Search

Translocation renal cell carcinoma (tRCC) is an aggressive subtype of kidney cancer driven by TFE3 gene fusions, which act via poorly characterized downstream mechanisms. Here we report that TFE3 fusions transcriptionally rewire tRCCs toward oxidative phosphorylation (OXPHOS), contrasting with the highly glycolytic metabolism of most other renal cancers. This TFE3 fusion-driven OXPHOS program, together with heightened glutathione levels found in renal cancers, renders tRCCs sensitive to reductive stress - a metabolic stress state induced by an imbalance of reducing equivalents. Genome-scale CRISPR screening identifies tRCC-selective vulnerabilities linked to this metabolic state, including EGLN1 , which hydroxylates HIF-1α and targets it for proteolysis. Inhibition of EGLN1 compromises tRCC cell growth by stabilizing HIF-1a and promoting metabolic reprogramming away from OXPHOS, thus representing a vulnerability to OXPHOS-dependent tRCC cells. Our study defines a distinctive tRCC-essential metabolic program driven by TFE3 fusions and nominates EGLN1 inhibition as a therapeutic strategy to counteract fusion-induced metabolic rewiring., Competing Interests: Declaration of Interests S.R.V. has consulted for Jnana Therapeutics within the past 3 years and receives research support from Bayer. L.B-P. is a co-founder, holds equity in and is a consultant for Scorpion Therapeutics.

Drought stress significantly impacts global rice production, highlighting the critical need to understand the genetic basis of drought resistance in rice. Here, through a genome-wide association study, we reveal that natural variations in DROUGHT RESISTANCE GENE 9 (DRG9), encoding a double-stranded RNA (dsRNA) binding protein, contribute to drought resistance. Under drought stress, DRG9 condenses into stress granules (SGs) through liquid-liquid phase separation via a crucial α-helix. DRG9 recruits the mRNAs of OsNCED4, a key gene for the biosynthesis of abscisic acid, into SGs and protects them from degradation. In drought-resistant DRG9 allele, natural variations in the coding region, causing an amino acid substitution (G267F) within the zinc finger domain, increase DRG9's binding ability to OsNCED4 mRNA and enhance drought resistance. Introgression of the drought-resistant DRG9 allele into the elite rice Huanghuazhan significantly improves its drought resistance. Thus, our study underscores the role of a dsRNA-binding protein in drought resistance and its promising value in breeding drought-resistant rice., (© 2024. The Author(s).)

Corn steep liquor-assisted microbial remediation has been proposed as a promising strategy to remediate cadmium (Cd)-contaminated soil. In this study, we determined Bacillus subtilis (K2) with a high cadmium (Cd) accumulation ability and Cd resistance. However, studies on this strategy used in the Cd uptake of Chinese cabbage are lacking, and the effect of the combined incorporation of corn steep liquor and K2 on the functions and microbial interactions of soil microbiomes is unclear. Here, we study the Cd uptake and transportation in Chinese cabbage by the combination of K2 and corn steep liquor (K2 + C7) in a Cd-contaminated soil and corresponding microbial regulation mechanisms. Results showed that compared to inoculant K2 treatment alone, a reduction of Cd concentration in the shoots by 14.4% and the dry weight biomass of the shoots and the roots in Chinese cabbage increased by 21.6% and 30.8%, respectively, under K2 + C7 treatment. Meanwhile, hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) levels were decreased by enhancing POD and SOD activity, thereby reversing Cd-induced oxidative damage. Importantly, inoculation of K2 would decrease the diversity of the microbial community while enhancing the abundance of dominant species. These findings provide a promising strategy for reducing the Cd accumulation in Chinese cabbage and recovering soil ecological functions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Gray leaf spot (GLS) caused by Cercospora zeina or C. zeae-maydis is a major maize disease throughout the world. Although more than 100 QTLs resistant against GLS have been identified, very few of them have been cloned. Here, we identified a major resistance QTL against GLS, qRglsSB, explaining 58.42% phenotypic variation in SB12×SA101 BC 1 F 1 population. By fine-mapping, it was narrowed down into a 928 kb region. By using transgenic lines, mutants and complementation lines, it was confirmed that the ZmWAK02 gene, encoding an RD wall-associated kinase, is the responsible gene in qRglsSB resistant against GLS. The introgression of the ZmWAK02 gene into hybrid lines significantly improves their grain yield in the presence of GLS pressure and does not reduce their grain yield in the absence of GLS. In summary, we cloned a gene, ZmWAK02, conferring large effect of GLS resistance and confirmed its great value in maize breeding., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Use of cationic lipid vesicles (liposomes) can yield large amounts of nucleic acid entrapped inside the vesicles and/or bound to the external surface of the vesicles. To show a method to prepare asymmetric lipid vesicles (liposomes) with high amounts of entrapped nucleic acid is possible, symmetric and asymmetric lipid vesicles composed of mixtures of neutral (zwitterionic), anionic, and/or cationic phospholipids were formed in the presence of oligo DNA. For symmetric large unilamellar vesicles nucleic acid association with vesicles was roughly 100 times greater for vesicles with a net cationic charge than for vesicles having a net neutral or anionic net charge. A high degree of association between nucleic acid and lipid was also achieved using asymmetric large unilamellar vesicles with a net cationic charge in their inner leaflet, even when they had an anionic charge in their outer leaflet. In contrast, asymmetric vesicles in which only the outer leaflet had a net cationic charge had only low amounts of vesicle-associated nucleic acid, similar in amount to the amount of nucleic acid associated with asymmetric vesicles with an outer leaflet having a net anionic charge. These results indicate that in asymmetric vesicles with cationic lipid enriched inner leaflets nucleic acid is largely entrapped inside the vesicle lumen rather than bound to their external surface, and that asymmetric vesicles can be used to trap high amounts of nucleic acid even when using a lipid composition in the outer leaflet of a lipid vesicle that does not associate with nucleic acids. Such asymmetrically charged vesicles should have applications in studies of membrane protein-nucleic acid interactions as well as in studies of how membrane charge asymmetry can influence membrane protein structure, orientation, and function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Gas protection is a crucial part of quality control in laser welding, especially for titanium alloy, which oxidizes easily at high temperatures. Substantial experiments concerning shielding gas characteristics in the welding process have been implemented. However, the common analysis conducted is simplistic and lacks a theoretical basis. This paper presented an investigation of the shielding gas behaviors based on numerical simulation and a titanium alloy laser welding experiment. The numerical model was established and validated by experiment. Subsequently, the temperature field and gas flow fields were calculated. By combining the two fields, the threshold temperature of gas protection was determined, and the influence of shielding gas parameters on the protection effect was examined. The results revealed that the protection of the high-temperature zone was primarily influenced by the nozzle height, nozzle inner diameter, and nozzle angle, while the plasma suppression effect was mainly correlated with the nozzle inner diameter and gas flow rate. These initial findings provide scientific guidance for the better quality production of laser beam welded components made of not only titanium alloy but also other metallic materials.

Diabetic chronic wound healing still faces huge clinical challenge. The arrangement and coordination of healing processes are disordered in diabetic wound caused by the persistent inflammatory response, microbial infection, impaired angiogenesis, resulting in the delayed and even non-healing wounds. Here, the dual-drug loaded nanocomposite polysaccharide-based self-healing hydrogels (OCM@P) with multifunctionality were developed to promote diabetic wound healing. Curcumin (Cur) loaded mesoporous polydopamine nanoparticles (MPDA@Cur NPs) and metformin (Met) were introduced into the polymer matrix formed by the dynamic imine bonds and electrostatic interactions between carboxymethyl chitosan and oxidized hyaluronic acid to fabricate OCM@P hydrogels. OCM@P hydrogels show homogeneous and interconnected porous microstructure, which possess good tissue adhesiveness, enhanced compression strength, great anti-fatigue behavior, excellent self-recovery capacity, low cytotoxicity, rapid hemostatic ability and robust broad-spectrum antibacterial activity. Interestingly, OCM@P hydrogels exhibit rapid release of Met and long-term sustained release of Cur, thereby to effectively scavenge extracellular and intracellular free radicals. Significantly, OCM@P hydrogels remarkably promote re-epithelization, granulation tissue formation, collagen deposition and arrangement, angiogenesis as well as wound contraction in diabetic wound healing. Overall, the multifunctional synergy of OCM@P hydrogels greatly contributes to accelerating diabetic wound healing, which demonstrate promising application as scaffolds in regenerative medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Waterlogging has been shown to have a significant inhibitory effect on plant growth. However, the response mechanisms of the soil environment of sugar beet seedlings under waterlogging conditions still need to be fully understood. This study aimed to investigate the effects of waterlogging treatments on the content of effective nutrients and the microbial communities in the rhizosphere and non-rhizosphere using high-throughput sequencing. We set up waterlogging and non-waterlogging treatments, sampled sugar beet seedlings after 10 days of waterlogging, determined the effective soil nutrients in the rhizosphere and non-rhizosphere of the plants, and analyzed the differences in microbial diversity at ten days of waterlogging. The results showed that waterlogging significantly affected available potassium (AK) content. The Ak content of waterlogged soil was significantly higher than that of non-waterlogged soil. Waterlogging caused no significant difference in available nitrogen (AN) content and pH. Moreover, the plant growth-promoting bacteria Pseudomonas was significantly enriched in sugar beet waterlogged rhizospheres compared with the non-waterlogged ones. Similarly, the harmful fungi Gibellulopsis and Alternaria were enriched in sugar beet non-waterlogged rhizosphere. The network analysis revealed that waterlogging built a less complex root-microbial network than non-waterlogging. These findings implied that sugar beets subjected to waterlogging stress were enriched with beneficial microorganisms in the rhizosphere, potentially alleviating the stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Key Message: Here, we report that ZmAGO18b encoding an argonaute protein is a negative regulator of maize resistance against southern leaf blight. Southern leaf blight caused by fungal pathogen Cochliobolus heterostrophus is a destructive disease on maize throughout the world. Argonaute (AGO) proteins, key regulators in small RNA pathway, play important roles in plant defense. But whether they have function in maize resistance against C. heterostrophus is unknown. Association analysis between the nucleic variation of 18 ZmAGO loci with disease phenotype against C. heterostrophus was performed, and the ZmAGO18b locus was identified to be associated with resistance against C. heterostrophus. Overexpression of ZmAGO18b gene suppresses maize resistance against C. heterostrophus, and mutation of ZmAGO18b enhances maize resistance against C. heterostrophus. Further, we identified the resistant haplotype of ZmAGO18b by association analysis of natural variation in ZmAGO18b genomic DNA sequences with seedling resistance phenotypes against C. heterostrophus and confirmed the resistant haplotype is co-segregated with resistance phenotypes against C. heterostrophus in two F 2 populations. In sum, this study reports that ZmAGO18b negatively regulates maize resistance against C. heterostrophus., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

With the wide application of carbon fiber reinforced polymer (CFRP) plate, used for strengthening existed concrete structures, the prestressing technology of CFRP plate is becoming a hot topic, in order to sufficiently develop its high-strength peculiarity. In this paper, a full-scale hollow-section beam with length of 16 m taken from an old bridge which was in service for about 20 years was first examined for existed cracks and repaired by filling epoxy adhesive, and then the beam was strengthened with prestressed CFRP plates. The CFRP plates were tensioned and fixed with flat-plate anchorages at ends and bonded with adhesive on the bottom surface of the beam. The strengthened beam was experimentally studied using a four-point test to measure the concrete strain along the height of the mid-span section and the mid-span deflection. The finite element model of the strengthened beam was verified by the comparison of test results and used for an extending study of parametric analysis considering the effect of the length and amount of CFRP plates. Results indicated that with an increase in the length and amount of CFRP plates, the mid-span deflection of the beam decreases with the increased cracking resistance and bearing capacity, while the ultimate failure mode transfers from the under-reinforcement to the over-reinforcement.

The mechanism behind PM2.5 pollution is complex, and its performance at multi-scales is still unclear. Based on PM2.5 monitoring data collected from 2015 to 2021, we used the GeoDetector model to assess the multi-scale effects of meteorological conditions and anthropogenic emissions, as well as their interactions with PM2.5 concentrations in major cities in the Yellow River Basin (YRB). Our study confirms that PM2.5 concentrations in the YRB from 2015 to 2021 show an inter-annual and inter-season decreasing trend and that PM2.5 concentrations varied more significantly in winter. The inter-month variation of PM2.5 concentrations shows a sinusoidal pattern from 2015 to 2021, with the highest concentrations in January and December and the lowest from June to August. The PM2.5 concentrations for major cities in the middle and downstream regions of the YRB are higher than in the upper areas, with high spatial distribution in the east and low spatial distribution in the west. Anthropogenic emissions and meteorological conditions have similar inter-annual effects, while air pressure and temperature are the two main drivers across the whole basin. At the sub-basin scale, meteorological conditions have stronger inter-annual effects on PM2.5 concentrations, of which temperature is the dominant impact factor. Wind speed has a significant effect on PM2.5 concentrations across the four seasons in the downstream region and has the strongest effect in winter. Primary PM2.5 and ammonia are the two main emission factors. Interactions between the factors significantly enhanced the PM2.5 concentrations. The interaction between ammonia and other emissions plays a dominant role at the whole and sub-basin scales in summer, while the interaction between meteorological factors plays a dominant role at the whole-basin scale in winter. Our study not only provides cases and references for the development of PM2.5 pollution prevention and control policies in YRB but can also shed light on similar regions in China as well as in other regions of the world.

The raphidiopteran fauna of Xinjiang in northwestern China is poorly known, although it is near Central Asia where the diversity of this group is high. Herein we report a new species and a new Chinese record of the raphidiid genus Mongoloraphidia H. Aspck U. Aspck, 1968 from Xinjiang, namely Mongoloraphidia xinjiangana sp. nov. and Mongoloraphidia (Mongoloraphidia) kaszabi (H. Aspck U. Aspck, 1967), respectively. A key to the identification of the Mongoloraphidia species from China is provided.

Frequency-modulated continuous-wave lidar realizes 4D (three-dimensional space and velocity) imaging of the scene by emitting positive and negative frequency sweep laser signals. The premise of it is to identify the frequency points corresponding to the same target in the positive and negative sweep echo signals. For dechirp receiving, there is usually one peak in the frequency spectrum of the positive and negative sweep signals, respectively. Therefore, it is easy to identify and match the peaks. But in a complex environment, the laser beam will irradiate multiple targets at the same time. In addition, beam scanning and target motion cause the echo spectrum to broaden. The above reasons make it extremely difficult to identify and match peaks in practice. To solve this problem, the waveform-matching algorithm based on the skeleton tree is first applied to multitarget echo pairing. The basic idea of the algorithm is to quantify the target echo hierarchically to generate a skeleton tree. The generation of nodes is based on the relative amplitude of waveform peaks and reflects the characteristics of wave crests nesting. Then the similarity of the signal is determined by comparing the distance between the two signal waveform feature trees. Finally, the waveforms are matched in terms of similarity. To further substantiate the role of the proposed algorithm, imaging experiments and related comparative data for different targets have been completed. The results show that the accuracy of matching processed by the algorithm exceeds 90%, which is improved by about 50% compared with not using the algorithm for the target whose overlapping part accounts for a large proportion of itself.

Background: The incidence of insomnia is very high and seriously affects the lives of its patients. Long-term insomnia can induce other diseases and even cause sudden death. Tian Meng oral liquid is a type of Chinese patent medicine that has been used in the clinical treatment of insomnia and has certain clinical effects. However, its wide application is limited by the lack of evidence-based medical evaluation., Methods: Using retrieval strategies, randomized controlled trials on Tian Meng oral liquid for insomnia were obtained from China National Knowledge Infrastructure, WanFang, Chinese Scientific Journals Database PubMed, Embase, and Cochrane Library, regardless of publication date or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using RevMan 5.3 and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated., Results: This study aims to evaluate the efficacy and safety of Tian Meng oral liquid in the treatment of insomnia and to provide a more reasonable option for clinical medication., Conclusion: Our findings will provide a strong basis for the effectiveness and safety of Tian Meng oral liquid in the treatment of insomnia., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Studying the interaction of pore-forming toxins, including perfringolysin O (PFO), with lipid is crucial to understanding how they insert into membranes, assemble, and associate with membrane domains. In almost all past studies, symmetric lipid bilayers, i.e., bilayers having the same lipid composition in each monolayer (leaflet), have been used to study this process. However, practical methods to make asymmetric lipid vesicles have now been developed. These involve a cyclodextrin-catalyzed lipid exchange process in which the outer leaflet lipids are switched between two lipid vesicle populations with different lipid compositions. By use of alpha class cyclodextrins, it is practical to include a wide range of sterol concentrations in asymmetric vesicles. In this article, protocols for preparing asymmetric lipid vesicles are described, and to illustrate how they may be applied to studies of pore-forming toxin behavior, we summarize what has been learned about PFO conformation and its lipid interaction in symmetric and in asymmetric artificial lipid vesicles., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We have developed cyclodextrin-catalyzed lipid exchange methods to prepare large unilamellar vesicles (LUVs) with asymmetric charge distributions, i.e., with different net charges on the lipids in the inner and outer leaflets. LUVs contained a mixture of a zwitterionic lipid (phosphatidylcholine), cholesterol, and various cationic lipids ( O -ethyl phosphatidylcholine or dioleoyl-3-trimethylammonium propane) or anionic lipids (phosphatidylglycerol, phosphatidylserine, or phosphatidic acid). Symmetric and asymmetric LUVs with a wide variety of lipid combinations were prepared. The asymmetric LUVs contained cationic or anionic outer leaflets and inner leaflets that had either the opposite charge or were uncharged. The behavior of symmetric LUVs prepared with zwitterionic, anionic, or cationic leaflets was compared to those of asymmetric LUVs. Lipid exchange was confirmed by quantitative thin-layer chromatography, and lipid asymmetry by a novel assay measuring binding of a cationic fluorescent probe to the LUV outer leaflet. For both symmetric and asymmetric LUVs, the level of entrapment of the cationic drug doxorubicin was controlled by the charge on the inner leaflet, with the greatest entrapment and slowest leakage in vesicles with an anionic inner leaflet. This shows that it is possible to choose inner leaflet lipids to maximize liposomal loading of charged drugs independently of the identity of outer-leaflet lipids. This implies that it should also be possible to independently vary outer-leaflet lipids to, for example, impart favorable bioavailability and biodistribution properties to lipid vesicles.

In space defense, utilizing the micromotion features to distinguish real targets from interfering targets and decoys is effective. Due to the imaging of the high-speed precession target by microwave radar consisting of isolated scattering centers, there are many difficulties in using inverse synthetic aperture radar (ISAR) images for feature extraction. On the other hand, the inverse synthetic aperture ladar (ISAL) image is relatively continuous because of the short wavelength of laser, and the image sequence contains information about the variation in image length and Doppler width caused by target precession, which can be used for inverse motion parameters. By establishing an observation model of the precession target and performing image processing on the obtained ISAL image at different times, the image length sequence and Doppler width sequence can be obtained. Using the ellipse fitting method to process the obtained sequence, the precession parameters of the target can be obtained. The algorithm does not require prior information such as the radius and speed of the target motion, effectively improving the practicability of the algorithm. Finally, the effectiveness of the algorithm is verified by experimental results, and the error is controlled within 2%.

Background: Acute cerebral infarction (ACI) has a high incidence, recurrence rate, and mortality. Chinese herbal injections (CHIs) are widely used in the substitution therapy of ACI. Due to the lack of randomized trials comparing the efficacy of various injections directly, it is still difficult to judge the relative efficacy. Therefore, we intend to conduct a network meta-analysis to evaluate the benefit among these CHIs., Methods: According to the retrieval strategies, randomized controlled trials (RCTs) on CHI therapies for ACI will be obtained from China National Knowledge Infrastructure, WanFang, Chinese Scientific Journals Database, PubMed, Embase and Cochrane Library, regardless of publication date or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool will be used to evaluate the quality of the literature. The network meta-analysis will be performed in Markov Chain Monte Carlo method and carried out with Stata 14 and WinBUGS 1.4.3 software. Ultimately, the evidentiary grade for the results will be evaluated., Results: This study will compare the efficacy and safety of CHIs in the treatment of ACI, and give a more reasonable choice., Conclusion: Our findings will provide references for future clinical decision and guidance developing.INPLASY registration number: INPLASY202060087.

Background: From the end of 2019 to the present, coronavirus disease 2019 (COVID-19) has put considerable pressure on the worlds medical system and caused significant mortality and economic losses around the world. In China, the Shufeng Jiedu capsule has been widely used in the treatment of COVID-19, but there is still a lack of evidence-based medical evaluation., Methods: According to the retrieval strategies, randomized controlled trials (RCTs) on the Shufeng Jiedu capsule for COVID-19 were obtained from CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, regardless of publication date, or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using RevMan 5.3 and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated., Results: This study will evaluate the efficacy and safety of the Shufeng Jiedu capsule in the treatment of COVID-19 and provide a more reasonable choice of medication in clinical practice., Conclusion: Our findings will provide references for future clinical decision and guidance development., Registration: INPLASY registration number: INPLASY202070024.

Four metabolites of mogrol were separated, identified and characterized. Their antitumor activity was evaluated, and the results showed side chain modification would probably enhance the cytotoxicity. Therefore, three types of amines, alcohols and rigid planar derivatives were synthesized. Compounds 20 and 21 containing a tetrahydro- β -carboline structure at the end of the side chain exhibited IC 50 values around 2-9 μM against A549 and CNE1 cell comparing with 80-90 μM of mogrol. Structure analysis suggested that the perhydrocyclopentanophenanthrene moiety and the tetrahydro- β -carboline moiety could probably enhance the activity through an intramolecular synergistic effect.[Formula: see text].

New types of diodes, such as molecular and ionic diodes, have drawn considerable attention because of their advantages from the viewpoint of potential applications such as the downscaling of electronic devices, ionic circuits, and biological systems. Researchers are motivated to develop a simple, scalable, and promising system that can overcome the existing limitations because this can enable their application in various devices. This study proposes a system that not only integrates the advantages of ionic and single-molecule diodes but also avoids their disadvantages, denoting the rectification behavior due to ionic charge-selective electron transfer between two redox species, i.e., Fe(CN) 6 3- and Ru(NH 3 ) 6 3+ , on the polyelectrolyte multilayer (PEM)-modified flexible indium tin oxide (ITO) electrodes. Flexible current rectification devices were easily prepared by sandwiching an electrolytic solution of ionic redox species using bare and PEM-modified plastic ITO electrodes. An ionic bilayer was initially formed via Coulombic interactions on a PEM-modified charge-selective ITO surface. The ionic bilayer was analogous to a conventional single-molecule diode's monolayer with consecutive molecular orbitals of two ionic redox species. Furthermore, the rectification ratio (RR) was increased from ∼6 to ∼10 using a conducting polymer to construct PEMs.

Major depression disorder, also known as depression, with a significant and persistent low mood as the main clinical features, is the main type of mood disorders. L-menthol (LM), the main active ingredient of mint, has been considered as safe and healthy natural ingredient by the Food and Drug Administration in the USA. In this study, LM (40 mg/kg, i.g.) produced antidepressant-like effect in the forced swimming test (FST) in mice. The sub-effective dose (5 mg/kg, i.g.) of LM combined with the sub-effective dose of fluoxetine (5 mg/kg, i.p.) or reboxetine (2.5 mg/kg, i.p.) could significantly shorten the immobility time in the FST. Pretreatment with ondansetron (a highly selective 5-HT 3 receptor antagonist, 8 mg/kg, i.p.), bicuculline [a competitive γ-aminobutyric acid (GABA) antagonist, 4 mg/kg, i.p.] and haloperidol (a non-selective D 2 receptor antagonist, 0.2 mg/kg, i.p.) significantly reversed the antidepressant-like effect of LM (40 mg/kg, i.g.). In contrast, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p.) and N -methyl-d-aspartic acid (an agonist at the glutamate site, 75 mg/kg, i.p.) did not eliminate the antidepressant-like effect of LM. All of these above indicated that LM is able to induce an antidepressant-like effect mediated by the modification of 5-HTergic, GABAergic and DAergic systems in the FST. LM might be used as combination therapy in depressed patients and is a potential antidepressant., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.

To improve the structural application of steel fiber-reinforced concrete with recycled aggregates (SFRC-RA) composited in gradation by large-particle natural coarse aggregate and small-particle recycled coarse aggregate, the large eccentric compression behavior of eight SFRC-RA columns was experimentally investigated in this paper. The main parameters considered were the strength of the SFRC-RA and the volume fraction of the steel fiber. Details about the sectional concrete strain, the longitudinal steel bar strain, the lateral displacement, the cracking load, the crack distribution and crack width, and the ultimate load of the SFRC-RA columns were measured. The beneficial effects of steel fiber on these attributes were discussed, and the ductility corresponding to the lateral displacement of the SFRC-RA columns was also analyzed. Based on the test results and design principles, formulas were proposed for predicting the cracking resistance, crack width, and lateral displacement of SFRC-RA columns in a normal service state. The ultimate loads of the SFRC-RA columns under a large eccentric compression load were calculated, considering the second-order effects.

It is extremely important for quantifying trace microRNAs in the biomedical applications. In this study, an ultrasensitive, rapid and efficient label-free fluorescence method was proposed and applied for detecting microRNA-21 in serum of gastric cancer patients based on DNA hybridization chain reaction (HCR). DNA H1 and DNA H2 were designed and used as hairpin probes, the HCR was proceeded in the presence of target microRNAs. Amounts of SYBR Green І dyes were used as signal molecules to intercalate long DNA concatemers from HCR, which guaranteed the model of label-free fluorescence and strong fluorescence density. The detection method showed a wide linear region from 1 fM to 10 5  fM, and the limit of detection was 0.2554 fM (at S/N = 3) for microRNAs. The results showed that this method had an excellent specificity and reproducibility. Furthermore, the label-free fluorescence strategy exhibited a sensitive response to microRNA-21 in real serum samples of gastric cancer patients and the results obtained were in accordance with reference method (R 2  = 0.994). Overall, the proposed strategy could be satisfactory for rapid, ultrasensitive and efficient detection of microRNA-21, and held great potentials in clinic diagnosis of gastric cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

MicroRNAs play crucial role in post-transcriptional regulation for gene expression in animals, plants, and viruses. For the better understanding of microRNA and its functions, it is very important to develop effectively analytical method for microRNA detection. Herein, a novel electrochemical biosensor was fabricated for sensitive and selective detection of microRNA based on poly(U) polymerase mediated isothermal signal amplification, where poly(U) polymerase can catalyze the template independent addition of UMP from UTP to the 3' end of RNA. Using this activity, the target microRNA can be successfully labeled with biotin conjugated UMPs at its 3'-end using biotin conjugated UTP (biotin-UTP) as donor. Then, the avidin conjugated alkaline phosphatase can be further captured to the 3'-end of the target microRNA based on the specific interaction between biotin and avidin. Finally, under the catalytic activity of alkaline phosphatase, the substrate of p-nitrophenyl phosphate disodium salt hexahydrate can be hydrolyzed to produce 4-nitrophenol. According to the relationship between the electrochemical signal of p-nitrophenol and the concentration of microRNA-319a, the content of microRNA-319a can be detected. This signal amplification method is simple and sensitive. The developed method can detect as low as 1.7 fM microRNA and produce precise and accurate linear dynamic range from 10 to 1000 fM. The fabricated biosensor was further applied to detect the expression level change of microRNA-319a in rice seedlings after incubation with five kinds of different phytohormones., (Copyright © 2015 Elsevier B.V. All rights reserved.)

MicroRNA (miRNA) is riveting nowadays due to its close relevance to human malignancies. Exploiting a fast and convenient biosensor for sensitive and specific detecting miRNA is necessary and it has significant meaning for oncology. In this work, to understand the relationship between miRNA-21 and gastric cancer, we employ T4 RNA ligase 2 to initiate specific ligation reaction depending on the sequence of target RNA, and T7 exonuclease to catalyze the first stage cyclic enzymatic amplification method (CEAM) specifically, which also resting on the target RNA sequence, and the second stage CEAM to further amplify the response resulting from the initial target RNA. Our two-stage CEAM strategy can detect miRNA-21 as low as 0.36fM with remarkable specificity, and most importantly, it can be used to inspect the expression level of miRNA-21 in blood serum of gastric cancer patients. This will offer new perspective for figuring out the pathways of miRNA-21 involving in cancer., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In this report, stable copper nanoparticles (Cu NPs) were prepared through a facile annealing process using humic acid as the reducing and stabilizing agents. The products were characterized by X-ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. The prepared Cu NPs show remarkably intrinsic peroxidase-like activity, which can rapidly catalyze the oxidation of the peroxidase substrate, 3,3',5,5'-tetramethylbenzidine (TMB), in the presence of H 2 O 2 to produce a blue-color reaction. The detection limit of H 2 O 2 by Cu NPs can be as low as 1.32 × 10 -7 M. More importantly, the prepared Cu NPs show excellent stability, which can hardly be oxidized even after 6 months. Based on the aforementioned mechanism, a simple, rapid and selective colorimetric method for glucose detection was developed, and the detection limit of glucose was 6.86 × 10 -7 M. This study provides a novel method for the preparation of stable Cu NPs, which may have widespread applications in the detection of glucose in the human body and pear juice.

Herein, an electrochemical biosensor was fabricated for DNA demethylase detection based on DNA demethylation triggered endonuclease BstUI and Exonuclease III digestion. After the double-strand DNA was demethylated, it can be further digested by BstUI and formed a blunt end at the electrode surface. Then, the remained fragment of DNA-DNA duplex was further cleaved by exonuclease III and led to increased electrochemical signal. Based on this detection strategy, the biosensor showed high sensitivity with low detection limit of 0.15ng/mL. Moreover, the developed method also presented high selectivity and acceptable reproducibility. This work provides a novel detection platform for DNA demethylase detection., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A highly sensitive and selective photoelectrochemical (PEC) biosensor is fabricated for the detection of protein kinase activity based on visible-light active graphite-like carbon nitride (g-C3N4) and the specific recognition utility of Phos-tag for protein kinase A (PKA)-induced phosphopeptides. For assembling the substrate peptides, g-C3N4 and gold nanoparticles (g-C3N4-AuNPs) complex is synthesized and characterized. When the immobilized peptides on g-C3N4-AuNPs modified ITO electrode are phosphorylated under PKA catalysis, they can be specifically identified and binded with biotin functionalized Phos-tag (Phos-tag-biotin) in the presence of Zn(2+). Then, through the specific interaction between biotin and avidin, avidin functionalized alkaline phosphatase (avidin-ALP) is further assembled to catalyze its substrate of l-ascorbic acid-2-phosphate trisodium salt (AAP) to produce electron donor of ascorbic acid (AA), resulting an increased photocurrent compared with the absence of phosphorylation event. Based on the specific identification effect of Phos-tag, the fabricated biosensor presents excellent selectivity for capturing the phosphorylated serine residues in the substrate peptides. With the good photoactivity of g-C3N4 and ALP-catalyzed signal amplification, the fabricated biosensor presents high sensitivity and low detection limit (0.015 unit/mL, S/N = 3) for PKA. The applicability of this PEC biosensor is further testified by the evaluation of PKA inhibition by HA-1077 with the IC50 value of 1.18μM. This new strategy is also successfully applied to detect the change of PKA activity in cancer cell lysate with and without drug stimulation. Therefore, the developed PEC method has great potential in screening of kinase inhibitors and highly sensitive detection of kinase activity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A simple, highly sensitive and selective electrochemical assay is developed for the detection of protein kinase A (PKA) activity based on the specific recognition utility of Phos-tag for kinase-induced phosphopeptides and enzymatic signal amplification. When the substrate peptide was phosphorylated by PKA reaction, they could specifically bind with Phos-tag-biotin in the presence of Zn(2+) through the formation of a specific noncovalent complex with the phosphomonoester dianion in phosphorylated peptides. Through the further specific interaction between biotin and avidin, avidin functionalized horseradish peroxidase (HRP) can be captured on the electrode surface. Under the catalytic effect of HRP, a sensitive electrochemical signal for benzoquinone was obtained, which was related to PKA activity. Under the optimal experiment conditions, the proposed electrochemical method presented dynamic range from 0.5 to 25 unit/mL with low detection limit of 0.15 unit/mL. This new detection strategy was also successfully applied to analyze the inhibition effect of inhibitors (ellagic acid and H-89) on PKA activity and monitored the PKA activity in cell lysates. Therefore, this Phos-tag-based electrochemical assay offers an alternative platform for PKA activity assay and inhibitor screening, and thus it might be a valuable tool for development of targeted therapy and clinical diagnosis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A novel electrochemical method is developed for detection of DNA demethylation and assay of DNA demethylase activity. This method is constructed by hybridizing the probe with biotin tagged hemi-methylated complementary DNA and further capturing streptavidin tagged alkaline phosphatase (SA-ALP) to catalyze the hydrolysis reaction of p-nitrophenyl phosphate. The hydrolysate of p-nitrophenol (PNP) is then used as electrochemical probe for detecting DNA demethylation and assaying the activity of DNA demethylase. Demethylation of target DNA initiates a degradation reaction of the double-stranded DNA (dsDNA) by restriction endonuclease of BstUI. It makes the failed immobilization of ALP, resulting in a decreased electrochemical oxidation signal of PNP. Through the change of this electrochemical signal, the DNA demethylation is identified and the activity of DNA demethylase is analyzed with low detection limit of 1.3 ng mL(-1). This method shows the advantages of simple operation, cheap and miniaturized instrument, high selectivity. Thus, it provides a useful platform for detecting DNA demethylation, analyzing demethylase activity and screening inhibited drug., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Taking advantage of the special exodeoxyribonuclease activity of T7 exonuclease, a simple, sensitive, selective, and label-free microRNA biosensor based on the cyclic enzymatic amplification method (CEAM) has been proposed. First, thiol functionalized DNA probes were assembled onto a gold nanoparticles modified gold electrode surface through a Au-S bond, followed by hybridizing with target miRNA. Subsequently, DNA in RNA/DNA duplexes was digested by T7 exonuclease, which can release the microRNA molecules from the electrode surface and return into the buffer solution. Meanwhile, the released microRNA can further hybridize with the unhybridized DNA probes on the modified electrode surface. On the basis of it, an isothermal amplification cycle is realized. The T7 exonuclease-assisted CEAM achieved a low detection limit of 0.17 fM. Moreover, this assay presents excellent specificity with discriminating only a single-base mismatched microRNA sequence. Furthermore, this work can also be applied to detect avian leukemia based on the decreased expression level of microRNA-21.

Objective: To evaluate the restoration of function after spinal cord injury (SCI) in patients of different ages who have underwent intraspinal transplantation of olfactory ensheathing cells (OECs)., Methods: One hundred and seventy-one SCI patients were included in this study. Of them, 139 were male and 32 were female, with age ranging from 2 to 64 years (mean, 34.9 years). In all SCI patients the lesions were injected at the time of operation with OECs. According to their ages, the patients were divided into 5 groups: 51 years group (n = 14). The spinal cord function was assessed based on the American Spinal Injury Association (ASIA) Classification System before and 2 - 8 weeks after OECs transplantation. One-way ANOVA and q test were used for statistical analysis, and the data were expressed as mean +/- SD., Results: After surgery, the motor scores increased by 5.2 +/- 4.8, 8.6 +/- 8.0, 8.3 +/- 8.8, 5.7 +/- 7.3 and 8.2 +/- 7.6 in 5 age groups respectively (F = 1.009, P = 0.404); light touch scores increased by 13.9 +/- 8.1, 15.5 +/- 14.3, 12.0 +/- 14.4, 14.1 +/- 18.5 and 24.8 +/- 25.3 respectively (F = 1.837, P = 0.124); and pin prick scores increased by 11.1 +/- 7.9, 17.2 +/- 14.3, 13.2 +/- 11.8, 13.6 +/- 13.9 and 25.4 +/- 24.3 respectively (F = 2.651, P = 0.035). Restoration of pin prick in > 51 years group was better than other age groups except 21 - 30 years group., Conclusion: OECs transplantation can improve the neurological function of spinal cord of SCI patients regardless of their ages. Further research into the long-term outcomes of the treatment will be required.