Chemical interference with DSIF complex formation lowers synthesis of mutant huntingtin gene products and curtails mutant phenotypes.

Earlier work has shown that siRNA-mediated reduction of the SUPT4H or SUPT5H proteins, which interact to form the DSIF complex and facilitate transcript elongation by RNA polymerase II (RNAPII), can decrease expression of mutant gene alleles containing nucleotide repeat expansions differentially. Using luminescence and fluorescence assays, we identified chemical compounds that interfere with the SUPT4H-SUPT5H interaction and then investigated their effects on synthesis of mRNA and protein encoded by mutant alleles containing repeat expansions in the huntingtin gene (HTT), which causes the inherited neurodegenerative disorder, Huntington's Disease (HD). Here we report that such chemical interference can differentially affect expression of HTT mutant alleles, and that a prototypical chemical, 6-azauridine (6-AZA), that targets the SUPT4H-SUPT5H interaction can modify the biological response to mutant HTT gene expression. Selective and dose-dependent effects of 6-AZA on expression of HTT alleles containing nucleotide repeat expansions were seen in multiple types of cells cultured in vitro, and in a Drosophila melanogaster animal model for HD. Lowering of mutant HD protein and mitigation of the Drosophila "rough eye" phenotype associated with degeneration of photoreceptor neurons in vivo were observed. Our findings indicate that chemical interference with DSIF complex formation can decrease biochemical and phenotypic effects of nucleotide repeat expansions.

Image-Guided Photothermal and Immune Therapy of Tumors via Melanin-Producing Genetically Engineered Bacteria.

Photothermal therapy (PTT) is a new treatment modality for tumors. However, the efficient delivery of photothermal agents into tumors remains difficult, especially in hypoxic tumor regions. In this study, an approach to deliver melanin, a natural photothermal agent, into tumors using genetically engineered bacteria for image-guided photothermal and immune therapy is developed. An Escherichia coli MG1655 is transformed with a recombinant plasmid harboring a tyrosinase gene to produce melanin nanoparticles. Melanin-producing genetically engineered bacteria (MG1655-M) are systemically administered to 4T1 tumor-bearing mice. The tumor-targeting properties of MG1655-M in the hypoxic environment integrate the properties of hypoxia targeting, photoacoustic imaging, and photothermal therapeutic agents in an "all-in-one" manner. This eliminates the need for post-modification to achieve image-guided hypoxia-targeted cancer photothermal therapy. Tumor growth is significantly suppressed by irradiating the tumor with an 808 nm laser. Furthermore, strong antitumor immunity is triggered by PTT, thereby producing long-term immune memory effects that effectively inhibit tumor metastasis and recurrence. This work proposes a new photothermal and immune therapy guided by an "all-in-one" melanin-producing genetically engineered bacteria, which can offer broad potential applications in cancer treatment.

Longitudinal Associations Between Physical Activity and Depressive Symptoms in Chinese Children: Evidence from the Tongji Mental Health Cohort Study.

BACKGROUND: We aimed to examine the associations between depressive symptoms and physical activity parameters (e.g., intensity, frequency, and duration) among Chinese school-aged children. METHOD: Participants in this study were extracted from the Tongji Mental Health Cohort Study. The baseline survey was conducted in June 2020 involving 2588 school-aged children from two primary schools in Hubei Province, China. A total of 2435 children were followed up successfully in December 2020. The Children's Depression Inventory Short Form (CDI-S) was applied to evaluate depressive symptoms among school-aged children. The Physical Activity Rating Scale-3 (PARS-3) was adopted to estimate children's physical activity parameters including the intensity, frequency, and duration. Generalized estimation equation models were used to explore the longitudinal associations between physical activity and depressive symptoms among school-aged children. RESULTS: Engaging in moderate levels of physical activity (OR, 0.800; 95%CI, 0.692-0.924) or high levels of physical activity (OR, 0.808; 95%CI, 0.689-0.947) in the baseline survey was associated with a reduced risk of developing depressive symptoms in the follow-up survey compared with children engaging in low levels of physical activity. Stratified analyses revealed that the associations between physical activity and depressive symptoms exhibited a significant correlation among boys and children in the older age group (11-12 years). Our findings showed that engaging in physical activity more than once a week, with each session lasting 20 min or longer, was related to significant reductions in depressive symptoms by 43.8% and 22.3%, respectively. CONCLUSION: Self-reported physical activity is positively associated with improved mental health among Chinese school-aged children, especially when considering parameters such as frequency and duration. The association between vigorous-intensity physical activity and depressive symptoms in children should be cautiously interpreted. Future research should continue to explore the effects of vigorous-intensity physical activity on depressive symptoms in children.

Impact of CD40 gene polymorphisms on the risk of cervical squamous cell carcinoma: a case-control study.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical cancer risk. Therefore, we aimed to investigate the correlation between single nucleotide polymorphisms (SNPs) of the CD40 gene and susceptibility to cervical squamous cell carcinoma (CSCC) in a population from the northeastern Han Chinese population. METHODS: The three SNPs (rs1800686, rs3765459, and rs4810485) of the CD40 gene were analyzed by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods in 421 patients with CSCC, 594 patients with high-grade squamous intraepithelial lesions (HSIL), and 504 healthy females. Multivariate logistic regression analysis was used to analyze the potential relationship between CD40 gene polymorphisms and CSCC, or HSIL. RESULTS: Our research results showed the AA genotype of rs1800686 had a protective effect on CSCC in comparison to the GG genotype and AG+GG genotypes (AA vs. GG: p = 0.0389 and AA vs. AG+GG: p = 0.0280, respectively). After FDR correction, the results were still statistically significant (p = 0.0389 and p = 0.0389, respectively). Similarly, rs3765459 showed a reduced risk association for CSCC in the codominant and recessive models (AA vs. GG: p = 0.0286 and AA vs. AG+GG: p = 0.0222, respectively). Significant differences remained after FDR correction (p = 0.0286 and p = 0.0286, respectively). However, these differences were no longer significant after the Bonferroni correction. In addition, the genotypes for the rs4810485 polymorphisms were associated with parity of the patients with CSCC. The genotypes for the rs3765459 polymorphisms were significantly correlated with the D-dimer of the patients with CSCC. The 3 SNPs genotypes of the CD40 gene were closely related to the squamous cell carcinoma antigen (SCC) of the patients with HSIL. CONCLUSIONS: The CD40 gene may play a role in the occurrence and development of CSCC.

Effects of PM2.5 and high-fat diet interaction on blood glucose metabolism in adolescent male Wistar rats: A serum metabolomics analysis based on ultra-high performance liquid chromatography/mass spectrometry.

Fine particulate matter (PM2.5) and high-fat diet (HFD) are known to contribute to blood glucose metabolic disorders. However, limited research has investigated the combined impact of PM2.5 and HFD on blood glucose metabolism. This study aimed to explore the joint effects of PM2.5 and HFD on blood glucose metabolism in rats using serum metabolomics and to identify involved metabolites and metabolic pathways. The 32 male Wistar rats were exposed to filtered air (FA) or PM2.5 (real-world inhaled, concentrated PM2.5, 8 times the ambient level, ranging from 131.42 to 773.44 µg/m3) and fed normal diet (ND) or HFD for 8 weeks. The rats were divided into four groups (n = 8/group): ND-FA, ND-PM2.5, HFD-FA and HFD-PM2.5 groups. Blood samples were collected to determine fasting glucose (FBG), plasma insulin and glucose tolerance test and HOMA Insulin Resistance (HOMA-IR) index was calculated. Finally, the serum metabolism of rats was analyzed by ultra-high performance liquid chromatography/mass spectrometry (UHPLC-MS). Then we constructed the partial least squares discriminant analysis (PLS-DA) model to screen the differential metabolites, and performed pathway analysis to screen the main metabolic pathways. Results showed that combined effect of PM2.5 and HFD caused changes in glucose tolerance, increased FBG levels and HOMA-IR in rats and there were interactions between PM2.5 and HFD in FBG and insulin. By metabonomic analysis, the serum differential metabolites pregnenolone and progesterone, which involved in steroid hormone biosynthesis, were two different metabolites in the ND groups. In the HFD groups, the serum differential metabolites were L-tyrosine and phosphorylcholine, which involved in glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. When PM2.5 and HFD coexist, they may lead to more severe and complex effects on glucose metabolism by affecting lipid metabolism and amino acid metabolism. Therefore, reducing PM2.5 exposure and controlling dietary structure are important measures for preventing and reducing glucose metabolism disorders.

[Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease].

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

[Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway].

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid ß oxidation in the liver.

Triple-Wavelength Lasing with a Stabilized ß-LaBSiO5:Nd3+ Crystal.

Multi-wavelength lasers, especially the triple-wavelength laser around 1060 nm, could be produced by the 4F3/2 → 4I11/2 transition of Nd3+ and present numerous challenges and opportunities in the field of optoelectronics. The Nd3+-doped high-temperature phase of LaBSiO5 (ß-LBSO) is an ideal crystal to produce triple-wavelength lasers; however, the crystal growth is challenging because of the phase transition from ß-LBSO to low-temperature phase (α-LBSO) at 162 °C. This phase transition is successfully suppressed when the doping content of Nd3+ is larger than 6.3 at. %, and the Nd3+-doped ß-LBSO is stable at room temperature. The local disorder of BO4 tetrahedra due to Nd3+ doping is essential to the stabilization of ß-LBSO. For the first time, the ß-LBSO:8%Nd3+ crystal with a dimension of 1.8 × 1.8 × 1.8 cm3 is obtained through the top-seeded solution method. The crystal shows strong optical absorption in the range of 785-815 nm, matching well with the commercial laser diode pumping source. The optical emission of 4F3/2 → 4I11/2 splits into four peaks with the highest optical emission cross section of 2.14 × 10-20 cm2 at 1068 nm. The continuous-wave triple-wavelength generation of coherent light at 1047, 1071, and 1092 nm is achieved with the highest output power of 235 mW and efficiency of 12.1%.

Genome-wide investigation and expression analysis of the AP2/ERF family for selection of agarwood-related genes in Aquilaria sinensis (Lour.) Gilg.

Aquilaria sinensis is an important non-timber tree species for producing high-value agarwood, which is widely used as a traditional medicine and incense. Agarwood is the product of Aquilaria trees in response to injury and fungal infection. The APETALA2/ethylene responsive factor (AP2/ERF) transcription factors (TFs) play important roles in plant stress responses and metabolite biosynthesis. In this study, 119 AsAP2/ERF genes were identified from the A. sinensis genome and divided into ERF, AP2, RAV, and Soloist subfamilies. Their conserved motif, gene structure, chromosomal localization, and subcellular localization were characterized. A stress/defense-related ERF-associated amphiphilic repression (EAR) motif and an EDLL motif were identified. Moreover, 11 genes that were highly expressed in the agarwood layer in response to whole-tree agarwood induction technique (Agar-Wit) treatment were chosen, and their expression levels in response to methyl jasmonate (MeJA), salicylic acid (SA), or salt treatment were further analyzed using the quantitative real time PCR (qRT-PCR). Among the 11 genes, eight belonged to subgroup B-3. All 11 genes were significantly upregulated under salt treatment, while eight genes were significantly induced by both MeJA and SA. In addition, the gene clusters containing these upregulated genes on chromosomes were observed. The results obtained from this research not only provide useful information for understanding the functions of AP2/ERF genes in A. sinensis but also identify candidate genes and gene clusters to dissect their regulatory roles in agarwood formation for future research.

Therapeutic potential and research progress of diosgenin for lipid metabolism diseases.

Diosgenin, a steroidal saponin, is a natural product found in many plants. Diosgenin has a wide range of pharmacological activities, and has been used to treat cancer, nervous system diseases, inflammation, and infections. Numerous studies have shown that diosgenin has potential therapeutic value for lipid metabolism diseases via various pathways and mechanisms, such as controlling lipid synthesis, absorption, and inhibition of oxidative stress. These mechanisms and pathways have provided ideas for researchers to develop related drugs. In this review, we focus on data from animal and clinical studies, summarizing the toxicity of diosgenin, its pharmacological mechanism, recent research advances, and the related mechanisms of diosgenin as a drug for the treatment of lipid metabolism, especially in obesity, hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and diabetes. This systematic review will briefly describe the advantages of diosgenin as a potential therapeutic drug and seek to enhance our understanding of the pharmacological mechanism, recipe-construction, and the development of novel therapeutics against lipid metabolism diseases.

Reticular Synthesis of Hydrogen-Bonded Organic Frameworks and Their Derivatives via Mechanochemistry.

Rational synthesis of hydrogen-bonded organic frameworks (HOFs) with predicted structure has been a long-term challenge. Herein, by using the efficient, simple, low-cost, and scalable mechanosynthesis, we demonstrate that reticular chemistry is applicable to HOF assemblies based on building blocks with different geometry, connectivity, and functionality. The obtained crystalline HOFs show uniform nano-sized morphology, which is challenging or unachievable for conventional solution-based methods. Furthermore, the one-pot mechanosynthesis generated a series of Pd@HOF composites with noticeably different CO oxidation activities. In situ DRIFTS studies indicate that the most efficient composite, counterintuitively, shows the weakest CO affinity to Pd sites while the strongest CO affinity to HOF matrix, revealing the vital role of porous matrix to the catalytic performance. This work paves a new avenue for rational synthesis of HOF and HOF-based composites for broad application potential.

Biochemical characterization and redesign of the coenzyme specificity of a novel monofunctional NAD+-dependent homoserine dehydrogenase from the human pathogen Neisseria gonorrhoeae.

Gonorrhoea, caused by Neisseria gonorrhoeae, is a major global public health concern. Homoserine dehydrogenase (HSD), a key enzyme in the aspartate pathway, is a promising metabolic target against pathogenic infections. In this study, a monofunctional HSD from N. gonorrhoeae (NgHSD) was overexpressed in Escherichia coli and purified to >95% homogeneity for biochemical characterization. Unlike the classic dimeric structure, the purified recombinant NgHSD exists as a tetramer in solution. We determined the enzymatic activity of recombinant NgHSD for l-homoserine oxidation, which revealed that this enzyme was NAD+ dependent, with an approximate 479-fold (kcat/Km) preference for NAD+ over NADP+, and that optimal activity for l-homoserine oxidation occurred at pH 10.5 and 40 °C. At 800 mM, neither NaCl nor KCl increased the activity of NgHSD, in contrast to the behavior of several reported NAD+-independent homologs. Moreover, threonine did not markedly inhibit the oxidation activity of NgHSD. To gain insight into the cofactor specificity, site-directed mutagenesis was used to alter coenzyme specificity. The double mutant L45R/S46R, showing the highest affinity for NADP+, caused a shift in coenzyme preference from NAD+ to NADP+ by a factor of ~974, with a catalytic efficiency comparable with naturally occurring NAD+-independent homologs. Collectively, our results should allow the exploration of drugs targeting NgHSD to treat gonococcal infections and contribute to the prediction of the coenzyme specificity of novel HSDs.

Highly Dispersive Ni@C and Co@C Nanoparticles Derived from Metal-Organic Monolayers for Enhanced Photocatalytic CO2 Reduction.

The metal/carbon composites prepared by direct pyrolysis of metal-organic frameworks (MOFs) are regarded as ideal catalysts. However, conventional MOFs show a three-dimensional bulk structure. For bulk MOF-derived catalysts, most active metal sites are confined in the interior and not fully utilized. In this work, metal-organic monolayers (MOLs) are used as the starting precursors to prepare carbon-wrapped metal nanoparticles, which are further employed as catalysts for photocatalytic CO2 reduction. The as-prepared Ni-MOLs and Co-MOLs have an ultrathin thickness of ∼1 nm. It is interestingly found that their derived Ni@C and Co@C nanoparticles are highly dispersive and connected with each other like a piece of paper. As compared with bulk MOF-derived counterparts, MOL-derived catalysts increase the accessibility of active metal sites, which can accelerate electron transfer from photosensitizers to Ni@C and Co@C nanoparticles. In this way, the catalytic activity can be greatly improved. Besides, the magnetic nature of Ni@C and Co@C nanoparticles enables the easy separation and recycling of catalysts. It is expected that this work will provide instructive guidelines for the rational design of MOL-derived catalysts.

Quantification of the Masseter Muscle Hardness of Stroke Patients Using the MyotonPRO Apparatus: Intra- and Inter-Rater Reliability and Its Correlation with Masticatory Performance.

BACKGROUND Chewing dysfunction is one of the most common serious complications after a stroke. It may be influenced by the hardness of the masseter muscle and masticatory performance; however, the association between these 2 factors is not explicit. Thus, it is meaningful to explore the functional status of the masseter muscle among stroke patients. The main objectives of this study were to examine the intra- and inter-rater reliability of the MyotonPRO apparatus in measuring masseter muscle hardness in stroke patients and to investigate the correlation between the bilateral masseter muscle hardness and masticatory performance in these patients. MATERIAL AND METHODS A total of 20 stroke patients participated in our study. The hardness of the masseter muscle was measured by 2 physiotherapists using the MyotonPRO apparatus. Overall, each patient masticated 2 pieces of red-blue bicolor chewing gum for 20 chewing cycles each. The chewing pieces were analyzed using ViewGum software for masticatory performance. RESULTS The intra- and inter-rater reliability of the MyotonPRO apparatus for measuring bilateral masseter hardness of stroke patients was excellent. The correlation analysis showed that the hardness index of the masseter muscle on the affected side was moderately correlated with the masticatory performance of the same side. CONCLUSIONS The MyotonPRO device can be used for measuring the masseter muscle hardness of stroke patients, with excellent reliability. This study established the construct validity between the stiffness of the masseter muscle and masticatory performance.

Knowledge, attitudes, and practices towards COVID-19 among primary school students in Hubei Province, China.

This study was aimed to investigate the knowledge, attitudes, and practices (KAP) towards coronavirus disease 2019 (COVID-19) among school-aged children in the Hubei province when children were being confined to their homes. The questionnaire included questions of KAP about COVID-19, depressive and anxiety symptoms scales. Multivariable generalized linear regressions models were applied to estimate the unstandardized regression coefficients (ß) of KAP. The awareness rates about COVID-19 were 70.1%-99.5% for all 1650 valid questionnaires. 37.2% of the participants quite worried about being infected with COVID-19. Approximately 96% of them washed hands in certain situations, while 85.6% of them washed hands after coughing or sneezing. Compared to the students without depressive symptoms, those who had depressive symptoms scored lower of total KAP, knowledge, attitudes, and practice. The findings suggest that primary students had a relatively good awareness of COVID-19 during the epidemic, as well as optimistic attitudes and appropriate practices. However, some items of appropriate practices still needed to be enhanced.

Systematic analysis of lncRNA expression profiles and atherosclerosis-associated lncRNA-mRNA network revealing functional lncRNAs in carotid atherosclerotic rabbit models.

Atherosclerosis, a multifactorial and chronic immune inflammatory disorder, is the main cause of multiple cardiovascular diseases. Researchers recently reported that lncRNAs may exert important functions in the progression of atherosclerosis (AS). Some studies found that lncRNAs can act as ceRNAs to communicate with each other by the competition of common miRNA response elements. However, lncRNA-associated ceRNA network in terms of atherosclerosis is limited. In present study, we pioneered to construct and systematically analyze the lncRNA-mRNA network and reveal its potential roles in carotid atherosclerotic rabbit models. Atherosclerosis was induced in rabbits (n = 3) carotid arteries via a high-fat diet and balloon injury, while age-matched rabbits (n = 3) were treated with normal chow as controls. RNA-seq analysis was conducted on rabbits carotid arteries (n = 6) with or without plaque formation. Based on the ceRNA mechanism, a ternary interaction network including lncRNA, mRNA, and miRNA was generated and an AS-related lncRNA-mRNA network (ASLMN) was extracted. Furthermore, we analyzed the properties of ASLMN and discovered that six lncRNAs (MSTRG.10603.16, 5258.4, 12799.3, 5352.1, 12022.1, and 12250.4) were highly related to AS through topological analysis. GO and KEGG enrichment analysis indicated that lncRNA MSTRG.5258.4 may downregulate inducible co-stimulator to perform a downregulated role in AS through T cell receptor signaling pathway and downregulate THBS1 to conduct a upregulated function in AS through ECM-receptor interaction pathway. Finally, our results elucidated the important function of lncRNAs in the origination and progression of AS. We provided an ASLMN of atherosclerosis development in carotid arteries of rabbits and probable targets which may lay the foundation for future research of clinical applications.

The pre membrane and envelope protein is the crucial virulence determinant of Japanese encephalitis virus.

After sequence comparison, it was found that there are multiple amino acid mutations in pre-M and envelope (E) protein of Japanese encephalitis virus vaccine strain comparison with wild type (WT) strain SA14. It is generally acknowledged it is the mutations that have caused the virulence attenuation of vaccine strain, but lack of sufficient experimental evidences. For a better understanding of the mechanism of attenuation of Japanese encephalitis virus (JEV), in this study, we assessed whether prM/E is critical neurovirulence determinants of JEV with infectious cDNA clones technique. Substitutions prM/E of vaccine strain with that of WT SA14 did significantly increase the virulence of JEV to the similar level of wild type SA14, and simultaneously, replacement prM/E of JEV WT strain SA14 with that of vaccine strain SA14-14-2 decreased the virulence of JEV significantly to the similar level of vaccine stain. The results indicate that the prM/E protein is the crucial virulence determinant of Japanese encephalitis virus, although other proteins take part in the process to some extent.

Objective Assessment of Regional Stiffness in Achilles Tendon in Different Ankle Joint Positions Using the MyotonPRO.

BACKGROUND Achilles tendinopathy commonly occurs in specific regions of the tendon, and Achilles tendon stiffness can be related to local pathological changes in the tendon. The MyotonPRO is a new handheld device that conveniently assesses stiffness of muscles and tendons. This study aimed to 1) evaluate the intra- and inter-rater reliability of stiffness measurements of the Achilles tendon at different ankle positions, 2) investigate the modulation of stiffness at different ankle joint angles, and 3) examine the differences between 2 regions of Achilles tendon stiffness. MATERIAL AND METHODS Thirty healthy young adults (15 men and 15 women) participated in this study. The regional Achilles tendon stiffness at 0 cm (AT-0) and 6 cm (AT-6) above the tendon insertion were evaluated by the MyotonPRO in the neutral position and 10° dorsiflexion of the ankle joint. Measurements of stiffness were taken by 2 raters on the first day and 5 days later. The stiffness data were compared by repeated measures analysis of variance (ANOVA). RESULTS The intra- and inter-rater reliability of stiffness measurements at AT-0 and AT-6 for each ankle position were good (all intraclass correlation coefficients >0.84). A significant modulation of Achilles tendon stiffness was obtained at different ankle joint angles (P<0.05). Stiffness at AT-0 was higher than at AT-6 (P<0.05) in both positions. CONCLUSIONS These results suggest the MyotonPRO reliably assessed Achilles tendon stiffness and monitors its modulation, and tendon stiffness increased with ankle dorsiflexion. Stiffness was also nonuniform along the length of the tendon.

Association of renalase gene polymorphisms with the risk of hypertensive disorders of pregnancy in northeastern Han Chinese population.

Renalase is a novel enzyme that can regulate blood pressure by degrading circulating catecholamines. We aimed to evaluate the possible effect of rs2296545, rs2576178 and rs10887800 polymorphisms of the renalase gene (RNLS) on the development of hypertensive disorders of pregnancy (HDP). This case-control study consisted of 185 patients with HDP and 380 normotensive pregnant women from the northeastern Chinese Han population. Association analyses were performed using PLINK, to compare allele and genotype frequencies in cases and controls. Adjustment for logistic regression analysis was performed by permutation testing. In the HDP patients compared with controls, we found that there was statistically significant difference in genotype distribution of rs2296545 (p = .037). Rs2296545 and rs2576178 polymorphisms have 1.91-fold (p = .004) and 1.73-fold (p = .015) increased risk of HDP in the dominant model, respectively. When compared preeclampsia (PE) to control, the RNLS rs2296545 polymorphism was significantly associated with PE risk in the dominant model (p = .021). We next analyzed the haplotypes of these SNPs and there was no difference between controls and HDP or PE. These findings suggest that rs2296545 was significantly associated with HDP and PE risk and the rs2576178 polymorphism may increase the susceptibility to HDP.

Dealing with missing data by EM in single-case studies.

Single-case experimental design (SCED) research plays an important role in establishing and confirming evidence-based practices. Due to multiple measures of a target behavior in such studies, missing information is common in their data. The expectation-maximization (EM) algorithm has been successfully applied to deal with missing data in between-subjects designs, but only in a handful of SCED studies. The present study extends the findings from Smith, Borckardt, and Nash (2012) and Velicer and Colby (2005b, Study 2) by systematically examining the performance of EM in a baseline-intervention (or AB) design under various missing rates, autocorrelations, intervention phase lengths, and magnitudes of effects, as well as two fitted models. Three indicators of an intervention effect (baseline slope, level shift, and slope change) were estimated. The estimates' relative bias, root-mean squared error, and relative bias of the estimated standard error were used to assess EM's performance. The findings revealed that autocorrelation impacted the estimates' qualities most profoundly. Autocorrelation interacted with missing rate in impacting the relative bias of the estimates, impacted the root-mean squared error nonlinearly, and interacted with the fitted model in impacting the relative bias of the estimated standard errors. A simpler model without autocorrelation can be used to estimate baseline slope and slope change in time-series data. EM is recommended as a principled method to handle missing data in SCED studies. Two decision trees are presented to assist researchers and practitioners in applying EM. Emerging research directions are identified for treating missing data in SCED studies.