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Water and graphene have been used separately to effectively broaden absorption bandwidth in the design of metamaterial absorbers (MAs). In this paper, a broad terahertz MA is presented, in which water and graphene are used together for improving absorption performance. The absorptivity of the presented MA exceeds 90% over the frequency range of 2.81–6.74 THz. It is found that the proposed MA has superior absorption performance to those using water or graphene separately. The impedance matching theory as well as the distribution of the field and power loss are used to provide a deep insight into the absorption mechanism. Furthermore, the proposed MA exhibits excellent thermal stability as well as good insensitivity to polarization and incident angle. This work provides a reference for designing broadband MA in terahertz frequency band. [ABSTRACT FROM AUTHOR]

A recent outbreak of porcine circovirus-like virus (PCLV), a virus that may be associated with porcine diarrhea, has been reported in swine herds in China. The virus is spreading rapidly, causing huge economic losses to the swine farming industry. To achieve the rapid, inexpensive, and sensitive detection of PCLV, we combined loop-mediated isothermal amplification (LAMP) and the CRISPR/Cas12a system, whose fluorescence intensity readout can detect PCLV ORF4 gene levels as low as 10 copies. To overcome the need for sophisticated equipment, lateral flow strip reading technology was introduced for the first time in a LAMP-Cas12a-based system to detect PCLV. The lateral flow strip (LFS) results were readout by the naked eye, and the method was highly sensitive with a detection limit of 10 copies, with a detection time of about 60 min. In addition, the method is highly specific and has no cross-reactivity with other related viruses. In conclusion, LAMP-CRISPR/Cas12a-based assays have the advantages of rapidity, accuracy, portability, low cost, and visualization of the results. They therefore have great potential, especially for areas where specialized equipment is lacking, and can expect to be an ideal method for early diagnosis and on-site detection of PCLV. [ABSTRACT FROM AUTHOR]

Low temperatures severely impair the performance of lithium-ion batteries, which demand powerful electrolytes with wide liquidity ranges, facilitated ion diffusion, and lower desolvation energy. The keys lie in establishing mild interactions between Li+ and solvent molecules internally, which are hard to achieve in commercial ethylene-carbonate based electrolytes. Herein, we tailor the solvation structure with low-ε solvent-dominated coordination, and unlock ethylene-carbonate via electronegativity regulation of carbonyl oxygen. The modified electrolyte exhibits high ion conductivity (1.46 mS·cm−1) at −90 °C, and remains liquid at −110 °C. Consequently, 4.5 V graphite-based pouch cells achieve ~98% capacity over 200 cycles at −10 °C without lithium dendrite. These cells also retain ~60% of their room-temperature discharge capacity at −70 °C, and miraculously retain discharge functionality even at ~−100 °C after being fully charged at 25 °C. This strategy of disrupting solvation dominance of ethylene-carbonate through molecular charge engineering, opens new avenues for advanced electrolyte design. Low-temperature operation remains challenging for batteries. Here, the authors report an electrolyte solvation structure design strategy to break solvation dominance of ethylene carbonate to facilitate the desolvation process that improves the low-temperature performance of lithium-ion batteries even below −100 °C. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas. The dysregulation of the m6A epitranscriptomic networks have been reported to contribute to the development of gliomas. Here, the authors utilize induced pluripotent stem cell-derived astrocytes with a p53 mutation and demonstrate that mutant p53 upregulates the m6A reader YTHDF2, resulting in the initiation of gliomas. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the efficacy and safety of dicycloplatin as chemotherapeutic regimen in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods: In this randomized, open-label, phase II trial, patients with unresectable HCC who were TACE treatment–naïve or experienced recurrence after surgical resection or ablation were enrolled at 7 centers in China from March 2019 to November 2019. Participants were randomly assigned (1:1:1) to receive TACE with chemotherapeutic regimen of dicycloplatin alone (group A1), dicycloplatin plus epirubicin (group A2), or epirubicin alone (group B). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety. Results: The ORR at 6 months in group A1 (n = 22) was significantly better than that in group B (p = 0.093; 90% confidence interval [CI], 1.03–9.45). The DCR in group A1 was significantly higher than that in group B (p = 0.045; 90% CI, 1.29–12.88). There was no significant difference in DOR among the groups (p = 0.271). The median PFS were 6.00 and 3.05 months in groups A2 (n = 25) and B (n = 24), respectively (p = 0.061). Grade 3 or worse adverse events were similar among groups in the safety population (p = 0.173). Conclusion: TACE with dicycloplatin was comparably safe and well tolerable as epirubicin alone in patients with unresectable HCC. Compared with epirubicin alone, significant improvement in ORR and DCR when dicycloplatin was applied, as well as prolonged PFS when dicycloplatin plus epirubicin was applied, was generated. Key Points: • To our knowledge, this is the first multicenter randomized trial to assess the efficacy and safety of TACE with dicycloplatin in patients with unresectable HCC. • This phase II trial showed that TACE with dicycloplatin alone or plus epirubicin was comparably safe and well tolerable as epirubicin alone. • Significant improvements in ORR, DCR when dicycloplatin was applied, and prolonged PFS when dicycloplatin plus epirubicin was applied were recorded compared with epirubicin alone. [ABSTRACT FROM AUTHOR]

Avian pathogenic Escherichia coli (APEC) is the main pathogens that inflict the poultry industry. Biofilm as the pathogenic factors of APEC, which can enhance the anti-host immune system of APEC and improve its survival in the environment. In order to screen for new genes related to APEC biofilm. The APEC strain APEC81 was used to construct a mutant library by Tn5 insertion mutagenesis. Moreover the 28 mutant strains with severely weakened biofilm were successfully screened from 1500 mutant strains by crystal violet staining, in which 17 genes were obtained by high-efficiency thermal asymmetric interlaced PCR. The reported genes include 3 flagella genes (fliS, fliD, and fliR), 4 curli fimbriae genes (csgD, csgA, csgF, and csgG) and 3 type 1 fimbriae genes (fimA, fimD, and fimC). The novel genes include 3 coenzyme genes (gltA, bglX, and mltF) and 4 putative protein genes (yehE, 07045, 11735, 11255). To investigate whether these 17 genes co-regulate the biofilm, the 17 identified genes were deleted from APEC strain APEC81. The results showed that except for the 11735 and 11255 genes, the deletion of 15 genes significantly reduced the biofilm formation ability of APEC81 (P < 0.05). The result of rdar (red, dry and rough) colony morphology showed that curli fimbriae genes (csgD, csgA, csgF, and csgG) and other functional genes (fimC, glxK, yehE, 07045, and 11255) affected the colony morphology. In particular, the hypothetical protein YehE had the greatest influence on the biofilm. It was predicted to have the same structure as the type 1 fimbria protein. When yehE was deleted, the fimE transcription was up-regulated, and the fimA and fimB transcription were down-regulated, resulting in a decrease in type 1 fimbriae. Hence, the yehE mutant significantly reduced the biofilm and the adhesion and invasion ability to cells (P < 0.05). This study identified 5 novel genes (gltA, bglX, mltF, yehE, and 07045) related to biofilm formation and confirmed that yehE affects biofilm formation by type 1 fimbriae, which will benefit further study of the mechanism of biofilm regulation in APEC. [ABSTRACT FROM AUTHOR]

Microbial indicators are often used to monitor microbial safety of aquatic environments. However, information regarding the correlation between microbial indicators and ecotoxicological factors such as potential pathogens and antibiotic resistance genes (ARGs) in anthropogenically impacted waters remains highly limited. Here, we investigated the bacterial community composition, potential pathogens, ARGs diversity, ARG hosts, and horizontal gene transfer (HGT) potential in urban river and wastewater samples from Chaohu Lake Basin using 16S rRNA and metagenomic sequencing. The composition of the microbial community and potential pathogens differed significantly in wastewater and river water samples, and the total relative abundance of fecal indicator bacteria was positively correlated with the total relative abundance of potential pathogens (p < 0.001 and Pearson's r = 0.758). Network analysis indicated that partial ARG subtypes such as dfrE, sul2, and PmrE were significantly correlated with indicator bacteria (p < 0.05 and Pearson's r > 0.6). Notably, Klebsiella was the indicator bacteria significantly correlated with 4 potential pathogens and 14 ARG subtypes. ARGs coexisting with mobile gene elements were mainly found in Thauera, Pseudomonas, Escherichia, and Acinetobacter. Next-generation sequencing (NGS) can be used to conduct preliminary surveys of environmental samples to access potential health risks, thereby facilitating water resources management. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute watery diarrhea and vomiting in unweaned piglets, and is associated with high mortality, thus causing severe economic losses in the pig industry. Currently, although attenuated vaccines are commonly used in commercial pig farms in China, they do not completely protect against all mutated wild-type strains. Existing nucleic acid assays have high sensitivity and specificity, but the complexity of the assay process and expensive instrumentation hinder disease detection. Here, reverse transcription–enzymatic recombinase amplification (RT-ERA) was combined with the CRISPR-Cas12a system to develop a rapid diagnostic method to distinguish PEDV wild-type strains from attenuated vaccine strains. The protocol used crRNA and RT-ERA amplification primers against open reading frame 3 (ORF3), followed by Cas12a/crRNA complex detection of predefined target sequences at 37 °C for 30 min, thus producing results visible to the naked eye under LED blue light. The assay is highly sensitive and specific, detecting as few as two copies of the target gene per test and showing no cross-reactivity with other porcine pathogens. Overall, this integrated RT-ERA pre-amplification and Cas12a/crRNA cleavage assay is a practical tool for reliable and rapid detection of PEDV for diagnostic differentiation. [ABSTRACT FROM AUTHOR]

Studies on biological functions of N6-methyladenosine (m6A) modification in mRNA have sprung up in recent years. We find m6A can positively regulate the glycolysis of cancer cells. Specifically, m6A-sequencing and functional studies confirm that pyruvate dehydrogenase kinase 4 (PDK4) is involved in m6A regulated glycolysis and ATP generation. The m6A modified 5′UTR of PDK4 positively regulates its translation elongation and mRNA stability via binding with YTHDF1/eEF-2 complex and IGF2BP3, respectively. Targeted specific demethylation of PDK4 m6A by dm6ACRISPR system can significantly decrease the expression of PDK4 and glycolysis of cancer cells. Further, TATA-binding protein (TBP) can transcriptionally increase the expression of Mettl3 in cervical cancer cells via binding to its promoter. In vivo and clinical data confirm the positive roles of m6A/PDK4 in tumor growth and progression of cervical and liver cancer. Our study reveals that m6A regulates glycolysis of cancer cells through PDK4. Dysregulation of N6-Methyladenosine (m6A) is associated with cancer progression. Here, authors show that m6A methylation of pyruvate dehydrogenase kinase 4 (PDK4) positively regulates its mRNA stability and translation, and consequently affects glycolysis in cancer cells [ABSTRACT FROM AUTHOR]

TGF-β1 is a main inducer of epithelial to mesenchymal transition (EMT). However, many breast cancer cells are not sensitive to the EMT induction by TGF-β1 alone. So far, the mechanisms underlying the induction of TGF-β1-insensitive breast cancer cells remains unclear. Here we report that TNF-α can induce EMT and invasiveness of breast cancer cells which are insensitive to TGF-β1. Intriguingly, TGF-β1 could cooperate with TNF-α to promote the EMT and invasiveness of breast cancer cells. The prolonged co-stimulation with TGF-β1 and TNF-α could enhance the sustained activation of Smad2/3, p38 MAPK, ERK, JNK and NF-κB pathways by enhancing the activation of TAK1, which was mediated by the gradually up-regulated TβRs. Except for JNK, all of these pathways were required for the effects of TGF-β1 and TNF-α. Importantly, the activation of p38 MAPK and ERK pathways resulted in a positive feed-back effect on TAK1 activation by up-regulating the expression of TβRs, favoring the activation of multiple signaling pathways. Moreover, SLUG was up-regulated and required for the TGF-β1/TNF-α-induced EMT and invasiveness. In addition, SLUG could also enhance the activation of signaling pathways by promoting TβRII expression. These findings suggest that the up-regulation of TβRs contributes to the sustained activation of TAK1 induced by TGF-β1/TNF-α and the following activation of multiple signaling pathways, resulting in EMT and invasiveness of breast cancer cells. [ABSTRACT FROM AUTHOR]

The subgrain effect of NiTi shape memory alloy during canning compression at 400 °C is investigated through electron back-scattered diffraction (EBSD) experiment, transmission electron microscope (TEM) experiment and crystal plasticity finite element (CPFE) simulation in explicit consideration of subgrain within each grain. Experimental investigations based on TEM and EBSD measurements confirm that the formation of subgrain actually results from the dislocation motion during canning compression. Numerical simulations based on the constructed polycrystalline models with various subgrains are used to investigate the subgrain effect during canning compression from a different point of view. In terms of texture evolution, subgrain effect does not change the tendency of texture evolution, but it contributes to the dispersed distribution with respect to the deformed grain/subgrain orientations. As for accumulative shear strain, subgrain effect contributes to sustaining larger plastic strain inside each grain, and it also results in the strain concentration near grain boundaries. With respect to von Mises stress, the subgrain effect facilitates the ease of stress concentration near grain boundaries and it contributes to possessing a homogeneous stress distribution within the inner part of each grain. [ABSTRACT FROM AUTHOR]

The approximately equimolar ratio AlCrNiSiTi multi-principal element alloy (MPEA) coatings were fabricated by laser cladding on Ti-6Al-4V (Ti64) alloy. Scanning electron microscopy (SEM), equipped with an energy-dispersive spectroscopy (EDS), and X-ray diffraction (XRD) were used to characterize the microstructure and composition. Investigations show that the coatings consist of (Ti, Cr)Si and NiAl phases, formed by in situ reaction. The phase composition is initially explicated according to obtainable binary and ternary phase diagrams, and the formation Gibbs energy of TiSi, VSi and CrSi. Dry sliding reciprocating friction and wear tests of the AlCrNiSiTi coating and Ti64 alloy substrate without coating were evaluated. A surface mapping profiler was used to evaluate the wear volume. The worn surface was characterized by SEM-EDS. The hardness and wear resistance of the AlCrNiSiTi coating are well compared with that of the basal material (Ti64). The main wear mechanism of the AlCrNiSiTi coating is slightly adhesive transfer from GCr15 counterpart, and a mixed layer composed of transferred materials and oxide is formed. [ABSTRACT FROM AUTHOR]

Vascular dementia (VD) is defined as a progressive neurodegenerative disease of cognitive decline, attributable to cerebrovascular factors. Numerous studies have demonstrated that chronic cerebral hypoperfusion (CCH) is associated with the initiation and progression of VD and Alzheimer's disease (AD). Suitable animal models were established to replicate such pathological condition in experimental research, which contributes largely to comprehending causal relationships between CCH and cognitive impairment. The most widely used experimental model of VD and CCH is permanent bilateral common carotid artery occlusion in rats. In CCH models, changes of learning and memory, cerebral blood flow (CBF), energy metabolism, and neuropathology initiated by ischemia were revealed. However, in order to achieve potential therapeutic targets, particular mechanisms in cognitive and neuropathological changes from CCH to dementia should be investigated. Recent studies have shown that hypoperfusion resulted in a chain of disruption of homeostatic interactions, including oxidative stress, neuroinflammation, neurotransmitter system dysfunction, mitochondrial dysfunction, disturbance of lipid metabolism, and alterations of growth factors. Evidence from experimental studies that elucidate the damaging effects of such imbalances suggests their critical roles in the pathogenesis of VD. The present review provides a summary of the achievements in mechanisms made with the CCH models, permits an understanding of the causative role played by CCH in VD, and highlights preventative and therapeutic prospects. [ABSTRACT FROM AUTHOR]

A generalized (3+1)-dimensional nonlinear wave is investigated, which describes many nonlinear phenomena in liquid containing gas bubbles. In this paper, a lucid and systematic approach is proposed to systematically study the complete integrability of the equation by using Bell's polynomials scheme. Its bilinear equation, N-soliton solution and Bäcklund transformation with explicit formulas are successfully structured, which can be reduced to the analogues of (3+1)-dimensional KP equation, (3+1)-dimensional nonlinear wave equation and Korteweg-de Vries equation, respectively. Moreover, the infinite conservation laws of the equation are found by using its Bäcklund transformation. All conserved densities and fluxes are presented with explicit recursion formulas. Furthermore, by employing Riemann theta function, the one- and two-periodic wave solutions for the equation are constructed well. Finally, an asymptotic relation is presented, which implies that the periodic wave solutions can be degenerated to the soliton solutions under some special conditions. [ABSTRACT FROM AUTHOR]

Under investigation in this paper is a generalized $$(2+1)$$ -dimensional Korteweg-de Vries equation, which could describe many nonlinear phenomena in plasma physics. By virtue of the Bell's polynomials, a straightforward way is presented to succinctly construct its bilinear form, bilinear Bäcklund transformation and Lax pairs. Once the Lax pairs obtained, the important infinite conservation laws of the equation are directly found. Moreover, based on the bilinear formalism, we construct the Riemann theta function periodic wave solutions and soliton solutions. Finally, the relationships between the periodic wave solutions and soliton solutions are strictly established, and the asymptotic behavior of the periodic waves is also presented with detailed proof. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to introduce a novel combined hemipelvic endoprosthesis for pelvic reconstruction after Enneking type I/II/IV resection and to evaluate the biomechanical properties of the endoprosthesis using finite element analysis.Methods: A three-dimensional finite element model of the postoperative pelvis was developed based on computed tomography (CT) images of the patient with the best post-operative limb function. A force of 400 N was applied along the longitudinal axis of the normal and post-operative pelvis for two positions: standing on two feet and sitting. Stress-distribution analysis was performed in both positions, and results were compared. Prosthesis improvements were simulated by intervertebral fusion and extra screw fixation.Results: In the normal pelvis, stress distributions were mostly concentrated on the superior area of the acetabulum, arcuate line, sacroiliac joint and sacral midline in both static conditions, and peak stresses of 1.52 MPa and 4.53 MPa were observed at the superior area of the greater sciatic notch and ischial tuberosity, respectively. For the reconstructed hemipelvis, stress distributions were concentrated on the connecting rods of the acetabular component and the proximal segment of the pedicle rods, and peak stresses of 252 MPa and 213 MPa were observed on the proximal pedicle rods of the fourth lumbar vertebra for standing and sitting, respectively. Interbody fusion of the fourth and fifth lumbar vertebrae and extra screw fixation to the sacrum decreased the peak stresses by 33.0 % and 18.3 % while standing and by 10.8 % and 6.6 % while sitting.Conclusion: Reconstruction with combined hemipelvic endoprosthesis after types I/II/IV resection of the pelvis fulfilled physiological and biomechanical demands of the hemipelvis and yielded good biomechanical characteristics. [ABSTRACT FROM AUTHOR]

Prions are the only convincingly demonstrated proteinaceous infectious particle, yet recent studies find that amyloid-β peptide (Aβ) aggregates are capable of self-propagation, which induces amyloidosis pathology in Alzheimer's disease (AD) model mice that is similar to the self-propagation phenomenon of prions in neurons. Gliosis is a common hallmark of AD and prion diseases, in which activated microglia accumulate around abnormal protein deposits. Analyses of the characteristics of activated microglia induced by Aβ in comparison with those induced by prions will provide new insight into the pathogenesis of AD. Therefore, we compared the characteristics of BV-2 cells (model microglia) activated by Aβ fibrillar peptides (Aβ1-42) and prions (PrP106-126). Aβ1-42 and PrP106-126, as well as the supernatants of the media collected from BV-2 cells cocultured with Aβ1-42 and PrP106-126, were potent activators of BV-2 microglial activity, but the chemotaxis index (CI) induced by Aβ1-42 was significantly higher than that induced by PrP106-126 at each concentration. Aβ1-42 and PrP106-126 increased the proliferation index (PI) and upregulated monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta 1 (TGF-β1) expression after 12 h of exposure. Our results show that Aβ activates microglia and regulates microglial protein expression in a manner similar to prions and, thus, provide new insight into the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

A Cu-50Cr alloy was treated by the high current pulsed electron beam (HCPEB) at 20 and 30 keV with pulse numbers ranging from 1 to 100. Surface morphologies and microstructures of specimens before and after the treatments were investigated by employing scanning electron microscopy and X-ray diffraction. Results show that the HCPEB technique is able to induce remarkable surface modifications for the Cu-50Cr alloy. Cracks in Cr phases appear even after one-pulse treatment and their density always increases with the pulse number. Formation reason for these cracks is attributed to quasi-static thermal stresses accumulated along the specimen surface. Craters with typical morphologies are formed due to the dynamic thermal field induced by the HCPEB and they are found to prefer the sites near cracks or boundaries between neighboring Cr phases. Another microstructural characteristic produced by the HCPEB is the fine Cr spheroids, which are determined to be due to occurrence of liquid phase separation in the Cu-50Cr alloy. Finally, a general microstructural evolution profile that incorporates various HCPEB-induced surface features is tentatively outlined. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) play important roles in human diseases including vascular disease. Given the large number of lncRNAs, however, whether the majority of them are associated with vascular disease remains unknown. For this purpose, here we present a genomic location based bioinformatics method to predict the lncRNAs associated with vascular disease. We applied the presented method to globally screen the human lncRNAs potentially involved in vascular disease. As a result, we predicted 3043 putative vascular disease associated lncRNAs. To test the accuracy of the method, we selected 10 lncRNAs predicted to be implicated in proliferation and migration of vascular smooth muscle cells (VSMCs) for further experimental validation. The results confirmed that eight of the 10 lncRNAs (80%) are validated. This result suggests that the presented method has a reliable prediction performance. Finally, the presented bioinformatics method and the predicted vascular disease associated lncRNAs together may provide helps for not only better understanding of the roles of lncRNAs in vascular disease but also the identification of novel molecules for the diagnosis and therapy of vascular disease. [ABSTRACT FROM AUTHOR]

We study a generalization of the vertex cover problem. For a given graph with weights on the vertices and an integer k, we aim to find a subset of the vertices with minimum total weight, so that at least k edges in the graph are covered. The problem is called the k-partial vertex cover problem. There are some 2-approximation algorithms for the problem. In the paper we do not improve on the approximation ratios of the previous algorithms, but we derive an iterative rounding algorithm. We present our technique in two algorithms. The first is an iterative rounding algorithm and gives a (2 + $\tfrac{Q} {{OPT}}$)-approximation for the k-partial vertex cover problem where Q is the largest finite weight in the problem definition and OPT is the optimal value for the instance. The second algorithm uses the first as a subroutine and achieves an approximation ratio of 2. [ABSTRACT FROM AUTHOR]

Transmissible spongiform encephalopathies (TSEs) and Alzheimer's disease (AD) belong to a growing family of neurodegenerative disorders that is characterized by the generation of toxic protein aggregates in affected brains (PrP and Aβ in TSEs and AD, respectively). To better understand how protein aggregates can modulate microglial processes in these diseases, we treated BV-2 microglia with PrP or Aβ peptides individually at three different concentrations (25-100 μM PrP and 2.5-10 μM Aβ) or with a mixture of PrP and Aβ peptides at specified concentrations for 6-24 h. BV-2 microglia chemotaxis, proliferation, and monocyte chemoattractant protein-1 and transforming growth factor-β1 (TGF-β1) secretion were measured and compared between treatments. The results demonstrate that PrP and Aβ peptides induce increases in all four parameters from 6 to 12 h. However, the measured indices plateaued beyond 12 h in BV-2 cells treated >50 μM PrP or >5 μM Aβ, with the exception of TGF-β1 secretion, which continued to increase gradually. Overall, the results of this study indicate that these two peptides may mutually inhibit microglial chemotaxis and proliferation simultaneously via changes induced at the protein level. [ABSTRACT FROM AUTHOR]

Aim:To investigate the mechanisms underlying the protective effects of sodium tanshinone IIA sulfonate (STS) in an ischemia-reperfusion (I/R)-induced rat myocardial injury model.Methods:Male SD rats were iv injected with STS, STS+LY294002 or saline (NS) for 15 d. Then the hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function, infarction size and area at risk were assessed. Cell apoptosis was evaluated with TUNEL staining, DNA laddering and measuring caspase-3 activity. In addition, isolated cardiomyocytes of neonatal rats were pretreated with the above drugs, then exposed to H2O2 (200 mol/L) for 1 h. Cell apoptosis was detected using flow cytometric assay. The levels of p-Akt, p-FOXO3A and Bim were examined with immunoblotting.Results:Compared to NS group, administration of STS (20 mg/kg) significantly reduced myocardial infarct size (40.28%±5.36% in STS group vs 59.52%±7.28% in NS group), and improved the myocardial function as demonstrated by the increased values of dp/dtmax, LVDP and coronary flow at different reperfusion time stages. Furthermore, STS significantly decreased the rate of apoptotic cells (15.11%±3.71% in STS group vs 38.21%±7.83% in NS group), and reduced caspase-3 activity to nearly a quarter of that in NS group. Moreover, STS significantly increased the phosphorylation of Akt and its downstream target FOXO3A, and decreased the expression of pro-apoptotic gene Bim. Co-treatment with the PI3K inhibitor LY294002 (40 mg/kg) partially countered the protective effects induced by STS treatment. In isolated cardiomyocytes, STS exerted similar protective effects as shown in the ex vivo I/R model.Conclusion:STS pretreatment reduces infarct size and improves cardiac function in an I/R-induced rat myocardial injury model via activation of Akt/FOXO3A/Bim-mediated signal pathway. [ABSTRACT FROM AUTHOR]

Tau is a microtubule-associated protein and expressed in normal breast epithelial cells and breast cancer. Tau expression in breast cancer may be important for chemotherapy optimization. This study is to investigate the expression of Tau in advanced breast cancer and its significance in taxane-containing neoadjuvant chemotherapy. Levels of Tau protein in advanced breast cancer were detected immunohistochemically. The chemotherapeutic efficacy indexes in Tau group, which includes the remission rate, Miller-Payne pathological reactive grade, and pathologic complete response rate, were improved compared with that in Tau group. There was difference in the efficacy indexes among ER+ subgroups but not among ER− patients. In addition, Tau expression was positively correlated ( r = 0.32, P < 0.00). In multivariate analysis, when age, clinical stage, postoperative lymph node metastasis, ER, PR, HER2, Ki-67, TP53, or Tau status were included, postoperative lymph node metastasis and Tau-negative status were identified as independent predictors of pathologic complete response. In conclusion, negative Tau protein expression may be an effective predictor for taxane-containing neoadjuvant chemotherapy, especially in ER+ subgroups. Further study on the molecular mechanism and utility of Tau for individualizing adjuvant chemotherapy is warranted. [ABSTRACT FROM AUTHOR]

Recently, the {10-12} twin variants activated during dynamic plastic deformation (DPD) of Mg alloy have been investigated by analyzing their Schmid factors (SFs), and their contributions to deformation have been calculated. During DPD of Mg–3%Al–1%Zn alloy, different {10-12} variants are generated relative to their SFs when initial grains have defined orientations with one a-axis of the crystal lattice at roughly 0 or 30° from the compression direction. The volume fraction of twins deeply influences the strain accommodated by twinning. The {10-12} variant pair with the maximum SF accommodated about 90% of the twinning strain. Its high volume fraction indicated that both nucleation and growth mechanisms played important roles in the strain accommodation. Other {10-12} variants had a lower volume fraction and accommodated twinning strain mainly by twin nucleation and made a lesser contribution to the total deformation. [ABSTRACT FROM AUTHOR]

Aim:To investigate the effects of the major component of high-density lipoprotein apolipoprotein A-I (apoA-I) on the development of atherosclerosis in LPS-challenged ApoE−/− mice and the underlying mechanisms.Methods:Male ApoE-KO mice were daily injected with LPS (25 μg, sc) or PBS for 4 weeks. The LPS-challenged mice were intravenously injected with rAAV-apoA-I-GFP or rAAV-GFP. After the animals were killed, blood, livers and aortas were collected for biochemical and histological analyses. For ex vivo experiments, the abdominal cavity macrophages were harvested from each treatment group of mice, and cultured with autologous serum, then treated with LPS.Results:Chronic administration of LPS in ApoE−/− mice significantly increased the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1), increased infiltration of inflammatory cells, and enhanced the development of atherosclerosis. In LPS-challenged mice injected with rAAV-apoA-I-GFP, viral particles and human apoA-I were detected in the livers, total plasma human apoA-I levels were grammatically increased; HDL-cholesterol level was significantly increased, TG and TC were slightly increased. Furthermore, overexpression of apoA-I significantly suppressed the expression of proinflammatory cytokines, reduced the infiltration of inflammatory cells, and decreased the extent of atherosclerotic lesions. Moreover, overexpression of apoA-I significantly increased the expression of the cytokine mRNA-destabilizing protein tristetraprolin (TTP), and phosphorylation of JAK2 and STAT3 in aortas. In ex vivo mouse macrophages, the serum from mice overexpressing apoA-I significantly increased the expression of TTP, accompanied by accelerated decay of mRNAs of the inflammatory cytokines.Conclusion:ApoA-I potently suppresses LPS-induced atherosclerosis by inhibiting the inflammatory response possibly via activation of STAT3 and upregulation of TTP. [ABSTRACT FROM AUTHOR]

Single-stranded DNA (ssDNA) aptamers against four organophosphorus pesticides (phorate, profenofos, isocarbophos and omethoate) were simultaneously isolated from an immobilized random ssDNA library by systematic evolution of ligands by exponential enrichment (SELEX) technique. After 12 rounds of in vitro selection, five ssDNA aptamer candidates were selected and their binding affinities were identified by a novel method using a molecular beacon. Two of the five ssDNA sequences, SS2-55 and SS4-54, demonstrated higher affinities and specificities to the four organophosphorus pesticides. They were defined as broad-spectrum aptamers binding to four different targets and their simulated secondary structures showed highly distinct features with typical stem and loop structures. The dissociation constant of SS2-55 and SS4-54 binding to the four organophosphorus pesticides ranged from 0.8 to 2.5 μM. These aptamers offered application potential in the analysis and/or neutralization of the residues of the four organophosphorus pesticides. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the predictive values of gene expressions of ribonucleotide reductase M1 ( RRM1) and breast cancer susceptibility gene 1 ( BRCA1) in peripheral blood from Chinese patients with non-small-cell lung cancer (NSCLC) treated with gemcitabine plus platinum. Methods: Forty Chinese patients with advanced NSCLC were recruited and received gemcitabine 1 200 mg/m on Days 1 and 8 plus carboplatin AUC 5 on Day 1. RRM1 and BRCA1 expression levels in peripheral blood were detected by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Kaplan-Meier survival curve and log-rank test were performed to evaluate the correlation between gene expression and overall survival for these subjects. Results: No correlation was observed between gene expression of RRM1 and that of BRCA1 ( P>0.05), but there was a strong correlation between the expression of RRM1 and the response to chemotherapy ( P=0.003). Subjects with low RRM1 expression levels in peripheral blood had longer survival time than those with high RRM1 expression levels (16.95 vs. 12.76 months, log-rank 3.989, P=0.046). However, no significant association between BRCA1 expression levels and survival time was found (16.80 vs. 13.77 months, log-rank 0.830, P=0.362). Conclusions: Patients with low RRM1 expression levels in peripheral blood have a greater response to chemotherapy and longer survival time. Advanced NSCLC patients with low RRM1 expression levels may benefit from gemcitabine plus platinum therapy. RRM1 mRNA expression in peripheral blood could be used to predict the prognosis of NSCLC treated by gemcitabine and platinum. [ABSTRACT FROM AUTHOR]

More than a quarter of patients with spinal cord injury develop syringomyelia, often with progressive neurological deficit. Treatment options remain limited and long-term failure rates are high. The current poor understanding is impeding development of improved therapies. The source and route of fluid flow into syringes has been investigated using cerebrospinal fluid (CSF) tracers. Previous work using a model of canalicular syringomyelia has shown that fluid enters the dilated central canal from perivascular spaces. The aim of this study was to determine the source and route of fluid flow in an animal model of extracanalicular (post-traumatic) syringomyelia. A model of post-traumatic syringomyelia was established in 25 Sprague-Dawley rats with intraparenchymal injections of quisqualic acid and kaolin-induced arachnoiditis. Rats survived for 6 weeks before injection of the CSF tracer horseradish peroxidase into the cisterna magna. Examination of the spatial distribution of horseradish peroxidase at 0, 3, 5, 10, or 20 min after injection was used to determine the route of fluid flow. Horseradish peroxidase rapidly spread to the ventromedian fissure, perivascular spaces, central canal, and extracanalicular syrinx. Flow occurred into the syrinx prior to significant perivascular flow in the rostral spinal cord. Preferential flow into the syrinx occurred from the perivascular spaces of the central penetrating branches of the anterior spinal artery in the grey matter. Transparenchymal flow into the syrinx was less prominent than perivascular flow. This is the first report of fluid flow within the spinal cord in a model of post-traumatic syringomyelia. Fluid from perivascular spaces moves preferentially into extracanalicular syringes and the surrounding parenchyma. Obstruction to CSF flow and loss of compliance from traumatic arachnoiditis might potentiate fluid flow in the perivascular space. [ABSTRACT FROM AUTHOR]

Rearing systems play an important role in animal welfare, health and the composition of the gut microbiome. Therefore, the purpose of this study was to investigate the effects of different rearing systems on the composition and function of cecal microbiota in chickens. The 120-day-old Lohmann hens of cage rearing systems (CRS) and free-range systems (FRS) were studied. The cecal bacterial populations of hens were surveyed by high-throughput sequencing (HTS) of the bacterial 16S rRNA hypervariable region V3–V4 combined with metagenomic sequencing analysis. The 16S rRNA sequencing analysis showed that the cecal microbiota differed between the FRS and CRS. The three most abundant bacteria phyla in the two systems were the Bacteroidetes (> 48%), Firmicutes (> 37%), and Proteobacteria (> 6%), the Deferribacteres (> 2.4%) were found in FRS and almost absent in CRS (< 0.01%). The three most abundant genera were the Bacteroides, Rikenellaceae_RC9, and Faecalibacterium, and we found relative abundance of the Parabacteroides (P < 0.05), Prevotellaceae_Ga6A1 (P < 0.01), unclassified Proteobacteria (P < 0.05), and unclassified Spirochaetaceae (P < 0.01) was greater in FRS, whereas abundance of Faecalibacterium, Ruminococcaceae, and Helicobacter was greater in CRS (P < 0.05). Functional gene classification of metagenomic sequencing suggested that energy production and conversion, carbohydrate transport and metabolism, as well as amino acid transport and metabolism were significantly more abundant in FRS, and we identified a range of antibiotic resistance categories in gut microbes of hens reared under both systems. We confirmed differences in microbe gut composition and function in hens reared using two contrasting systems, and ARGs were also identified in the microbiota of these hens. This work has produced new data for laying hens in different production systems and increased the understanding of intestinal microorganisms in laying hens. [ABSTRACT FROM AUTHOR]