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The process of fermenting tofu extends back thousands of years and is an indispensable part of Chinese culture. Despite a cultural resurgence in fermented foods and interest in microbiomes, there is little knowledge on the microbial diversity represented in fermented ‘hairy’ tofu, known locally in China as Mao tofu. High-throughput metagenomic sequencing of the ITS, LSU and 16S rDNA was used to determine Mao tofu’s fungal and bacterial community diversity across four wet markets in Yunnan, China. The results show that hairy tofu in this region consists of around 170 fungal and 365 bacterial taxa, and that microbial taxa differ between markets. Diversity also differed based on the specific niche of the tofu block, comparing the outside rind-like niche to that of the inside of the tofu block. Machine learning random forest models were able to accurately classify both the market and niche of sample origin. An over-abundance of yeast and Geotrichum was found, and Mucor (Mucoromycota) was abundant in the outside rind-like niche, which consists of the visible ‘hairy’ mycelium. The majority of the bacterial OTUs belonged to Proteobacteria, Firmicutes, and Bacteroidetes, with Acinetobacter, Lactobacillus, Sphingobacterium and Flavobacterium the most abundant genera. Putative fungal pathogens of plants (Cercospora, Diaporthe, Fusarium) and animals (Metarhizium, Entomomortierella, Pyxidiophora, Candida, Clavispora) were also detected, as were putative bacterial pathogens identified as Legionella. Non-fungal eukaryotic taxa detected by LSU amplicon sequencing included soybean (Glycine max), Protozoa, Metazoa (e.g., Nematoda and Platyhelminthes), Rhizaria and Chromista, indicating that additional biodiversity exists in the hairy tofu microbiome.

UDP-glucuronosyltransferases (UGTs), being multifunctional detoxification enzymes, play a major role in the process of resistance to various pesticides in insects. However, the mechanism underlying the molecular regulation of pesticide resistance remains unclear, especially in Apis cerana cerana. In this study, all of the UGTs in Apis cerana cerana (AccUGT) have been identified through the multiple alignment and phylogenetic analysis. Expression of AccUGT genes under different pesticides, and antioxidant genes after silencing of AccUGT2B20-like, were detected by qRT-PCR. The resistance of overexpressed AccUGT2B20-like to oxidative stress was investigated by an Escherichia coli overexpression system. Also, antioxidant-related enzyme activity was detected after silencing of the AccUGT2B20-like gene. Expression pattern analysis showed that almost all UGT genes were upregulated under different pesticide treatments. This result indicated that AccUGTs participate in the detoxification process of pesticides. AccUGT2B20-like was the major gene because it was more highly induced than the others. Overexpression of AccUGT2B20-like in E. coli could effectively improve oxidative stress resistance. Specifically, silencing the AccUGT2B20-like gene increased oxidative stress by repressing the expression of oxidation-related genes, decreasing antioxidant-related enzyme activity, and increasing malondialdehyde concentration. Taken together, our results indicate that AccUGTs are involved in pesticide resistance, among which, AccUGT2B20-like contributes to the detoxification of pesticides by eliminating oxidative stress in Apis cerana cerana. This study explains the molecular basis for the resistance of bees to pesticides and provides an important safeguard for maintaining ecological balance.

Background Regulating T-cell metabolism is crucial for their anticancer activity. Therefore, understanding the function and metabolism of human tumor-infiltrating T cells is of broad interest and clinical importance.Methods CD3+CD45+ T cells were sorted from adjacent area or tumor core of human hepatocellular carcinoma (HCC), then the clusters and heterogeneity of T cells were further interrogated by single-cell transcriptomic profiling. 118 surgical samples from patients with HCC were histologically examined for infiltration of CD8+ T cells in tumor and adjacent tissue.Results Single-cell transcriptomic profiling indicated that several exhausted T-cell (Tex) populations differentially coexisted in the tumor and adjacent tissue. CD137 identifies and enriches Tex with superior effector functions and proliferation capacity. Furthermore, enhanced fatty acid-binding protein 5 (FABP5) expression along with increased mitochondrial oxidative metabolism were evident in these CD137-enriched Tex. Inhibiting FABP5 expression and mitochondrial fatty acid oxidation impaired the anti-apoptosis and proliferation of CD137-enriched Tex. These observations have been verified by generating CD137 CART. Immunohistochemistry staining on the tissue microarray of 118 patients with HCC showed intra-tumoral FABP5 high CD8+ T-cell infiltration was linked to overall and recurrence-free survival.Conclusions The tumor microenvironment can impose metabolic restrictions on T-cell function. CD137, a costimulatory molecule highly expressed on some Tex, uses exogenous fatty acids and oxidative metabolism to mediate antitumor immunity. The immunometabolic marker FABP5 should be investigated in larger, longitudinal studies to determine their potential as prognostic biomarkers for HCC.

After the discovery of complete ammonia-oxidizing (comammox) Nitrospira, detection and assessments of the contribution of comammox Nitrospira communities to nitrogen cycling are in great demand. PCR-based approach, a common method for the detection of comammox, depends strongly on accurate amplification of the amoA genes from the original DNA samples using appropriate primers. In this study, we reported an evaluation of the performance of two commonly used primer sets, Ntsp-amoA 162F/359R and comaA/B-244f/659r, for amplifying the comammox amoA genes from three representative wetland soils in China [Sangsang (SS), Sanjiang (SJ), and Xianghai (XH)]. Our results demonstrated the two primer sets could both successfully amplify the clades with high relative abundances (RA), and further revealed a broadly similar diversity and community composition of dominant comammox operational taxonomic units (OTUs) (RA ≥ 1%) in each of the three wetland soils. However, the clades with low RA, such as the clade A (1.26%) in SJ and the clade B (11.54%) in XH that were recovered by metagenomics analysis, failed to be amplified using comaA/B-244f/659r, but were successfully amplified and sequenced using Ntsp-amoA 162F/359R. It indicated that, compared to comaA/B-244f/659r, Ntsp-amoA 162F/359R was more sensitive to the clades with low RA. However, it is worth noting that Ntsp-amoA 162F/359R would overestimate the RA of some rare clades. For example, the RAs of clade B in XH were overestimated by 32-fold. Furthermore, high levels of non-target amplification were detected via gel electrophoresis using both primer sets, especially for comammox Clade B amoA genes, implying that we should treat qPCR results based on these primers with caution. Taken together, our study comprehensively compared the performance of the two primer sets on the sensitivity and specificity of amplifying comammox amoA genes in three wetland soils, pointing out the necessity of further development of new primers for the efficient and accurate detection of comammox in various environments.

BackgroundDual-specificity phosphatase 9 (DUSP9) belongs to the dual-specificity protein phosphatase subfamily. Recently, increasing attention has been paid on the role of DUSP9 in a variety of cancers. However, its functional role in tumor development is still unclear, especially in colorectal cancer (CRC).MethodsThe functional role of DUSP9 in inhibiting the progression of CRC was verified using colony formation assay, wound healing assay, nude mice xenograft model, etc. RNA-seq was performed to assess the gene expression profiling in SW480 cells with DUSP9 stable knockdown and shControl cells. Bisulfite sequencing (BSE) was performed to reveal the methylation status of CpG island in the promoter of DUSP9.ResultsDUSP9 was significantly downregulated in tumor tissues compared with peritumor tissues. Mechanistically, the high methylation status of CpG island in the promoter of DUSP9 may lead to the downregulation of DUSP9 in CRC. Clinically, low DUSP9 expression in CRC was closely associated with depth of invasion, metastasis (TNM) stage, and poor survival, indicating that DUSP9 may be involved in the progression of CRC. Functional study revealed that DUSP9 inhibited proliferation, migration, invasion, and epithelial–mesenchymal transition of CRC cells both in vitro and in vivo. Transcriptome profiling studies revealed that Erk signaling was involved in the tumor progression mediated by DUSP9 silencing, which is confirmed by cell experiments and clinical tissue sample staining analysis.ConclusionOur findings demonstrate that DUSP9 plays a critical role in the progression of CRC, and therapeutic intervention to increase the expression or activity of DUSP9 may be a potential target for CRC treatment in the future.

Ross syndrome (RS) is a rare peripheral autonomic system disorder characterized by tonic pupil, hyporeflexia, and segmental anhidrosis. Neuropathological studies show that RS results from the selective cholinergic nerve degeneration. However, the cause and underlying mechanisms are largely unknown. Here, we show α-synuclein accumulation in the autonomic nerve terminals in the lesser curvature of stomach of patients with RS. In addition, immunohistochemical findings demonstrate that a dominant degeneration of cholinergic fibers is exhibited in patients with RS, while main degeneration of adrenergic fibers is demonstrated in patients with pure autonomic failure in their gastrointestinal and urinary system. Our study suggests that RS belongs to α-synucleinopathies. Moreover, our findings indicate that adrenergic nerves and cholinergic nerves are not equally damaged in different types of pure autonomic dysfunctions.

Rolling mills vibration is a key factor that hinders the production of thin-strip steel. Currently, vibration is mainly suppressed by adjusting rolling mill parameters which is not a common approach. Due to special working conditions, the information of work roll, such as displacement and velocity, cannot be directly measured. Therefore, based on extended state observer, new resonance ratio control method, which is a common approach, is proposed to suppress the rolling mill vibration. First, the equivalent mass of the back roll is identified. Then, the interaction force between the work roll and the back roll and the velocity of the back roll are estimated using the extended state observer. Finally, these values are introduced into the input of the servo valve to compensate. The simulation results indicate that vibrations of both the work roll and the back roll are suppressed, and this method has a great tolerance for the identification error of the back-roll equivalent mass, and extended state observer compensation possesses a more superior vibration suppression than disturbance observer compensation.

Clathrin-mediated endocytosis (CME) in mammalian cells is driven by resilient machinery that includes >70 endocytic accessory proteins (EAP). Accordingly, perturbation of individual EAPs often results in minor effects on biochemical measurements of CME, thus providing inconclusive/misleading information regarding EAP function. Live-cell imaging can detect earlier roles of EAPs preceding cargo internalization; however, this approach has been limited because unambiguously distinguishing abortive coats (ACs) from bona fide clathrin-coated pits (CCPs) is required but unaccomplished. Here, we develop a thermodynamics-inspired method, “disassembly asymmetry score classification (DASC)”, that resolves ACs from CCPs based on single channel fluorescent movies. After extensive verification, we use DASC-resolved ACs and CCPs to quantify CME progression in 11 EAP knockdown conditions. We show that DASC is a sensitive detector of phenotypic variation in CCP dynamics that is uncorrelated to the variation in biochemical measurements of CME. Thus, DASC is an essential tool for uncovering EAP function.

To evaluate the effect of cold application on pain and bruising after the subcutaneous injection of low-molecular-weight heparin, 8 electronic databases were searched for randomized controlled trials and quasiexperimental studies from the inception of the databases to June 2019. Review Manager 5.3 software was used for the heterogeneity test and meta-analysis. A total of 8 studies including 694 participants were analyzed. The cold application group assessed with the Verbal Descriptor Scale pain assessment tool showed significant reductions in pain intensity immediately after injection. Compared to the control group, the cold application group showed a reduction in the occurrence of bruises at 12 hours, 24 hours, and 48 hours after injection. There was no significant difference in the area of bruising in the cold application group at 48 hours after injection, but the area of bruising at 72 hours after injection was significantly reduced. These results show that cold application can reduce the incidence of pain and bruising after subcutaneous injection of low-molecular-weight heparin and reduce the area of bruising 72 hours after injection. Additional studies with larger sample sizes are needed to confirm these findings.

BackgroundAnxiety and depression are common symptoms in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). The 24-form Tai Chi may exert a protective function for CHD patients after PCI by improving anxiety and depression.MethodsPatients who received PCI after 1–4 days were randomly assigned to the 24-form Tai Chi group (TG) and the control group (CG). The differences in anxiety and depression, using the Medical Outcomes Study 36−item Short−Form Health Survey (SF-36), before and after an average of 10 months of Tai Chi intervention were compared in both groups to analyze the effects of Tai Chi on the emotion and the life quality of CHD patients. Meanwhile, the relative levels of miR-17-92 were measured by using real-time qPCR. The association between the relative levels of miR-17-92 and the anxiety and the depression of CHD patients after PCI was analyzed. Adjusted Cox models were used to explore the effect of Tai Chi exercise in CHD patients.ResultsAfter 10 months of intervention, the changes in the anxiety subscale (P = 0.002), in the depression subscale (P = 0.008), and in the stress (P = 0.015) scores were higher in the TG group when compared to those of the CG group. The proportion of anxious (P = 0.045) and depressed subjects (P = 0.042) in the TG group was lower than that in the CG group. On the other hand, the increase in the SF-36 scores and in the relative levels of miR-17-92 was significantly higher in the TG group when compared with that of the CG group (P < 0.05). The serum level of miR-17-92 had a negative correlation with the anxiety, the depression, and the stress scores (P < 0.01).ConclusionThe 24-form Tai Chi improved the anxiety and the depression symptoms and upregulated the miR-17-92 levels in CHD patients after PCI.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are promising for the treatment of Alzheimer’s disease (AD). However, their low rate of migration and survival in the brain limit their clinical applicability. This study is designed to improve the therapeutic potential of hUC-MSCs by preincubating them with resveratrol, a natural polyphenol capable of regulating cell destiny. Herein, we demonstrate that resveratrol preincubation enhances the migration of hUC-MSCs in vitro, as well as their survival and homing into the hippocampus of AD mice in vivo. Moreover, resveratrol-primed MSCs were better able to inhibit amyloid-β peptide (Aβ) deposition, Tau hyperphosphorylation, and oxidative stress, all while improving learning and memory. Notably, we found that hUC-MSCs inhibited neuroinflammation by reacting with astrocytes and microglial cells and suppressing mitogen-activated protein kinases (MAPKs), extracellular signal kinases (ERK), p38 kinases (p38), and c-Jun N-terminal kinases (JNK) signaling pathways in the hippocampus of AD mice. Furthermore, resveratrol pretreatment enhanced these effects. Conclusively, the current study revealed that resveratrol preconditioning protected hUC-MSCs against the hostile microenvironment characteristic of AD and enhanced their viability and homing into the brain of AD mice. The use of resveratrol-pretreated hUC-MSCs is thereby proposed to be a promising therapy for AD.

Based on the Computing with Words (CW), double hierarchy hesitant fuzzy linguistic term set (DHHFLTS) can be used to express complex linguistic information accurately with two simple linguistic hierarchies. This paper proposes a group decision making (GDM) model based on multiplicative consistency and consensus with double hierarchy hesitant fuzzy linguistic preference relations (DHHFLPRs). Firstly, a correlation coefficient of DHHFLTSs is defined based on the distance measures of double hierarchy hesitant fuzzy linguistic elements (DHHFLEs). Then, a multiplicative consistency property of DHHFLPRs is investigated, and a consistency checking method and a feedback mechanism-based repairing algorithm are developed to ensure all DHHFLPRs with acceptable multiplicative consistency. Furthermore, a correlation measure for DHHFLPRs based on the correlation coefficient of DHHFLTSs is proposed, and a new consensus reaching method on the basis of the correlation measure is developed, which can be used to fully obtain the consensus degree from both positive and negative angles. Finally, we make some comparative analyses with other existing consistency checking and repairing method as well as the consensus reaching approach to illustrate the effectiveness of the proposed method by a case study concerning the assessment of the venture capital project about real estate market in some cities of China. First published online 8 October 2019

As lactoferrin (LF) plays an essential role in physiological processes, the detection of LF has attracted increasing attention in the field of disease diagnosis. However, most current methods require expensive equipment, laborious pretreatment, and long processing time. In this work, carboxyl-rich carbon dots (COOH-CDs) were facilely prepared through a one-step, low-cost hydrothermal process with tartaric acid as the precursor. The COOH-CDs had abundant carboxyl on the surface and showed strong blue emission. Moreover, COOH-CDs were used as a fluorescent sensor toward Fe3+ and showed high selectivity for Fe3+ with the limit of detection (LoD) of 3.18 nM. Density functional theory (DFT) calculations were performed to reveal the mechanism of excellent performance for Fe3+ detection. Meanwhile, COOH-CDs showed no obvious effect on lactobacillus plantarum growth, which means that COOH-CDs have good biocompatibility. Due to the nontoxicity and excellent detection performance for Fe3+, COOH-CDs were employed as a fluorescent sensor toward LF and showed satisfying performance with an LoD of 0.776 µg/mL, which was better than those of the other methods.

There is an increasing interest in the use of Saccharina latissima (sugar kelp) as food, but the high iodine content in raw sugar kelp limits the daily recommended intake to relatively low levels. Processing strategies for iodine reduction are therefore needed. Boiling may reduce the iodine content effectively, but not predictably, since reductions from 38–94% have been reported. Thus, more information on which factors affect the reduction of iodine are needed. In this paper, sugar kelp cultivated at different depths were rinsed and boiled, to assess the effect of cultivation depth on the removal efficacy of potentially toxic elements (PTEs), especially iodine, cadmium, and arsenic, during processing. Raw kelp cultivated at 9 m contained significantly more iodine than kelp cultivated at 1 m, but the difference disappeared after processing. Furthermore, the content of cadmium and arsenic was not significantly affected by cultivation depth. The average reduction during rinsing and boiling was 85% for iodine and 43% for arsenic, but no significant amount of cadmium, lead, or mercury was removed. Cultivation depths determined the relative effect of processing on the iodine content, with a higher reduction for kelp cultivated at 9 m (87%) compared to 1 m (82%). When not taken into consideration, cultivation depth could mask small reductions in iodine content during rinsing or washing. Furthermore, since the final content of PTEs was not dependent on the cultivation depth, the type and extent of processing determines whether cultivation depth should be considered as a factor in cultivation infrastructure design and implementation, or alternatively, in product segmentation.

Based on fractal theory, a regular fractal is used to construct symmetrical reef models (e.g., cube and triangle reef models) with different fractal levels (n = 1, 2, 3). Using the concept of fractal dimension, we can better understand the spatial effectiveness of artificial reefs. The void space complexity index is defined to quantify the complexity of the internal spatial distribution of artificial reefs models under different levels. The computational fluid dynamics (CFD) flow simulation approach was used to investigate the effects of void space complexity on the flow field performances of the symmetrical artificial reef models. The upwelling convection index (Hupwelling/HAR, Vupwelling/VAR), wake recirculating index (Lwake/LAR, Vwake/VAR) and non-dimensionalized velocity ratio range were used to evaluate the efficiency of the flow field effect inside or around artificial reefs. The surface area and spatial complexity index of artificial reefs increase with increasing fractal level. The numerical simulation data shows that the Menger-type artificial reef models with a higher spatial complexity index have better flow field performances in the upwelling and wake regions. Compared to the traditional artificial reef models, the upwelling convection index (Vupwelling/VAR) and recirculating index (Vwake/VAR) of n = 3 fractal cube artificial reef increase by 37.5% and 46.8%, respectively. The efficiency indices of the upwelling region and wake region around the fractal triangle artificial reef model are 2–3 times those of the fractal cube artificial reef model when the fractal level is 3.

Abstract Background Knee osteoarthritis (KOA) is a degenerative knee disease commonly found in the ageing population. DNA methylation works with histone acetylation to participate in aging. Alterations of DNA methylation may involve the joint chondrocyte degeneration in KOA. The aim of this study is to detect DNA methylation changes in chondrocytes of rats with KOA. Methods The rat KOA model was established with the Hulth method (n = 10), while rats receiving sham operation served as the control (n = 10). At 16 weeks after modeling, the knee joint tissue was collected from half of the rats in each group for Micro-CT scanning, Haematoxylin& Eosin (HE) staining, ABH/OG staining, immunohistochemistry for Bax, Bcl-2 and Fas, and TUNNEL staining. Meanwhile, the articular cartilage was collected from the other half to detect promoter methylation in target genes with the MethylTarget approach. Results Micro-CT scanning, HE staining, ABH/OG staining, immunohistochemistry, and TUNNEL staining all showed more severe cartilage injury in the KOA group than in the control group, indicating successful establishment of KOA model. The methylation rate in the KOA group was significantly decreased for C/ebpα-2 (within a CpG island -452 bp to the initiation codon on chromosome 1 91,363,511), Cdk2 (within a CpG island -55 bp to the initiation codon on chromosome 7 3,132,362), Bak1 (within a CpG island 6452 bp to the initiation codon on chromosome 20 5,622,277), and Fas (within a CpG island on the entire chromosome 1 gene), compared with the sham group (P = 0.005, 0.008, 0.022 and 0.027, respectively). Conclusion The chondrocyte apoptosis and significantly reduced methylation levels of C/ebpα-2, Cdk2, Bak1, and Fas may participate in the pathogenesis of KOA. However, the exact mechanisms remain to be determined.

Background: Gain-of-function of fibroblast growth factor receptor 3 (FGFR3) is involved in the pathogenesis of many tumors. More and more studies have focused on the potential usage of therapeutic single-chain Fv (ScFv) antibodies against FGFR3. RNA interference (RNAi) has been considered as a promising therapeutic method against cancer. A tool which can deliver small interference RNAs (siRNAs) into FGFR3 positive cancer cells is very promising for anti-tumor therapy. Results: In this study, a novel fusion protein R3P, which consists of FGFR3-ScFv and protamine, was generated in Escherichia coli by inclusion body expression strategy and Ni-NTA chromatography. Its yield reached 10 mg per liter of bacterial culture and its purity was shown to be higher than 95%. 1 μg of R3P could efficiently bind to about 2.5 pmol siRNAs and deliver siRNAs into FGFR3 positive RT112 and K562 cells. Annexin V staining results showed that R3P can deliver the amplified breast cancer 1 (AIB1) siRNAs to induce RT112 cell apoptosis. Conclusion: These results indicated that R3P was a promising carrier tool to deliver siRNAs into FGFR3 positive cancer cells and to exert anti-tumor effect.

Purpose: Poor sleep quality is harmful for everyone and potentially even more harmful for older adults with atrial fibrillation-associated stroke (AFAS). This study aims to explore the effects of eight-section brocade (ESB) on sleep quality, memory, and cardiopulmonary function in the older adults with AFAS.Methods: Older adults with AFAS and sleep disorders were recruited and divided into the ESB (EG, n = 85) and control groups (CG, general exercise, n = 85). EG patients received 60 min ESB exercises 5 times a week for 12 weeks; CG patients received normal exercise. Pittsburgh sleep quality index (PSQI) scores (poor sleepers ≥8 and normal sleepers < 8), memory for word pairs (poor memory ≤ 7 and normal memory > 7), left ventricular posterior wall (LVPW) thickness, and maximum ventilation (MV, to evaluate cardiopulmonary function) values were measured. The correlation between sleep and memory quality was analyzed using PSQI scores and word pairs via the Pearson correlation coefficients test. Adjusted Cox models were used to explore an interaction between PSQI and ESB exercise.Results: After 12-week exercise intervention, ESB improved sleep quality, latency, duration, disturbance and daytime dysfunction when compared to conventional exercise. In similar cases, the MV values in the EG were also higher than that in the CG (p = 0.009). ESB intervention could not affect the cardiac structure and left ventricular ejection fraction. Compared with the CG, the ESB intervention reduced PSQI scores and increased memorized word pairs (p < 0.001 for poor and normal sleepers in both unadjusted and adjusted analysis, p = 0.012 and 0.003 for poor and normal memory). The test of Pearson correlation coefficients showed that PSQI scores were strongly associated with the number of word pairs in both unadjusted and adjusted analyses (p < 0.0001).Conclusion: Eight-section brocade exercise improved sleep quality and memory consolidation and cardiopulmonary function by reducing PSQI scores, increasing word pairs and MV values in the older adults with AFAS.

On the basis of the historical classics of Guangxu emperor’s wedding held in the Forbidden City, we build a website to preserve and reappear Guangxu Emperor’s wedding, with the purpose of promoting the rite and the royal wedding culture of Qing dynasty.

Agaricus bisporus distributed in the Tibetan Plateau of China has high-stress resistance that is valuable for breeding improvements. However, its evolutionary history, specialization, and adaptation to the extreme Tibetan Plateau environment are largely unknown. Here, we performed de novo genome sequencing of a representative Tibetan Plateau wild strain ABM and comparative genomic analysis with the reported European strain H97 and H39. The assembled ABM genome was 30.4 Mb in size, and comprised 8,562 protein-coding genes. The ABM genome shared highly conserved syntenic blocks and a few inversions with H97 and H39. The phylogenetic tree constructed by 1,276 single-copy orthologous genes in nine fungal species showed that the Tibetan Plateau and European A. bisporus diverged ∼5.5 million years ago. Population genomic analysis using genome resequencing of 29 strains revealed that the Tibetan Plateau population underwent significant differentiation from the European and American populations and evolved independently, and the global climate changes critically shaped the demographic history of the Tibetan Plateau population. Moreover, we identified key genes that are related to the cell wall and membrane system, and the development and defense systems regulated A. bisporus adapting to the harsh Tibetan Plateau environment. These findings highlight the value of genomic data in assessing the evolution and adaptation of mushrooms and will enhance future genetic improvements of A. bisporus.

Hollow cathode discharge and micro-hollow cathode discharge have numerous applications in the fields of industry, medical treatment, environmental protection, and analytical chemistry. However, many of them lack the typical features of hollow cathode mode, especially the applications at atmospheric pressure. In order to investigate the underlying basic science of hollow cathode discharge, the hollow cathode discharge in argon was studied by experiments. The range for the operation of the hollow cathode mode in the argon–aluminum device was quantitatively determined to be from 0.8 to 4 Torr cm, no matter how small the cathode cavity is. The atmospheric pressure operation of the hollow cathode mode was realised with the aluminum cathode of a 50 μm cavity. The hollow cathode discharges were consistent with Townsend similarity law when the anode was very close to the cathode and the value of p·D was chosen at the lower limit of the range for hollow cathode mode. In contrast, if the anode was moved a little bit far from the cathode and the value of p D was significantly increased, the results followed Allis–White scaling law. The reason for the deviation of Allis–White scaling law from Townsend similarity law was given.

Microalgae are regarded as a promising alternative that can replace fishmeal and fish oil in aquaculture. Under N-limitation, many microalgae species change their carbon storage patterns in favor of neutral lipids (NLs) mainly in the form of triacylglycerol (TAG), but fatty acids in polar lipids (PL) are nutritionally more available for fish than those esterified into NLs. In the present study, the effect of N-limitation on the lipid content and fatty acid profiles in different lipid classes of Phaeodactylum tricornutum, Isochrysis aff. galbana clone T-Iso, Rhodomonas baltica, and Nannochloropsis oceanica were investigated. The microalgae cells were cultivated by two different methods, batch and semi-continuous culture, to create strong and moderate N-limitation, and this in turn will significantly affect the biomass and lipid productivity. All four species accumulated lipids mainly in the form of TAG, in response to strong nitrogen limitation. N. oceanica, however, accumulated 51% of the dry weight as lipid in moderate nitrogen limitation and up to 87% of the fatty acid was in TAG. Isochrysis aff. galbana clone T-Iso was the only species where the fraction of polyunsaturated fatty acid (PUFA), especially the fraction of docosahexaenoic acid (DHA), increased with increasing nitrogen limitation. Total lipid productivity showed no increase in batch culture although stronger nitrogen limitation led to lipid accumulation. P. tricornutum had the highest eicosapentaenoic acid (EPA) content, while N. oceanica showed the highest EPA productivity due to the high content of lipid. The highest DHA productivity was found in Isochrysis aff. galbana clone T-Iso from moderate N-limitation, mainly due to the high biomass productivity. Based on the results from the current study, N. oceanica and T-Iso are two promising microalgae strains ass long-term sustainable sources of n-3 long chain -PUFAs under moderate N-limitation. As shown in the present study, increased lipid content in microalgal cells due to strong N-limitation induction may not increase the lipid productivity because biomass production is usually reduced. Therefore, a combination of approaches such as metabolic engineering, conditioning and selection may be needed to further increase the n-3 LC-PUFA productivity without substantial loss of biomass.

Aluminum (Al3+) toxicity is a typical abiotic stress that severely limits crop production in acidic soils. In this study, an RIL (recombinant inbred line, F12) population derived from the cross of Zhonghuang 24 (ZH 24) and Huaxia 3 (HX 3) (160 lines) was tested using hydroponic cultivation. Relative root elongation (RRE) and apical Al3+ content (AAC) were evaluated for each line, and a significant negative correlation was detected between the two indicators. Based on a high-density genetic linkage map, the phenotypic data were used to identify quantitative trait loci (QTLs) associated with these traits. With composite interval mapping (CIM) of the linkage map, five QTLs that explained 39.65% of RRE and AAC variation were detected on chromosomes (Chrs) Gm04, Gm16, Gm17 and Gm19. Two new QTLs, qRRE_04 and qAAC_04, were located on the same region of bin93-bin94 on Chr Gm04, which explained 7.09% and 8.98% phenotypic variation, respectively. Furthermore, the results of the expression analysis of candidate genes in the five genetic regions of the QTLs showed that six genes (Glyma.04g218700, Glyma.04g212800, Glyma.04g213300, Glyma.04g217400, Glyma.04g216100 and Glyma.04g220600) exhibited significant differential expression between the Al3+ treatment and the control of two parents. The results of qRT-PCR analysis indicated that Glyma.04g218700 was upregulated by Al3+ treatment with the hundreds-fold increased expression level and may be a candidate gene with potential roles in the response to aluminum stress. Therefore, our efforts will enable future functional analysis of candidate genes and will contribute to the strategies for improvement of aluminum tolerance in soybean.

Electrical explosion of a wire (EEW) has been investigated for more than ten years at Tsinghua University, and the main results are reviewed in this paper. Based on EEW in vacuum, an X-pinch was used as an x-ray source for phase-contrast imaging of small insects such as mosquitoes and ants in which it was possible to observe clearly their detailed internal structures, which can never be seen with conventional x-ray radiography. Electrical explosion of a wire array (EEWA) in vacuum is the initial stage in the formation of a wire-array Z-pinch. The evolution of EEWA was observed with x-ray backlighting using two X-pinches as x-ray sources. It was found that each wire in an EEWA exhibits a core–corona structure instead of forming a fully vaporized metallic vapor. This structure is detrimental to the plasma implosion of a Z-pinch. By inserting an insulator as a flashover switch into the cathode, formation of a core–corona structure was suppressed and core-free EEWA was realized. EEW in gases was used for nanopowder production. Three parameters (vaporization rate, gas pressure, and energy deposited in the exploding plasma) were found to influence the nanoparticle size. EEW in water was used for shock-wave generation. The shock wave generated by melting could be recorded with a piezoelectric gauge only in underheat EEW. For EEW with a given stored energy but different energy-storage capacitor banks, the small capacitor bank produced a rapidly rising current that deposited more energy into the wire and generated a stronger shock wave.

Purpose: Epilepsy is a highly disabling neurological disorder. Brain insult is the most critical cause of epilepsy in adults. This study aimed to find reliable and efficient biomarkers for predicting secondary epilepsy.Materials and methods: The LiCl-pilocarpine (LiCl-Pilo) chronic epilepsy rat model was used, and rat cerebrospinal fluid (CSF) was collected 5 days after status epilepticus (SE). The CSF was analyzed using the label-free LC-ESI-Q-TOF-MS/MS. Differential expression of proteins was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The corresponding protein level in the CSF of patients with encephalitis in the postacute phase was determined using ELISA and compared between patients with and without symptomatic epilepsy after encephalitis during a 2-year follow-up.Results: The proteomics and ELISA results showed that the protein level of kininogen (KNG) was obviously elevated in both CSF and hippocampus, but not in serum, 5 days after the onset of SE in LiCl-Pilo chronic epilepsy model rats. In patients with encephalitis, the protein level of KNG in the CSF in the postacute phase was significantly elevated in patients with a recurrent epileptic seizure during a 2-year follow-up than in patients without a recurrent seizure.Conclusion: KNG in the CSF may serve as a potential biomarker for predicting epileptogenesis in patients with encephalitis.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22629-8

With the continuous expansion of the market of indoor localization, the requirements of indoor localization technology are becoming higher and higher. Existing indoor floor localization (IFL) systems based on Wi-Fi signal and barometer data are susceptible to external environment changes, resulting in large errors. A method for indoor floor localization using multiple intelligent sensors (MIS-IFL) is proposed to decrease the localization errors, which consists of a fingerprint database construction phase and a floor localization phase. In the fingerprint database construction phase, data acquisition is performed using magnetometer sensor, accelerator sensor and gyro sensor in the smartphone. In the floor localization phase, an active pattern recognition is performed through the collaborative work of multiple intelligent sensors and machine learning classifiers. Then floor localization is performed using magnetic data mapping, Euclidean closest approximation and majority principle. Finally, the inter-floor detection link based on machine learning is added to improve the overall localization accuracy of MIS-IFL. The experimental results show that the performance of the proposed method is superior to the existing IFL.

Peroxisome proliferator-activated receptor α (PPARα) is a key regulator to ameliorate liver injury in cases of acute liver failure (ALF). However, its regulatory mechanisms remain largely undetermined. Endoplasmic reticulum stress (ER stress) plays an important role in a number of liver diseases. This study aimed to investigate whether PPARα activation inhibits ER stress-induced hepatocyte apoptosis, thereby protecting against ALF. In a murine model of D-galactosamine (D-GalN)- and lipopolysaccharide (LPS)-induced ALF, Wy-14643 was administered to activate PPARα, and 4-phenylbutyric acid (4-PBA) was administered to attenuate ER stress. PPARα activation ameliorated liver injury, because pre-administration of its specific inducer, Wy-14643, reduced the serum aminotransferase levels and preserved liver architecture compared with that of controls. The protective effect of PPARα activation resulted from the suppression of ER stress-induced hepatocyte apoptosis. Indeed, (1) PPARα activation decreased the expression of glucose-regulated protein 78 (Grp78), Grp94 and C/EBP-homologous protein (CHOP) in vivo; (2) the liver protection by 4-PBA resulted from the induction of PPARα expression, as 4-PBA pre-treatment promoted upregulation of PPARα, and inhibition of PPARα by small interfering RNA (siRNA) treatment reversed liver protection and increased hepatocyte apoptosis; (3) in vitro PPARα activation by Wy-14643 decreased hepatocyte apoptosis induced by severe ER stress, and PPARα inhibition by siRNA treatment decreased the hepatocyte survival induced by mild ER stress. Here, we demonstrate that PPARα activation contributes to liver protection and decreases hepatocyte apoptosis in ALF, particularly through regulating ER stress. Therefore, targeting PPARα could be a potential therapeutic strategy to ameliorate ALF.

The p38 MAP kinase is a promising cancer drug target but its therapeutic effect is not fully understood. Here we report that the response of colorectal cancer (CRC) to p38 inhibitors (p38i) is highly variable: while p38i induces regression of one subgroup of CRCs, it stimulates growth of another subgroup. We further show that PP2AC is differentially expressed in the two different CRC subgroups, which determines the programing of p38-TSC-mTORC1 signaling through differential TSC2 phosphorylation at S664, 1254 and 1798, and the antitumor activity by p38i. Remarkably, modulation of PP2AC level is sufficient to reprogram p38-to-mTORC1 signaling and antitumor response. PP2AC expression accurately predicts therapeutic response to p38i in several CRC models, including a large cohort of patient-derived xenografts (PDXs). Moreover, we demonstrate that combination of p38 and mTOR kinase inhibitors effectively overcomes resistance to either inhibitor in single agent therapy. These results demonstrate that alternative routing of signal transduction underlies differential response to p38 and mTOR targeted therapies. The biomarker-guided therapeutic strategies described herein provide a compelling reason for testing in metastatic CRC patients who suffer very poor prognosis due to lack of efficacious drug therapies.

Most research about Light and elevated Temperature Induced Degradation (LeTID) is focused on multicrystalline silicon (mc-Si). In this work, the degradation kinetics of Czochralski-grown monocrystalline silicon (Cz-Si) induced by light at an elevated temperature were studied in detail. The lifetime evolutions over time during (1) light soaking (LS), (2) dark annealing–light soaking (DA–LS), and (3) DA–LS cycling experiments were analyzed. Ratios of the capture coefficients for the electrons and holes (k-values) were used to characterize the possible defects responsible for degradation. We found that the behavior of degradation and recovery under light soaking with or without a dark annealing treatment was mostly like boron–oxygen (BO)-related degradation but gave k-values from 19 to 25. In the DA–LS cycling experiment, the max degradation amplitudes hardly changed from the second cycle, and the k-values decreased with an increase in the cycling number. We then analyzed the possible reactions in Cz-Si and discuss the relationship between BO defects and LeTID.

A novel CoS@Fe3O4@rGO aerogel with a unique 3D porous heterostructure was prepared via the solvothermal method, in which cobalt sulfide (CoS) microspheres embedded with Fe3O4 nanoparticles were randomly scattered on reduced graphene oxide (rGO) flakes. The introduction of magnetic Fe3O4 nanoparticles and rGO regulated the impedance matching, and the excellent electromagnetic wave (EMW) absorption capability of the CoS@Fe3O4@rGO aerogel could be attributed to optimal dielectric loss and abundant conductive networks. The results demonstrated that the minimum reflection loss (RL) value of CoS@Fe3O4@rGO aerogel was −60.65 dB at a 2.5 mm coating thickness with an ultra-wide bandwidth of 6.36 GHz (10.24–16.6 GHz), as the filler loading was only 6 wt%. Such a lightweight CoS@Fe3O4@rGO aerogel with an outstanding absorbing intensity and an ultra-wide effective absorption bandwidth could become a potential EMW absorber.

Morels (Morchella spp.) are popular edible fungi with significant economic and scientific value. However, white mold disease, caused by Paecilomyces penicillatus, can reduce morel yield by up to 80% in the main cultivation area in China. Paecilomyces is a polyphyletic genus and the exact phylogenetic placement of P. penicillatus is currently still unclear. Here, we obtained the first high-quality genome sequence of P. penicillatus generated through the single-molecule real-time (SMRT) sequencing platform. The assembled draft genome of P. penicillatus was 40.2 Mb, had an N50 value of 2.6 Mb and encoded 9454 genes. Phylogenetic analysis of single-copy orthologous genes revealed that P. penicillatus is in Hypocreales and closely related to Hypocreaceae, which includes several genera exhibiting a mycoparasitic lifestyle. CAZymes analysis demonstrated that P. penicillatus encodes a large number of fungal cell wall degradation enzymes. We identified many gene clusters involved in the production of secondary metabolites known to exhibit antifungal, antibacterial, or insecticidal activities. We further demonstrated through dual culture assays that P. penicillatus secretes certain soluble compounds that are inhibitory to the mycelial growth of Morchella sextelata. This study provides insights into the correct phylogenetic placement of P. penicillatus and the molecular mechanisms that underlie P. penicillatus pathogenesis.

As a typical two-dimensional material, MXene possesses excellent conductivity and tunable interlayer space, which makes it have an impressive development potential in the field of electromagnetic (EM) waves absorbing materials. In this work, we fabricated a sandwich structure CoS@Ti3C2Tx composite using a simple solvothermal process. The CoS nanoparticles are anchored on the Ti3C2Tx MXene sheets, forming a heterolayered structure. The results demonstrate that the CoS@Ti3C2Tx composites with the sandwich-like architecture showed excellent EM absorbing performance due to the synergistic effects of the conductivity loss, interface polarization, and dipole polarization. When the doping ratio was 40 wt %, the maximum reflection loss value of CoS@Ti3C2Tx was up to –59.2 dB at 14.6 GHz, and the corresponding effective absorption bandwidth (below –10 dB) reached 5.0 GHz when the thickness was only 2.0 mm. This work endows a new candidate for the design of MXene-based absorption materials with optimal performance.

The crowdsourcing-based wireless local area network (WLAN) indoor localization system has been widely promoted for the effective reduction of the workload from the offline phase data collection while constructing radio maps. Aiming at the problem of the diverse terminal devices and the inaccurate location annotation of the crowdsourced samples, which will result in the construction of the wrong radio map, an effective indoor radio map construction scheme (RMPAEC) is proposed based on position adjustment and equipment calibration. The RMPAEC consists of three main modules: terminal equipment calibration, pedestrian dead reckoning (PDR) estimated position adjustment, and fingerprint amendment. A position adjustment algorithm based on selective particle filtering is used by RMPAEC to reduce the cumulative error in PDR tracking. Moreover, an inter-device calibration algorithm is put forward based on receiver pattern analysis to obtain a device-independent grid fingerprint. The experimental results demonstrate that the proposed solution achieves higher localization accuracy than the peer schemes, and it possesses good effectiveness at the same time.

The effect of hyporheic exchange on macroinvertebrates is a significant topic in ecohydraulics. A field study was conducted during May and June 2017 to investigate the impacts of magnitude and patterns of hyporheic exchange on the sediment macroinvertebrate community in the Weihe River basin. The results demonstrate that upwelling flows cause resuspension of riverbed sediment, increasing the proportion of swimmer groups (such as Baetidae) in the macroinvertebrate community. However, large resuspension of river bed sediment results in a reduced abundance of macroinvertebrates. By controlling the transport processes of dissolved oxygen (DO), dissolved organic carbon (DOC), nutrients, temperature, and different patterns of hyporheic exchange strongly influence the structure of macroinvertebrate communities. Downwelling is more likely to produce rich invertebrate communities than upwelling. The magnitude for the hyporheic flux of 150−200 mm/d was optimal for the macroinvertebrate community in the Weihe River Basin. Above or below this rate results in a decline in community abundance and diversity. We suggest that research is conducted to better understand the effects of hyporheic exchange across bedforms on macroinvertebrate communities. The study supports any activities to preserve the ecological functions and health of rivers dominated by fine-grained sediments.

Cobalt sulfide composites have exhibited great potential in terms of microwave absorption, owing to their low price, relatively high capacitance, and excellent electrocatalytic activity. Thus, a novel core-shell like structure comprising cobalt sulfide@polypyrrole (CoS@PPy) composite was synthesized by a facile solvothermal synthesis method and in situ polymerization. When coated by the heterostructure polypyrrole aerogel, CoS@PPy composite exhibited excellent microwave absorption properties with an optimal reflection loss (RL) of −41.8 dB at 6.96 GHz. Furthermore, the absorption bandwidth (RL < −10 dB) of 5.4 GHz could be reached at a coating thickness of 2.05 mm, probably attributing to the synergistic effect of good impedance matching, interfacial polarization, dipole polarization, and conductivity loss. Moreover, this work proposed a loss mechanism mode which probably occurred in the CoS@PPy composites. It was demonstrated that the CoS@PPy composite is a promising material in the field of electromagnetic wave absorption.

After long time operation of the manufactured gas pipeline, the naphthalene in the gas will jam the pipeline and threaten the safety of the pipeline seriously. To study the naphthalene particle deposition law in the manufactured gas pipeline, a horizontal straight pipe of Kunming manufactured gas pipeline is taken as an example; based on Reynolds stress model and discrete phase model, ANSYS Fluent software is used to carry out the numerical simulation in different pipe diameters, particle size, inlet velocity, temperature, and pressure conditions. The main conclusion can be obtained as follows (1) in the horizontal straight pipe section, particle diameter and temperature are positively correlated with the deposition rate and the deposition velocity of naphthalene particle and the inlet velocity and pressure are negatively correlated with them; (2) the naphthalene particle deposition rate is mainly affected by the particle size and the inlet velocity; (3) the larger the pipeline diameters, the greater the particle mass flow rate under the same particle inlet concentration, the lower the carrying capacity of the fluid to particles, the greater the naphthalene particle deposition rate; (4) the naphthalene particle deposition can be suppressed by increasing the gas transmission velocity and pressure and reducing the temperature, thus ensuring the safe operation of manufactured gas pipeline.

Rabies virus (RABV) invades the central nervous system and nearly always causes fatal disease in humans. How RABV interacts with host neuron membrane receptors to become internalized and cause rabid symptoms is not yet fully understood. Here, we identified a novel receptor of RABV, which RABV uses to infect neurons. We found that metabotropic glutamate receptor subtype 2 (mGluR2), a member of the G protein-coupled receptor family that is abundant in the central nervous system, directly interacts with RABV glycoprotein to mediate virus entry. RABV infection was drastically decreased after mGluR2 siRNA knock-down in cells. Antibodies to mGluR2 blocked RABV infection in cells in vitro. Moreover, mGluR2 ectodomain soluble protein neutralized the infectivity of RABV cell-adapted strains and a street strain in cells (in vitro) and in mice (in vivo). We further found that RABV and mGluR2 are internalized into cells and transported to early and late endosomes together. These results suggest that mGluR2 is a functional cellular entry receptor for RABV. Our findings may open a door to explore and understand the neuropathogenesis of rabies.

Dynamin Guanosine Triphosphate hydrolases (GTPases) are best studied for their role in the terminal membrane fission process of clathrin-mediated endocytosis (CME), but they have also been proposed to regulate earlier stages of CME. Although highly enriched in neurons, dynamin-1 (Dyn1) is, in fact, widely expressed along with Dyn2 but inactivated in non-neuronal cells via phosphorylation by glycogen synthase kinase-3 beta (GSK3β) kinase. Here, we study the differential, isoform-specific functions of Dyn1 and Dyn2 as regulators of CME. Endogenously expressed Dyn1 and Dyn2 were fluorescently tagged either separately or together in two cell lines with contrasting Dyn1 expression levels. By quantitative live cell dual- and triple-channel total internal reflection fluorescence microscopy, we find that Dyn2 is more efficiently recruited to clathrin-coated pits (CCPs) than Dyn1, and that Dyn2 but not Dyn1 exhibits a pronounced burst of assembly, presumably into supramolecular collar-like structures that drive membrane scission and clathrin-coated vesicle (CCV) formation. Activation of Dyn1 by acute inhibition of GSK3β results in more rapid endocytosis of transferrin receptors, increased rates of CCP initiation, and decreased CCP lifetimes but did not significantly affect the extent of Dyn1 recruitment to CCPs. Thus, activated Dyn1 can regulate early stages of CME that occur well upstream of fission, even when present at low, substoichiometric levels relative to Dyn2. Under physiological conditions, Dyn1 is activated downstream of epidermal growth factor receptor (EGFR) signaling to alter CCP dynamics. We identify sorting nexin 9 (SNX9) as a preferred binding partner to activated Dyn1 that is partially required for Dyn1-dependent effects on early stages of CCP maturation. Together, we decouple regulatory and scission functions of dynamins and report a scission-independent, isoform-specific regulatory role for Dyn1 in CME.

Fibrinogen-like protein 2 (Fgl2) is critical for immune regulation in the inflammatory state. Elevated Fgl2 levels are observed in patients with inflammatory bowel disease (IBD), but little is known about its functional significance. In this study, we sought to investigate the role of Fgl2 in the development of intestinal inflammation and colitis-associated colorectal cancer (CAC). Here, we report that Fgl2 deficiency increased susceptibility to dextran sodium sulfate-induced colitis and CAC in a mouse model. During colitis development, the expression of the membrane-bound and secreted forms of Fgl2 (mFgl2 and sFgl2, respectively) in the colon were increased and predominantly expressed by colonic macrophages. In addition, using bone marrow chimeric mice, we determined that Fgl2 function in colitis is strictly related to its expression in the hematopoietic cells. Loss of Fgl2 induced the polarization of M1, but suppressed that of M2 both in vivo and in vitro, independent of intestinal inflammation. Thus, Fgl2 suppresses intestinal inflammation and CAC development through its role in macrophage polarization and may serve as a therapeutic target in inflammatory diseases, including IBD.

Surgical ablation is a generally established treatment for patients with atrial fibrillation undergoing concomitant cardiac surgery. Left atrial (LA) lesion set for ablation is a simplified procedure suggested to reduce the surgery time and morbidity after procedure. The present meta-analysis aims to explore the outcomes of left atrial lesion set versus no ablative treatment in patients with AF undergoing cardiac surgery.A literature research was performed in six database from their inception to July 2017, identifying all relevant randomized controlled trials (RCTs) comparing left atrial lesion set versus no ablative treatment in AF patient undergoing cardiac surgery. Data were extracted and analyzed according to predefined clinical endpoints.Eleven relevant RCTs were included for analysis in the present study. The prevalence of sinus rhythm in ablation group was significantly higher at discharge, 6-month and 1-year follow-up period. The morbidity including 30 day mortality, late all-cause mortality, reoperation for bleeding, permanent pacemaker implantation and neurological events were of no significant difference between two groups.The result of our meta-analysis demonstrates that left atrial lesion set is an effective and safe surgical ablation strategy for AF patients undergoing concomitant cardiac surgery.

We present a Master Equation approach to calculating polymerization dynamics and force generation by branched actin networks at membranes. The method treats the time evolution of the F-actin distribution in three dimensions, with branching included as a directional spreading term. It is validated by comparison with stochastic simulations of force generation by actin polymerization at obstacles coated with actin "nucleation promoting factors" (NPFs). The method is then used to treat the dynamics of actin polymerization and force generation during endocytosis in yeast, using a model in which NPFs form a ring around the endocytic site, centered by a spot of molecules attaching the actin network strongly to the membrane. We find that a spontaneous actin filament nucleation mechanism is required for adequate forces to drive the process, that partial inhibition of branching and polymerization lead to different characteristic responses, and that a limited range of polymerization-rate values provide effective invagination and obtain correct predictions for the effects of mutations in the active regions of the NPFs.

Background: Overexpression or mutated activation of Fibroblast growth factor receptor 3 (FGFR3) is involved in the pathogenesis of many tumors. More and more studies focus on the potential usage of therapeutic antibodies against FGFR3. Results: In this study, a novel single-chain Fv (ScFv) against FGFR3 was prepared and characterized. To achieve the soluble expression, ScFv was fused with Sumo (Small ubiquitin-related modifier) by polymerase chain reaction (PCR), and cloned into pET-20b. The recombinant bacteria were induced by 0.5 mM Isopropyl-β-d-thiogalactopyranoside (IPTG) for 16 h at 20°C, and the supernatant liquid of Sumo-ScFv was harvested and purified by Ni-NTA chromatography. After being cleaved by the Sumo protease, the recombinant ScFv was released from the fusion protein, and further purified by Ni-NTA chromatography. The purity of ScFv was shown to be higher than 95% and their yield reached 4 mg per liter of bacterial culture. In vitro data showed that ScFv can significantly attenuate FGF9-induced phosphorylation of FGFR3. Conclusion: We provide a novel method to produce soluble expression and bioactive functions of ScFv in Escherichia coli.

Background: Creating healthy cities promotes socio-economic development, thus, the creation of such cities has been receiving more attention from the Chinese government and the Chinese people. In the current study, the intention was to conduct a comprehensive evaluation of the creation of healthy cities in Henan province in central China. Methods: We randomly selected 18 cities (7 healthy cities and 11 non-healthy cities) in middle regions of China in 2013 and established evaluation indices to evaluate the beneficial effects by horizontal and vertical comparison analyses. Results: Creating the healthy cities promoted health service, economic development, spiritual and ecological success. This was achieved by constructing cities and changing work style among the officials and establishment of patriotic health organizations. Conclusion: This is the first comprehensive, in-depth, appraisal of the healthy cities in China. We suggest that creating the healthy cities should be promoted a larger extend world-wide since it is beneficial at many levels.

Spectral-spatial classification of hyperspectral images (HSIs) has recently attracted great attention in the research domain of remote sensing. It is well-known that, in remote sensing applications, spectral features are the fundamental information and spatial patterns provide the complementary information. With both spectral features and spatial patterns, hyperspectral image (HSI) applications can be fully explored and the classification performance can be greatly improved. In reality, spatial patterns can be extracted to represent a line, a clustering of points or image texture, which denote the local or global spatial characteristic of HSIs. In this paper, we propose a spectral-spatial HSI classification model based on superpixel pattern (SP) and kernel based extreme learning machine (KELM), called SP-KELM, to identify the land covers of pixels in HSIs. In the proposed SP-KELM model, superpixel pattern features are extracted by an advanced principal component analysis (PCA), which is based on superpixel segmentation in HSIs and used to denote spatial information. The KELM method is then employed to be a classifier in the proposed spectral-spatial model with both the original spectral features and the extracted spatial pattern features. Experimental results on three publicly available HSI datasets verify the effectiveness of the proposed SP-KELM model, with the performance improvement of 10% over the spectral approaches.

A new electrochemical immunosensor for cancer cell detection based on a specific interaction between the metastasis-related antigen of epithelial cell adhesion molecule (EpCAM) on the cell membrane and its monoclonal antibody (Anti-EpCAM) immobilized on a gold electrode has been developed. The amino-terminated polyamidoamine dendrimer (G6 PAMAM) was first covalently attached to the 3-mercaptopropionic acid (MPA)-functionalized gold electrode to obtain a thin film, and then completely carboxylated by succinic anhydride (SA). Next, the Anti-EpCAM was covalently bound with the G6 PAMAM to obtain a stable recognition layer. In the presence of the EpCAM expressing hepatocellular carcinomas cell line of HepG2, the specific immune recognition (Anti-EpCAM/EpCAM) led to an obvious change of the electron transfer ability. The properties of the layer-by-layer assembly process was examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The final determination of HepG2 cells was performed in the presence of the reversible [Fe(CN)6]3−/4− redox couple using impedance technique. Based on the advantages of PAMAM nanomaterial and immune reaction, a linear response to HepG2 cells ranging from 1 × 104 to 1 × 106 cells mL−1 with a calculated detection limit of 2.1 × 103 cells mL−1 was obtained. We expect this method can provide a potential tool for cancer cell monitoring and protein expression analysis.

Track association is an important technology in military and civilian fields. Due to the increasingly complex environment and the diversity of the sensors, it is a key factor to separate the corresponding track from multiple maneuvering targets by multisensors with a consensus. In this paper, we first transform the track association problem to multiattribute group decision making (MAGDM), and describe the MAGDM with nested probabilistic-numerical linguistic term sets (NPNLTSs). Then, a consensus model with NPNLTSs is constructed which has two key processes. One is a consensus checking process, and the other is a consensus modifying process. Based on which, a track association algorithm with automatic modification is put forward based on the consensus model. After that, the solution of a case study in practice is given to obtain the corresponding track by the proposed method, and it provides technical support for the track association problems. Finally, we make comparisons with other methods from three aspects, and the results show that the proposed method is effective, feasible, and applicable. Moreover, some discussions about the situation where there is only one echo point at a time are provided, and we give a discriminant analysis method.