Asymmetric Core-Expanded BOPYOs: Facile Synthesis and Optical Properties.

N,O-bidentate BF2 complexes with five- and six-membered core rings have been thoroughly investigated. However, the development of seven-membered N,O-boron complexes is still an area to be explored. We have developed BF3 ⋅ OEt2 -induced self-condensation and coordination reactions based on a single starting material, which had been elucidated by experiment and calculation. This parent asymmetric core-expanded borondifluoride-(Z)-1,3-di(1H-pyrrol-2-yl)but-2-en-1-one (BOPYO) showed reactivity with a wide range of aldehydes, thus providing a series of conjugation BOPYOs. Moreover, a BOPYO derivative with a dimethylamino group was developed as a new NIR dye that responds to acid with favorable photophysical properties based on intramolecular charge transfer effect.

Cheese whey supports high riboflavin synthesis by the engineered strains of the flavinogenic yeast Candida famata.

BACKGROUND: Riboflavin is a precursor of FMN and FAD which act as coenzymes of numerous enzymes. Riboflavin is an important biotechnological commodity with annual market sales exceeding nine billion US dollars. It is used primarily as a component of feed premixes, a food colorant, a component of multivitamin mixtures and medicines. Currently, industrial riboflavin production uses the bacterium, Bacillus subtilis, and the filamentous fungus, Ashbya gossypii, and utilizes glucose and/or oils as carbon substrates. RESULTS: We studied riboflavin biosynthesis in the flavinogenic yeast Candida famata that is a genetically stable riboflavin overproducer. Here it was found that the wild type C. famata is characterized by robust growth on lactose and cheese whey and the engineered strains also overproduce riboflavin on whey. The riboflavin synthesis on whey was close to that obtained on glucose. To further enhance riboflavin production on whey, the gene of the transcription activator SEF1 was expressed under control of the lactose-induced promoter of the native ß-galactosidase gene LAC4. These transformants produced elevated amounts of riboflavin on lactose and especially on whey. The strain with additional overexpression of gene RIB6 involved in conversion of ribulose-5-phosphate to riboflavin precursor had the highest titer of accumulated riboflavin in flasks during cultivation on whey. Activation of riboflavin synthesis was also obtained after overexpression of the GND1 gene that is involved in the synthesis of the riboflavin precursor ribulose-5-phosphate. The best engineered strains accumulated 2.5 g of riboflavin/L on whey supplemented only with (NH4)2SO4 during batch cultivation in bioreactor with high yield (more than 300 mg/g dry cell weight). The use of concentrated whey inhibited growth of wild-type and engineered strains of C. famata, so the mutants tolerant to concentrated whey were isolated. CONCLUSIONS: Our data show that the waste of dairy industry is a promising substrate for riboflavin production by C. famata. Possibilities for using the engineered strains of C. famata to produce high-value commodity (riboflavin) from whey are discussed.

AIP1 and Cofilin control the actin dynamics to modulate the asymmetric division and cytokinesis in mouse oocytes.

Actin-interacting protein 1 (AIP1), also known as WD repeat-containing protein 1 (WDR1), is ubiquitous in eukaryotic organisms, and it plays critical roles in the dynamic reorganization of the actin cytoskeleton. However, the biological function and mechanism of AIP1 in mammalian oocyte maturation is still largely unclear. In this study, we demonstrated that AIP1 boosts ADF/Cofilin activity in mouse oocytes. AIP1 is primarily distributed around the spindle region during oocyte maturation, and its depletion impairs meiotic spindle migration and asymmetric division. The knockdown of AIP1 resulted in the gathering of a large number of actin-positive patches around the spindle region. This effect was reduced by human AIP1 (hAIP1) or Cofilin (S3A) expression. AIP1 knockdown also reduced the phosphorylation of Cofilin near the spindle, indicating that AIP1 interacts with ADF/Cofilin-decorated actin filaments and enhances filament disassembly. Moreover, the deletion of AIP1 disrupts Cofilin localization in metaphase I (MI) and induces cytokinesis defects in metaphase II (MII). Taken together, our results provide evidence that AIP1 promotes actin dynamics and cytokinesis via Cofilin in the gametes of female mice.

Brain-specific deletion of TRIM13 promotes metabolic stress-triggered insulin resistance, glucose intolerance, and neuroinflammation.

Diabetes has been associated with metabolic disorder, insulin resistance and neuroinflammation. However, the pathogenesis for HFD-induced injury of central nervous system (CNS) is still unclear. Tripartite Motif Containing 13 (TRIM13), also known as RFP2, is a member of TRIM proteins, and is associated with multiple cellular processes, such as apoptosis, survival and inflammation. However, the effects of TRIM13 on brain injury, especially the HFD-induced CNS damage, have not been investigated. To address this issue, the TRIM13flox/flox (fl/fl) mice were produced and then crossed them with Nestin-Cre mice to delete TRIM13 specifically in the brain (cKO). Then, T2D mice with obesity were established by chronic feeding of HFD. We found that brain-specific deletion of TRIM13 accelerated HFD-induced metabolic disorder, insulin resistance and systematic inflammatory response. In addition, HFDcKO mice exhibited significantly higher pro-inflammatory cytokines, including interleukin (IL)-6, IL-1ß and tumor necrosis factor-α (TNF-α), in cortex, hippocampus and hypothalamus tissues, which were comparable to the HFDfl/fl mice. Consistently, the activation of nuclear factor-κB (NF-κB) induced by HFD was further aggravated in mice with brain-specific loss of TRIM13. Moreover, glial activation in CNS stimulated by HFD was further promoted by TRIM13 knockout in brain, as evidenced by the up-regulated expression of glial fibrillary acidic protein (GFAP) and Iba-1. In hypothalamus, HFD reduced proopiomelanocortin (POMC) and enhanced neuropeptide Y (NPY) expression, which were further promoted in mice with brain-specific deletion of TRIM13. Meanwhile, insulin signaling pathway was disrupted by HFD in hypothalamus of mice, and these effects were exacerbated in HFDcKO mice. The in vitro analysis confirmed that TRIM13 knockout in glial cells considerably promoted palmitate (PAL)-induced inflammatory response by accelerating NF-κB signal, contributing to the insulin resistance in the isolated primary neurons. Together, these findings demonstrated that TRIM13 was involved in HFD-induced CNS injury and insulin resistance through regulating neuroinflammatory response, contributing to the modulation of peripheral metabolic disorders.

Tuning the excited-state intramolecular proton transfer (ESIPT) process of indole-pyrrole systems by π-conjugation and substitution effects: experimental and computational studies.

A series of amino (NH)-type hydrogen-bonding (H-bonding) compounds, BNDAB-1-4, containing π-enlarged indole and ß-ethoxycarbonyl-substituted pyrrole units were designed and synthesized. BNDAB-1 and BNDAB-3 exhibited dual emission and BNDAB-2 and BNDAB-4 exhibited a single emission with a large Stokes shift in dichloromethane, methanol, DMSO and toluene except for a dual emission for BNDAB-4 in toluene. Inspired by their photophysical properties, the ESIPT process was speculated and further investigated by theoretical calculations including geometry and thermodynamic analyses. The results showed that the ester substitution on the proton donor unit and π-conjugation on the proton acceptor unit by structural modification can regulate the ESIPT behaviors of these compounds. First, a strong electron-withdrawing group promoted the ESIPT process according to the comparison of the ESIPT processes of NDAB-H and NDAB-6, BNDAB-1 and BNDAB-2, and BNDAB-3 and BNDAB-4. Second, π-conjugation in different positions ([g]- and [e]-position) of the indole unit decreased the speed of the ESIPT process irrespective of whether ethoxycarbonyl was substituted on the pyrrole ring based on the ESIPT process of Series 1 and 2. Finally, this work elucidated that the ESIPT process can be rationally tuned by π-conjugation and substitution, which is in good agreement with the experimental results.

A Simple Central Seven-Membered BOPYIN: Synthesis, Structural, Spectroscopic Properties, and Cellular Imaging Application.

A two-step, one-flask synthesis of central seven-membered borondifluoride-3,3-dimethyl-2-[2-(2-pyrrolyl)ethenyl] indole (BOPYIN) ligands has been developed by using the unexplored 3,3-dimethyl-2-[2-(2-pyrrolyl)ethenyl] indole. The simple synthetic approach has enabled modification of the electronic structure by changing the substituents on the indole unit. X-ray analysis indicated that conformations of the seven-membered BF2 complex including BOPYIN and diazaborepin differ from that of the five- and six-membered organoboron complexes. Interestingly, the bond angle of the N⋅⋅⋅B-N bond increases with the number of atoms in the core ring, based on Baeyer strain theory. These unsymmetric BOPYIN derivatives have excellent photophysical properties, including high fluorescence quantum yields, except for BOPYIN-4 in the solution state, large Stokes shifts, and good molar absorptivity. The dipole moment of BOPYIN-3 in the first excited singlet state and ground state was demonstrated by a linear Lippert-Mataga plot. The absorption and emission spectra were not mirror images for BOPYIN-1-3 and 5, in contradiction to Kasha's rule, as determined by TDDFT. The synthesized BOPYINs have been shown to be biocompatible fluorophores in cell bioimaging.

Are fungi from adult orchid roots the best symbionts at germination? A case study.

We studied mycobionts from advanced seedlings and adult mycorrhizal roots of the terrestrial orchid Arundina graminifolia. Fungi were isolated, identified by ITS sequencing, and tested for their impact on seed germination, protocorm formation, and development of advanced seedlings (emergence of first leaf) in vitro. Among the six fungal species isolated, four were not standard orchid mycorrhizal fungi (Fusarium solani, Cylindrocarpon sp., Acremonium sp., and Phlebiopsis flavidoalba) and did not support germination beyond imbibition and greening of the seeds during a span of 35 days. Over the same time, one Tulasnella species isolated from adult mycorrhiza allowed protocorm formation but not further development. However, another Tulasnella species isolated from advanced seedlings facilitated development to the advanced seedling stage. Our results support (i) the inability of occasional orchid root colonizers to support late seed germination, and (ii) the growing literature showing that fungal associates can change over orchid development. Functionally, we show that mycorrhizal taxa isolated from advanced seedlings can be more efficient than those from adults in supporting germination in some species, leading to recommendations for ex situ orchid conservation.

The effects of Natucin C-Natucin P mixture on blood biochemical parameters, antioxidant activity and non-specific immune responses in tilapia (Oreochromis niloticus).

Natucin C (NC) and Natucin P (NP) are two kinds of antimicrobial peptides (AMPs). In the present study, the effects of NC-NP mixture on a tilapia species (Oreochromis niloticus) were examined. Animals were fed with either a control diet or one of five AMP-supplemented diets for eight weeks. AMP-supplemented diets contained five increasing levels of NP from G1 to G5 and one level of NC (200 mg/kg). Results showed that fish in the G3, G4 and G5 groups had significantly higher levels of total protein (TP), albumin (ALB) and globulin (GLO) in serum than fish in the control group. Fish fed with G4 and G5 diets exhibited significantly higher high-density lipoprotein cholesterol (HDL-C) levels compared to the control fish. Lipopolysaccharide (LPS) levels in all AMP-supplemented groups were significantly lower than the control. In addition, the total antioxidant capacity (TAOC) and lysozyme (LZM) activities were significantly increased in fish fed with the G3 and G4 diets, respectively compared to the control. The serum malondialdehyde (MDA) levels in fish fed with AMP-supplemented diets were significantly decreased compared to those not supplemented with AMPs. Furthermore, the mRNA expressions of tumor necrosis factor alpha (TNF-α), interleukin-1-beta (IL-1ß), gamma interferon (IFN-γ) and heat shock protein 70 (HSP70) in the hepatopancreas, spleen, kidney and gill were measured. Overall, the expression levels were enhanced in an NP dose-dependent and tissue-specific manner. The expressions of four genes in four organs (except IL-1ß in spleen, and TNF-α and HSP70 in gill) were significantly upregulated in fish fed with the G5 diet. Fish fed with the G4 diet had increased expression levels of IL-1ß in spleen and IFN-γ in kidney. The relative expression levels of TNF-α, IL-1ß and HSP70 in the hepatopancreas in fish fed with the G3 diet were significantly upregulated compared to the control. Transcriptional levels of IL-1ß and HSP70 in the hepatopancreas, IFN-γ and HSP70 in the kidney and IL-1ß in the gills of fish fed with the G2 diet were upregulated. Taken together, our results indicated that the NC-NP mixture can enhance the antioxidant capacity and innate immune ability of O. niloticus, indicating that this mixture might be a potential alternative to antibiotics when used as a feed additive.

Study of Condylar Asymmetry in Angle Class III Malocclusion With Mandibular Deviation.

OBJECTIVE: Differences in the condylar between both sides in class III cases with mandibular deviated are important for the diagnosis, treatment, and retention in this kind of patient. To detect the subtle differences, we analyzed the size, shape, and bone density with three-dimensional reconstructed technology. METHODS: The symmetry group and the asymmetry group each with 20 cases were chosen according to some standards. The computed tomographic data obtained and three-dimensional model were built with SimPlant software. The distance and angle were measured in the three-dimensional model, and the bone density was measured with the SimPlant software. The differences between the separated side in each group and the difference between the 2 groups were analyzed. RESULTS: In the asymmetry group, some measurement projects of the bilateral condyles showed significant differences, such as the ramal height, condylar perpendicular height, the area of maximum cross section of condylar, condylar medialateral diameter, length of posterior slope, and angle of posterior slope. When the asymmetry group was compared with the symmetry group, the condyles of the asymmetry group showed more asymmetrical variations in morphology, such as the ramal height, the condylar perpendicular height, the area of maximum cross section of condylar, the medialateral diameter, the length of anterior slope, and angle of posterior slope. The bone mineral density of the condylar anterior and condylar medial point was higher in the nondeviated side, and the bone mineral density of the condylar posterior was higher in the deviated side, and no statistically significant difference was found in the symmetry group. CONCLUSIONS: In class III malocclusion with mandibular deviation patients, the three-dimensional morphology and bone density of condylar on the deviated side differ from the nondeviated side, which indicates the association between asymmetrical jaw function and joint remodeling.

[Mutation and clinical relevance in a large cohort of unrelated Chinese patients with hypertrophic cardiomyopathy].

OBJECTIVE: To explore the genetic basis and phenotypic correlation with disease severity in a large cohort of Chinese patients with hypertrophic cardiomyopathy (HCM). METHODS: A total of 179 unrelated Chinese HCM patients admitted to our department from 2002 to 2011 were enrolled in this study. Direct gene sequencing of ß-myosin heavy chain (MYH7), myosin binding protein-C ( MYBPC3), and cardiac troponin T (TNNT2) were performed and clinical data were obtained in these patients. RESULTS: A total of 34 mutations were identified in 40 patients (22.3%), 79.4% (27/34) mutations occurred only once and a possible hot spot, A26 in MYH7, was found. Distribution of mutations was 52.9% (18/34) (MYBPC3), 35.3% (12/34) ( MYH7) and 11.8% (4/34) (TNNT2) respectively. Double mutations were identified in 2.2% (4/179) patients. Genotype-positive patients were associated with an earlier symptom onset, severer left ventricular hypertrophy, a higher incidence of syncope, and were more likely to have positive family history of HCM or sudden cardiac death (SCD) , and were more likely to progress into heart failure (24.2% vs. 5.0%, P = 0.002) and at a higher risk of SCD (9.1% vs. 0, P = 0.009) during the 6.5-year follow-up. No statistical difference in any clinical parameters and outcomes was found between patients carrying MYBPC3 and MYH7 mutations. Double mutations were associated with malignant clinical progression in this cohort. Different phenotype severity could be seen in HCM patients with same genotype (e. g. MYH7-1736T, TNNT2-R92W). CONCLUSION: MYBPC3 is the most predominant gene mutation in this HCM cohort. The presence of a sarcomere mutation in patients with HCM is associated with poor clinical outcome, although no specific genes or mutations can exactly predict the severity of clinical phenotypes.

[Identification of herbal tea ingredient Plumeria rubra and its adulterants using DNA barcoding].

ITS2 sequence was used as a barcode to identify herbal tea ingredient Plumeria rubra and its adulterants. Genomic DNAs from forty eight samples were extracted, the ITS2 sequences were amplified and sequenced bi-direstionlly, and then assembled and obtained using CodonCode Aligner. The sequences were aligned using ClustalW, the genetic distances were computed by kimura 2-parameter (K2P) model and the Neighbor-joining (NJ) phylogenetic trees were constructed using MEGA5.0. Results showed that the length of ITS2 sequence of P. rubra were 244 bp. The intra-specific genetic distances (0-0. 016 6) were much smaller than inter-specific ones between P. rubra and its adulterants(0.320 8-0.650 4). The NJ tree indicated that P. rubra and its adulterants could be distinguished clearly. Therefore, Using ITS2 barcode can accurately andeffectively distinguish herbal tea ingredient P. rubra from its adulterants, which providesa new molecular method to identify P. rubra and ensure its safety in use.

Clinical value of positive CNVs results by NIPT without fetal ultrasonography-identified structural anomalies.

OBJECTIVE: To evaluate the clinical value of positive copy number variations (CNVs) results by non-invasive prenatal testing (NIPT) without fetal ultrasonography-identified structural anomalies, especially with several known CNVs results. METHODS: A total of 135,981 results of NIPT performed between April 1, 2017, and March 31, 2020, enrolled in the free NIPT service program implemented by the local government were retrospectively analyzed. Of these, 87 cases with positive NIPT screens for CNVs and no fetal ultrasonography-identified anomalies were recalled and provided genetic counseling. After obtaining full informed consent, these cases were provided invasive prenatal diagnosis by karyotyping and chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV-seq) with follow-up. One case was lost, while 86 cases were successfully followed up. RESULTS: A total of 44 (50.6%) cases underwent invasive prenatal diagnosis, of which six cases were detected with abnormal karyotype. CMA/CNV-Seq revealed 11 fetuses with positive results for CNVs, among whom eight were consistent with NIPT results, two were partially consistent, one was inconsistent, and positive predictive value (PPV) was 22.7% (10/44). For known CNVs, PPVs were 20% (15q11.2-q13 microdeletion) and 33.3% (5p end deletions). Among 11 pregnant women with positive prenatal diagnosis, seven were confirmed to have pathogenic CNVs in their fetuses; four had CNVs of unknown clinical significance. CONCLUSIONS: Even in pregnancies without ultrasonography-identified anomalies, a positive NIPT screen for CNVs must be interpreted with caution and validated by additional diagnostic study.

Impact of urban and rural residents medical insurance on self-rated health of residents in China: a panel study from the China family panel studies national baseline survey.

Objective: This study aimed to investigate the health performance of the Urban and Rural Residents Medical Insurance (URRMI) scheme in China and to make practical recommendations and scientific references for its full implementation in China. Methods: This is a panel study that uses data from the China Family Panel Studies from 2018 to 2020, which is separated into treated and control groups each year, utilizing the key approach of propensity score matching and difference-in-difference (PSM-DID). Using 1-to-1 k-nearest neighbor matching, we proportionate the baseline data. Using difference-in-difference model, we examine the mean treatment impact of the outcome variables. Using a 500-time random sample regression model, we validate the robustness of the model estimation. Results: The result was credible after matching, minimizing discrepancies. Good overall performance of self-rated health with an average Hukou status of, respectively, 0.8 and 0.4 in the treated and control group, primarily in rural and urban regions separately. The participation of URRMI significantly impacted self-rated health of residents, with a 0.456-unit improvement probabilities observed (p < 0.1). Additionally, the individuals are categorized into urban and rural, and those with urban hukou had a 0.311 expansion in the probability of having better health status compared to rural hukou (p < 0.05). Other factors, such as age, highest education, annual income, medical expenditure, hospital scale, clinic satisfaction, and napping, also impacted self-rated health. Moreover, elder individuals, higher education levels, and higher medical expenditure having a higher probability of improvement. The study utilized a placebo test to verify the robustness of the URRMI regression. The estimated coefficients showed that basic medical insurance did not significantly improve the health of insured residents under the URRMI scheme. Conclusion: The study demonstrates the crucial role of PSM-DID in determining the influence of URRMI on self-rated health status. It indicates that purchasing in URRMI has a favorable influence on the health of residents, advancing enhanced self-rated health effectiveness. It does, however, reveal geographical disparities in health, with urban dwellers faring far better than those who live in the suburb. Study suggests expanding URRMI coverage, narrowing urban-rural divide, increasing insurance subsidies, reforming laws, and developing effective advertising strategies.

Nano-gold micelles loaded Dox and Elacridar for reversing drug resistance of breast cancer.

The aim of this study was to provide a new effective carrier for rescuing the sensitivity of drug-resistant in breast cancer cells. Nano-gold micelles loaded with Dox and Elacridar (FP-ssD@A-E) were chemically synthesised. With the increase in the amount of Dox and Elacridar, the encapsulation rate of FP-ssD@A-E gradually increased, and the drug loading rate gradually decreased. FP-ss@A-E had a sustained-release effect. Dox, Elacridar, FP-ss@AuNPs, and FP-ssD@A-E significantly improved cell apoptosis, in which, FP-ssD@A-E was the most significant. FP-ssD@A-E significantly decreased the cell viability and improved the Dox uptake. The levels of VEGFR-1, P-gp, IL-6, and i-NOS were significantly decreased after Dox, Dox + Elacridar, FP-ss@AuNPs, and FP-ssD@A-E treatment. It was worth noting that FP-ssD@A-E had the most significant effects. The prepared FP-ssD@A-E micelles, which were spherical in shape, uniform in particle size distribution, and had good drug loading performance and encapsulation efficiency.

Numerical analysis of the effects of canal wall-up and canal wall-down mastoidectomy on the sound transmission characteristics of human ears.

PURPOSE: The aim of this work was to study the effect of canal wall-up (CWU) and canal wall-down (CWD) and mastoid obliteration in conjunction with CWD (CWD-MO) mastoidectomy on the sound transmission characteristics of the human ear. METHODS: Three mastoidectomy surgical methods, CWU, CWD and CWD-MO, were simulated on the freshly dissected cadaver heads. Then, the finite element (FE) models corresponding to these surgical methods were established by micro-computed tomography (Micro-CT) and reverse engineering technology, and the accuracy of the models was verified. Finally, the FE Models were used to analyze the effects of different surgical methods on the sound transmission characteristics of the human ear. RESULTS: For CWU, since the integrity of the outer wall of the ear canal is ensured, the sound pressure (SP) gain of the ear canal and the stapes footplate displacement (FPD) gain after this operation are close to normal values. For CWD, due to severe damage to the outer wall of the ear canal, a negative gain of the ear canal SP occurs in the high-frequency range, and the resonance frequency is significantly reduced. For CWD-MO, the frequency range of SP negative gain in the ear canal is reduced due to the addition of fillers in the ear canal to reduce the degree of damage, and the resonance frequency is increased compared to CWD. CONCLUSIONS: The impact of three types of mastoidectomy, including CWU, CWD, and CWDMO, on the sound transmission characteristics of the human ear after surgery is relatively small.

cAMP-Epac1 signaling is activated in DDAVP-induced endolymphatic hydrops of guinea pigs.

OBJECTIVE: To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. METHODS: Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 µg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. RESULTS: Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p <  0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p <  0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p <  0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p <  0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p <  0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. CONCLUSION: DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. OXFORD CENTRE FOR EVIDENCE-BASED MEDICINE 2011 LEVELS OF EVIDENCE: Level 5.

Dose-response effects of an antimicrobial peptide, a cecropin hybrid, on growth performance, nutrient utilisation, bacterial counts in the digesta and intestinal morphology in broilers.

The aim of the present study was to evaluate the feasibility of an antimicrobial peptide, cecropin A(1-11)-D(12-37)-Asn (CADN), as an alternative to antibiotic growth promoter (AGP) in poultry diets. A total of 1500 14-d-old indigenous male chickens (222 (sd 13) g) were randomly allocated to five groups with five replicate cages of sixty birds each, and fed ad libitum five grower diets and subsequently five finisher diets for 14 d each. The diets were made up by supplementing their basal diets with a CADN liquid sample (CADNL) at 0, 2, 4, 6 and 8 ml/kg, respectively. During the feeding period, a metabolic experiment was carried out to determine the apparent digestibility of diethyl ether extract, nitrogen retention and apparent metabolisable energy of the diet sample fed to each cage of chicks. At the end of the feeding experiment, one chick from each cage was killed for bacteriological, light microscopic and scanning electron microscopic examination of the intestinal villi. CADN had a negative linear, positive quadratic and negative linear effect on feed intake (F), weight gain (G) and feed:gain ratio (F:G), respectively, for the growers; it had a quadratic effect on F, G or F:G for the finishers; it increased nutrient utilisation for both growers and finishers; it decreased aerobic bacterial counts in both jejunal and caecal digesta in a dose-dependent manner; it enhanced intestinal villus heights in a dose-dependent manner and made the duodenum villi of the CADNL8 group at 42 d appear as a netted leaf-like structure. CADN is therefore a possible alternative to AGP in broiler feeds.

Rapid analysis of abused drugs using nanostructured silicon surface assisted laser desorption/ionization mass spectrometry.

This study developed a rapid, sensitive, and matrix-free method for the determination of amphetamine (AMP), methamphetamine (MA), codeine (COD), morphine (MOR), and ketamine (KET) using nanostructured silicon surface assisted laser desorption/ionization mass spectrometry (nSi-MS). The nanostructured silicon (nSi) chip used in this study was created by employing the metal-assisted etching process. Drug standard tests were applied to the nSi chip platform to evaluate the nSi-MS performance, including detection sensitivity, limit of detection, linearity, and repeatability. Real urine samples obtained from drug addict detainees were directly applied to the nSi chip for drug analysis. By observing the nSi-MS spectra, the target drug peaks can be identified; and an antibody pull-down assay was performed to confirm the specificity of the detected targets. nSi-MS drug quantification was assayed, yielding comparable results with those from using the GC-MS approach. The advantages of applying nSi-MS to analyze AMP, MA, COD, MOR, and KET in the urine of addicts are simple, extremely small urine volumes (∼10 µL), and a fast analysis procedure (<15 minutes).

[A preliminary study on the measurement of (1,3)-ß-D-glucan in bronchoalveolar lavage for the diagnosis of pulmonary fungal infections].

OBJECTIVE: To explore the measurement of (1,3)-ß-D-glucan bronchoalveolar lavage fluid (BALF) for the diagnosis of pulmonary fungal infections. METHODS: A total of 135 patients in the General Hospital of Tianjin Medical University from February 2010 to February 2011 were enrolled. There were 34 cases of confirmed or clinically diagnosed pulmonary fungal infections, 53 cases of bacterial pneumonia, and 48 cases of non-infection diseases. All patients underwent BAL and the BALF samples were obtained. (1,3)-ß-D-glucan content (G test), in BALF and plasma were tested and the data were analyzed statistically by Mann-Whitney while the receiver operating characteristic curve (ROC curve) was established, from which the best threshold of the 2 G tests was derived. RESULTS: The median of BALF G test in the fungal infection group, pneumonia group and non-infection group was 281, 28 and 10 ng/L, respectively; the level in the fungal infection group being significantly higher than those of the other 2 groups (P < 0.001), but no significant difference being observed between the pneumonia group and the non-infection group (P > 0.05). The median of plasma G tests in the fungal infection group, the pneumonia group and the non-infection group was 27, 10, and 5 ng/L, respectively; the level in the fungal infection group being significantly higher than those in the other 2 groups (P < 0.001), but there was no significant difference between the pneumonia group and the non-infection group (P > 0.05). The best threshold of BALF G test was 67 ng/L, while the best threshold of G test of plasma was 17 ng/L. CONCLUSION: As compared to G test of plasma, G test of BALF may be more accurate, and have a higher clinical value for the earlier diagnosis of pulmonary fungal infections.

Research on supporting mechanism of ancillary service of PV system to grid energy efficiency based on multi-time and space-time operation.

Under the background of high-energy penetration of new energy into the power grid, this paper takes the ancillary service capability of photovoltaic energy integrated into the grid as the starting point and builds a photovoltaic system reactive power service impact evaluation model on the grid energy efficiency. This is based on the multi-temporal and spatial scale operation mode, in order to study the supporting principles of photovoltaic system reactive power services on the energy efficiency of grid operation and the law of influence on system energy efficiency changes. In this way, the space for power system energy efficiency improvement and the reactive power service market value of renewable energy are explored to improve the renewable energy auxiliary services participation in the theoretical system of electric power spot market transactions. The research conclusions can provide a decision-making reference for system dynamic energy efficiency management and can assist relevant market entities to make optimal decisions in spot market transactions, and provide empirical data for improving the theory of renewable energy participation in auxiliary service market transactions.