Neuron-Specific HuR-Deficient Mice Spontaneously Develop Motor Neuron Disease

Human Ag R (HuR) is an RNA binding protein in the ELAVL protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared with littermate control mice, indicating coordination deficiency. Using the grip-strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice. Immunostaining of the brain and cervical spinal cord showed that HuR-deficient neurons had increased levels of cleaved caspase-3, a hallmark of cell apoptosis. Caspase-3 cleavage was especially strong in pyramidal neurons and α motor neurons of HuR-deficient mice. Genome-wide microarray and real-time PCR analysis further indicated that HuR deficiency in neurons resulted in altered expression of genes in the brain involved in cell growth, including trichoplein keratin filament-binding protein, Cdkn2c, G-protein signaling modulator 2, immediate early response 2, superoxide dismutase 1, and Bcl2. The additional enriched Gene Ontology terms in the brain tissues of neuron-specific HuR-deficient mice were largely related to inflammation, including IFN-induced genes and complement components. Importantly, some of these HuR-regulated genes were also significantly altered in the brain and spinal cord of patients with amyotrophic lateral sclerosis. Additionally, neuronal HuR deficiency resulted in the redistribution of TDP43 to cytosolic granules, which has been linked to motor neuron disease. Taken together, we propose that this neuron-specific HuR-deficient mouse strain can potentially be used as a motor neuron disease model

Potential effectiveness of traditional Chinese medicine for cardiac syndrome X (CSX): a systematic review and meta-analysis

BACKGROUND: Treatment of cardiac syndrome X with unknown pathological mechanism remains a big challenge for clinicians. Complementary and alternative medicine may bring a new choice for its management. The aim of this study is to evaluate the clinical effects of traditional Chinese medicine on cardiac syndrome X patients. METHODS: We systematically searched databases such as Cochrane CENTRAL, PubMed, EMBASE, CBM, Chinese National Knowledge Infrastructure (CNKI), WanFang and VIP, and handsearched relevant journals to identify randomized controlled trials. Following the steps of systematic review recommended by the Cochrane group, we assessed the quality of included studies, extracted valid data and undertook meta-analysis. RESULTS: Twenty one moderate-to low-quality randomized controlled trials involving 1143 patients were included. The results showed that traditional Chinese medicine could improve angina [OR=1.34, 95% CI: 1.2 to 1.50], electrocardiogram (ECG), endothelin-1 (ET-1) levels, prolong exercise duration in treadmill tests, and reduce angina frequency per week compared with routine treatment. No other side effect was reported except two cases of stomach pain. CONCLUSION: Compared with conventional treatment, traditional Chinese medicine shows the potential of optimizing symptomatic outcomes and improving ECG and exercise duration. The efficacy of TCM may find explanation in its pharmacological activity of adjusting the endothelial function. TCM, as a kind of alternative and complementary medicine, may provide another choice for CSX patients

An Exposure Meter of Lijiang Fiber-fed High-Resolution Spectrograph

In 2016, an exposure meter was installed on the Lijiang Fiber-fed High-Resolution Spectrograph to monitor the coupling of starlight to the science fiber during observations. Based on it, we investigated a method to estimate the exposure flux of the CCD in real time by using the counts of the photomultiplier tubes (PMT) of the exposure meter, and developed a piece of software to optimize the control of the exposure time. First, by using flat-field lamp observations, we determined that there is a linear and proportional relationship between the total counts of the PMT and the exposure flux of the CCD. Second, using historical observations of different spectral types, the corresponding relational conversion factors were determined and obtained separately. Third, the method was validated using actual observation data, which showed that all values of the coefficient of determination were greater than 0.92. Finally, software was developed to display the counts of the PMT and the estimated exposure flux of the CCD in real-time during the observation, providing a visual reference for optimizing the exposure time control.Comment: Published in Research in Astronomy and Astrophysic

Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritis

ObjectiveThe aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP.MethodsNinety patients with biopsy-proven lupus nephritis were included from a Chinese cohort. Plasma samples collected on the day of renal biopsy were tested for anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies. The associations between these two autoantibodies and clinicopathologic features and long-term prognosis were analyzed. The interaction between C1q and mCRP was further investigated by ELISA, and the key linear epitopes of the combination of cholesterol binding sequence (CBS; a.a.35-47) and C1qA08 were tested by competitive inhibition assays. The surface plasmon resonance (SPR) was used to further verify the results.ResultsThe prevalence of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were 50/90 (61.1%) and 45/90 (50.0%), respectively. Levels of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were negatively correlated with serum C3 concentrations ((0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L, P=0.002) and (0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L, P=0.028), respectively. Levels of anti-C1qA08 antibodies were correlated with the score of fibrous crescents and tubular atrophy (r=-0.256, P=0.014 and r=-0.25, P=0.016, respectively). The patients with double positive antibodies showed worse renal prognosis than that of the double negative group (HR 0.899 (95% CI: 0.739-1.059), P=0.0336). The binding of mCRP to C1q was confirmed by ELISA. The key linear epitopes of the combination were a.a.35-47 and C1qA08, which were confirmed by competitive inhibition experiments and SPR.ConclusionThe combination of anti-C1qA08 and anti-mCRP a.a.35-47 autoantibodies could predict a poor renal outcome. The key linear epitopes of the combination of C1q and mCRP were C1qA08 and a.a.35-47. A08 was an important epitope for the classical pathway complement activation and a.a.35-47 could inhibit this process

Association of methylenetetrahydrofolate reductase C677T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

<p>Abstract</p> <p>Background</p> <p>The association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and serum lipid profiles is still controversial in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. The aim of the present study was to eveluate the association of MTHFR C677T polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.</p> <p>Methods</p> <p>A total of 780 subjects of Bai Ku Yao and 686 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the MTHFR C677T was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.</p> <p>Results</p> <p>The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (<it>P </it>< 0.05-0.001). The frequency of C and T alleles was 77.4% and 22.6% in Bai Ku Yao, and 60.9% and 39.1% in Han (<it>P </it>< 0.001); respectively. The frequency of CC, CT and TT genotypes was 58.7%, 37.3% and 4.0% in Bai Ku Yao, and 32.6%, 56.4% and 11.0% in Han (<it>P </it>< 0.001); respectively. The levels of TC and LDL-C in both ethnic groups were significant differences among the three genotypes (<it>P </it>< 0.05-0.01). The T allele carriers had higher serum TC and LDL-C levels than the T allele noncarriers. The levels of ApoB in Han were significant differences among the three genotypes (<it>P </it>< 0.05). The T allele carriers had higher serum ApoB levels as compared with the T allele noncarriers. The levels of TC, TG and LDL-C in Bai Ku Yao were correlated with genotypes (<it>P </it>< 0.05-0.001), whereas the levels of LDL-C in Han were associated with genotypes (<it>P </it>< 0.001). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, cigarette smoking, and blood pressure in the both ethnic groups.</p> <p>Conclusions</p> <p>The differences in serum TC, TG, LDL-C and ApoB levels between the two ethnic groups might partly result from different genotypic and allelic frequencies of the MTHFR C677T or different MTHFR gene-enviromental interactions.</p

Assessing Nurses' Workplace Social Capital : A Study Protocol for Culturally Appropriate Instrument Development

Workplace social capital positively influences the quality but reduces the cost of healthcare services. Academic research suffers from limited and inadequate culturally sensitive nurses' workplace social capital instruments. Here we report on the design and protocol of a culturally focused instrument development study in China. The overarching objective of our dual phase study is to develop and validate a questionnaire measuring nurses' workplace social capital tailored toward Chinese cultural values and norms. In the first phase of INSTRUMENT DEVELOPMENT, the qualitative phase, we will conduct interviews with purposefully sampled nurses from five geographically diverse regions capturing 16 provinces in China to formulate the initial version of the Nurses' Workplace Social Capital Questionnaire (NWSCQ). Data collection will be stopped at the saturation point and content analysis will be performed for interview data in parallel. The initial version of the NWSCQ will be evaluated and confirmed by two-rounds of expert consultation (target N = 20) and pre-tested among 70 nurses. During the second phase of INSTRUMENT VALIDATION or the quantitative phase, we will validate the psychometric properties of the NWSCQ. The validity and reliability of the questionnaire will be examined and validated through three cross-sectional surveys among nurses (target N = 1154) randomly selected from 12 tertiary hospitals. We have reported our study protocol with the intention of sharing our experience with researchers in other countries who are striving to advance the phenomenon of culturally sensitive and social normatively appropriate nurses' workplace social capital. Findings from our study should advance the development of culturally appropriate and valid instrument of nurses' workplace social capital, another important step toward recognition and incorporation of cultural diversity in the daily operation of healthcare industry.Peer reviewe

Targeting Lactobacillus johnsonii to reverse chronic kidney disease.

Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1-5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients

Laser Direct Writing of Visible Spin Defects in Hexagonal Boron Nitride for Applications in Spin-Based Technologies

Optically addressable spins in two-dimensional hexagonal boron nitride (hBN) attract widespread attention for their potential advantage in on-chip quantum devices, such as quantum sensors and quantum network. A variety of spin defects have been found in hBN, but no convenient and deterministic generation methods have been reported for other defects except negatively charged boron vacancy ($V_B^-$). Here we report that by using femtosecond laser direct writing technology, we can deterministically create spin defect ensembles with spectra range from 550 nm to 800 nm on nanoscale hBN flakes. Positive single-peak optically detected magnetic resonance (ODMR) signals are detected in the presence of magnetic field perpendicular to the substrate, and the contrast can reach 0.8%. With the appropriate thickness of hBN flakes, substrate and femtosecond laser pulse energy, we can deterministically and efficiently generate bright spin defect array. Our results provide a convenient deterministic method to create spin defects in hBN, which will motivate more endeavors for future researches and applications of spin-based technologies such as quantum magnetometer array