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Prenatal exposures to ambient air pollution have been proved to be associated with adverse perinatal outcomes in previous studies. However, few studies have examined the interaction between air pollution and season of conception on term low birth weight (TLBW) or macrosomia. Birth registry data of singleton live births in Wenzhou, China between January 2015 to December 2016 were accessed from the Wenzhou maternal and child health information management platform, and the ambient air pollutants in Wenzhou were obtained on the Chinese Air Quality Online Monitoring and Analysis Platform. Single/two-pollutant binary logistic regression models were used to assess the associations between ambient air pollutants (PM2.5, PM10, NO2, SO2, and O3) and TLBW/macrosomia, further exploring if the season of conception interacts with air pollution to impact birth weight. Finally, 213,959 term newborns were selected, including 2452 (1.1 %) TLBW infants and 13173 (6.1 %) macrosomia. In single/two-pollutant models, we observed an increased risk of TLBW associated with maternal exposure to PM2.5, PM10, SO2, and NO2 during the entire pregnancy, especially in the the 2nd trimester. Maternal exposure to O3 during the 1st trimester was associated with increased macrosomia risk, and O3 exposure during the 3rd trimester was associated with increased TLBW risk contrarily. Pregnant women conceived in the warm season may undergo more adverse ambient air environment that is related to the risks of TLBW.

We propose and demonstrate a cascaded Raman fiber laser with arbitrary spectral shape and ultra-wide tuning range by controlling the spatial-to-spectral mapping of light in multimode fibers using intracavity wavefront shaping.

Imaging through opacity is proposed based on auto-modulated multimode fiber speckle illumination. The imaging resolution is improved by making use of the intrinsic characteristics of the speckle illumination and a localization strategy.

A self-modulated coherent random fiber laser is proposed for both memory-effect-based imaging and ghost imaging, filling the gap that the two imaging scenarios haven’t been realized using a same light source.

In this work, we demonstrate that the amorphous silica-alumina composite (ASA) is an efficient solid acid for the steam reforming of dimethyl ether (SRD). Thus, a series of ASA with different Si/Al molar ratios was synthesized via the modified hydrolytic method by using Al(NO3)3·9H2O and/or NaAlO2 as Al precursor and tetraethoxysilane as Si precursor, respectively. Irrespective of the synthesis conditions, all of ASA composites were in an amorphous nature. However, both the acidity and the surface area were significantly affected by the synthesis conditions, the extent of which depends on the specific precursor and Si/Al molar ratios. The ASA physically mixed with a commercial Cu/ZnO/Al2O3 was investigated as a bifunctional catalyst for SRD under the conditions of P=0.1 MPa and gas hourly space velocity of 4000 h−1. Results indicate that both the conversion of dimethyl ether (DME) and the hydrogen yield were strongly dependent on the acidic property of ASA and the ASA to Cu/ZnO/Al2O3 ratios. Following the two-step consecutive mechanism of SRD, the catalytic results were well explained based on the acidic property of ASA, and the synergetic effect between the two catalytic functions was found to play a crucial role in determining the activity and stability of the bifunctional catalyst. Moreover, the DME hydrolysis was revealed to be the rate-limiting step for SRD reactions in the case of ASA as an acidic catalyst. By optimizing the synthesis conditions of ASA and the composition of the bifunctional catalyst, greater than 99% of DME conversion and hydrogen yield was achieved, and was kept for a time on stream of 66 h without an observable decrease. Thus, ASA is a very efficient solid acid for SRD.

We investigate the effects of ordering-timing strategies on radio-frequency identification (RFID) adoption sequences and firms’ profitability in a supply chain with a manufacturer and two retailers, both of whom suffer from misplaced inventory problems. The manufacturer is the Stackelberg leader, the two retailers engage in a quantity competition and simultaneously/sequentially make decisions on RFID adoption under two ordering-timing strategies. We derive the equilibrium strategies for RFID adoption and characterize each partner’s optimal order quantity and profit. We show that the equilibrium strategies for RFID adoption are identical regardless of the two competing retailers’ RFID adoption sequences. The retailer with a smaller misplacement rate will never adopt RFID alone. However, for the retailer with a higher misplacement rate: the more intense the competition is, the more likely he is to adopt RFID; ordering later always promotes him to adopt RFID; ordering earlier is more attractive than adopting RFID when the tagging cost is intermediate. Furthermore, as long as one or both retailers adopt RFID, ordering simultaneously can achieve Pareto improvement for both retailers. When neither retailer adopts RFID, the optimal ordering strategies depend on the misplacement rates and competition intensity.

Metabolic clearance of drugs from the body is a key element for future clinical applications. Compared with the liver-bile metabolic route, the renal-urinary route is the most desirable and efficient clearance pathway for practical use in clinical trials and can effectively decrease the long-term risk of unpredictable intracellular catabolism and the potential toxicity to normal organs. However, renal clearable photothermal therapy (PTT) agents were limited. In this paper, a permethyl-β-cyclodextrin-modified quaterrylene bisimide derivative (QDI-CD) was developed. QDI-CD as a biocompatible molecule could effectively be cleared with the renal clearance efficiency of (67.00 ± 2.37)% at 24 h by the renal-urinary route when administered by tail vein injection. Importantly, the structure of QDI-CD in urine after metabolism does not change. Furthermore, QDI-CD, as a potent photoacoustic and photothermal agent, could effectively be enriched in tumor tissue after 4 h of injection and showed the effective PTT in mice. This work developed a potent organic PTT agent with good renal clearance from the body and with promise for future clinical applications.

Soft film corrosion-preventive compounds (CPC) were studied using ASTM B117 accelerated corrosion testing method and a special test specimen. The tested CPCs included a commercial product and homem...

Rationale: Choroidal neovascularization (CNV) is a major cause of severe vision loss and occurs in many ocular diseases, especially neovascular age-related macular degeneration (nAMD). Circular RNAs (circRNAs) are emerging as a new class of endogenous noncoding RNAs, which have been implicated in the regulation of endothelial cell dysfunction in diabetes mellitus and cancer. In this study, we aimed to determine the role of circRNA-ZBTB44 (cZBTB44) in the pathogenesis of CNV. Methods: Quantitative polymerase chain reaction was conducted to detect cZBTB44 expression pattern during CNV development. Isolectin B4 staining, hematoxylin and eosin (HE) staining, and choroidal sprouting assay ex vivo were conducted to evaluate the role of cZBTB44 in the development of CNV. Endothelial cell proliferation, migration and tube formation assays were conducted to determine the role of cZBTB44 in angiogenic effect in vitro. Bioinformatics analysis, RNA immunoprecipitation assay, luciferase assay, and in vitro studies were conducted to investigate the mechanism of cZBTB44-mediated CNV development. Results: cZBTB44 expression was significantly up-regulated in a laser-induced CNV mouse model in vivo and in endothelial cells upon hypoxia stress in vitro. cZBTB44 silencing retarded CNV development, while overexpression of cZBTB44 showed the opposite effects. The role of cZBTB44 in CNV development was confirmed in choroidal sprouting assay ex vivo. cZBTB44 silencing reduced endothelial cell viability, proliferation, migration and tube formation in vitro. cZBTB44 acted as miR-578 sponge to sequester and inhibit miR-578 activity, which led to increased expression of vascular endothelial growth factor A (VEGFA) and vascular cell adhesion molecule-1 (VCAM1). Overexpression of miR-578 mimicked cZBTB44 silencing-mediated anti-angiogenic effects in vivo and in vitro. Furthermore, dysregulated cZBTB44 expression was detected in the clinical samples of nAMD patients. Conclusions: This study provided novel insights into the molecular pathogenesis of CNV. The cZBTB44-miR-578-VEGFA/VCAM1 axis might be a potential source of novel therapeutic targets for neovascularization-related diseases.

A novel glucose biosensor was fabricated by loading a glassy carbon electrode with a 1-methyl imidazole based ionic liquid-functionalized graphene/carbon nanotubes(CNTs) composite, which was used to immobilize horse radish peroxidase (HRP) and glucose oxidase (GOD) for glucose detection. SEM, AFM and FTIR were used to investigate the microstructure and morphology of the electrode. The electrochemical performance of the electrode was investigated by cyclic voltammetry(CV) and electrochemical impedance spectroscopy. Results indicates that the electrode has excellent electrocatalytic activity towards glucose. The biosensor prepared at the optimal loading amount and ratio of HRP to GOD has a linear range of 0.004-5 mmol/L, a detection limit of 3.99×10−7mol/L and a sensitivity of 53.89 μA mmol/L−1cm−2 for glucose detection with an excellent stability and reproducibility. The excellent performance of the biosensor is ascribed to the stable three-dimensional structure, where graphene sheets provide a large surface area for immobilizing two enzymes and CNTs insert between graphene sheets to decrease electron transfer resistance.

The evaluation of developmental and reproductive toxicity of food contact materials (FCMs) is an important task for food safety. Since traditional experiments are both time-consuming and labor-intensive, only a small number of FCMs have sufficient toxicological data for evaluating their effects on human health. While computational methods such as structural alerts and quantitative structure–activity relationships can serve as first-line tools for the identification of chemicals of high toxicity concern, models with binary outputs and unsatisfied accuracy and coverage prevent the use of computational methods for prioritizing chemicals of high concern. This study proposed a genetic algorithm-based method to develop a weight-of-evidence (WoE) model leveraging complementary methods of structural alerts, quantitative structure–activity relationships and in silico toxicogenomics models for chemical prioritization. The WoE model was applied to evaluate 623 food contact chemicals and identify 26 chemicals of high toxicity concern, where 13 chemicals have been reported to be developmental or reproductive toxic and further experiments are suggested for the remaining 13 chemicals without toxicity data related to developmental and reproductive effects. The proposed WoE model is potentially useful for prioritizing chemicals of high toxicity concern and the methodology may be applied to toxicities other than developmental and reproductive toxicity.

Ecofriendly green biosynthesis of bacterial cellulose (BC) using a low-cost carbon source from the shell extract of Sapindus mukorossi was studied by Komagataeibacter xylinus B2-1. After 7 d of incubation, strain B2-1 produced 1.31 g L−1 BC, which had similar micro-morphology and structural properties to that from Hestrin–Schramm medium based on scanning electron microscopy, X-ray diffraction and Fourier transform infrared analyses. While strain B2-1 grew well and produced BC efficiently at pHs ranging from 4.0 to 6.0, the considerable BC production was only found at temperature of 30 °C. The present investigation can provide a new low-cost carbon source for BC preparation and lead towards commercialization and industrial scale up BC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common subtype of all lung cancers, and KRAS is the most common mutation in this population. Unfortunately, this subgroup remains “undruggable” with the lack of an approved targeted therapy. Selumetinib has been investigated as a secondary therapy in several trials and compared to various drug regimens. Therefore, we conducted this systematic review and network meta-analysis to determine the comparative effectiveness of this drug as compared to others in patients with late-stage and malignant NSCLC. METHODS: Up to July 1, 2020, 9 databases (PubMed, Scopus, Web of Science, mRCT, ICTRP, clinicaltrials.gov, VHL, SIGLE, and Google Scholar) were searched for studies following the PICOS framework: randomized trials reporting the efficacy (rate of disease progression/lack of response) of selumetinib compared to other therapies in patients with late-stage/metastatic NSCLC. The quality of retrieved studies were assessed with the revised Cochrane risk-of-bias tool. Frequentist network meta-analysis was conducted to estimate the efficacy of selumetinib as compared to other therapies and/or placebo. RESULTS: Out of the 163 articles yielded from the primary search, 9 studies (1,195 patients) were finally included in our systematic review. The majority of clinical cases had a performance status (PS) of 0–2, and the mean age was 62 years. The overall efficacy of selumetinib was 71.77% (95% CI: 63.24–81.45%), with selumetinib administered alone having better efficacy compared to combined therapy (65.20% vs. 74.08%). In the network analysis, selumetinib had higher efficacy compared to chemo- or immune therapy, but not significantly so. The overall SAE rate of selumetinib was 42.96% (95% CI: 34.74–53.13%), with selumetinib having a significantly better safety profile compared to combined therapy (10.49% vs. 47.38%). In the network analysis, the placebo had the best safety profile followed by selumetinib and chemo- and immune therapy. Five studies had high risk of bias, 2 had some concerns, and 2 had low risk of bias. DISCUSSION: The efficacy of selumetinib is not superior compared to combined therapy for treating NSCLC but does have a better safety profile. Current evidence is still limited, and more robust trials are still required.

Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population.Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations.Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10–6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10–4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (β = −1.32, P < 0.001), Bifidobacteriaceae (β = −1.70, P < 0.001), and Bifidobacterium (β = −1.70, P < 0.001) compared to the CC genotype.Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.

AIM: To explore the performance in diabetic retinopathy (DR) screening of artificial intelligence (AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional tabletop fundus cameras and the diagnostic accuracy of DR of the two modalities. METHODS: Overall, 630 eyes were included from three centers and screened by a handheld camera (Aurora, Optomed, Oulu, Finland) and a table-top camera. Image quality was graded by three masked and experienced ophthalmologists. The diagnostic accuracy of the handheld camera and AI system was evaluated in assessing DR lesions and referable DR. RESULTS: Under nonmydriasis status, the handheld fundus camera had better image quality in centration, clarity, and visible range (1.47, 1.48, and 1.40) than conventional tabletop cameras (1.30, 1.28, and 1.18; P

In mainland China, there remains a shortage of pediatric drugs. The Chinese government has recently launched policies and incentives to encourage pediatric drug development and clinical trials. However, data on the characteristics or development trends of these trials are limited. In this review, we extracted source data from the Chinese Clinical Trials Registry and Information Transparency Platform and systematically reviewed the pediatric clinical trials conducted in mainland China from 2009 to 2020, a comprehensive process evaluation of the pediatric drug clinical trials development in the past decade, providing data support to policy makers and industry stakeholders. We included 487 pediatric clinical trials. Over the past decade, the number of pediatric trials has increased, especially since 2016. The most common therapeutic areas were infectious diseases (n = 108, 22.2%), agents for preventive purpose (n = 99, 20.3%), and neurological and psychiatric diseases (n = 71, 14.6%). The number of clinical trials involving epilepsy (39, 10.1%), asthma (33, 8.5%), and influenza (24, 6.2%) were the highest. The distribution of leading institutions is unbalanced in mainland China, with most units in East China (34.0%) and few in Southwest China (6.9%). China has made progress in improving the research and development environment of pediatric drugs and increasing pediatric trials. However, a wide gap in pediatric drug development and clinical trials quality exists between China and the developed countries. The pharmaceutical industry in China has faced grim setbacks, including study duplication, lack of innovation, poor research design, and unbalanced resource allocation. Thus, we suggest that the Chinese government should adjust their policies to improve innovation and clinical design capacity, and optimize resource allocation between regions.

With the development of high-throughput sequencing technology, the posttranscriptional mechanism of alternative splicing is becoming better understood. From decades of studies, alternative splicing has been shown to occur in multiple tissues, including the brain, heart, testis, skeletal muscle, and liver. This regulatory mechanism plays an important role in physiological functions in most liver diseases. Currently, due to the absence of symptoms, chronic pediatric liver diseases have a significant impact on public health. Furthermore, the progression of the disease is accelerated in children, leading to severe damage to their liver tissue if no precautions are taken. To this end, this review article summarizes the current knowledge of alternative splicing in pediatric liver diseases, paying special attention to liver damage in the child stage. The discussion of the regulatory role of splicing in liver diseases and its potential as a new therapeutic target is also included.

As the unique component of Dendrobium, dendrobine-type sesquiterpenoid alkaloids (DSAs) possess a variety of medicinal properties. It has been well documented that plant endophytes can in vitro synthesize secondary metabolites identical or similar to metabolites produced by their host plants. This study aimed to investigate the composition and distribution of endophytic bacteria of Dendrobium stems by Illumina MiSeq platform sequencing and cultivation-dependent methods and then to assess the potential for endophytic bacteria to produce DSAs. Results indicated that it was necessary to combine both cultivation-dependent and cultivation-independent methods to analyze the community structure of endophytic bacterial in plants comprehensively. The length of the Dendrobium stems influenced the endophytic bacterial community. The diversity and richness of endophytic bacteria in group J10_15cm of stems were the highest, which showed a significant difference from the other stem groups. However, there was no certain connection between the diversity and richness of endophytic bacteria and the content of dendrobine. It was most likely due to the influence of several specific endophytic bacteria genera, such as Sphingomonas and Rhodococcus. Athelia rolfsii, Myrothecium roridum, as pathogenic fungi, and Pectobacterium carotovorum subsp. actinidiae, as pathogenic bacteria of Dendrobium, were used to determine the antimicrobial activities. In these assays, six strains belonging to five genera showed antimicrobial activity against at least two phytopathogens. The strain BL-YJ10_15-29 (Paracoccus pueri THG-N2.35, 98.98%) showed the best antimicrobial activity against the three phytopathogens. In addition, 2 DSAs (6-hydroxydendrobine and nobilonine) were identified in the fermentation supernatant of the strain CM-YJ10_15-44 (Pseudomonas protegens CHA0, 99.24%), whereas the whole-genome analysis results further demonstrated that the precursors of the two DSAs [geranyl-PP and (E, E)-famesyl-PP] were synthesized mainly through the methyl-D-erythritol 4-phosphate pathway in this strain. This study provides new insight into the studies on the biosynthesis of DSAs and provides potential biocontrol bacteria.

Accumulation of iron in seeds is essential for both plant reproduction and human nutrition. Transport of iron to seeds requires the chelator nicotianamine (NA) to prevent its precipitation in the plant vascular tissues. However, how NA is transported to the apoplast for forming metal-NA complexes remains unknown. Here, we report that two members of the nitrate/peptide transporter family, NAET1 and NAET2, function as NA transporters required for translocation of both iron and copper to seeds. We show that

Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population. Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations. Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10–6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10–4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (β = −1.32, P < 0.001), Bifidobacteriaceae (β = −1.70, P < 0.001), and Bifidobacterium (β = −1.70, P < 0.001) compared to the CC genotype. Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.

Compounds(1-6) were isolated and identified from 90% ethanol extract of the stems and leaves of Cassia occidentalis through column chromatography with silica gel, ODS, and Sephadex LH-20. These compounds were identified as 7-hydroxy-5-(3-hydroxy-2-oxopropyl)-2-methyl-4H-chromen-4-one(1), saccharonol A(2), S-6-hydroxymullein(3), 2-methyl-5-acetonyl-7-hydroxy-chromone(4), 2-(2'-hydroxypropyl)-5-methyl-7-hydroxychromone(5) and 7,4'-dihydroxyflavone(6) based on their physicochemical and spectroscopic data. Among them, compound 1 was a new compound, and all the compounds were isolated from this plant for the first time. DPPH method was employed to determine the antioxidant activities of these compounds in vitro. Six compounds exhibited weak antioxidant activities.

Low dimensional ferroelectrics are highly desired for applications and full of exotic physics. Here a functionalized MXene Hf$_2$CF$_2$ monolayer is theoretically studied, which manifests a nonpolar to polar transition upon moderate biaxial compressive strain. Accompanying this structural transition, a metal-semiconductor transition occurs. The in-plane shift of unilateral fluorine layer leads to a polarization pointing out-of-plane. Such ferroelectricity is unconventional, similar to the recently-proposed interlayer-sliding ferroelectricity but not identical. Due to its specific hexapetalous potential energy profile, the possible ferroelectric switching paths and domain walls are nontrivial, which are mediated via the metallic paraelectric state. In this sense, the metallic walls can be manipulated by reshaping the ferroelectric domains., 7 pages, 6 figures

The regulation of adult neural stem cells (NSCs) is critical for lifelong neurogenesis. MicroRNAs (miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, miR-103-3p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that miR-103-3p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, miR-103-3p negatively regulated NudE neurodevelopment protein 1-like 1 (Ndel1) expression by binding to the 3' untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel miR-103-3p target and that miR-103-3p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20200826-003) on August 26, 2020.

To evaluate the clinical therapeutic effect of electroacupuncture (EA) atThe data of 318 patients undergoing anal fistula surgery were analyzed retrospectively. In accordance with whether accepted the combined treatment with EA at bilateralFor VAS score, there was an interaction between therapeutic method and treatment duration (Electroacupuncture at

The active zone of a presynaptic nerve terminal defines sites for neurotransmitter release. Its protein machinery may be organized through liquid–liquid phase separation, a mechanism for the formation of membrane-less subcellular compartments. Here, we show that the active zone protein Liprin-α3 rapidly and reversibly undergoes phase separation in transfected HEK293T cells. Condensate formation is triggered by Liprin-α3 PKC-phosphorylation at serine-760, and RIM and Munc13 are co-recruited into membrane-attached condensates. Phospho-specific antibodies establish phosphorylation of Liprin-α3 serine-760 in transfected cells and mouse brain tissue. In primary hippocampal neurons of newly generated Liprin-α2/α3 double knockout mice, synaptic levels of RIM and Munc13 are reduced and the pool of releasable vesicles is decreased. Re-expression of Liprin-α3 restored these presynaptic defects, while mutating the Liprin-α3 phosphorylation site to abolish phase condensation prevented this rescue. Finally, PKC activation in these neurons acutely increased RIM, Munc13 and neurotransmitter release, which depended on the presence of phosphorylatable Liprin-α3. Our findings indicate that PKC-mediated phosphorylation of Liprin-α3 triggers its phase separation and modulates active zone structure and function., Liquid–liquid phase separation may be a mechanism for organizing the presynaptic nerve terminal. Here, the authors show that PKC-mediated phosphorylation of Liprin-α3 triggers phase separation in cell lines and modulates active zone structure and function in primary hippocampal neurons.

Glioblastoma multiform (GBM) is the most common and malignant primary brain cancer in adults, and thus, novel potential therapeutic targets for diagnosis and treatment are urgently needed. Circular RNAs (circRNAs) are a class of widespread and diverse endogenous RNAs that have been suggested as potential critical mediators during progression of various tumors. In this study, we investigated the involvement of circHECTD1 in GBM progression. CircHECTD1 Lentivirus, miR-320-5p mimic, and SLC2A1 Lentivirus were transduced into cancer cells independently or together. circHECTD1, miR-320-5p, and SLC2A1 level were detected by qRT-PCR. Western blot and qRT-PCR were applied to measure the expression of SLC2A1, CyclinD1, CDK2, and PCNA. Flow cytometry, EdU, colony formation, Transwell and wound-healing assays were conducted to assess cell proliferation and migration. Luciferase reporter assays were performed to determine the effect of miR-320-5p on circHECTD1 or SLC2A1. Xenograft experiments were implemented to evaluate tumor growth in vivo. CircHECTD1 expression led to the promotion of proliferation and migration of GBM cells. In addition, circHECTD1 acted as a ceRNA to interact with miR-320-5p, which targeted the solute carrier family 2 member 1 (SLC2A1). In vivo experiments also revealed that circHECTD1 promoted tumor growth. Collectively, our findings showed that the circHECTD1-miR-320-5p-SLC2A1 regulatory pathway promoted the progression of GBM, suggesting that circHECTD1 may be a therapeutic target for GBM.

Purpose The purpose of this paper is to study how to improve the performance of RFID robot system by anti-collision algorithms. For radio frequency identification (RFID) robots operating in mobile scenes, effective anti-collision algorithm not only reduces missed reading but also enhances the speed of RFID robots movement. Design/methodology/approach An effective anti-collision algorithm is proposed to accelerate tag identification in RFID robots systems in this paper. The tag collisions in the current time slot are detected by a new method, and then further resolve each small tag collision to improve system throughput, rather than the total tags number estimation. After the reader detected the collision, three different collision resolution methods were described and studied, and the situation of missing tag caused by reader moving is also discussed. Findings The proposed algorithm achieves theoretical system throughput of about 0.48, 0.50 and 0.61 and simulates to show that the proposed algorithm performance is significantly improved compared with the existing ALOHA-based algorithm. Originality/value The proposed RFID anti-collision algorithm is beneficial to improve the moving speed and identification reliability of the RFID robots in complex environments.

The evolution process of sulfate ion diffusion coefficient is investigated using the probabilistic approach base on a mesoscopic physical model of concrete subjected to external sulfate attack. The effects of randomness from multi-factors are comprehensively discussed. Furthermore, the calculation results are compared with the experimental data in the literature. The results show that the experimental data are some samples of a random event, occurring with some probability. Compared with the conventional deterministic model of the diffusion coefficient, the stochastic model using the probabilistic approach proposed in this article can be used to describe the evolution process of the diffusion coefficient with different initial conditions. And the probability density functions (PDFs) of the diffusion coefficient at different time steps can be obtained conveniently. In addition, it is also shown that the variability of the diffusion coefficient essentially comes from the uncertainty of the porosity of concrete.

A general one-step synthesis of symmetrical or unsymmetrical 1,4-di(organo)fullerenes from organo(hydro)fullerenes (RC60H) is realized by direct oxidative arylation. The new combination of catalytic trifluoromethanesulfonic acid (TfOH) and stoichiometric o-chloranil is the first to be used to directly generate an R-C60+ intermediate from common RC60H. Unexpectedly, the in situ generated R-C60+ intermediate is shown to be quite stable in whole 13C NMR spectroscopy characterization in the absence of cation quenching reagents. Because the direct oxidation of common RC60H to form the corresponding R-C60+ has never been realized, the present combination of TfOH and o-chloranil solves the challenges associated with the formation of stable RC60+ cations from common RC60H without any coordination of an R group.

Dendrobium is known for its pharmacological actions including anti-cancer effect, anti-fatigue effect, gastric ulcer protective effect, and so on. At present, only studies on endophytic fungi of Dendrobium affecting the metabolites of host plants have been reported, very little research has been done on endophytic bacteria. In this study, we have demonstrated the great diversity of endophytic bacteria in 6 Dendrobium samples from different origins and cultivars. According to the results of the culture-independent method, the endophytic bacterial community in Dendrobium stems showed obvious different in the 6 samples and was influenced by origin and cultivar. Some bacteria including Ralstonia, Comamonas and Lelliottia were first detected in Dendrobium in this study. Based on the culture-dependent method, a total of 165 cultivable endophytic bacteria isolates were isolated from the sterilized Dendrobium stems, and were classified into 43 species according to the 16S rRNA gene sequence analysis. Moreover, 14 of the 43 strains showed antimicrobial activity against phytopathogen using the Kirby-Bauer method. Strain NA-HTong-7 (Bacillus megaterium, 99.12%) showed the highest antimicrobial activity. This study was the first comprehensive study on endophytic bacteria of Dendrobium from different origins and cultivars, which provides new insights into the endophytic bacteria from Dendrobium.

Efficient hydrogen evolution via electrocatalytic water splitting holds great promise in modern energy devices. Herein, we demonstrate that the localized surface plasmon resonance (LSPR) excitation of Au nanorods (NRs) dramatically improves the electrocatalytic hydrogen evolution activity of CoFe-metal-organic framework nanosheets (CoFe-MOFNs), leading to a more than 4-fold increase of current density at -0.236 V (vs. RHE) for Au/CoFe-MOFNs composite under light irradiation versus in dark. Mechanistic investigations reveal that the hydrogen evolution enhancement can be largely attributed to the injection of hot electrons from AuNRs to CoFe-MOFNs, raising the Fermi level of CoFe-MOFNs, facilitating the reduction of H2 O and affording decreased activation energy for HER. This study highlights the superiority of plasmonic excitation on improving electrocatalytic efficiency of MOFs and provides a novel avenue towards the design of highly efficient water-splitting systems under light irradiation.

Background and purpose The Na+ /Ca2+ exchanger (NCX) working in either forward or reverse mode participates in maintaining intracellular Ca2+ ([Ca2+ ]i ) homeostasis, which is essential for determining cell fate. Previously, numerous blockers targeting reverse or forward NCX have been developed and studied in ischaemic tissue injury but barely examined in glioblastoma for the purpose of anti-tumour therapy. We assessed the effect of NCX blockers on glioblastoma growth and whether NCX can become a therapeutic target. Experimental approach Patch-clamp recording, Ca2+ imaging, flow cytometry, and Western blot were used to study the effects of specific and non-specific NCX blockers on cultured glioblastoma cells. In vivo bioluminescent imaging was used to measure effects on grafted glioblastoma. Key results Selectively blocking the reverse NCX with SEA0400, SN-6, and YM-244769 did not affect tumour cell viability. Blocking the forward NCX with bepridil, CB-DMB, or KB-R7943 elevated [Ca2+ ]i and killed glioblastoma cells. Bepridil and CB-DMB caused Ca2+ -dependent cell cycle arrest together with apoptosis, which were all attenuated by a Ca2+ chelator BAPTA-AM. Systemic administration of bepridil inhibited growth of brain-grafted glioblastoma. Bepridil did not appear to have a cytotoxic effect on human astrocytes, which have higher functional expression of NCX than glioblastoma cells. Conclusions and implications Low expression of the NCX makes glioblastoma cells sensitive to disturbance of [Ca2+ ]i . Interventions designed to block the forward NCX can cause Ca2+ -mediated injury to glioblastoma thus having therapeutic potential. Bepridil could be a lead compound for developing new anti-tumour drugs.

Background:Methotrexate (MTX) is one of the leading chemotherapeutic agents with the bestdemonstrated efficacies against childhood acute lymphoblastic leukemia (ALL). Due to the narrow therapeutic range, significant inter- and intra-patient variabilities of MTX, non-effectiveness and/or toxicity occur abruptly to cause chemotherapeutic interruption or discontinuation. The relationship between clinical outcome and the systemic concentration of MTX has been well established, making the monitoring of plasma MTX levels critical in the treatment of ALL. Besides metabolizing enzymes, multiple transporters are also involved in determining the intracellular drug levels. In this mini-review, we focused on the genetic polymorphisms of MTX-disposition related transporters and the potential association between the discussed genetic variants and MTX pharmacokinetics, efficacy, and toxicity in the context of MTX treatment.Methods:We searched PubMed for citations published in English using the terms “methotrexate”, “transporter”, “acute lymphoblastic leukemia”, “polymorphisms”, and “therapeutic drug monitoring”. The retrieval papers were critically reviewed and summarized according to the aims of this mini-review.Results:Solute carrier (SLC) transporters (SLC19A1, SLCO1A2, SLCO1B1, and SLC22A8) and ATP-binding cassette (ABC) transporters (ABCB1, ABCC2, ABCC3, ABCC4, ABCC5, and ABCG2) mediate MTX disposition. Of note, the influences of polymorphisms of SLC19A1, SLCO1B1 and ABCB1 genes on the clinical outcome of MTX have been extensively studied.Conclusion:Overall, the data critically reviewed in this mini-review article confirmed that polymorphisms in the genes encoding SLC and ABC transporters confer higher sensitivity to altered plasma levels, MTX-induced toxicity, and therapeutic response in pediatric patients with ALL. Pre-emptive determination may be helpful in individualizing treatment.

The platinum nanoparticles-reduced graphene oxide-multi-walled carbon nanotubes composite (PtNPs-rGO-MWCNTs) has been synthesised by one-step chemical co-reduction strategy in ethylene glycol (EG) ...

The field of plasmonics brings new opportunities in various fields such as photocatalysis, nanophotonics, photovoltaics and photothermal therapeutics. In particular, the generation of hot carriers (hot holes and electrons) as well as the phtothermal effect via excitation of localized surface plasmon resonance (LSPR) can be used to activate chemical reactions. Understanding the underlying mechanism requires quantitative measurements of catalytic enhancement on the plasmonic nanostructures. In this work, the plasmonic gold nanostar (AuNSs) activated electrocatalysis was investigated using ascorbic acid (AA) as a reaction model. We found that AuNSs shows significantly enhanced electrochemical performance upon LSPR excitation. By measurement of the reaction activation energy, open circuit potential (OCP), and the wavelength and light intensity-dependent current responses, it is proposed that the efficient hot carriers separation, reduced activation energy and considerate photothermal effect contribute to the promoted electrocatalysis. Based on the study, a direct plasmon-improved electrochemical sensor towards sensitive detection of AA is constructed, and AA concentration as low as 10.0 μM can be successfully detected. The present work would shed new mechanistic insights into the plasmon-mediated electrochemical processes.

In this work, Ni3S2/Ni foam was successfully synthesized using a facile gas-phase method of annealing Ni foam in H2S atmosphere. It was used as a binder free electrode for high-performance supercapacitors. The areal capacitance increases rapidly in the initial charge-discharge cycling and then reaches a stable stage. An ultrahigh areal capacitance of 9.88 F cm−2 at the current density of 10 mA cm−2 is achieved in the stable charge-discharge stage, which is around 88 times of initial capacitance (112.5 mF cm−2). Further studies reveal that surface Ni3S2 transforms into porous Ni(OH)2 during charge-discharge process, and surface area increases more than 100 times. The soaring specific surface area is the dominant factor contributing to the increased areal capacitance. More importantly, this self-formed porous structure exhibits ultra-stable long-time cycling ability, as no capacity fading is observed even after 60000 cycles of charge-discharge at high current density (150 mA cm−2). These results indicate that self-formed porous Ni(OH)2 structure during electrochemical cycling maybe a promising electrode for high performance supercapacitor applications.

The mechanisms of naso-ocular interaction in allergic rhinoconjunctivitis are not well understood. Neurogenic inflammation affects both eyes and nose via the same neurogenic factors. The purpose of this study was to investigate the effects of neurogenic inflammation on conjunctival inflammation following nasal allergen provocation. Sensitized rats were exposed to ovalbumin (OVA) via the nose. Parts of the nasal mucosa and conjunctivae were sliced and used for hematoxylin–eosin staining, immunohistochemical analysis, western blotting, and real-time polymerase chain reaction. The slides were observed under a light microscope, and the acquired images were analyzed. The levels of substance P (SP), vasoactive intestinal peptide (VIP), and nerve growth factor (NGF) were detected. The levels of SP, VIP, and NGF were increased in both nasal mucosa and conjunctivae 1 h and 24 h after OVA administration (p

MicroRNAs refer to a class of endogenous, short non-coding RNAs that mediate numerous biological functions. MicroRNAs regulate various physiological and pathological activities of peripheral nerves, including peripheral nerve repair and regeneration. Previously, using a rat sciatic nerve injury model, we identified many functionally annotated novel microRNAs, including miR-sc14. Here, we used real-time reverse transcription-polymerase chain reaction to examine miR-sc14 expression in rat sciatic nerve stumps. Our results show that miR-sc14 is noticeably altered following sciatic nerve injury, being up-regulated at 1 day and diminished at 7 days. EdU and transwell chamber assay results showed that miR-sc14 mimic promoted proliferation and migration of Schwann cells, while miR-sc14 inhibitor suppressed their proliferation and migration. Additionally, bioinformatic analysis examined potential target genes of miR-sc14, and found that fibroblast growth factor receptor 2 might be a potential target gene. Specifically, our results show changes of miR-sc14 expression in the sciatic nerve of rats at different time points after nerve injury. Appropriately, up-regulation of miR-sc14 promoted proliferation and migration of Schwann cells. Consequently, miR-sc14 may be an intervention target to promote repair of peripheral nerve injury. The study was approved by the Jiangsu Provincial Laboratory Animal Management Committee, China on March 4, 2015 (approval No. 20150304-004).

A phytochemical investigation on the whole plant of Oxytropis falcata Bunge yielded 16 glycoconjugated compounds with structurally diverse volatile aglycones but similar sugars. Of these, five were previously undescribed compounds with different volatile aglycones but same glucuronic acid (1 → 2) glucosyl moiety, including three octanol glucuronic acid (1 → 2) glucosides (1–3), one acyclic monoterpenoid glucuronic acid (1 → 2) glucoside (4), and one 4-phenyl-butan-2-ol glucuronic acid (1 → 2) glucoside (5), and 11 were biological related known glucoconjugated volatile compounds (6–16) isolated from genus Oxytropis for the first time. The structures of these compounds were determined by extensive spectroscopic analysis of MS, 1D and 2D NMR data. The absolute configurations of aglycones and sugar residues were assigned via enzymatic hydrolysis and subsequently comparison of the specific rotations. This is the first report of such structurally diverse glycoconjugated volatile compounds from O. falcata, which might be regarded as the precursor of free volatile compounds, and presents scientific evidences for better clarifying the volatile compositions of this medicinal plant and genus Oxytropis.