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Background Outdoor air pollution has been found to trigger systemic inflammatory responses and aggravate the activity of certain rheumatic diseases. However, few studies have explored the influence of air pollution on the activity of ankylosing spondylitis (AS). As patients with active AS in Taiwan can be reimbursed through the National Health Insurance programme for biological therapy, we investigated the association between air pollutants and the initiation of reimbursed biologics for active AS. Methods Since 2011, hourly concentrations of ambient air pollutants, including PM2.5, PM10, NO2, CO, SO2, and O3, have been estimated in Taiwan. Using Taiwanese National Health Insurance Research Database, we identified patients with newly diagnosed AS from 2003 to 2013. We selected 584 patients initiating biologics from 2012 to 2013 and 2336 gender-, age at biologic initiation-, year of AS diagnosis- and disease duration-matched controls. We examined the associations of biologics initiation with air pollutants exposure within 1 year prior to biologic use whilst adjusting for potential confounders, including disease duration, urbanisation level, monthly income, Charlson comorbidity index (CCI), uveitis, psoriasis and the use of medications for AS. Results are shown as adjusted odds ratio (aOR) with 95% confidence intervals (CIs). Results The initiation of biologics was associated with exposure to CO (per 1 ppm) (aOR, 8.57; 95% CI, 2.02–36.32) and NO2 (per 10 ppb) (aOR, 0.23; 95% CI, 0.11–0.50). Other independent predictors included disease duration (incremental year, aOR, 8.95), CCI (aOR, 1.31), psoriasis (aOR, 25.19), use of non-steroidal anti-inflammatory drugs (aOR, 23.66), methotrexate use (aOR, 4.50; 95% CI, 2.93–7.00), sulfasalazine use (aOR, 12.16; 95% CI, 8.98–15.45) and prednisolone equivalent dosages (mg/day, aOR, 1.12). Conclusions This nationwide, population-based study revealed the initiation of reimbursed biologics was positively associated with CO levels, but negatively associated with NO2 levels. Major limitations included lack of information on individual smoking status and multicollinearity amongst air pollutants.

Artificial molecular machines have captured the imagination of researchers, given their clear potential to mimic and influence human life. Key to behavior simulation is to reproduce the specific properties of physical or abstract systems. Dice throwing, as a stochastic model, is commonly used for result judgment or plan decision in real life. In this perspective we utilize DNA cube framework for the design of a dice device at the nanoscale to reproduce probabilistic events in different situations: equal probability, high probability, and low probability. We first discuss the randomness of DNA cube, or dice, adsorbing on graphene oxide, or table, and then explore a series of events that change the probability through the way in which the energy released from entropy-driven strand displacement reactions or changes in intermolecular forces. As such, the DNA nano-dice system provides guideline and possibilities for the design, engineering, and quantification of behavioral probability simulation, a currently emerging area of molecular simulation research.

Wild animals may encounter multiple challenges especially food shortage and altered diet composition in their suboptimal ranges. Yet, how the gut microbiome responds to dietary changes remains poorly understood. Prior studies on wild animal microbiomes have typically leaned upon relatively coarse dietary records and individually unresolved fecal samples. Here, we conducted a longitudinal study integrating 514 time-series individually recognized fecal samples with parallel fine-grained dietary data from two Skywalker hoolock gibbon (Hoolock tianxing) groups populating high-altitude mountainous forests in western Yunnan Province, China. 16S rRNA gene amplicon sequencing showed a remarkable seasonal fluctuation in the gibbons’ gut microbial community structure both across individuals and between the social groups, especially driven by the relative abundances of Lanchnospiraceae and Oscillospiraceae associated with fluctuating consumption of leaf. Metagenomic functional profiling revealed that diverse metabolisms associated with cellulose degradation and short-chain fatty acids (SCFAs) production were enriched in the high-leaf periods possibly to compensate for energy intake. Genome-resolved metagenomics further enabled the resolving metabolic capacities associated with carbohydrate breakdown among community members which exhibited a high degree of functional redundancy. Our results highlight a taxonomically and functionally sensitive gut microbiome actively responding to the seasonally shifting diet, facilitating the survival and reproduction of the endangered gibbon species in their suboptimal habitats.

Acute myeloid leukemia (AML) is a fast-growing and highly fatal blood cancer, and recent research has shown that targeting metabolism may be a promising therapeutic approach for treating AML. One promising target is the human mitochondrial NAD(P)+-dependent malic enzyme (ME2), which is involved in the production of pyruvate and NAD(P)H and the regulation of the NAD+/NADH redox balance. Inhibition of ME2 via silencing ME2 or utilizing its allosteric inhibitor disodium embonate (Na2EA) causes a decrease in pyruvate and NADH, leading to a decrease in producing ATP via cellular respiration and oxidative phosphorylation. ME2 inhibition also decreases NADPH levels, resulting in an increase in reactive oxygen species (ROS) and oxidative stress, which ultimately leads to cellular apoptosis. Additionally, ME2 inhibition reduces pyruvate metabolism and the biosynthetic pathway. ME2 silencing inhibits the growth of xenotransplanted human AML cells, and the allosteric ME2 inhibitor Na2EA demonstrates antileukemic activity against immune-deficient mice with disseminated AML. Both of these effects are a result of impaired energy metabolism in mitochondria. These findings suggest that the targeting ME2 may be an effective strategy for treating AML. Overall, ME2 plays an essential role in energy metabolism of AML cells, and its inhibition may offer a promising approach for AML treatment.

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p p = 0.073), especially among patients whose with an inactive disease activity was p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.

A wide array of microorganisms, including many novel, phylogenetically deeply rooted taxa, survive and thrive in extreme environments. These unique and reduced-complexity ecosystems offer a tremendous opportunity for studying the structure, function and evolution of natural microbial communities. Marker gene surveys have resolved patterns and ecological drivers of these extremophile assemblages, revealing a vast uncultured microbial diversity and the often predominance of archaea in the most extreme conditions. New omics studies have uncovered linkages between community function and environmental variables, and have enabled discovery and genomic characterization of major new lineages that substantially expand microbial diversity and change the structure of the tree of life. These efforts have significantly advanced our understanding of the diversity, ecology and evolution of microorganisms populating Earth’s extreme environments, and have facilitated the exploration of microbiota and processes in more complex ecosystems. Microbial life can thrive in extreme environments such as terrestrial hot springs and deep sea hydrothermal vents, glaciers and permafrost, hypersaline habitats, acid mine drainage and the subsurface. In this Review, Shu and Huang explore the diversity, functions and evolution of bacteria and archaea inhabiting Earth’s major extreme environments.

Objective To assess the usefulness of combined diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced MRI (DCE-MRI) in the differentiation of parotid gland tumors. Methods Seventy patients with 80 parotid gland tumors who underwent DKI and DCE-MRI were retrospectively enrolled and divided into four groups: pleomorphic adenomas (PAs), Warthin tumors (WTs), other benign tumors (OBTs), and malignant tumors (MTs). DCE-MRI and DKI quantitative parameters were measured. The Kruskal–Wallis H test and post hoc test with Bonferroni correction and ROC curve were used for statistical analysis. Results WTs demonstrated the highest Kep value (median 1.89, interquartile range [1.46–2.31] min−1) but lowest Ve value (0.20, [0.15–0.25]) compared with PAs (Kep, 0.34 [0.21–0.55] min−1; Ve, 0.36 [0.24–0.43]), OBTs (Kep, 1.22 [0.27–1.67] min−1; Ve, 0.28 [0.25–0.41]), and MTs (Kep, 0.71 [0.50–1.23] min−1; Ve, 0.35 [0.26–0.45]) (all p D value (1.10, [0.88–1.29] × 10−3 mm2/s) compared with PAs (1.81, [1.60–2.20] × 10−3 mm2/s) and OBTs (1.57, [1.32–1.89] × 10−3 mm2/s) (both p trans value (0.12, [0.07–0.18] min−1) compared with OBTs (0.28, [0.11–0.50] min−1) (p Kep and Ve, D, and Ktrans to distinguish WTs, MTs, and PAs sequentially were 1.06 min−1, 0.28, 1.46 × 10−3 mm2/s, and 0.21 min−1, respectively (accuracy, 89% [71/80], 91% [73/80], 78% [62/80], respectively). Conclusion The combined use of DKI and DCE-MRI may help differentiate parotid gland tumors. Key Points • The combined use of DKI and DCE-MRI could facilitate the understanding of the pathophysiological characteristics of parotid gland tumors. • A stepwise diagnostic diagram based on the combined use of DCE-MRI parameters and the diffusion coefficient is helpful for accurate preoperative diagnosis in parotid gland tumors and may further facilitate the clinical management of patients.

Traditional in vitro evaluation criteria of magnesium (Mg)-based stents cannot reflect the degradation process in vivo, due to the interdependence and interference between biodegradable properties and bioenvironment. The current direct and indirect evaluation approaches of in vitro biocompatibility do not have a hydrodynamic environment and vascular biological structure existing in vivo. Herein, we designed a vascular bioreactor to provide an ex vivo culture environment for vessels, which reveals the degradation behavior of Mg-Zn-Mn stent and the effect of its degradation on cells. We reported that rabbit carotid arteries could maintain native morphology and viability in the bioreactor under the best condition within a flow rate of 5.4 mL min-1 and a culture time of one week. With this culture condition, Mg-Zn-Mn stents were implanted into the arteries in the bioreactors and compared with in vivo rabbit models. The arteries maintained cell survival in the bioreactor, but the cell attachment was absent on the stent struts, associated with a fast degradation. Conversely, the stents achieved a rapid and complete endothelialization in vivo for two weeks. This study could provide a correlation and difference of the degradation behavior and cellular response to the degradation of Mg-based stent between ex vivo and in vivo approaches.

This work presents an audio watermarking scheme using minimum-amplitude scaling on the optimized lowest-frequency coefficients in the wavelet domain. Signal-to-noise ratio (SNR), bit-error-rate (BER) and Perceptual Evaluation of Audio Quality (PEAQ) are commonly utilized performance indexes in measuring the fidelity, robustness and quality of watermarking algorithms. However, there is a tradeoff relationship between audio quality and robustness. To overcome the drawback, this paper aims in proposing an optimization-based scaling scheme using optimal modification of low-frequency amplitude in the wavelet domain. A function connecting the multi-coefficients, composed of arbitrary scaling on the lowest DWT coefficients, and the group SNR of these coefficient is derived. Karush-Kuhn-Tucker (KKT) theorem and minimum length play two essential roles to obtain the optimal modification of low-frequency amplitude with optimal scaling factors. Furthermore, the almost invariant feature of these optimized scaling factors hold demonstrates resistance to amplitude modification manipulation. To practically evaluate the watermarked audio quality, an objective measurement using the PEAQ is also performed as well. Experimental results confirm that the embedded audio in the proposed method has high SNR, low BER, and good PEAQ, indicating strong robustness against various attacks, such as re-sampling, amplitude modification, and mp3 compression.

α-Glucosidase is a crucial enzyme for the production of isomaltooligosaccharide. In this study, a novel method comprising eosin Y (EY) and α-D-methylglucoside (AMG) in glass plates was tested for the primary screening of α-glucosidaseproducing strains. First, α-glucosidase-producing Aspergillus niger strains were selected on plates containing EY and AMG based on transparent zone formation resulting from the solubilization of EY by the hydrolyzed product. Conventional methods that use trypan blue (TB) and p-nitrophenyl-α-D-glucopyranoside (pPNP) as indicators were then compared with the new strategy. The results showed that EY-containing plates provide the advantages of low price and higher specificity for the screening of α-glucosidase-producing strains. We then evaluated the correlation between the hydrolytic activity of α-glucosidase and diffusion distance, and found that good linearity could be established within a 6-75 U/ml enzyme concentration range. Finally, the hydrolytic and transglycosylation activities of α-glucosidase obtained from the target isolates were determined by EY plate assay and 3,5-dinitrosalicylic acid-Saccharomyces cerevisiae assay, respectively. The results showed that the diameter of the transparent zone varied among isolates was positively correlated with α-glucosidase hydrolytic activity, while good linearity could also be established between α-glucosidase transglycosylation activity and non-fermentable reducing sugars content. With this strategy, 7 Aspergillus niger mutants with high yield of α-glucosidase from 200 obvious single colonies on the primary screen plate were obtained.

The objective of this study was to explore the effect of Alpiniae oxyphyllae Fructus (AOF) on a rat model of chronic intermittent hypoxia (CIH)–induced enuresis. Findings of this study may help identify therapeutic targets in children with nocturnal enuresis (NE). Female rats were randomly divided into a control group (saline gavage, 4 weeks of normal air), CIH group (saline gavage, 4 weeks of CIH), and AOF group (AOF gavage, 4 weeks of CIH). The variables measured in this study included water intake, urine output, bladder leak point pressure (BLPP), malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity. The expression levels of the purinergic P2X3 receptor, muscarinic M3 receptor, and s3-adrenergic receptor (s3-AR) in the bladder were also measured. The bladder was subjected to haematoxylin and eosin (HE) and Weigert staining, and histological changes were observed under a light microscope to evaluate the morphological changes in the bladder in each group. Compared with the control group, urine output was increased, and the BLPP was decreased in the CIH group, but AOF administration decreased urine output and increased BLPP. In addition, the serum MDA level increased and the SOD activity decreased in the CIH group compared with the control group. Administration of AOF decreased the MDA level and increased the SOD activity. Additionally, compared with the control group, HE and Weigert staining in the CIH group showed that the bladder detrusor muscle bundles were disordered and loose, some muscle bundles were broken, the content of collagen fibres in the gap was reduced, and the gap was significantly widened. However, following the administration of AOF, the bladder detrusor muscle bundles were neatly arranged, and the content of collagen fibres in the gap was increased. Furthermore, compared with the control group, the purinergic P2X3 receptor and muscarinic M3 receptor were expressed at higher levels, and s3-AR was expressed at lower levels in the CIH group, but AOF administration decreased the expression of the purinergic P2X3 receptor and muscarinic M3 receptor and increased the expression of the s3-AR. AOF improves enuresis by inhibiting oxidative stress and regulating the expression of the purinergic P2X3 receptor, muscarinic M3 receptor, and s3 adrenergic receptor.

Nowadays, the stability and heat transfer properties of nanofluids have been extensively studied. However, for the practical application, the dynamic stability, sedimentation, and fouling characteristics are also important issues. Whether nanofluids can maintain stable heat transfer characteristics during intermittent operation in the system is also a worthwhile issue. In this paper, the dynamic stability, sedimentation, and fouling characteristics as well as the time-dependent heat transfer characteristics of TiO2 and CNT nanofluids are investigated sequentially. The results show that compared with static condition, the dispersion stability of nanofluids is much better, and the sedimentation and fouling on solid surface are much less in dynamic condition. For the nanofluids in this paper, the sedimentation and fouling on solid surface are loose and can easily washed out after slight flushing. Rough surfaces are easier to adsorb the nanoparticles sedimentation and form fouling, but it can be greatly removed using ultrasonication. Long-term shutdown reduces the convective heat transfer enhancement of nanofluids, but it can be well restored after the action of ultrasonication.

The effects of surface adsorption of bovine serum albumin (BSA) and human gamma-globulin (HGG) on the tribological performance of a DLC film were investigated using a quartz crystal microbalance with dissipation (QCM-D), a ball-on-disk reciprocating tribometer, and a three-electrode electrochemical cell. The results showed that the wear depth in the BSA solution was higher than that in the HGG solution. In the HGG solution, the HGG-adsorbed layer could act as a lubricating layer and protect the DLC film from wear. The wear volume of DLC film in BSA and HGG mixture solution was higher than that in single HGG solution. This may be because the BSA molecules inhibit the formation of HGG adsorbed layer during sliding.

Background The biting midge, Forcipomyia taiwana, is one of the most annoying blood-sucking pests in Taiwan. Current chemical control methods only target the adult, not the immature stages (egg to pupa), of F. taiwana. Discovering new or alternative tactics to enhance or replace existing methods are urgently needed to improve the effectiveness of F. taiwana control. The egg is the least understood life stage in this pest species but may offer a novel point of control as addition of NaCl to the egg environment inhibits development. Thus, the objective of this study was to use RNA profiling to better understand the developmental differences between wild-type melanized (black) and NaCl-induced un-melanized (pink), infertile F. taiwana eggs. Results After de novo assembly with Trinity, 87,415 non-redundant transcripts (Ft-nr) with an N50 of 1099 were obtained. Of these, 26,247 (30%) transcripts were predicted to have long open reading frames (ORFs, defined here as ≥300 nt) and 15,270 (17.5%) transcripts have at least one predicted functional domain. A comparison between two biological replicates each of black and pink egg samples, although limited in sample size, revealed 5898 differentially expressed genes (DEGs; 40.9% of the transcripts with long ORFs) with ≥2-fold difference. Of these, 2030 were annotated to a Gene Ontology biological process and along with gene expression patterns can be separated into 5 clusters. KEGG pathway analysis revealed that 1589 transcripts could be assigned to 18 significantly enriched pathways in 2 main categories (metabolism and environmental information processing). As expected, most (88.32%) of these DEGs were down-regulated in the pink eggs. Surprisingly, the majority of genes associated with the pigmentation GO term were up-regulated in the pink egg samples. However, the two key terminal genes of the melanin synthesis pathway, laccase2 and DCE/yellow, were significantly down-regulated, and further verified by qRT-PCR. Conclusion We have assembled and annotated the first egg transcriptome for F. taiwana, a biting midge. Our results suggest that down-regulation of the laccase2 and DCE/yellow genes might be the mechanism responsible for the NaCl-induced inhibition of melanization of F. taiwana eggs.

Since the advances in protein engineering and manufacture, over the last 30 years, antibody-based immunotherapeutic has become a powerful strategy to treat diseases. The T-cell engaging bispecific antibody (BsAb) by combining the Fab binding domain of tumor antigens and Fab or single-chain variable fragments (scFvs) binding domain of CD3 molecules, could redirect cytotoxic T cells to kill tumor cells. The IgG-scFv format of BsAb is a dual bivalent and asymmetrical design, which adds the benefit of potent cytotoxicity and less complicated for manufacture but limits the stability and production. Here, we engineered a series of interchain disulfide bonds in the Fab region of IgG-svFv BsAbs and evaluated its biophysical and biological properties. We found that simultaneously replaced the position of VH44-VL100 and CH1126-CL121 residues with cysteine, to form two additional disulfide bonds, could markedly increase monomeric BsAb formation and yield. The thermostability and stability against aggregation and degradation also performed better than BsAbs without extra disulfide bonds introduction. Besides, the affinity of engineered BsAbs was maintained, and the h8B-BsAb antibody had a slight enhancement in an inhibitory effect on target cells.

Surface modification with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is an effective method for improving hemocompatibility. Peptide GREDVY immobilized on Ti is of great benefit to endothelialization. Micropattern of PMPC and GREDVY can regulate cells distribution, behaviors, and nitric oxide (NO) release. Copper can be used as catalytic to release NO from a donor in vitro, which can inhibit platelets adhesion, activation, and aggregation. The Ti-PDA(Cu)-M/R(P) micropattern was fabricated with PMMPC-HD {PMMPC [monomer contain MPC and methacrylic acid (MA)] was cross-linked with hexamethylene diamine} and peptide Gly-Arg-Glu-Asp-Val-Tyr (GREDVY) using PDMS stamp, and it was characterized by SEM, FTIR, and XPS. The results demonstrated that the PMPC and peptide GREDVY were immobilized onto polydopamine successfully. Simultaneously, the copper existed in polydopamine was confirmed by XPS. The rate of NO release in vitro catalyzed by copper ions was 1.5–5.3 × 10−10 mol/(cm2 min). It will be beneficial to inhibiting platelets adhesion and proliferation of ECs.

Sea container has been identified as a major pathway for the unintended entry and spread of alien ant species. In Japan, red imported fire ants, Solenopsis invicta Buren (Hymenoptera: Formicidae), which are among the most harmful alien ants, were first detected in a shipping container from China in May 2017, and the invasion into Japan via the trade pathway is still continuing. To prevent containers contaminated with S. invicta and its establishment in Japan, control measures, such as repellents, are urgently required. The present study is the first to evaluate repellency of microencapsulated allyl isothiocyanate (AITC) against S. invicta, as a preliminary step to use the innovative equipment for invasive species management in sea containers. In a field in Taiwan heavily infested with S. invicta, a repellent test of microencapsulated AITC using bait traps showed that the equipment completely prevents S. invicta from accessing the bait. Due to its volatility and irritancy, AITC, a safe natural repellant in wasabi (Eutrema japonicum (Miq.) Kiudz), has not been used for pest management in containerized cargo. However, the encapsulation of AITC solves this problem by allowing controlled vapor release. Microencapsulated AITC has considerable potential as an effective measure to stop the spread of S. invicta through global trade.

Bauxite residue disposal areas (BRDAs) are physically degraded and hostile to plant growth. Nevertheless, natural plant colonization was observed in an abandoned BRDA in Central China. The pioneer plant species at the disposal area were identified, whilst distribution characteristics of salt ions such as Na+, K+, and Ca2+ in plant tissues and rhizosphere residues were investigated. The mean concentration of exchangeable Na+ in the rhizosphere soils was 19.5 cmol/kg, which suggested that these pioneer plants had relatively high salinity resistance. Sodium content varied from 0.84 cmol/kg (Digitaria sanguinalis) to 39.7 cmol/kg (Kochia scoparia), whilst K to Na ratio varied from 0.71 (Myricaria bracteata) to 32.39 (Digitaria sanguinalis) in the shoots, which demonstrated that the salinity tolerance mechanisms of these pioneer species differed significantly. Accumulation factors of Na+ in local plant species ranged from 0.04 (D. sanguinalis) to 3.29 (M. bracteata), whilst the translocation factor varied from 0.13 (D. sanguinalis) to 2.92 (M. bracteata). The results suggested that four pioneer plant species including K. scoparia, M. bracteate, Cynodon dactylon and D. sanguinalis could be suitable for revegetation at other disposal areas.

We present QUBO objective functions for the maximum common subgraph isomorphism problem, proved their correctness and illustrate them with a few toy problems. Very small-scale problems can be solved by the D-Wave 2X machine with high enough success probabilities; however, for larger scale problems, the success probability drops significantly.

A Correction to this paper has been published: https://doi.org/10.1038/s41427-021-00293-0

Background Dendritic spines, the actin-rich protrusions emerging from dendrites, are the subcellular locations of excitatory synapses in the mammalian brain. Many actin-regulating molecules modulate dendritic spine morphology. Since dendritic spines are neuron-specific structures, it is reasonable to speculate that neuron-specific or -predominant factors are involved in dendritic spine formation. KLHL17 (Kelch-like 17, also known as Actinfilin), an actin-binding protein, is predominantly expressed in brain. Human genetic study has indicated an association of KLHL17/Actinfilin with infantile spasms, a rare form of childhood epilepsy also resulting in autism and mental retardation, indicating that KLHL17/Actinfilin plays a role in neuronal function. However, it remains elusive if and how KLHL17/Actinfilin regulates neuronal development and brain function. Methods Fluorescent immunostaining and electrophysiological recording were performed to evaluate dendritic spine formation and activity in cultured hippocampal neurons. Knockdown and knockout of KLHL17/Actinfilin and expression of truncated fragments of KLHL17/Actinfilin were conducted to investigate the function of KLHL17/Actinfilin in neurons. Mouse behavioral assays were used to evaluate the role of KLHL17/Actinfilin in brain function. Results We found that KLHL17/Actinfilin tends to form circular puncta in dendritic spines and are surrounded by or adjacent to F-actin. Klhl17 deficiency impairs F-actin enrichment at dendritic spines. Knockdown and knockout of KLHL17/Actinfilin specifically impair dendritic spine enlargement, but not the density or length of dendritic spines. Both N-terminal Broad-Complex, Tramtrack and Bric-a-brac (BTB) domain and C-terminal Kelch domains of KLHL17/Actinfilin are required for F-actin remodeling and enrichment at dendritic spines, as well as dendritic spine enlargement. A reduction of postsynaptic and presynsptic markers at dendritic spines and altered mEPSC profiles due to Klhl17 deficiency evidence impaired synaptic activity in Klhl17-deficient neurons. Our behavioral assays further indicate that Klhl17 deficiency results in hyperactivity and reduced social interaction, strengthening evidence for the physiological role of KLHL17/Actinfilin. Conclusion Our findings provide evidence that KLHL17/Actinfilin modulates F-actin remodeling and contributes to regulation of neuronal morphogenesis, maturation and activity, which is likely relevant to behavioral impairment in Klhl17-deficient mice. Trial registration Non-applicable.

Background Recent studies have significantly expanded our knowledge of viral diversity and functions in the environment. Exploring the ecological relationships between viruses, hosts, and the environment is a crucial first step towards a deeper understanding of the complex and dynamic interplays among them. Results Here, we obtained extensive 16S rRNA gene amplicon, metagenomics sequencing, and geochemical datasets from different depths of two highly stratified sulfidic mine tailings cores with steep geochemical gradients especially pH, and explored how variations in viral community composition and functions were coupled to the co-existing prokaryotic assemblages and the varying environmental conditions. Our data showed that many viruses in the mine tailings represented novel genera, based on gene-sharing networks. Siphoviridae, Podoviridae, and Myoviridae dominated the classified viruses in the surface tailings and deeper layers. Both viral richness and normalized coverage increased with depth in the tailings cores and were significantly correlated with geochemical properties, for example, pH. Viral richness was also coupled to prokaryotic richness (Pearson’s r = 0.65, P = 0.032). The enrichment of prophages in the surface mine tailings suggested a preference of lysogenic viral lifestyle in more acidic conditions. Community-wide comparative analyses clearly showed that viruses in the surface tailings encoded genes mostly with unknown functions while viruses in the deeper layers contained genes mainly annotated as conventional functions related to metabolism and structure. Notably, significantly abundant assimilatory sulfate reduction genes were identified from the deeper tailings layers and they were widespread in viruses predicted to infect diverse bacterial phyla. Conclusions Overall, our results revealed a depth-related distribution of viral populations in the extreme and heterogeneous tailings system. The viruses may interact with diverse hosts and dynamic environmental conditions and likely play a role in the functioning of microbial community and modulate sulfur cycles in situ.

Economic order quantity (EOQ) model has been used extensively over a century. Many studies have altered and modified the model in order to imitate the actual inventory problem. This article is concerned with the finding of the optimal replenishment cycle time for the inventory issues where items received are partly with imperfect quality and involve deterioration after the inspection time. Also, for financial safety, for the supplier, when the permissible delay in payments can promote their sales and reduce their on-hand stock level. For the retailer, he/she can sell the items and accumulate revenue and earn interest within the trade-credit period. At the end of the period, it is usually assumed that the retailer pays off all units bought, and starts to pay the capital opportunity cost for the items in stock. Different scenarios based on the combination of the inspection time, the certain period of time in which the item has no deterioration and the trade-credit period have been considered here. In order to minimize the total relevant inventory cost, mathematical theorems have been developed to determine the existence and the uniqueness of the optimal solution. Numerical calculations and illustrations demonstrate the application and the performance of the proposed theories.

Background N6-Methyladenosine (m6A) modification has been implicated in many biological processes. It is important for the regulation of messenger RNA (mRNA) stability, splicing, and translation. However, its role in cancer has not been studied in detail. Here we investigated the biological role and underlying mechanism of m6A modification in hepatoblastoma (HB). Methods We used Reverse transcription quantitative real-time PCR (RT-qPCR) and Western blotting to determine the expression of m6A related factors. And we clarified the effects of these factors on HB cells using cell proliferation assay, colony formation, apoptotic assay. Then we investigated of methyltransferase-like 13 (METTL3) and its correlation with clinicopathological features and used xenograft experiment to check METTL3 effect in vivo. m6A-Seq was used to profiled m6A transcriptome-wide in hepatoblastoma tumor tissue and normal tissue. Finally, methylated RNA immunoprecipitation (MeRIP) assay, RNA remaining assay to perform the regulator mechanism of MEETL3 on the target CTNNB1 in HB. Results In this research, we discovered that m6A modifications are increased in hepatoblastoma, and METTL3 is the main factor involved with aberrant m6A modification. We also profiled m6A across the whole transcriptome in hepatoblastoma tumor tissues and normal tissues. Our findings suggest that m6A is highly expressed in hepatoblastoma tumors. Also, m6A is enriched not only around the stop codon, but also around the coding sequence (CDS) region. Gene ontology analysis indicates that m6A mRNA methylation contributes significantly to regulate the Wnt/β-catenin pathway. Reduced m6A methylation can lead to a decrease in expression and stability of the CTNNB1. Conclusion Overall our findings suggest enhanced m6A mRNA methylation as an oncogenic mechanism in hepatoblastoma, METTL3 is significantly up-regulated in HB and promotes HB development. And identify CTNNB1 as a regulator of METTL3 guided m6A modification in HB.

The unique advantages of nitric oxide (NO) in cardiovascular disease therapy have driven the development of methods to functionalize cardiovascular stents for local generation of NO. However, current NO-generating materials used for surface engineering stents have limitations such as a complex fabrication process, poor stent adhesion strength, and low control of NO release. Herein, we apply synergetic coordination and catecholamine surface chemistry to develop an adhesive NO-generating coating with a copper-catecholamine framework through a simple, one-step molecule/ion co-assembly process. The copper-catecholic-selenocystamine framework provides glutathione peroxidase (GPx)-like interfacial catalytic activity, which results in long-term, stable, adjustable NO release rates from the coating. The resulting desirable therapeutic dose and release kinetics of NO endow the vascular stent with the ability to simultaneously inhibit platelet activation and smooth muscle cell (SMC) proliferation, and enhances endothelial cell (EC) adhesion, proliferation, and migration in vitro. Vascular stent functionalized by the optimized copper-catecholic-selenocystamine coating significantly suppresses thrombosis, promotes re-endothelialization, and reduces intimal hyperplasia in vivo, and may be promising to address the clinical complications associated with restenosis and late stent thrombosis. A simple method to create a coronary stent with a coating that releases nitric oxide has been developed by Chinese scientists and could be important for treating heart disease. Coronary stents keep the arteries open and the blood flowing, but they can damage the surrounding tissue, leading to post-surgery complications. Zhilu Yang, Nan Huang and co-workers from Southwest Jiaotong University in Chengdu have developed a stent that generates nitric oxide to promote the healing of lesions and prevent thrombosis. Previous stents generating nitric oxide are complicated to fabricate, exhibited poor adhesion, and allow little control over the release of nitric oxide. The team devised a simple one-step process to produce a coating that includes an adhesive amino acid to allow long-term, stable, and controllable catalytic generation of nitric oxide. Synergetic coordination- and catecholamine surface chemistry was developed to construct an adhesive nitric oxide generating coating with copper-catecholic-selenocystamine framework through a simple one-step molecule/ion co-assembling process. The copper-catecholic-selenocystamine framework provides glutathione peroxidase (GPx)-like interfacial catalytic activity, which results in a long-term, stable and adjustable range of NO release rates from the coating. Surface functionalization by this coating endows the cardiovascular stent with the abilities to impressively improve antithrombogenicity, promote regeneration of endothelium and inhibit restenosis.

Ti-Cu films with different Cu concentrations were fabricated by high-power pulsed magnetron sputtering (HPPMS) to release copper ions and catalyze NO to improve the blood compatibility. The Cu concentrations of films were 25.7at% and 68.8at%. Pure Ti films were also fabricated. Copper release, catalytic release of nitric oxide (NO), and blood platelet adhesion of Ti-Cu films were studied. Ti-Cu films released copper ions in PBS solution and more Cu ions were released from films with 68.8at% Cu. Ti-Cu films had excellent ability of catalytical decomposition of exogenous donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) and as a result, nitric oxide (NO) was generated. The NO generation catalyzed by Ti-Cu films was significantly higher than that by pure Ti films. This was more eminent in the Ti-Cu films with 68.8 at% Cu. The platelet adhesion and activation of Ti-Cu films were significantly inhibited compared to that of pure Ti films in the presence of SNAP. The Ti-Cu film fabricated by HPPMS showed the ability of releasing Cu ions to catalyze SNAP to generate NO to inhibit platelet adhesion and activation.

Biodegradable magnesium (Mg)-based vascular stents have been designed as temporary scaffolds to treat angiostenotic lesions for the maintenance of normal blood flow. Numerous studies have presented in vitro and in vivo tests for the evaluation of the safety and feasibility of Mg-based vascular stents and the related materials. Therein the cytocompatibility is a basic and important parameter in the evaluation system. In this review, we summarize the applications and limitations of in vitro evaluation methods including basic characterization methods and direct and indirect cytotoxicity tests. We discuss the influencing factors on cytotoxicity, such as surface roughness, preconditioning of sample surface, cell type for the biocompatibility evaluation in direct contact as well as conditions for the formation of extracts/degradation products for indirect assays. Besides, we highlight the recent in vivo animal tests and clinical trials about Mg-based stents along with some associated results. The aim of this review is to provide a meaningful reference in the further developments and related evaluation methods of Mg-based stents.

7055 aluminum alloy plates with the same size were rolled by two processes: small percentage reduction per pass (PRPP) and large percentage reduction per pass, respectively. Meanwhile, the effect of PRPP on the precipitates and corrosion resistance of 7055 aluminum alloy plate was investigated. The mechanisms were analyzed and discussed by optical microscopy (OM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and electron back-scattered diffraction (EBSD) technique. Large PRPP can improve the corrosion resistance. For the plate rolled by small PRPP, the main precipitate is guinier–preston (GP) zone and continuous grain boundary precipitates (GBPs), while, for the plate rolled by large PRPP, the main precipitates are the GP zone and η′ precipitate, and the GBPs are discontinuous.

Small acidophilic archaea belonging to Micrarchaeota and Parvarchaeota phyla are known to physically interact with some Thermoplasmatales members in nature. However, due to a lack of cultivation and limited genomes on hand, their biodiversity, metabolisms, and physiologies remain largely unresolved. Here, we obtained 39 genomes from acid mine drainage (AMD) and hot spring environments around the world. 16S rRNA gene based analyses revealed that Parvarchaeota were only detected in AMD and hot spring habitats, while Micrarchaeota were also detected in others including soil, peat, hypersaline mat, and freshwater, suggesting a considerable higher diversity and broader than expected habitat distribution for this phylum. Despite their small genomes (0.64-1.08 Mb), these archaea may contribute to carbon and nitrogen cycling by degrading multiple saccharides and proteins, and produce ATP via aerobic respiration and fermentation. Additionally, we identified several syntenic genes with homology to those involved in iron oxidation in six Parvarchaeota genomes, suggesting their potential role in iron cycling. However, both phyla lack biosynthetic pathways for amino acids and nucleotides, suggesting that they likely scavenge these biomolecules from the environment and/or other community members. Moreover, low-oxygen enrichments in laboratory confirmed our speculation that both phyla are microaerobic/anaerobic, based on several specific genes identified in them. Furthermore, phylogenetic analyses provide insights into the close evolutionary history of energy related functionalities between both phyla with Thermoplasmatales. These results expand our understanding of these elusive archaea by revealing their involvement in carbon, nitrogen, and iron cycling, and suggest their potential interactions with Thermoplasmatales on genomic scale.

For high-power impulse magnetron sputtering (HIPIMS), the peak power applied to the target is of great importance for regulating the ionization degree of the metal target and ion/atom flux ratio. In this work, chromium (Cr) films were deposited on 316-L stainless steel substrates and silicon (100) wafers with different peak powers by HIPIMS. The relationship between peak target power and properties of Cr films was explored in detail. The resulting structure and mechanical properties of deposited Cr films were characterized by X-ray diffraction (XRD), transmission electron microscope (TEM), atomic force microscopy (AFM), indentation hardness and scratch tester. The results indicate that the ionization degree of metal target and ion/atom flux ratio increase with the increase in peak power but without the loss of deposition rate at the same time. At low ionization degree, the deposited Cr film has low compressive residual stress and low hardness but good adhesion strength. When the ionization degree of target metal increases with increasing peak power, Cr film exhibits finer size and smoother surface with improved hardness but decreased adhesion strength.

The gamma degradation of toxic non-oxidizing biocide dodecyl dimethyl benzyl ammonium chloride (DDBAC) was investigated. The degradation of DDBAC achieved 70–100% depending on the initial concentration and the absorbed dose, but only 10–33% dissolved organic carbon was removed. The presence of NO3 −, HCO3 −, 2-propanol and tert-butanol inhibited the degradation of DDBAC. The DDBAC degradation rate constant ratios of ·OH, ·H and e aq − was calculated as 7.4:1.4:1. The acute toxicity of 10 mg L−1 DDBAC was removed by 60% at absorbed doses of 0.5–3.0 kGy. The results showed that gamma irradiation was effective to remove DDBAC and its toxicity.

We demonstrate experimentally all-optical wavelength conversion based on four-wave mixing in dispersion-engineered silicon nanowaveguides with a picosecond pulse pump. We find that the conversion efficiency is significantly limited by nonlinear losses induced by the two-photon absorption and freecarrier absorption. Using a picosecond pulse pump centered at 1,550 nm, we show that the input continuous-wave signals can efficiently be converted into a broadband idler pulse in silicon waveguides with various dimensions. Conversion efficiencies versus signal wavelengths are different for silicon waveguides with different dimensions due to the variation in the phase mismatch; we obtain a conversion efficiency of – 32 dB in silicon nanowaveguides with a length of 5.8 mm. Such on-chip optical wavelength converters can find important potential applications in highly-integrated optical circuits for all-optical ultrafast signal processing.

It is hereby certified that there is no shared co-first authorship in this paper. Dr. Nan HUANG is the only first author of this article.

Wheat dependent exercise-induced anaphylaxis (WDEIA) is a rare but potentially severe food allergy caused by the combination of wheat ingestion and physical exercise. The impact of WDEIA on quality of life (QOL) is unclear. This study characterized the clinical and laboratory features and investigated the QOL in WDEIA patients from Central China. Twenty-eight WDEIA patients were analyzed, and QOL was measured by validated Chinese version Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) and Food Allergy Independent Measure (FAIM) after obtaining the diagnosis. The results showed that half of the patients were females. The median onset age was 37 years old. The symptoms occurred within 1 h after wheat ingestion (26/28). Symptoms of anaphylaxis included cutaneous (26/28), respiratory (11/28), gastro-intestinal (5/28) and cardiovascular manifestations (27/28). Skin prick tests were positive to salt soluble (89.3%) and salt insoluble wheat allergen extracts (100%). Positive rate to wheat, gluten and omega-5 gliadin specific IgE was 64.3%, 92.9% and 92.9% respectively. Specific IgE to omega-5 gliadin with a cut-off value 0.83 KU/L offered highly efficient diagnostic criterion for WDEIA (sensitivity: 89.3%; and specificity: 88.9%). The mean scores of FAQLQ-AF and FAIM were 4.70 and 4.98 respectively and level of anti-omega-5 gliadin IgE had positive correlations with FAQLQ scores. Thereby, WDEIA is commonly found in mid-age adults. In most cases, multi-organs especially skin and cardiovascular systems are involved. Salt insoluble wheat allergen skin test and serum specific IgE to gluten and omega-5 gliadin help to diagnose WDEIA. QOL in WDEIA patients is severely impaired.

Deriving frequent itemsets from databases is an important research issue in data mining. The number of frequent itemsets may be unusually large when a low minimum support threshold is given. As such, the design of a compact representation to compress and describe them is an interesting topic. In the past, most related research on compact representation focused on frequent closed itemsets and frequent maximal itemsets. The former is a lossless compact technology that can totally recover all frequent itemsets and their frequencies. Contrarily, the latter may lose some information regarding frequent itemsets, because it reserves frequent itemsets only and is unable to identify their frequency. In this paper, we propose a new compact representation that lies between closed itemsets and maximal itemsets. It can reserve all frequent itemsets and identify their approximate frequency. In addition, an efficient algorithm that corresponds to this new concept is designed to find related key information in databases. Finally, a series of experiments are conducted to show the effectiveness of compact representation and the performance of the proposed algorithm.

Wafer curvature method has been applied to determine the internal stress in the films using Stoney’s equation. During the film deposition, the wafer fixation on the sample holder will restrict the deformation of the rectangle-shaped wafer, which may result in the stress datum difference along length and width direction. In this paper, the effect of wafer size and the wafer fixation on the TiN film internal stress measured by wafer curvature method was discussed. The rectangle-shaped wafers with different length/width ratios (L/W=1:1, 2:1, 3:1 and 4:1) were fixed as a cantilever beam. After the TiN films deposition, the profiles of the film/wafer were measured using a stylus profilometer and then the internal stress was calculated using the Stoney equation in the film. The results showed that the fixed end of the wafers limited to some degree the curvature of the wafers along the width direction. For film internal stress measured by wafer curvature method, the wafer profile should be scanned along the length direction and the scan distance should be greater than or equal to half of wafer length. When the length/width ratio of the wafer reached 3:1, the wafer curvature and the calculated stress were basically the same at different positions along the length direction. For film internal stress measured by wafer curvature method, it was recommended that the length/width ratio of wafer should be considered to be greater than or equal to 3:1, and the deformed profile was scanned along the length direction.

Under physiological conditions, the opening and closing of the leaflets of an implanted artificial heart valve (AHV) affects the blood components and therefore may cause various complications to the patient such as hemolysis or platelet activation. In this paper, a computational fluid model is presented. The regional distribution of flow shear stress in an AHV is analyzed using computational fluid dynamics and AHV performance is evaluated in terms of the variation of flow velocity and pressure when blood passes the leaflets in the aortic valve. The results suggest that for the design of a mechanical AHV, the maximum opening angle and internal orifice diameter should be increased to improve the fluid structure interaction and decrease the possibility of damage to blood components. Finally, the fluid stress distribution of the AHV leaflet structure was calculated and analyzed under pulsating flow conditions.

Modern bolometers generally consist of large-scale arrays of detectors. Implemented in conventional technologies, such bolometer arrays suffer from integrability and productivity issues. Recently, the development of CMOS technologies has presented an opportunity for the massive production of high-performance and highly integrated bolometers. This paper presents a 65-nm CMOS LNA designed for a millimeter-wave bolometer’s pre-amplification stage. By properly applying some positive feedback, the noise figure of the proposed LNA is minimized at under 6 dB and the bandwidth is extended to 30 GHz.

A two-step equal channel angular extrusion (ECAE) procedure was used to process pure Mg. The effects of ECAE processing temperature on the microstructure, mechanical properties, and corrosion behavior of pure Mg were studied. The results show that the average grain size of pure Mg decreases with decreasing extrusion temperature. After ECAE processing at 473 K, fine and equiaxed grains (~9 μm) are obtained. The sample processed at 473 K exhibits the excellent mechanical properties, whereas the sample processed at 633 K has the lowest corrosion rate. The improved corrosion resistance and mechanical properties of pure Mg by ECAE are ascribed to grain refinement and microstructural modification.

This study presents an optimization-based image watermarking scheme with integrated quantization embedding. First, peak signal to noise ratio (PSNR) is rewritten as a performance index in matrix form. In order to guarantee the robustness, this study embeds a watermark into the low-frequency coefficients of discrete wavelet transform (DWT). Unlike traditional way of single-coefficient quantization, this study applies amplitude quantization to embed the watermark and then rewrite this amplitude quantization as a constraint with embedding state. Then, an optimization-based equation connecting the performance index and amplitude-quantization constraint is obtained. Second, Lagrange Principle is used to solve the equation and then the optimal results are applied to embed the watermark. In detection, the hidden watermark can be extracted without original image. Finally, the performance of the proposed scheme is evaluated by PSNR and BER.

Surface modification of cardiovascular devices with biological molecules has been generally accepted as a promising method of treating in-stent thrombosis and hyperplasia. Therefore, a novel layer composed of hyaluronan (HA) and type IV collagen (CoIV) was prepared on titanium (Ti) for the purpose of promoting vascular smooth muscle cells contractile phenotype previously. However, endothelialization as another important function of the modified layer has not been investigated. Thus, in this study, HA as the solvent, the bio-functional layers fabricated with the CoIV concentration of 200 μg/ml (200M) and 500 μg/ml (500M), respectively, which possessed better anti-hyperplasia property, were chosen for the endothelialization test. The endothelial cell (EC) adhesion and proliferation experiment showed that the 200M layer, 500M layer, and the single CoIV layer significantly improved the ECs growth compared with the Ti and single HA layer, and the ECs on the 500M layer had larger major/minor index and cell spreading areas which were related to the EC functions. The functional factor release results showed that ECs on the 500M layer release more nitric oxide, prostacyclin, thrombomodulin, and tissue factor pathway inhibitor compared to ECs on the other surfaces. The result of ECs shedding experiment under blood flow shear stress indicated that the retention of ECs on 200M layer, 500M layer, and the single CoIV layer was remarkably larger than the value of the other groups, but it seemed that several parts of the ECs layer on the single CoIV surface disappeared under BFSS, and this may lead to the occurrence of in-stent thrombosis and atherosclerosis, so 200M layer and 500M layer were considered as possessing the best function of anti-EC-shedding. We hope this research can provide more helpful exploration and application for enhancing endothelialization of the cardiovascular stents.

The microbial communities in acid mine drainage have been extensively studied to reveal their roles in acid generation and adaption to this environment. Lacking, however, are integrated community- and organism-wide comparative gene transcriptional analyses that could reveal the response and adaptation mechanisms of these extraordinary microorganisms to different environmental conditions. In this study, comparative metagenomics and metatranscriptomics were performed on microbial assemblages collected from four geochemically distinct acid mine drainage (AMD) sites. Taxonomic analysis uncovered unexpectedly high microbial biodiversity of these extremely acidophilic communities, and the abundant taxa of Acidithiobacillus, Leptospirillum and Acidiphilium exhibited high transcriptional activities. Community-wide comparative analyses clearly showed that the AMD microorganisms adapted to the different environmental conditions via regulating the expression of genes involved in multiple in situ functional activities, including low-pH adaptation, carbon, nitrogen and phosphate assimilation, energy generation, environmental stress resistance, and other functions. Organism-wide comparative analyses of the active taxa revealed environment-dependent gene transcriptional profiles, especially the distinct strategies used by Acidithiobacillus ferrivorans and Leptospirillum ferrodiazotrophum in nutrients assimilation and energy generation for survival under different conditions. Overall, these findings demonstrate that the gene transcriptional profiles of AMD microorganisms are closely related to the site physiochemical characteristics, providing clues into the microbial response and adaptation mechanisms in the oligotrophic, extremely acidic environments.