Personalized Porous Gelatin Methacryloyl Sustained-Release Nicotinamide Protects Against Noise-Induced Hearing Loss.

There are no Food and Drug Administration-approved drugs for treating noise-induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM-encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro-computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained-release and long-term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug-based treatment of NIHL.

PBPK/PD Modeling of Nifedipine for Precision Medicine in Pregnant Women: Enhancing Clinical Decision-Making for Optimal Drug Therapy.

OBJECTIVE: This study aims to develop physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) predictive models for nifedipine in pregnant women, enhancing precision medicine and reducing adverse reactions for both mothers and infants. METHODS: A PBPK/PD model was constructed using PK-Sim, MoBi, and MATLAB software, integrating literature and pregnancy-specific physiological information. The process involved: (1) establishing and validating a PBPK model for serum clearance after intravenous administration in non-pregnant individuals, (2) establishing and validating a PBPK model for serum clearance after oral administration in non-pregnant individuals, (3) constructing and validating a PBPK model for enzyme clearance after oral administration in non-pregnant individuals, and (4) adjusting the PBPK model structure and enzyme parameters according to pregnant women and validating it in oral administration. (5) PK/PD model was explored through MATLAB, and the PBPK and PK/PD models were integrated to form the PBPK/PD model. RESULTS: The Nifedipine PBPK model's predictive accuracy was confirmed by non-pregnant and pregnant validation studies. The developed PBPK/PD model accurately predicted maximum antihypertensive effects for clinical doses of 5, 10, and 20 mg. The model suggested peak effect at 0.86 h post-administration, achieving blood pressure reductions of 5.4 mmHg, 14.3 mmHg, and 21.3 mmHg, respectively. This model provides guidance for tailored dosing in pregnancy-induced hypertension based on targeted blood pressure reduction. CONCLUSION: Based on available literature data, the PBPK/PD model of Nifedipine in pregnancy demonstrated good predictive performance. It will help optimize individualized dosing of Nifedipine, improve treatment outcomes, and minimize the risk of adverse reactions in mothers and infants.

Danggui Sini decoction treatment of refractory allergic cutaneous vasculitis: A case report.

BACKGROUND: Allergic cutaneous vasculitis (ACV) is a difficult disease to treat. At present, there is no effective treatment for this condition. Traditionally, immunosuppressants and hormones have been primarily used in its management, but the treatment effect is suboptimal, and it has several side effects. CASE SUMMARY: We present the case of a 19-year-old woman who presented at our hospital with a four-year history of symmetric skin lesions mainly affecting her lower extremities. She had previously undergone treatment with prednisolone acetate, cetirizine hydrochloride, and loratadine tablets but had not experienced any relief in her condition. Thereafter, she was treated with oral traditional Chinese medicine. Her skin damage gradually improved within two months of treatment initiation. After six months, the skin ulcers had completely subsided. No evidence of skin ulcer recurrence was observed during the subsequent follow-up. This report presents the first case of a female patient who received oral Danggui Sini decoction for the treatment of ACV. CONCLUSION: Danggui Sini decoction may be a promising oral treatment for ACV patients.

Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain.

Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus (LEC-DG) are considered responsible for the chronification of pain. However, the underlying alterations in fan cells, which are the predominant neurons in the LEC that project to the DG, remain elusive. Here, we investigated possible mechanisms using a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents (Ih), which led to the hyperexcitability of LEC fan cells of CFA slices. This phenomenon was attenuated in CFA slices by activating dopamine D2, but not D1, receptors. Chemogenetic activation of the ventral tegmental area -LEC projection had a D2 receptor-dependent analgesic effect. Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity, and this effect was attenuated by pre-activation of the Ih. Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.

Efficient production of D-glucosamine by diacetylchitobiose deacetylase catalyzed deacetylation of N-acetyl-D-glucosamine.

OBJECTIVE: D-Glucosamine (GlcN) is an important amino sugar with various applications in medicine, food & beverages, nutritional supplements, and dairy products. This study aimed to produce GlcN from N-acetyl-D-glucosamine (GlcNAc) with an efficient deacetylase, and apply different strategies to enhance GlcN production. RESULTS: We screened a series of deacetylases that involved in the deacetylation of GlcNAc to form GlcN. A diacetylchitobiose deacetylase (TKDac) from Thermococcus kodakarensis exhibited high-efficient deacetylation activity for GlcNAc, yet mostly in the form of inclusion bodies. The soluble expression of TKDac was improved by a co-expressing molecular chaperone (groEL) and TKDac, and insertion of rare codon ATA encoding isoleucine. As such, the recombinant strain TKEL4 was constructed to express TKDac, and 48 g/L GlcN was achieved by TKDac-catalyzed deacetylation. To overcome the inhibition of byproduct (acetate), immobilized TKDac was carried out to produce GlcN from GlcNAc. The immobilized TKDac was conveniently re-used for several batches (above 8) with a 90% conversion rate. CONCLUSIONS: TKDac from T. kodakarensis was found to be an efficient deacetylase to produce GlcN. Co-expression of molecular chaperone and target protein, and insertion of rare codons were effective to improve the soluble expression of TKDac. The immobilized TKDac represents a promising method for future GlcN production.

Systemic L-ornithine supplementation specifically increases ovarian putrescine levels during ovulation in mice†.

In all mammalian species examined thus far, the ovaries produce a burst of ornithine decarboxylase (ODC) and putrescine during ovulation or after application of human chorionic gonadotropin (hCG). Aged mice have significantly reduced levels of this periovulatory ODC and putrescine rise. Putrescine supplementation, in vitro during oocyte maturation or in mouse drinking water during the periovulatory period, reduces egg aneuploidies and embryo resorption, improving fertility of aged mice. These studies suggest that periovulatory putrescine supplementation may be a simple and effective therapy for reproductive aging for women. However, putrescine supplementation is expected to increase widespread tissue putrescine levels, raising concerns of nonspecific and unwanted side effects. Given that ODC is highly expressed in the ovaries during ovulation but otherwise exhibits low activity in most tissues, we hypothesized that periovulatory supplementation of L-ornithine, the substrate of ODC, might be suitable for delivering putrescine specifically to the ovaries. In this study, we have demonstrated that systemic application of L-ornithine via oral gavage or subcutaneous injection increased ovarian putrescine levels; the increase was restricted to animals that had been injected with hCG. Furthermore, L-ornithine specifically increased ovarian putrescine levels without affecting putrescine levels in any other tissues. However, our attempts to improve fertility of aged mice through L-ornithine supplementation in mouse drinking water produced either no effects (1% L-ornithine) or negative impact on fertility (4% ornithine). Our results suggest that it might not be feasible to achieve fertility-enhancing ovarian putrescine levels via L-ornithine supplementation in drinking water without encountering undesired consequences of high dose of exogenous L-ornithine.

Efficient bioconversion of raspberry ketone in Escherichia coli using fatty acids feedstocks.

BACKGROUND: Phenylpropanoid including raspberry ketone, is a kind of important natural plant product and widely used in pharmaceuticals, chemicals, cosmetics, and healthcare products. Bioproduction of phenylpropanoid in Escherichia coli and other microbial cell factories is an attractive approach considering the low phenylpropanoid contents in plants. However, it is usually difficult to produce high titer phenylpropanoid production when fermentation using glucose as carbon source. Developing novel bioprocess using alternative sources might provide a solution to this problem. In this study, typical phenylpropanoid raspberry ketone was used as the target product to develop a biosynthesis pathway for phenylpropanoid production from fatty acids, a promising alternative low-cost feedstock. RESULTS: A raspberry ketone biosynthesis module was developed and optimized by introducing 4-coumarate-CoA ligase (4CL), benzalacetone synthase (BAS), and raspberry ketone reductase (RZS) in Escherichia coli strains CR1-CR4. Then strain CR5 was developed by introducing raspberry ketone biosynthesis module into a fatty acids-utilization chassis FA09 to achieve production of raspberry ketone from fatty acids feedstock. However, the production of raspberry ketone was still limited by the low biomass and unable to substantiate whole-cell bioconversion process. Thus, a process by coordinately using fatty-acids and glycerol was developed. In addition, we systematically screened and optimized fatty acids-response promoters. The optimized promoter Pfrd3 was then successfully used for the efficient expression of key enzymes of raspberry ketone biosynthesis module during bioconversion from fatty acids. The final engineered strain CR8 could efficiently produce raspberry ketone repeatedly using bioconversion from fatty acids feedstock strategy, and was able to produce raspberry ketone to a concentration of 180.94 mg/L from soybean oil in a 1-L fermentation process. CONCLUSION: Metabolically engineered Escherichia coli strains were successfully developed for raspberry ketone production from fatty acids using several strategies, including optimization of bioconversion process and fine-tuning key enzyme expression. This study provides an essential reference to establish the low-cost biological manufacture of phenylpropanoids compounds.

Fine tuning of medium chain fatty acids levels increases fruity ester production during alcoholic fermentation.

Pichia fermentans Z9Y-3 and its intracellular enzymes were inoculated along with S. cerevisiae in synthetic grape must to modulate fruity ester production. The levels of ester-related enzymes, ester precursors, and fruity esters were monitored every 24 h during fermentation. Results showed that the levels of ethyl acetate, acetate higher alcohol esters (AHEs), short chain fatty acid ethyl esters (SFEs), and medium chain fatty acid ethyl esters (MFEs) were significantly enhanced in mixed fermentation. Pearson correlation analysis further revealed that higher alcohols and fatty acids played a more important role in fruity ester production than enzymes; Particularly, the correlation coefficient between fatty acids and MFEs was 0.940. In addition, supplementation of medium chain fatty acids (7.2 mg/L) at the metaphase of single S. cerevisiae fermentation improved ethyl acetate, AHE, SFE, and MFE production by 42.56%, 21.00%, 61.33%, and 90.04%, respectively, although the high level of ethyl acetate might result in off-flavors.

Enhancing wine ester biosynthesis in mixed Hanseniaspora uvarum/Saccharomyces cerevisiae fermentation by nitrogen nutrient addition.

The dynamic changes of wine ester production during mixed fermentation with Hanseniaspora uvarum Yun268 and Saccharomyces cerevisiae F5 was investigated at different levels and timings of nitrogen nutrient addition. Nitrogen additions were performed by supplementing yeast assimilable nitrogen (YAN) into a synthetic grape must with defined composition. Ester precursors and extracellular metabolites involved in ester synthesis were analyzed throughout the fermentation. Results showed that nitrogen additions covering 50-200 mg/L YAN at the point of yeast inoculation slightly affected yeast competition and ester profiles. Interestingly, when YAN was supplemented in the mid-stage, the survival of H. uvarum Yun268 was enhanced, resulting in more than a 2-fold increase in the levels of higher alcohol acetates compared to that at the initial stage. Furthermore, carbon fluxes may be redistributed in the central pathway, which contributed to the production of medium-chain fatty acids and eventually triggered a 1.2-fold elevation in corresponding ethyl ester levels.

Efficient production of 3-hydroxypropionate from fatty acids feedstock in Escherichia coli.

The production of chemicals from renewable biomass resources is usually limited by factors including high-cost processes and low efficiency of biosynthetic pathways. Fatty acids (FAs) are an ideal alternative biomass. Their advantages include high-efficiently producing acetyl-CoA and reducing power, coupling chemical production with CO2 fixation, and the fact that they are readily obtained from inexpensive feedstocks. The important platform chemical 3-hydroxypropionate (3HP) can be produced from FAs as the feedstock with a theoretical yield of 2.49 g/g, much higher than the theoretical yield from other feedstocks. In this study, we first systematically analyzed the limiting factors in FA-utilization pathways in Escherichia coli. Then, we optimized FA utilization in Escherichia coli by using a combination of metabolic engineering and optimization of fermentation conditions. The 3HP biosynthesis module was introduced into a FA-utilizing strain, and the flux balance was finely optimized to maximize 3HP production. The resulting strain was able to produce 3HP from FAs with a yield of 1.56 g/g, and was able to produce 3HP to a concentration of 52 g/L from FAs in a 5-L fermentation process. The strain also could produce 3HP from various type of FAs feedstock including gutter oil. This is the first report of a technique for the efficient production of the platform chemical 3HP from FAs.

Production of myo-inositol from glucose by a novel trienzymatic cascade of polyphosphate glucokinase, inositol 1-phosphate synthase and inositol monophosphatase.

Myo-inositol (inositol) is important in the cosmetics, pharmaceutical and functional food industries. Here, we report a novel pathway to produce inositol from glucose by a trienzymatic cascade system involving polyphosphate glucokinase (PPGK), inositol 1-phosphate synthase (IPS) and inositol monophosphatase (IMP). The system contained three highly active enzymes, AspPPGK from Arthrobacter sp. OY3WO11, TbIPS from Trypanosoma brucei TREU927, and EcIMP from Escherichia coli. A trienzymatic cascade reaction was implemented, and the conversion ratio from glucose to inositol reached 90%, which is promising for the enzymatic synthesis of inositol without ATP supplementation.

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents.

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.

Aroma modulation of Cabernet Gernischt dry red wine by optimal enzyme treatment strategy in winemaking.

Cabernet Gernischt (CG) is a famous Chinese wine grape cultivar, the red wine of which is known for its green trait, especially when produced from grapes cultivated in regions with monsoon climate. To modify CG wine aroma, three enzyme preparations (H. uvarum extracellular enzyme, AR2000, and pectinase) were introduced in different winemaking stages with Saccharomyces cerevisiae. Free and bound aroma compounds in young wines were detected using headspace solid-phase micro-extraction and gas chromatography-mass spectrometry, and aroma characteristics were quantified by trained panelists. Results showed that simultaneous inoculation of enzymes and yeasts improved wine aroma. Partial least-squares regression revealed that the green trait was due mainly to varietal compounds, especially C6 compounds, and could be partly weakened by fermentative compounds. Moreover, H. uvarum enzyme treatments enriched the acid fruit note of CG wine by enhancing the synergistic effect of varietal volatiles and certain fermentative compounds, such as esters and phenylethyls.

Traditional Chinese Medicine Curcumin Sensitizes Human Colon Cancer to Radiation by Altering the Expression of DNA Repair-related Genes.

BACKGROUND/AIM: The aim of the present study was to investigate the radio-sensitizing efficacy of curcumin, a traditional Chinese medicine (TCM) on colon cancer cells in vitro and in vivo. MATERIALS AND METHODS: Human colon cancer HT-29 cells were treated with curcumin (2.5 µM), irradiation (10 Gy) and the combination of irradiation and curcumin. Cell proliferation was assessed using the MTT assay. Apoptotic cells were detected by Annexin V-PE/7-AAD analysis. PCR was performed to determine differential-expression profiling of 95 DNA-repair genes in irradiated cells and cells treated with both irradiation and curcumin. Differentially-expressed genes were confirmed by Western blotting. In vivo radio-sensitizing efficacy of curcumin was assessed in a xenograft mouse model of HT-29 colon cancer. Curcumin was administrated daily by intraperitoneal injection at 20 mg/kg/dose. Mice received irradiation (10 Gy) twice weekly. Apoptosis of the cancer cells following treatment was determined by TUNEL staining. RESULTS: Irradiation induced proliferation inhibition and apoptosis of HT-29 cells in vitro. Concurrent curcumin treatment sensitized the HT-29 tumor to irradiation (p<0.01). DNA repair-related genes CCNH and XRCC5 were upregulated and LIG4 and PNKP downregulated by the combination of curcumin and irradiation compared with irradiation alone (p<0.05). Combined treatment of curcumin and irradiation resulted in a significantly greater tumor-growth inhibition and apoptosis compared to irradiation treatment alone (p<0.01). CONCLUSION: Curcumin sensitizes human colon cancer in vitro and in vivo to radiation. Downregulation of LIG4 and PNKP and upregulation of XRCC5 and CCNH DNA-repair-related genes were involved in the radio-sensitizing efficacy of curcumin in colon cancer.

Vitamin D and risk of preterm birth: Up-to-date meta-analysis of randomized controlled trials and observational studies.

AIM: We performed a meta-analysis of randomized controlled trials (RCT) and observational studies to answer the two following questions: (i) whether low maternal circulating 25 hydroxyvitamin D (25-OHD) is associated with an increased risk of preterm birth (PTB) or spontaneous PTB (sPTB); and (ii) whether vitamin D supplementation alone during pregnancy can reduce the risk of PTB. METHODS: Literature search was carried out using Pubmed, Web of Science and Embase databases up to June 2016. Pooled OR or relative risk (RR) with 95%CI were computed using fixed or random effects models depending on the size of heterogeneity. Subgroup analysis was used to explore potential sources of between-study heterogeneity. Publication bias was evaluated using Egger's test and Begg's test. RESULTS: Twenty-four articles (six RCT and 18 observational studies) were identified. Maternal circulating 25-OHD deficiency (pooled OR, 1.25; 95%CI: 1.13-1.38) rather than insufficiency (pooled OR, 1.09; 95%CI: 0.89-1.35) was associated with an increased risk of PTB, and vitamin D supplementation alone during pregnancy could reduce the risk of PTB (pooled RR, 0.57; 95%CI: 0.36-0.91). This was also the case for the sPTB subgroup (circulating 25-OHD <50 vs >50 nmol/L; pooled OR, 1.45; 95%CI: 1.20-1.75). CONCLUSIONS: Maternal circulating 25-OHD deficiency could increase PTB risk and vitamin D supplementation alone during pregnancy could reduce PTB risk. Extrapolation of the results, however, must be done with caution, and there is urgent need for larger, better-designed RCT to confirm this effect.

[Preliminary analysis on spectrum-efficient correlation model for anti-influenza virus of Lonicerae Japonicae Flos by partial least squares method].

Forty batches of Lonicerae Japonica Fse i collected extensively and prepared as the test solution. Their chromatographic fingerprints and anti-influenza virus IC50 value (half maximal inhibitory concentration) were determined respectively. Then Unscrambler software was used, and spectrum-efficient correlation analysis was done for chromatographic fingerprints data and IC50 data by partial least squares regression method, to establish spectrum-efficient correlation model for anti-influenza virus of Lonicerae Japonicae Flos. Then the other 10 batches of Lonicerae Japonicae Flos were used to verify the model and explore the adaptability of this spectrum-efficient correlation model based on partial least squares regression method. The mathematical model obtained R2 of 0.969489 and RM-SEC of 0.070691 for calibration set; R2 of 0.959042 and RMSECV of 0.084005 for cross validation set. The verification experiment results showed that the relative error between the predicted values and measured values was within 10% in all 10 hatches, and within 5% in 80% of them. The results showed that the established spectrum-efficient correlation model could be used to evaluate the biological activity of anti-influenza virus of Lonicerae Japonicae Flos by determining its HPLC fingerprints.

Continued decline of aqueous interleukin-8 after multiple intravitreal injections of ganciclovir for cytomegalovirus retinitis.

PURPOSE: To evaluate the relationship between aqueous inflammation cytokines and cytomegalovirus (CMV) particles in patients with cytomegalovirus retinitis (CMVR), and evaluate the changes in aqueous inflammation cytokines during multiple intravitreal injections of antiviral drugs for CMVR. METHODS: There were 10 patients (12 eyes; 16 courses of treatment per eye) who underwent continued intravitreal ganciclovir or foscarnet for treatment of CMVR. Before each intravitreal injection, 50-100 µL of aqueous humor was removed and sent to the laboratory to examine the concentration of the CMV DNA load by using polymerase chain reaction and to examine the concentration of interleukin (IL)-1ß, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and IL-12p70 using a cytometric bead array. RESULTS: A Kendall correlation test showed that the concentration of the CMV DNA load in the aqueous humor was significantly associated with the aqueous level of IL-6 (P<0.001, r=0.327) and IL-8 (P<0.001, r=0.381), but not significantly associated with IL-1ß, IL-10, IL-12p70, and TNF-α. The boxplots showed that the concentration of the aqueous CMV DNA load, IL-8 and IL-10 continuously declined after multiple intravitreal injections of antiviral drugs, and the decline trend of IL-8 was most remarkable. IL-1ß, IL-10, TNF-α, and IL-12p70 were negative in some of the aqueous levels of CMVR patients throughout the course of treatment (25.0%-62.5%). CONCLUSIONS: Our study showed that IL-8 was significantly associated with the aqueous level of CMV copies and continuously declined during a course of treatment that involved multiple intravitreal injections of antiviral drugs. IL-8 may be considered a good quantitative laboratory indicator of the recovery of CMVR.

Outcome assessment alternatives for young children during the first 12 months after pediatric hearing-aid fittings.

OBJECTIVE: Perform longitudinal evaluations of young children during the first 12 months after initial hearing-aid fitting. Document evidence of early prelingual auditory development (EPLAD), identify factors that affect EPLAD, and define performance milestones that can guide best practices. DESIGN: Unblinded, prospective, within-subject, repeated-measures design. Audiological measures and measures of EPLAD were taken at baseline, 3, 6, and 12 months after hearing-aid fitting. STUDY SAMPLE: Subjects were 45 pediatric patients initially fitted with hearing aids between 1 and 5.5 years of age. Four groups were formed for analysis purposes based on severity of hearing loss (moderate-to-severe and profound) and initial fitting age (≤ 30 months and > 30 months). RESULTS: All groups exhibited statistically significant increases in EPLAD within six months of hearing-aid fitting, and those with profound losses exhibited further statistically significant improvement between six and 12 months. Similar EPLAD levels were reached at 12 months regardless of severity of hearing loss. The EPLAD trajectory is similar to that following early cochlear implantation. CONCLUSIONS: Measures of EPLAD provide a means of evaluating outcomes following early pediatric hearing-aid intervention, supplementing behavioral audiological measures.

[Reduction of selenite to elemental red selenium under aerobic condition by Pseudomonas alcaliphila MBR].

OBJECTIVE: We studied the reduction of soluble and highly toxic selenite to elemental red selenium, under aerobic condition by Pseudomonas alcaliphila MBR, with organic carbon as electron donor. RESULTS: The strain could grow under pH 6-11 and resist to high concentration of selenite with the minimal inhibitory concentration of 50 mmol/L. After 5 days, the strain used sodium citrate as electron donor, and reduced 2.0 mmol/L selenite to elemental red selenium from the culture fluid, the elemental red selenium was stored outside the cells. The glutathione and nitrate could increase the number of reduction rate. CONCLUSION: This study implies the application of Pseudomonas alcaliphila MBR to convert selenite to elemental red selenium.

Development of the Mandarin pediatric speech intelligibility (MPSI) test.

The objective of this research was to create a Mandarin closed-set sentence recognition test based on the English pediatric speech intelligibility (PSI) test (Jerger & Jerger, 1984 ) for evaluation of speech perception in children as young as three years of age. Developmentally normal children (N = 93), 3-6 years of age, were administered the Mandarin PSI (MPSI) via a computer-controlled protocol. Perfect performance was observed for all children in quiet and at +10 and +5 dB signal-to-noise ratios (SNRs). Significant age and developmental trends were seen for the more difficult SNRs, 0 dB, -5 dB, and -10 dB, with 75% of 5-6 year olds reaching the most difficult SNR. Children who reached each of the more difficult SNRs, regardless of age, exhibited the same pattern of performance on all easier conditions, indicating that the final SNR achieved, rather than percent correct scores, may be a better descriptor of performance. The MPSI comprises part of a hierarchical assessment battery for pediatric speech perception for evaluation of intervention alternatives for Mandarin-speaking children with hearing impairment.