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Alzheimer’s disease (AD) is characterized by the accumulation of β-amyloid (Aβ) plaques and tau neurofibrillary tangles in the brain. Although the exact details of the neuronal protective effect of high-intensity interval training (HIIT) on AD remain unclear, the preclinical phase of AD appears to be the important time point for such intervention. The described experiment investigates the neuroprotective effect of HIIT on AD in APP/PS1 mice. In total, 14 C57BL6 healthy control (C) mice and 14 APP/PS1 AD mice were each randomly assigned into two groups, one that did not participate in HIIT (C and AD groups, respectively) and the other subject to HIIT intervention (control HIIT (CE) and AD HIIT (ADE) groups, respectively). Visualization of hippocampal neuronal cells via HE and Congo red staining showed significant improvement in cell status and a significant reduction in amyloidosis in ADE compared with AD. The results of behavioral analysis show that the HIIT intervention significantly improved cognitive decline and reduced spatial exploration in both the C and AD groups. Immunofluorescence showed that the overall brain and the hippocampus of aged rats in the C and AD groups had different degrees of neuroglial responses and astrocyte GFAP proliferation and hypertrophy, with obvious improvement in the CE and ADE groups after 10 weeks of HIIT intervention. These results show that HIIT significantly improves the status of mitochondrial kinetic proteins and related proteins, with the mechanism differing between the normal aging C and the AD groups. 10 weeks of HIIT improved the imbalance in mitochondrial dynamics present in normal control mice and in AD mice. We conclude that preclinical training intervention has a significant positive effect on the exploratory behavior and cognitive functioning of mice.

As the primary source of norepinephrine (NE) in the brain, the locus coeruleus (LC) regulates both arousal and stress responses1,2. However, how local neuromodulatory inputs contribute to LC function remains unresolved. Here we identify a network of transcriptionally and functionally diverse GABAergic neurons in the LC dendritic field that integrate distant inputs and modulate modes of LC firing to control arousal. We define peri-LC anatomy using viral tracing and combine single-cell RNA sequencing and spatial transcriptomics to molecularly define both LC and peri-LC cell types. We identify several cell types which underlie peri-LC functional diversity using a series of complementary approaches in behaving mice. Our findings indicate that LC and peri-LC neurons comprise transcriptionally and functionally heterogenous neuronal populations, alongside anatomically segregated features which coordinate specific influences on behavioral arousal and avoidance states. Defining the molecular, cellular and functional diversity in the LC provides a road map for understanding the neurobiological basis of arousal alongside hyperarousal-related neuropsychiatric phenotypes.

Protein dimerization systems controlled by red light with increased tissue penetration depth are a highly needed tool for clinical applications such as cell and gene therapies. However, mammalian applications of existing red light-induced dimerization systems are hampered by limitations of their two components: a photosensory protein (or photoreceptor) which often requires a mammalian exogenous chromophore and a naturally occurring photoreceptor binding protein typically having a complex structure and non-ideal binding properties. Here, we introduce an efficient, generalizable method (COMBINES-LID) for creating highly specific, reversible light-induced heterodimerization systems independent of any existing binders to a photoreceptor. It involves a two-step binder screen (phage display and yeast two-hybrid) of a combinatorial nanobody library to obtain binders that selectively engage a light-activated form of a photoswitchable protein or domain not the dark form. Proof-of-principle was provided by engineering nanobody-based, red light-induced dimerization (nanoReD) systems comprising a truncated bacterial phytochrome sensory module using a mammalian endogenous chromophore, biliverdin, and light-form specific nanobodies. Selected nanoReD systems were biochemically characterized, exhibiting low dark activity and high induction specificity, and further demonstrated for the reversible control of protein translocation and activation of gene expression in mice. Overall, COMBINES-LID opens new opportunities for creating genetically encoded actuators for the optical manipulation of biological processes.

MicroRNAs are important coordinators of circadian regulation that mediate the fine-tuning of gene expression. Although many studies have shown the effects of individual miRNAs on the circadian clock, the global functional miRNA-mRNA interaction network involved in the circadian system remains poorly understood. Here, we used CLEAR (Covalent Ligation of Endogenous Argonaute-bound RNAs)-CLIP (Cross-Linking and Immuno-Precipitation) to explore the regulatory functions of miRNAs in the circadian system by comparing the miRNA-mRNA interactions between Drosophila wild-type strain W(1118) and a mutant of the key circadian transcriptional regulator Clock (Clk(jrk)). This experimental approach unambiguously identified tens of thousands of miRNA-mRNA interactions in both the head and body. The miRNA-mRNA interactome showed dramatic changes in the Clk(jrk) flies. Particularly, among ~300 miRNA-mRNA circadian relevant interactions, multiple interactions involving core clock genes pdp1, tim and vri displayed distinct changes as a result of the Clk mutation. Based on the CLEAR-CLIP analysis, we found a novel regulation of the circadian rhythm and sleep by the miR-375-timeless interaction. The results indicated that Clk disruption abolished normal rhythmic expression of miR-375 and the functional regulation occurred in the l-LNv neurons, where miR-375 modulated circadian rhythm and sleep via targeting timeless. This work provides the first global view of miRNA regulation in the circadian rhythm.

Methods for acquiring spatially resolved omics data from complex tissues use barcoded DNA arrays of low- to sub-micrometer features to achieve single-cell resolution. However, fabricating such arrays (randomly assembled beads, DNA nanoballs, or clusters) requires sequencing barcodes in each array, limiting cost-effectiveness and throughput. Here, we describe a vastly scalable stamping method to fabricate polony gels, arrays of ∼1-micrometer clonal DNA clusters bearing unique barcodes. By enabling repeatable enzymatic replication of barcode-patterned gels, this method, compared with the sequencing-dependent array fabrication, reduced cost by at least 35-fold and time to approximately 7 h. The gel stamping was implemented with a simple robotic arm and off-the-shelf reagents. We leveraged the resolution and RNA capture efficiency of polony gels to develop Pixel-seq, a single-cell spatial transcriptomic assay, and applied it to map the mouse parabrachial nucleus and analyze changes in neuropathic pain-regulated transcriptomes and cell-cell communication after nerve ligation.

Chemically induced dimerization (CID) systems, in which two proteins dimerize only in the presence of a small molecule ligand, offer versatile tools for small molecule sensing and actuation. However, only a handful of CID systems exist and creating one with the desired sensitivity and specificity for any given ligand is an unsolved problem. Here, we developed a combinatorial binders-enabled selection of CID (COMBINES-CID) method broadly applicable to different ligands. We demonstrated a proof-of-principle by generating nanobody-based heterodimerization systems induced by cannabidiol with high ligand selectivity. We applied the CID system to a sensitive sandwich enzyme-linked immunosorbent assay-like assay of cannabidiol in body fluids with a detection limit of ∼0.25 ng/mL. COMBINES-CID provides an efficient, cost-effective solution for expanding the biosensor toolkit for small molecule detection.

Current technologies for acquiring spatial transcript information from tissue sections rely on either RNA probes or spatial barcodes. The former methods require a priori knowledge for probeset formulation; the latter have yet to achieve single cell resolution and/or transcript capture efficiencies approaching dissociative, single-cell methods. Here, we describe a novel spatial transcriptome assay called polony (or DNA cluster)-indexed library-sequencing (PIXEL-seq). It improves upon other spatial barcoding methods by employing “continuous” polony oligos arrayed across a customized gel surface. In terms of assay performance, PIXEL-seq attains ≤ 1 µm resolution and captures >1,000 unique molecular identifiers/10×10 µm2. In other words, this global, naive platform achieves subcellular spatial transcriptome mapping while maintaining high transcript capture efficiencies.

Protein dimerization systems that can be controlled by red light with increased tissue penetration depth are a highly needed optogenetic tool for clinical applications such as cell and gene therapies. However, existing red light-induced dimerization systems are all based on phytochrome photoreceptors and naturally occurring binding partners with complex structures and suboptimal in vivo performance, limiting mammalian applications. Here, we introduce an efficient, generalizable method (COMBINES-LID) for creating highly specific light-induced dimerization systems. Proof-of-principle was provided by creating nanobody-based, red light-induced dimerization (nanoReD) systems comprising a truncated bacterial phytochrome sensory module using a mammalian endogenous chromophore, biliverdin, and light-form specific nanobodies. Selected nanoReD systems were biochemically characterized and exhibited low dark activity and high induction specificity for in vivo activation of gene expression. Overall, COMBINES-LID opens new opportunities for creating genetically encoded actuators for the optical manipulation of biological processes.

Krüppel homologue 1 (Kr-h1) is a zinc finger transcription factor that is upregulated in insects by juvenile hormone (JH) in metamorphosis and adult reproduction. The molecular function of Kr-h1 in reproduction remains largely unknown. Here we report that AaKr-h1 functions as an important transcription regulator in adult female Aedes aegypti mosquitoes. The amount of AaKr-h1 protein increases with rising JH levels after adult emergence, reaches its peak at 48 h after eclosion, then decreases gradually and disappears after blood feeding. RNA interference (RNAi)-mediated depletion of AaKr-h1 substantially reduced egg production after blood feeding. Using a chromatin immunoprecipitation cloning approach, we identified in vivo AaKr-h1 binding sites in previtellogenic female mosquitoes. Binding of AaKr-h1 to the target genes correlated with its protein abundance. Interestingly, RNAi experiments indicated that AaKr-h1 played distinct roles when it bound to individual target genes. For example, depletion of AaKr-h1 led to substantial upregulation of AAEL005545 and AAEL004444, but also significantly decreased the expression of AAEL005957 and AAEL013177 when compared with the control mosquitoes. In summary, AaKr-h1 directly binds to the regulatory regions of its target genes and acts as a transcriptional activator or a repressor in a promoter-specific manner.

In this study, we found that let-7c-5p expression was clearly downregulated in breast cancer tissues compared with that of corresponding adjacent tissues. Furthermore, overexpression of let-7c-5p in MCF-7 breast cancer cells could significantly inhibit cell proliferation and induce cell apoptosis. The target genes of let-7c-5p were predicted by the way of bioinformatics, and validated by dual luciferase reporter assay and western blotting demonstrating that excision repair cross complementing 6 (ERCC6) gene was a direct target. Collectively, the present study suggested that let-7c-5p acted as a tumor suppressor in breast cancer possibly by negatively regulating ERCC6, which took an important part in nucleotide excision repair and it may provide a new potential strategy for breast cancer therapy.

MicroRNA is critical coordinator to circadian regulation by silencing gene expression. Although many circadian related miRNAs and some of its target are known, the global functional miRNA-mRNA interaction networks remain poorly understand which is hindered by imperfect base-pairing between miRNA and target mRNA. In this study, we used CLEAR (Covalent Ligation of Endogenous Argonaute-bound RNAs) -CLIP (Cross-Linking and Immuno-Precipitation) to explore the regulatory functions of miRNAs in the circadian system by comparing the miRNA-mRNA interactions between the Drosophila wild-type strain w1118 and the Clk mutant Clkjrk. We unambiguously identified thousands of miRNA-mRNA interactions from CLEAR-CLIP data set at unprecedented depth in vivo for the first time. Among them, about 300 miRNA-mRNA interactions were involved in the regulation of circadian, in which miRNAs targeting core clock genes pdp1, tim and vri presented distinct changes in response to Clkjrk. Particularly, the mir-375-timeless interaction from CLER-CLIP shows important effects on circadian, this functional event occurred in the l-LNv neurons. Overexpression of mir-375 in tim neurons caused decreases in TIM content resulting in arrhythmicity of daily locomotion and changes of sleep. This present work provides a global view of miRNA targeting in the circadian rhythm.

By using molecular-dynamics simulations, we demonstrate the existence of heat-pulse rectification in graphene Y junctions. Our results show that the heat pulse will separate into two parts when it flows from stem to branches. However, when it flows from branches to stem, substantial part of the heat pulse is reflected back into the branches with no separation. Moreover, we discuss rectification in different type of junctions and find that the preferred heat pulse transport direction depends on the structure of the junctions, which enable us to delicately control the heat rectification in graphene based structures.

Juvenile hormone (JH) regulates many aspects of insect development and reproduction. In some processes, JH plays a critical role in defining the action of the steroid hormone 20-hydroxyecdysone (20E). In Aedes aegypti mosquitoes, JH prepares newly emerged female adults to become competent to synthesize vitellogenin in response to 20E after blood ingestion. The molecular basis of this competence is still not well understood. Here, we report that JH regulates pre-mRNA splicing of the taiman gene, which encodes a key transcriptional regulator required for both JH- and 20E-controlled gene expression. JH stimulated the production of the Taiman isoforms A/B, while reducing the levels of the isoforms C/D, in the fat body after adult eclosion. The appearance of the A/B isoforms in maturing mosquitoes was accompanied by acquisition of the competence to respond to 20E. Depletion of the A/B isoforms, by inhibiting the alternative splicing or by isoform-specific RNA interference, considerably diminished the 20E-induced gene expression after a blood meal and substantially impaired oocyte development. In accordance with this observation, further studies indicated that in the presence of 20E, the Taiman A/B isoforms showed much stronger interactions with the 20E receptor complex than the Taiman C/D isoforms. In contrast, all four isoforms displayed similar capabilities of forming active JH receptor complexes with the methoprene-tolerant protein (Met). This study suggested that JH confers the competence to newly emerged female mosquitoes by regulating mRNA splicing to generate the Taiman isoforms that are essential for the vitellogenic 20E response. Published version

The vital role of microRNAs (miRNAs) involved in gene expression regulation has been confirmed in many biological processes. With the growing power and reducing cost of next-generation sequencing, more and more researchers turn to apply this high-throughput method to solve their biological problems. For miRNAs with known sequences, their expression profiles can be generated from the sequencing data. It also allows us to identify some novel miRNAs and explore the sequence variations under different conditions. Currently, there are a handful of tools available to analyze the miRNA sequencing data with separated or combined features, such as reads preprocessing, mapping and differential expression analysis. However, to our knowledge, a hands-on guideline for miRNA sequencing data analysis covering all steps is not available. Here we will utilize a set of published tools to perform the miRNA analysis with detailed explanation. Particularly, the miRNA target prediction and annotation may provide useful information for further experimental verification.

The vital role of microRNAs (miRNAs) involved in gene expression regulation has been confirmed in many biological processes. With the growing power and reducing cost of next-generation sequencing, more and more researchers turn to apply this high-throughput method to solve their biological problems. For miRNAs with known sequences, their expression profiles can be generated from the sequencing data. It also allows us to identify some novel miRNAs and explore the sequence variations under different conditions. Currently, there are a handful of tools available to analyze the miRNA sequencing data with separated or combined features, such as reads preprocessing, mapping and differential expression analysis. However, to our knowledge, a hands-on guideline for miRNA sequencing data analysis covering all steps is not available. Here we will utilize a set of published tools to perform the miRNA analysis with detailed explanation. Particularly, the miRNA target prediction and annotation may provide useful information for further experimental verification.

By using a molecular dynamics method with EAM potential, we study the evolution phenomena of metal twist grain boundaries (GBs) in the [100], [111] and [110] orientations, together with their bimetal interface, under anticlockwise and clockwise torsions. Our results show that there are different evolution behaviors of the GB screw dislocations for single metals (Al and Ni) and their bimetal interface (Al/Ni) under torsion. Specifically, for the single metals in the [100] and [111] orientations, their GBs evolve toward lower or higher angle twist GBs depending on the twist direction. For Ni in the [110] orientation, the dislocations spread not only in the GB region but also in the grain interior. However, for the bimetal interface, the propagation of dislocations is not only reduced dramatically but also limited to the interface region, showing that there is an inhibition effect. Therefore, such an inhibition effect can enhance the stability of nanomaterials which is very useful for the further design of nanodevices.

By using the first-principles calculations, the band gap properties of nanotubes formed by group IV elements have been investigated systemically. Our results reveal that for armchair nanotubes, the energy gaps at K points in the Brillouin zone decrease as 1/r scaling law with the radii (r) increasing, while they are scaled by −1/r 2 + C at Γ points, here, C is a constant. Further studies show that such scaling law of K points is independent of both the chiral vector and the type of elements. Therefore, the band gaps of nanotubes for a given radius can be determined by these scaling laws easily. Interestingly, we also predict the existence of indirect band gap for both germanium and tin nanotubes. Our new findings provide an efficient way to determine the band gaps of group IV element nanotubes by knowing the radii, as well as to facilitate the design of functional nanodevices.

Drastic changes in gene expression occur after adult female mosquitoes take a blood meal and use the nutrients for egg maturation. A growing body of evidence indicates that microRNAs (miRNAs) contribute to this tightly controlled tissue- and stage-specific gene expression. To investigate the role of miRNAs, we monitored miRNA expression in the mosquito Anopheles gambiae during the 72-h period immediately after blood feeding. We also measured the association of miRNAs with Argonaute 1 (Ago1) and Argonaute 2 (Ago2) to assess the functional status of individual miRNA species. Overall, 173 mature miRNAs were precipitated with Ago1 and Ago2, including 12 new miRNAs, the orthologs of which are found thus far only in other Anopheles species. Ago1 is the predominant carrier of miRNAs in Anopheles gambiae. The abundance and Ago loading of most of the mature miRNAs were relatively stable after blood ingestion. However, miRNAs of the miR-309/286/2944 cluster were considerably upregulated after blood feeding. Injection of the specific antagomir for miR-309 resulted in smaller developing oocytes and ultimately fewer eggs. In addition, the Ago association of some miRNAs was not proportional to their cellular abundance, suggesting that integration of miRNAs into the Ago complexes is regulated by additional mechanisms.

A SnSe monolayer with an orthorhombic Pnma GeS structure is an important two-dimensional (2D) indirect band gap material at room temperature. Based on first-principles density functional theory calculations, we present systematic studies on the electronic and magnetic properties of X (X = Ga, In, As, Sb) atom doped SnSe monolayers. The calculated electronic structures show that the Ga-doped system maintains its semiconducting properties while the In-doped SnSe monolayer is half-metal. The As- and Sb-doped SnSe systems present the characteristics of an n-type semiconductor. Moreover, all considered substitutional doping cases induce magnetic ground states with a magnetic moment of ∼ 1 μB. In addition, the calculated formation energies also show that four types of doped systems are thermodynamically stable. These results provide a new route for the potential applications of doped SnSe monolayers in 2D photoelectronic and magnetic semiconductor devices.

Eur J Clin Invest 2011; 41 (11): 1245–1253 Abstract Background Recent studies have shown that microRNAs (miRNA) could play a potential role as diagnostic and prognostic biomarkers of cancers. The aim of this meta-analysis is to summarize the global predicting role of miR-21 for survival in patients with a variety of carcinomas. Design Eligible studies were identified and assessed for quality through multiple search strategies. Data were collected from studies comparing overall, relapse-free or cancer-specific survival (CSS) in patients with cancer having higher miR-21 expression with those having lower levels. Pooled hazard ratios (HRs) of miR-21 for survival were calculated. Results A total of 17 studies dealing with various carcinomas were included for this global meta-analysis. For overall survival (OS), the pooled hazard ratio (HR) of higher miR-21 expression in cancerous tissue was 1·69 (95% CI: 1·33–2·16, P

Juvenile hormone (JH) controls many biological events in insects by triggering dramatic changes in gene expression in target cells. The Methoprene-tolerant (MET) protein, an intracellular JH receptor, acts as a transcriptional regulator and binds to the promoters of tissue- and stage-specific JH target genes when JH is present. Our recent study has demonstrated that the transcriptional activation by MET is modulated by a membrane- initiated JH signaling pathway, involving phospholipase C (PLC) and calcium/calmodulin-dependent protein kinase II (CaMKII). Here we report that protein kinase C (PKC) is another essential intermediate of this pathway. PKC was activated by JH and this action was PLC-dependent. Inhibition of the PKC activity substantially weakened the JH-induced gene expression in mosquito cells. RNAi experiments indicated that several PKC isoforms were involved in the JH action during the post- emergence development of adult female mosquitoes. JH treatment considerably increased the binding of MET to the promoters of JH response genes in cultured mosquito abdomens that were collected from newly emerged female adults. The JH-induced DNA binding of MET was hindered when the abdomens were treated with a PKC inhibitor and JH. Therefore, the results suggest that PKC modulates the transactivation activity of MET by enhancing the binding of MET to JH response elements in the JH target genes. This mechanism may allow for variable and stage- and tissue-specific genomic responses to JH.

By using the first-principles calculations based on density functional theory combined with quasi-harmonic approximation, we have studied the geometric structural, thermal properties, and the negative thermal expansion (NTE) properties of tetrahedral NbPO5. The variations of cell parameter and cell volume of tetrahedral NbPO5 with temperature show that it displays NTE behavior in the range of 473-800 K along a-axis and the corresponding average coefficient of thermal expansion (CTE) is approximately -0.766 ×10−6 K−1, while the c cell parameter and the cell volume display positive thermal expansion behaviors. These results are in consistent well with the experiment observations. Further vibrational modes analysis, together with Grüneisen parameters calculations, revealed that the transverse vibration of O corner atoms accompanying the rocking motions of corner-shared NbO6 octahedron and PO4 tetrahedron dominate the negative thermal properties of tetrahedral NbPO5. Our findings will provide an understanding for the underlying mechanisms of the NTE in oxides materials.

Background Recent studies have shown that C-reactive protein (CRP) may be associated with breast cancer. The purpose of this study is to summarize the predictive role of CRP for survival in breast cancer as shown in all available studies worldwide. Methods Related studies were identified and evaluated for quality through multiple search strategies. Data were collected from studies comparing overall, cancer-specific, and disease-free survival (OS, CSS, and DFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratios (HRs) of CRP for survival were calculated. Results A total of 10 studies (n=4,502) were included for this meta-analysis (9 for OS, 3 for CSS, and 3 for DFS). For overall and disease-free survival, the pooled HRs of CRP were significant at 1.62 (95% confidence interval [95% CI], 1.20-2.18) and 1.81 (95% CI, 1.44-2.26), respectively. For cancer-specific survival, the pooled HR in higher CRP expression in breast cancer was 2.08 (95% CI, 1.48-2.94), which could strongly predict poorer survival in breast cancer. Conclusions CRP has a critical prognostic value in patients with breast cancer as an inflammation biomarker.

Recent studies have shown that microRNAs (miRNA) could play a potential role as diagnostic and prognostic biomarkers of cancers. The aim of this meta-analysis is to summarize the global predicting role of miR-21 for survival in patients with a variety of carcinomas.Eligible studies were identified and assessed for quality through multiple search strategies. Data were collected from studies comparing overall, relapse-free or cancer-specific survival (CSS) in patients with cancer having higher miR-21 expression with those having lower levels. Pooled hazard ratios (HRs) of miR-21 for survival were calculated.A total of 17 studies dealing with various carcinomas were included for this global meta-analysis. For overall survival (OS), the pooled hazard ratio (HR) of higher miR-21 expression in cancerous tissue was 1·69 (95% CI: 1·33-2·16, P0·001), which could significantly predict poorer survival in general carcinomas. For relapse-free or CSS, elevated miR-21 was also a significant predictor, with a pooled HR of 1·48 (95% CI: 1·03-2·11, P = 0·033). Importantly, subgroup analysis suggested that higher expression of miR-21 correlated with worse OS in head and neck squamous cell carcinoma (HNSCC) (HR 1·46, 95% CI: 1·13-1·87, P = 0·004) and carcinomas in digestion system (HR 1·56, 95% CI: 1·08-2·26, P = 0·018).Our findings suggest that miR-21 detection has a prognostic value in patients with cancer, especially in HNSCC and digestion system cancers.

To summarize the global predicting role of systemic inflammatory response for survival in renal cell carcinoma.Eligible studies were identified and assessed for quality through multiple search strategies. Data were collected from studies comparing overall, cancer-specific or relapse-free survival in patients with elevated C-reactive protein (CRP), platelet count (PC) and erythrocyte sedimentation rate (ESR) levels with those with lower levels. Studies were pooled, and combined hazard ratios (HRs) of CRP, PC and ESR for survival were calculated, respectively.A total of 47 studies were included for meta-analysis (18 for CRP, 15 for PC and 14 for ESR). For overall survival, the pooled HR of CRP (3.23, 95% CI: 1.77, 5.89) was higher than that of PC (1.96, 95% CI: 1.40, 2.75) and that of ESR (1.86, 95% CI: 1.34, 2.59). These indicators were strong predictors for cancer-specific survival with individual HRs being 3.46 (95% CI, 2.80, 4.27) of CRP, 3.22 (95% CI, 2.25, 4.62) of PC, and 3.85 (95% CI, 3.31, 4.48) of ESR, respectively. All three inflammatory indictors also predicted relapse-free survival (HRs2.0).The systemic inflammatory response predicted poor survival in patients with renal cell carcinoma.

Objectives Thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, are widely used as antidiabetic agents. Here we present an updated meta-analysis of the respective effects of rosiglitazone and pioglitazone on the levels of C-reactive protein (CRP), a biomarker and predictor of CAD risks. Methods and results PubMed and EMBASE were systematically searched using the terms “C-reactive protein” and “rosiglitazone” or “pioglitazone” or “thiazolidinedione”. A total of 59 rosiglitazone studies and 36 pioglitazone studies were included for evaluation. These were classified as 2-group studies and 1-group studies according to their study design. Standard mean difference (SMD) of CRP and 95% CI were calculated to evaluate the effect of TZDs on CRP. The overall SMD for rosiglitazone treatment is −0.392 (95% CI, [−0.446, −0.338]) in 2-group studies and −0.424 (95% CI, [−0.501, −0.346]) in 1-group studies. The overall SMD for pioglitazone treatment is −0.577 (95% CI, [−0.732, −0.421]) in 2-group studies and −0.327 (95% CI, [−0.439, −0.216]) in 1-group studies. Moreover, TZDs were found to significantly reduce CRP levels in both diabetes mellitus (DM) and non-DM patients. Conclusions Our meta-analysis suggested that both rosiglitazone and pioglitazone significantly decrease serum CRP levels. TZDs presented their CRP-lowering effect in both DM and non-DM patients.

Silicon nanoporous pillar array (Si-NPA) has been prepared by a hydrothermal etching technique. Using Si-NPA as substrate, a Cu/Si-NPA nanocomposite thin film has been obtained with immersion plating method. Morphological and structural analysis indicates that Si-NPA is a typical structural composite system characterized by a triple hierarchical structure, i. e. the array of micron-sized silicon pillars, the nanopores densely distributed on the surface of the pillars, and the silicon nanocrystallites that constitute the pore walls. Cu/Si-NPA inherits the morphological characteristics of Si-NPA. The compactability of the deposited copper nanoparticles varies alternatively with the local geometrical features of Si-NPA and forms a quasi-periodical pattern. Such an experimental phenomenon is attributed to the velocity dependence of the copper deposition upon the local geometrical features of Si-NPA. These results indicate that Si-NPA might be used as an ideal template for preparing specially patterned, structured or functionalized metal/silicon nanocomposite systems.