurrent genetic screening. The hearing screening was performed with OAE or AABR. Blood sample was collected with a universal newborn genetic screening card. And three common gene, mtDNA 12S rRNA, GJB2 and SLC26A4 were screened with standard protocol. Results: Among all the 14,913 newborns, 86.1% (12,837/14,913) individuals passed the first-step hearing screening, 7.8% (1168/14,913) babies passed only one side, and the other 6.1% (908/14,913) were bilaterally referred. Gene screening found 306 individuals had one or two mutant alleles, the carrier rate is 2.05% (306/14,913) among the entire newborn population. The risk for hearing loss was 100% (7/7) for those newborns carrying causative GJB2 or SLC26A4 mutations (homozygotes or compound heterozygotes), 14.4% (23/160) for GJB2 heterozygote carriers, 12.3% (15/122) for SLC26A2 heterozygous carriers, and the total prevalence of referral hearing screening was approximately 14.7% (45/306). However, 85.3% (261/306) newborns passed hearing screening among these carriers including 18 newborns with 12S rRNA mt.1555A>G pathogenic mutation, who would suffer from sudden hearing loss once applying aminoglycoside drugs. Conclusion: The cohort studies provided the essential population parameters for developing effective programs for hearing care of newborns in China. Hearing concurrent gene screening in newborns may confirm the abnormal results from hearing screening tests, help to find the etiologic of the hearing loss, and better recognize infants at risk for late-onset hearing loss occurring prior to speech and language development. In conclusion, a survey on 14,913 Chinese newborns proved that concurrent genetic screening could improve newborn hearing screening for hearing defects.

This study investigated changes in accumulation and partitioning of nitrogen (N), phosphorus (P), and potassium (K) with harvest dates of early, middle, and late maturity sweet sorghum varieties in 2006 and 2007 in North China. All the varieties exhibited an obvious trend of decrease in concentrations of N, P and K in aboveground plants from elongation to 60 days after anthesis (DAA). The reduction in nutrient concentrations was found in the order of K (14.5 − 4.5 g kg−1) > N (13.3 − 7.4 g kg−1) > P (2.40 − 0.96 g kg−1). Conversely, N, P, and K accumulation significantly increased from elongation to anthesis, and continued to increase until 40 DAA. The accumulation of N, P, and K at maturity (40 DAA) was 128–339 kg ha−1, 30–75 kg ha−1 and 109–300 kg ha−1, respectively. Between elongation and anthesis, the middle and late maturity varieties had a higher ratio of N (50–82%), P (55–83%), and K (62–88%) accumulation than the early varieties (51–64% for N, 40–62% for P, and 55–75% for K). Sweet sorghum exhibited only one important K uptake stage from elongation to thesis according to the accumulation ratio (percentage of the nutrient accumulated at a given stage relative to that at physiological maturity) and rate (kilogram of nutrient accumulated per day per hectare). The stage from anthesis to grain maturity was the second important N and P uptake period. During the delay harvest period between 40 and 60 DAA, the early varieties exhibited significant increases in N accumulation; and the late varieties exhibited the reverse. P accumulation did not decrease significantly, whereas K accumulation decreased for all varieties in both years. Although of the N and P concentrations in straw were significantly lower than in grains, the N, P and K accumulation in straw was 2.2–9.3, 1.7–7.7, and 8.1–30.5 times higher than in grains, respectively. The concentrations of N and P in leaves were higher than in stems after anthesis. We found significantly higher accumulation of P and K in stems than in leaves, with a comparable N accumulation. The findings are helpful to make a fertilization regime recommendation for sweet sorghum production as a bioethanol crop in North China. It also suggests a further genetic improvement for optimizing nutrient use.

This investigation was carried out in order to evaluate changes in biomass, carbohydrates, and calculated ethanol yield (CEY) from anthesis to 40 days after anthesis (DAA) of five sweet sorghum (Sorghum biocolor (L.) Moench) cultivars with a crop cycle length of 111–165 days in Beijing (39°56′N, 116°20′E). Aboveground dry weight (AGDW) and total soluble sugar yield (TSSY, 1.3–10.5 t ha−1) increased with time after anthesis and with crop cycle length. Cellulose and hemicellulose contents at anthesis varied between 205–277 g kg−1 and 187–232 g kg−1, respectively, and were significantly (p < 0.05) higher than either 20 DAA or 40 DAA. Cellulose and hemicellulose yields changed between 1.6 and 6.6 t ha−1 from anthesis to 40 DAA. The stems comprised major sinks of soluble sugar, with 79.4–94.6% of TSSY, and major sinks of insoluble sugar, with 55.9–75.9% of the total cellulose and hemicellulose yield. The hybrids exhibited higher TSSY, cellulose, hemicellulose and grain yield, and therefore also CEY than the inbred cultivars with a similar crop cycle length. Total CEY from the carbohydrates increased with time after anthesis and with crop cycle length, ranging between 4867 and 13032 L ha−1 on 40 DAA during the two years. It is concluded that the effects of each factor of year, harvest time, and genotype on biomass, carbohydrates yield, and CEY are highly significant. The interaction of genotype with year (environment) has significant effects on the total CEY. We recommend beginning the harvest of sweet sorghum upon the early maturity of the cultivars from around 20 DAA. This will result in a harvest period of around two months until grain maturity of the late cultivars for ethanol production in North China.

LRP16 gene has been characterized as an estrogen-responsive gene. One 1/2ERE/GC-rich site was previously identified to be indispensable for -676/-214 (region A) fragment within LRP16 regulatory region to confer E2 action. Here, we report that -213/-24 fragment (region B) has higher E2-responsiveness than that of region A in MCF-7 cells, but not in HeLa cells. Deletion and mutation analyses of region B showed that multiple GC-sites are involved in the E2-stimulated response and one 30-bp fragment (-213 to -184 bp) is essential for conferring maximum E2-responsiveness. Results from the cotransfection assays containing Sp1-siRNA revealed that Sp1 is required for the basal transcription activity and E2-responsiveness of both regions A and B. Northern blot analysis demonstrated that inhibition of Sp1 in MCF-7 cells not only decreased the basal expression of LRP16, but markedly impaired its upregulation by E2. Results from gel mobility shift assays exhibited the direct binding of Sp1 protein to the 28-bp fragment (-211 to -184 bp), which was enhanced by the ERalpha titer. Moreover, the functional interaction of ERalpha and Sp1 proteins in the presence of E2 at the GC-rich sites in region B was confirmed by chromatin immunoprecipitation (ChIP) assays. In general, these results demonstrate that GC-rich sites in the proximal promoter of LRP16 gene are sufficient for E2 activation of LRP16 and the -213/-184 fragment containing only one GC site is essential for the maximal induction in MCF-7 cells. We also provide a model for Sp1-dependent regulation of genes by E2 through GC-rich motifs.

LRP16 was previously identified as an estrogen-induced gene in breast cancer cells. The responsiveness of LRP16 to estrogen and its functional effects in endometrial cancer (EC) cells are still unclear. Here, we show that the mRNA level and promoter activity of the LRP16 gene were significantly increased by 17beta-estradiol (E2) in estrogen receptor alpha (ER alpha)-positive Ishikawa human EC cells. Although the growth rate of Ishikawa cells was not obviously affected by ectopic expression of LRP16, the results of a Transwell assay showed an approximate one-third increase of the invasive capacity of LRP16-overexpressing cells. As a result of molecular screening, we observed that the expression of E-cadherin, an essential adhesion molecule associated with tumor metastasis, was repressed by LRP16. Further promoter analyses demonstrated that LRP16 inhibited E-cadherin transactivation in a dose-dependent manner. However, the inhibition was abolished by estrogen deprivation, indicating that the downregulation of E-cadherin transcription by LRP16 requires ER alpha mediation. Chromatin immunoprecipitation analyses revealed that the binding of ER alpha to the E-cadherin promoter was antagonized by LRP16, suggesting that LRP16 could interfere with ER alpha-mediated transcription. These results suggest that the upregulation of LRP16 by estrogen could be involved in invasive growth by downregulating E-cadherin in human ECs.

There is a worldwide interest in studying SLC26A4 mutations that are responsible for enlarged vestibular aqueduct (EVA) in different ethnic background and populations. The spectrum of SLC26A4 mutations in Chinese population is yet to be fully characterized. In this study, all the 21 exons of SLC26A4 were screened in 107 Chinese patients with hearing loss associated with EVA or both EVA and Mondini dysplasia (MD), taken from six multiplex and 95 simplex families. The two types of control populations consisted of 84 normal-hearing subjects and 46 sensorineural hearing loss subjects without inner ear malformations. Biallelic mutations were found in 12 patients from multiplex families and 84 patients (88.4%) from the simplex families. In addition, monoallelic variant was detected in nine patients in the remaining 11 simplex families. Overall, up to 97.9% patients were found having at least one possible pathogenic variant in SLC26A4, with most having biallelic variants consistent with recessive inheritance of this disorder. A total of 40 mutations including 25 novel mutations were identified in the Chinese patients but were not detected in all the controls except for one normal subject. For the Chinese mutation spectrum of SLC26A4 gene, IVS 7-2A>G mutation was the most common form accounting for 57.63% (102/177) of all the mutant alleles.

The resealing of porcine epidermis after electroporation is investigated. Porcine epidermis was subjected to electroporation (30 pulses at 100 V, 1 ms and at 1 Hz) in a vertical diffusion apparatus, in the presence of 2 mg/ml dimyristoylphosphatidylserine, to produce a long lasting permeable state. Resealing treatments include incubation in 0.0625–0.25 mM poloxamer 188 (P188), or incorporation of phosphatidylcholines (PC) and/or cationic lipids with additional pulses. The recovery of electric resistance of the epidermis samples after electroporation with or without resealing treatments was monitored. The transports of carboxyfluorescein and glucose were measured during the recovery process. Both P188 and PC were effective in resealing in terms of electric conductance and transport, with P188 reacting more rapidly and completely. P188 mediated lipid exchange between stratum corneum lipid particles was measured by fluorescence resonance energy transfer (FRET). Lipid reorganization facilitated by P188 and PC is suggested to be a major resealing mechanism of electroporation damage.

Transdermal transport of insulin and extraction of interstitial glucose under anodal iontophoresis (electroosmosis) following electroporation in the presence of 1,2-dimyristoylphophatidylserine (DMPS) was studied. An earlier study showed that DMPS increased the transport of insulin across porcine epidermis under electroporation by approximately fourfold. It was suggested that DMPS increased the lifetime of electropores in the epidermis resulting in an enhanced transport of permeants. When electroosmosis was applied across the epidermis following electroporation with DMPS, the enhancement of insulin transport was approximately 18-fold over electroporation alone. When the same strategy was applied to extract interstitial glucose, the enhancement was approximately 23-fold over electroporation alone. Real-time transdermal insulin transport kinetics was measured using FITC-labeled insulin and a custom-made vertical diffusion apparatus that had a fluorescence cuvette as the receiver compartment. Insulin transport by electroporation alone showed a nonlinear kinetics that is most likely due to the resealing of the electropores with time. The transport kinetics when electroporation was carried out in the presence of DMPS was more linear, confirming earlier studies that suggested the DMPS stabilizes transport paths formed by electroporation. The data suggests that in vivo, noninvasive insulin delivery to therapeutic levels and glucose extraction may be achieved by combining electroporation with anionic lipids and electroosmosis.

A needle-free method based on transcutaneous electroporation is described for delivering peptide vaccines. The K(b)-binding OVA-peptide SIINFEKL was used as an example to induce the peptide-specific cytotoxic T-lymphocytes (CTL) response in mice. A saturated anionic lipid was added during electroporation, and post-pulse electro-osmosis was applied to enhance the vaccine delivery. Electroporation was found to stimulate the exodus of Langerhans cells (LC) from the skin. The peptide transported into and through murine skin was measured using a Franz diffusion apparatus. Most peptide was retained in the skin rather than passing through the skin in the process. The peptide was delivered to the dorsal skin of mice by in vivo electroporation. An electroporation-transportable oligonucleotide with CpG motif was used as adjuvant. The efficacy of peptide delivery was comparable to that of intradermally injected with Freund's complete adjuvant (FCA). Peptide-specific CTL response to the vaccine delivered by needle-free electroporation/electro-osmosis was equivalent to that delivered by intradermal injection, as determined by production of the peptide-specific IFN-gamma in ELISPOT assay.

The therapeutic activity and toxicity of drugs often depends on the accumulation of drugs in the peripheral anatomical compartment rather than the central compartment. In the routine practice of therapeutic drug monitoring (TDM) and pharmacokinetic studies, drug concentration determined by intermittent blood sampling is used as a surrogate for calculating the drug concentration in the peripheral compartment tissues. Microdialysis, a relatively less invasive procedure, has been used for estimation of free drug levels in dermal, subcutaneous and muscle tissues. Transcutaneous extraction of drugs from the dermal tissue is a good noninvasive alternative to phlebotomy and microdialysis. This requires a technique, which can facilitate the extraction of significant and reproducible amounts of drugs from the dermal extracellular fluid (ECF) within a short sampling duration. In the present work, we assessed the feasibility of electroporation and transcutaneous extraction (ETE) method for determining the time course of drugs in dermal ECF, using salicylic acid (SA) as a test drug. Electroporation protocol was optimized based on the in vitro diffusion studies of salicylic acid across rat skin. The concentration-time profile of total SA was determined in rats after a single i.v. bolus administration. The in vivo permeability coefficient ( P in vivo ) of rat skin was determined under steady state plasma concentration of drug created by i.v. bolus followed by constant rate infusion of SA. The pharmacokinetic parameters of the drug were determined using a two-compartment pharmacokinetic model. The theoretical predicted time course of free SA in the dermal ECF after a single i.v. bolus administration was calculated using standard formulae. The concentration of free SA determined by ETE is in good agreement with that calculated using two-compartment pharmacokinetic model. This study thus provides a credible evidence for the validity of ETE technique for determining the concentration of SA in the dermal ECF.

To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction.Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR.The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memorye.Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases.

This genetic epidemiological study demonstrated that 26.65% of the prelingual deafness in Northern Chinese patients can be detected at younger ages by genetic testing of three common hearing loss genes (GJB2, SLC26A4 and mtDNA A1555G), and thus, early intervention measures could be undertaken to help them in language acquisition.The GJB2, SLC26A4 and mtDNA A1555G mutations are the prevalent causes of prelingual deafness worldwide. Numerous studies have revealed that the forms and frequencies of the mutations in the three genes are largely dependent on the ethnic or geographic origins. Hence, this study aimed to characterize the mutation profiles of the three genes in prelingual deafness in Northern Chinese patients. SUBECTS AND METHODS: An investigation of 514 patients with prelingual deafness and 117 controls with normal hearing was conducted. Bidirectional sequencing (or enzyme digestion) was applied to identify sequence variations.This study revealed that 26.65% patients had two mutated alleles (homozygote or compound heterozygote) of GJB2 (9.14%) or SLC26A4 (8.95%) and/or an mtDNA A1555G (8.56%) mutation. In detail, 19.26% patients carried GJB2 mutations including 10.12% single mutant carriers. 235delC was the most common type, making up 69.18% of all mutants for GJB2. The mutant carrier rate for SLC26A4 was 15.2%, including 6.23% single mutant carriers. The two most common types (IVS7-2AG and H723R) accounted for 51.61% and 33.06% mutations, respectively. Forty-five patients had mtDNA A1555G, giving a frequency of 8.75%. In the control group with normal hearing, 2.56%, 1.71% and 0% of the subjects carried a single mutant for GJB2, SLC26A4 and mtDNA A1555G, respectively.