Advanced progress of the relationship between PCSK9 monoclonal antibodies and hyperglycemic adverse events

Purpose of ReviewLong-term use of statins had been confirmed to cause an increase in hyperglycemic adverse events (HAEs), whose mechanism has been well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (PCSK9-mAbs), a kind of new lipid-lowering drug, can effectively reduce plasma low-density lipoprotein cholesterol levels in patients with CHD and have been widely used. However, animal experiments, Mendelian randomization studies, clinical researches and Meta-analyses which focused on the relationship between PCSK9-mAbs and HAEs had reached different conclusions, which has attracted great attention from clinicians.Recent FindingsThe newest FOURIER-OLE randomized controlled trial followed PCSK9-mAbs users for over 8 years, whose results suggested that long-term use of PCSK9-mAbs did not increase the incidence of HAEs. Newest Meta-analyses also indicated that there was no relationship between PCSK9-mAbs and NOD. Meanwhile, genetic polymorphisms and variants related to PCSK9 might have effects on HAEs.ConclusionAccording to the results of current studies, there is no significant relationship between PCSK9-mAbs and HAEs. However, longer-term follow-up studies are still needed to confirm it. Although PCSK9 genetic polymorphisms and variants may affect the possible occurrence of HAEs, there is no need to perform relevant genetic testing before applying PCSK9-mAbs

RefSelect: a reference sequence selection algorithm for planted (l, d) motif search

Background The planted (l, d) motif search (PMS) is an important yet challenging problem in computational biology. Pattern-driven PMS algorithms usually use k out of t input sequences as reference sequences to generate candidate motifs, and they can find all the (l, d) motifs in the input sequences. However, most of them simply take the first k sequences in the input as reference sequences without elaborate selection processes, and thus they may exhibit sharp fluctuations in running time, especially for large alphabets. Results In this paper, we build the reference sequence selection problem and propose a method named RefSelect to quickly solve it by evaluating the number of candidate motifs for the reference sequences. RefSelect can bring a practical time improvement of the state-of-the-art pattern-driven PMS algorithms. Experimental results show that RefSelect (1) makes the tested algorithms solve the PMS problem steadily in an efficient way, (2) particularly, makes them achieve a speedup of up to about 100× on the protein data, and (3) is also suitable for large data sets which contain hundreds or more sequences. Conclusions The proposed algorithm RefSelect can be used to solve the problem that many pattern-driven PMS algorithms present execution time instability. RefSelect requires a small amount of storage space and is capable of selecting reference sequences efficiently and effectively. Also, the parallel version of RefSelect is provided for handling large data sets

Universal scaling relation in high-temperature superconductors

Scaling laws express a systematic and universal simplicity among complex systems in nature. For example, such laws are of enormous significance in biology. Scaling relations are also important in the physical sciences. The seminal 1986 discovery of high transition-temperature (high-T_c) superconductivity in cuprate materials has sparked an intensive investigation of these and related complex oxides, yet the mechanism for superconductivity is still not agreed upon. In addition, no universal scaling law involving such fundamental properties as T_c and the superfluid density \rho_s, a quantity indicative of the number of charge carriers in the superconducting state, has been discovered. Here we demonstrate that the scaling relation \rho_s \propto \sigma_{dc} T_c, where the conductivity \sigma_{dc} characterizes the unidirectional, constant flow of electric charge carriers just above T_c, universally holds for a wide variety of materials and doping levels. This surprising unifying observation is likely to have important consequences for theories of high-T_c superconductivity.Comment: 11 pages, 2 figures, 2 table

ATP-Binding Cassette Transporter G5 and G8 Polymorphisms and Several Environmental Factors with Serum Lipid Levels

The association of ATP-binding cassette (ABC) transporter single nucleotide polymorphisms (SNPs) and serum lipid profiles is inconsistent. The present study was undertaken to detect the association of ABCG5/G8 SNPs and several environmental factors with serum lipid levels.Genotyping of the ABCG5 (rs4131229 and rs6720173) and ABCG8 (rs3806471 and rs4148211) SNPs was performed in 719 unrelated subjects of Mulao nationality and 782 participants of Han nationality. There were no differences in the genotypic and allelic frequencies of four SNPs between the two ethnic groups besides the genotypic frequencies of rs4131229 SNP in Han. The levels of triglyceride (TG), apolipoprotein (Apo) A1, and ApoA1/ApoB ratio (rs4131229); low-density lipoprotein cholesterol (LDL-C) and ApoB (rs6720173); high-density lipoprotein cholesterol (HDL-C), ApoA1, ApoB, and ApoA1/ApoB ratio (rs3806471); and HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han were different among their genotypes (P<0.05-0.001). The levels of LDL-C (rs6720173) and ApoA1 (rs3806471) in Mulao were also different among their genotypes (P<0.05 for each). The levels of TC, TG, HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4131229); LDL-C and ApoB (rs6720173); HDL-C, ApoA1, and ApoA1/ApoB ratio (rs3806471); and TG, HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han males; and ApoA1/ApoB ratio (rs4131229); LDL-C, ApoB, and ApoA1/ApoB ratio (rs3806471); HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han females were different between the genotypes (P<0.05-0.001). The levels of LDL-C in Mulao females were also different between GG and GC/CC genotypes of rs6720173 (P<0.05). The correlation between serum lipid parameters and genotypes of four SNPs was observed in Han, especially in Han males. Serum lipid parameters were also correlated with several environmental factors.The associations of four ABCG5/G8 SNPs and serum lipid levels are different between the Mulao and Han populations, or between males and females, suggesting that there may be a racial/ethnic- and/or sex-specific association between ABCG5/G8 SNPs and some serum lipid parameters

Face mask integrated with flexible and wearable manganite oxide respiration sensor

Face masks are key personal protective equipment for reducing exposure to viruses and other environmental hazards such as air pollution. Integrating flexible and wearable sensors into face masks can provide valuable insights into personal and public health. The advantages that a breath-monitoring face mask requires, including multi-functional sensing ability and continuous, long-term dynamic breathing process monitoring, have been underdeveloped to date. Here, we design an effective human breath monitoring face mask based on a flexible La0.7Sr0.3MnO3 (LSMO)/Mica respiration sensor. The sensor’s capabilities and systematic measurements are investigated under two application scenes, namely clinical monitoring mode and daily monitoring mode, to monitor, recognise, and analyse different human breath status, i.e., cough, normal breath, and deep breath. This sensing system exhibits super-stability and multi-modal capabilities in continuous and long-time monitoring of the human breath. We determine that during monitoring human breath, thermal diffusion in LSMO is responsible for the change of resistance in flexible LSMO/Mica sensor. Both simulated and experimental results demonstrate good discernibility of the flexible LSMO/Mica sensor operating at different breath status. Our work opens a route for the design of novel flexible and wearable electronic devices

Cancer risk associated single nucleotide polymorphisms of mitochondrial D-loop and 8-hydroxy-2'-deoxyguanosine levels in gastric cancer

The accumulation of mutations and single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) is related to gastric carcinogenesis. To evaluate the potential relationships between DNA damage and D-loop SNPs, we measured the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the gastric cancer tissue by immmunostaining. Our data showed that the gastric cancer susceptibility SNP of 16519C was associated with higher 8-OHdG levels. Taken together, the cancer-risk associated D-loop SNPs might initiate carcinogenesis through increasing oxidative damage

Single nucleotide polymorphisms at the microRNA-binding site of KIAA0423 are associated with colorectal cancer

MicroRNAs (miRNAs) binding to the 3′-untranslated regions (3′UTRs) of messenger RNAs to mediate translation and thereby regulate cell differentiation, apoptosis and tumorigenesis. Single nucleotide polymorphisms (SNPs) in the 3′UTRs of genes would alter the binding affinity between targeted genes and miRNA so as to change individual gene expression. We genotyped miRNA-binding-site SNPs in a case-control study with sporadic colorectal cancer (CRC) patients to identify CRC risk associated SNPs. Five miRNA-binding-site SNPs located in the 3′UTR of KRT81 (rs3660), RYR3 (rs1044129), KIAA0423 (rs1053667), C14orf101 (rs4901706) and GOLGA7 (rs11337) were genotyped in CRC patients, using polymerase chain reaction–ligase detection reaction (PCR–LDR) methods. Renilla luciferase reporter assays were used to measure the binding affinity between miRNA and the targeted gene. The χ2 test was used to study the association between carriership of miRNA-binding-site SNPs and CRC risk. The SNP of rs1053667 located in the 3’UTR of KIAA0423 gene was identified to be associated to CRC cancer risk, with the TT allele being associated with a 2.030-fold increased risk for CRC than that associated with the C/T+C/C genotype (odds ratio of 2.030; 95% confidence interval of 1.314–3.136; P < 0.01). The reduced Renilla luciferase activity of rs1053667 TT type comparing with that of CC genotype also demonstrated the different binding affinity of rs1053667 SNPs to the corresponding miRNA. The miRNA-binding-site SNP of rs1053667 in the KIAA0423 gene could be associated with risk of CRC

Quaternary history of the pine processionary moth: role of topography and host tree in shaping the population genetic structure

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