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To evaluate the efficacy and safety of low-dose trimethoprim (TMP)-sulfamethoxazole (SMX) (TMP-SMX) as the primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in adult recipients of kidney transplantation.Three kinds of prescriptions in kidney recipients were documented, including 20 mg TMP/100 mg SMX oral daily, 20 mg TMP/100 mg SMX oral every other day, and nonprophylaxis. The primary outcome was the incidence of PJP in the first 180 days of follow-up after kidney transplantation. The secondary outcomes were changes in renal and liver function.Among the 1469 recipients, 1066 (72.56%) received 20 mg TMP/100 mg SMX daily, 127 (8.65%) received 20 mg TMP/100 mg SMX every other day, and 276 (18.79%) did not have prophylaxis prescription. The 276 recipients in the nonprophylaxis group had 124.92 person-years of follow-up, during which PJP occurred in 29 patients, for an incidence rate of 23.21 (95% confidence interval 15.76-32.72) per 100 person-years. The TMP-SMX daily group and the TMP-SMX every other day group had 524.89 and 62.07 person-years of follow-up, respectively, with no occurrence of PJP. There was no significant difference among the three groups in changes in renal and liver function (P0.05, respectively). A total of 111 recipients in each group were enrolled in the propensity score matching analysis. It was revealed that the 111 nonprophylaxis recipients had 51.27 person-years of follow-up and 10 PJP cases. Prophylaxis was considered effective because there was a significant difference between the three groups (P0.001).Low-dose TMP-SMX prophylaxis significantly reduces the incidence of PJP within 6 months after kidney transplantation and has a favorable safety profile.

Evidence of the short-term effects of ambient sulfur dioxide (SO

Targeted delivery and labeling of single living cells in heterogeneous cell populations are of great importance to understand the molecular biology and physiological functions of individual cells. However, it remains challenging to perfuse fluorescence markers into single living cells with high spatial and temporal resolution without interfering neighboring cells. Here, we report a single cell perfusion and fluorescence labeling strategy based on nanoscale glass nanopipettes. With the nanoscale tip hole of 100 nm, the use of nanopipettes allows special perfusion and high-resolution fluorescence labeling of different subcellular regions in single cells of interest. The dynamic of various fluorescent probes has been studied to exemplify the feasibility of nanopipette-dependent targeted delivery. According to experimental results, the cytoplasm labeling of Sulfo-Cyanine5 and fluorescein isothiocyanate is mainly based on the Brownian movement due to the dyes themselves and does not have a targeting ability, while the nucleus labeling of 4',6-diamidino-2-phenylindole (DAPI) is originated from the adsorption between DAPI and DNA in the nucleus. From the finite element simulation, the precise manipulation of intracellular delivery is realized by controlling the electro-osmotic flow inside the nanopipettes, and the different delivery modes between nontargeting dyes and nucleus-targeting dyes were compared, showcasing the valuable ability of nanopipette-based method for the analysis of specially defined subcellular regions and the potential applications for single cell surgery, subcellular manipulation, and gene delivery.

Carbon dots (CDs), as new type of carbon-based nanoparticles, are considered to be an aggregate with irreversible polymerization. Achieving the reversible tunability of CDs luminescence based on their reversible polymerization is a challenging subject. Herein, we, for the first time, design and construct the blue-emitting CDs with reversible polymerization by a room-temperature Schiff base reaction between tannic acid and ethylenediamine. The formation of CDs is proven to be due to the crosslinking polymerization of precursors caused by imine bond. As a dynamic covalent bond, imine bond endows CDs with controllable structural transformation properties, and the prepared CDs can be depolymerized and polymerized reversibly by pH-controlled imine bond cleavage and re-formation. These properties of reversible fluorescence photoswitching make the CDs have a good application prospect in reversible information encryption.

Highly quantitative metabolomics studies of complex biological mixtures are facilitated by the resolution enhancement afforded by 2D NMR spectra such as 2D

p53 is a vital transcriptional protein implicated in regulating diverse cellular processes, including cell cycle arrest, DNA repair, mitochondrial metabolism, redox homeostasis, autophagy, senescence, and apoptosis. Recent studies have revealed that p53 levels and activity are substantially increased in affected neurons in cellular and animal models of Parkinson’s disease (PD) as well as in the brains of PD patients. p53 activation in response to neurodegenerative stress is closely associated with the degeneration of dopaminergic neurons accompanied by mitochondrial dysfunction, reactive oxygen species (ROS) production, abnormal protein aggregation, and impairment of autophagy, and these pathogenic events have been implicated in the pathogenesis of PD. Pathogenic p53 integrates diverse cellular stresses and activate these downstream events to induce the degeneration of dopaminergic neurons; thus, it plays a crucial role in the pathogenesis of PD and appears to be a potential target for the treatment of the disease. We reviewed the current knowledge concerning p53-dependent neurodegeneration to better understand the underlying mechanisms and provide possible strategies for PD treatment by targeting p53.

Surface-enhanced Raman spectroscopy (SERS) has been recognized as a promising analytical technique for its capability of providing molecular fingerprint information and avoiding interference of water. Nevertheless, direct SERS detection of complicated samples without pretreatment to achieve the high-efficiency identification and quantitation in a multiplexed way is still a challenge. In this study, a novel spectral extraction neural network (SENN) model was proposed for synchronous SERS detection of each component in mixed solutions using a demonstration sample containing diquat dibromide (DDM), methyl viologen dichloride (MVD), and tetramethylthiuram disulfide (TMTD). A SERS spectra dataset including 3600 spectra of DDM, MVD, TMTD, and their mixtures was first constructed to train the SENN model. After the training step, the cosine similarity of the SENN model can achieve 0.999, 0.997, and 0.994 for DDM, MVD, and TMTD, respectively, which means that the spectra extracted from the mixture are highly consistent with those collected by the SERS experiment of the corresponding pure samples. Furthermore, a convolutional neural network model for quantitative analysis is combined with the SENN, which can simultaneously and rapidly realize the qualitative and quantitative SERS analysis of mixture solutions with lower than 8.8% relative standard deviation. The result demonstrates that the proposed strategy has great potential in improving SERS analysis in environmental monitoring, food safety, and so on.

The endoplasmic reticulum (ER) is crucial for the regulation of multiple cellular processes, such as cellular responses to stress and protein synthesis, folding, and posttranslational modification. Nevertheless, monitoring ER physiological activity remains challenging due to the lack of powerful detection methods. Herein, we built a two-stage cascade recognition process to achieve dynamic visualization of ER stress in living cells based on a fluorescent carbon dot (CD) probe, which is synthesized by a facile one-pot hydrothermal method without additional modification. The fluorescent CD probe enables two-stage cascade ER recognition by first accumulating in the ER as the positively charged and lipophilic surface of the CD probe allows its fast crossing of multiple membrane barriers. Next, the CD probe can specifically anchor on the ER membrane via recognition between boronic acids and

Instantaneous frequency is an important parameter to non-linear frequency modulated (NLFM) signal in low probability intercept (LPI) radar. For electronic intelligence, it is very important to accurately estimate instantaneous frequency of NLFM signal. A multi-scale chirplet path pursuit (MCPP) method and its improved method are proposed for electronic intelligence systems to estimate instantaneous frequency of NLFM radar signal in this paper. Firstly, signal duration is divided into a set of dynamic time interval, multi-scale chirplet basis function is established on each time interval simultaneously. And then, projection coefficient in each dynamic interval is calculated basing on chirplet basis functions. And then, chirplet basis functions which have the largest projection coefficient with the analysis signal in each time interval are connected by path pursuit algorithm. Rough estimation of instantaneous frequency will be achieved by connecting the linear frequency of those chirplet basis functions. At last, to solve the problem that instantaneous frequency curve is not smooth for the impact of noise and chirplet errors, least square fitting method is used to further improve estimation accuracy. Experimental results show that, proposed improved MCPP algorithm is suitable for the instantaneous frequency of the NLFM radar signal at low SNR. Compared with time-frequency analysis method, it has higher estimation accuracy. Proposed method can also be applied to the instantaneous frequencies estimation of other NLFM signal without prior knowledge, such as seismic signals and fault diagnosis signals.

BackgroundRenal ischemia-reperfusion injury (IRI) is an inevitable occurrence during kidney transplantation. Mitophagy, ferroptosis, and the associated immune microenvironment (IME) have been shown to play important roles in renal IRI. However, the role of mitophagy-associated IME genes in IRI remains unclear. In this study, we aimed to construct a prediction model of IRI prognosis based on mitophagy-associated IME genes.MethodThe specific biological characteristics of the mitophagy-associated IME gene signature were comprehensively analyzed using public databases such as GEO, Pathway Unification, and FerrDb. Correlations between the expression of prognostic genes and immune-related genes and IRI prognosis were determined by Cox regression, LASSO analysis, and Pearson’s correlation. Molecular validation was performed using human kidney 2 (HK2) cells and culture supernatant as well as the serum and kidney tissues of mice after renal IRI. Gene expression was measured by PCR, and inflammatory cell infiltration was examined by ELISA and mass cytometry. Renal tissue damage was characterized using renal tissue homogenate and tissue sections.ResultsThe expression of the mitophagy-associated IME gene signature was significantly correlated with IRI prognosis. Excessive mitophagy and extensive immune infiltration were the primary factors affecting IRI. In particular, FUNDC1, SQSTM1, UBB, UBC, KLF2, CDKN1A, and GDF15 were the key influencing factors. In addition, B cells, neutrophils, T cells, and M1 macrophages were the key immune cells present in the IME after IRI. A prediction model for IRI prognosis was constructed based on the key factors associated with the mitophagy IME. Validation experiments in cells and mice indicated that the prediction model was reliable and applicable.ConclusionWe clarified the relationship between the mitophagy-related IME and IRI. The IRI prognostic prediction model based on the mitophagy-associated IME gene signature provides novel insights on the prognosis and treatment of renal IRI.

Background The development of affordable strategy to concurrently enhance microalgal biomass and biocomponents is warranted for commercial applications. Here, we investigated the efficacy of a cheap and natural polyphenol, tannic acid, on regulating metabolic and physiological properties of oleaginous microalga Phaeodactylum tricornutum to overproduce biocompounds. Result Tannic acid provision regulated the key metabolic pathways to enhance algal biomass and lipids in a dose-dependent manner without direct impact on photosynthesis. It reduced oxidative stress and reallocated carbon precursors towards lipogenesis. Lipidomic analyses showed that tannic acid provision unprecedentedly regulated the key lipogenic pathways, enhanced glyco- and neutral-lipids by 1.29- and 1.54-fold, respectively, whereas phospholipids were significantly altered. Tannic acid facilitated polyunsaturated fatty acid overproduction with a specific increment of EPA and DHA by 1.18- and 2.25-fold, respectively. Transcriptomic analysis demonstrated that tannic acid upregulated the expression of multiple genes involved in lipogenesis. Conclusion Here, we dissected the potential of tannic acid, a natural and cheaper polyphenol, on concurrently enhancing lipids and PUFAs without impairing physiological properties in P. tricornutum. The findings provide novel insights into the mechanistic roles of polyphenol as a potential chemical modulator.

Despite the promise of combination cancer therapy, it remains challenging to develop targeted strategies that are nontoxic to normal cells. Here we report a combination therapeutic strategy based on engineered DNAzyme molecular machines that can promote cancer apoptosis via dynamic inter- and intracellular regulation. To achieve external regulation of T-cell/cancer cell interactions, we designed a DNAzyme-based molecular machine with an aptamer and an i-motif, as the MUC-1-selective aptamer allows the specific recognition of cancer cells. The i-motif is folded under the tumor acidic microenvironment, shortening the intercellular distance. As a result, T-cells are released by metal ion activated DNAzyme cleavage. To achieve internal regulation of mitochondria, we delivered another DNAzyme-based molecular machine with mitochondria-targeted peptides into cancer cells to induce mitochondria aggregation. Our strategy achieved an enhanced killing effect in zinc deficient cancer cells.

Ratiometric fluorescence (FL) probes are highly desirable for highly sensitive and reliable assays. Dual-emitting carbonized polymer dots (CPDs) have great application prospects in building ratiometric FL sensors. However, dual-emitting CPDs are usually synthesized at high temperatures and high pressures, which not only increases the cost but also complicates the structure of CPDs. Here, we developed a facile strategy for the fabrication of dual-emitting CPDs at room temperature using tetrachlorobenzoquinone and ethylenediamine. The formation of CPDs was induced by Schiff base condensation reaction, enabling the following cross-linking polymerization process. The dual-emitting CPDs demonstrate good photostability and antioxidant capacity. Importantly, the typical dual-emission bands of the as-prepared CPDs are found to have a blue emission band at 445 nm with a maximum excitation of 350 nm and a yellow emission band at 575 nm with a maximum excitation of 440 nm. Based on the dual-emitting property of CPDs, a ratiometric FL nanoprobe is obtained for sensitive determination of vitamin B12 (VB12), as the inner filtering and static quenching effects between VB12 and CPDs allow effective quenching of the blue FL of CPDs, while the yellow FL is maintained. The established assay shows linear detection ranges of 0.25-100 μM with a low limit of detection of 0.14 μM. These findings provide new guidance for the facile preparation of CPDs with excellent dual-emitting optical properties, indicating good prospects in biosensing.

H2O2 is an essential signaling molecule in living cells that can cause direct damage to lipids, proteins, and DNA, resulting in cell membrane rupture. However, current studies mostly focus on probe-based sensing of intracellular H2O2, and these methods usually require sophisticated probe synthesis and instruments. In particular, local H2O2 treatment induces cell membrane rupture, but the level of cell membrane destruction is unknown because the mechanical properties of the cell membrane are difficult to accurately determine. Therefore, highly sensitive and label-free methods are required to measure and reflect mechanical changes in the cell membrane. Here, using an ultrasmall quartz nanopipette with a tip diameter less than 90 nm as a nanosensor, label-free and noninvasive electrochemical single-cell measurement is achieved for real-time monitoring of cell membrane rupture under H2O2 treatment. By spatially controlling the nanopipette tip to precisely approach a specific location on the membrane of a single living cell, stable cyclic membrane oscillations are observed under a constant direct current voltage. Specifically, upon nanopipette advancement, the mechanical status of the cell membrane can be sensibly displayed by continuous current versus time traces. The electrical signals are collected and processed, ultimately revealing the mechanical properties of the cell membrane and the degree of cell apoptosis. This nanopipette-based nanosensor paves the way for developing a facile, label-free, and noninvasive strategy to assay the mechanical properties of the cell membrane during external stimulation at the single-cell level.

Kiwi, a fruit from plants of the genus Actinidia, is one of the famous fruits with thousand years of edible history. In the past twenty years, a great deal of research has been done on the chemical constituents of the Actinidia species. A large number of secondary metabolites including triterpenoids, flavonoids, phenols, etc. have been identified from differents parts of Actinidia plants, which exhibited significant in vitro and in vivo pharmacological activities including anticancer, anti-inflammatory, neuroprotective, anti-oxidative, anti-bacterial, and anti-diabetic activities. In order to fully understand the chemical components and biological activities of Actinidia plants, and to improve their further research, development and utilization, this review summarizes the compounds extracted from different parts of Actinidia plants since 1959 to 2020, classifies the types of constituents, reports on the pharmacological activities of relative compounds and medicinal potentials.

Hydrogen peroxide (H2O2) widely involves in intracellular and intercellular redox signaling pathways, playing a vital role in regulating various physiological events. Nevertheless, current analytical methods for the H2O2 assay are often hindered by relatively long response time, low sensitivity, or self-interference. Herein, a zeolitic imidazolate framework-8 (ZIF-8)-based surface-enhanced Raman scattering (SERS) sensor has been developed to detect H2O2 released from living cells by depositing ZIF-8 over SERS active gold nanoparticles (AuNPs) grafted with H2O2-responsive probe molecules, 2-mercaptohydroquinone. Combining the superior fingerprint identification of SERS and the highly efficient enrichment and selective response of H2O2 by ZIF, the ZIF-8-based SERS sensor exhibits a high anti-interference ability for H2O2 detection, with a limit of detection as low as 0.357 nM. Satisfyingly, owing to the enhanced catalytic activity derived from the successful integration of AuNPs and ZIF, the response time as short as 1 min can be obtained, demonstrating the effectiveness of the SERS sensor for rapid H2O2 detection. Furthermore, the developed SERS sensor enables real-time detection of H2O2 secreted from living cells under phorbol myristate acetate stimulation, as cells can be cultured on-chip. This study will pave the way toward the development of a metal-organic framework-based SERS platform for application in the fields of biosensing and early disease diagnosis associated with H2O2 secretion, thus exhibiting promising potential for future therapies.

The transport of hydrated ions across nanochannels is central to biological systems and membrane-based applications, yet little is known about their hydrated structure during transport due to the absence of in situ characterization techniques. Herein, we report experimentally resolved ion dehydration during transmembrane transport using modified in situ liquid ToF-SIMS in combination with MD simulations for a mechanistic reasoning. Notably, complete dehydration was not necessary for transport to occur across membranes with sub-nanometer pores. Partial shedding of water molecules from ion solvation shells, observed as a decrease in the average hydration number, allowed the alkali-metal ions studied here (lithium, sodium, and potassium) to permeate membranes with pores smaller than their solvated size. We find that ions generally cannot hold more than two water molecules during this sterically limited transport. In nanopores larger than the size of the solvation shell, we show that ionic mobility governs the ion hydration number distribution. Viscous effects, such as interactions with carboxyl groups inside the membrane, preferentially hinder the transport of the mono- and dihydrates. Our novel technique for studying ion solvation in situ represents a significant technological leap for the nanofluidics field and may enable important advances in ion separation, biosensing, and battery applications.

Cytochrome P450s (P450s) are the most versatile catalysts utilized by plants to produce structurally and functionally diverse metabolites. Given the high degree of gene redundancy and challenge to functionally characterize plant P450s, protein engineering is used as a complementary strategy to study the mechanisms of P450-mediated reactions, or to alter their functions. We previously proposed an approach of engineering plant P450s based on combining high-accuracy homology models generated by Rosetta combined with data-driven design using evolutionary information of these enzymes. With this strategy, we repurposed a multi-functional P450 (CYP87D20) into a monooxygenase after redesigning its active site. Since most plant P450s are membrane-anchored proteins that are adapted to the micro-environments of plant cells, expressing them in heterologous hosts usually results in problems of expression or activity. Here, we applied computational design to tackle these issues by simultaneous optimization of the protein surface and active site. After screening 17 variants, effective substitutions of surface residues were observed to improve both expression and activity of CYP87D20. In addition, the identified substitutions were additive and by combining them a highly efficient C11 hydroxylase of cucurbitadienol was created to participate in the mogrol biosynthesis. This study shows the importance of considering the interplay between surface and active site residues for P450 engineering. Our integrated strategy also opens an avenue to create more tailoring enzymes with desired functions for the metabolic engineering of high-valued compounds like mogrol, the precursor of natural sweetener mogrosides.The online version contains supplementary material available at 10.1007/s42994-021-00056-z.

The redox homeostasis in living cells is greatly crucial for maintaining the redox biological function, whereas accurate and dynamic detection of intracellular redox states still remains challenging. Herein, a reversible surface-enhanced Raman scattering (SERS) nanosensor based on covalent organic frameworks (COFs) was prepared to dynamically monitor the redox processes in living cells. The nanosensor was fabricated by modifying the redox-responsive Raman reporter molecule, 2-Mercaptobenzoquione (2-MBQ), on the surface of gold nanoparticles (AuNPs), followed by the in situ coating of COFs shell. 2-MBQ molecules can repeatedly and quickly undergo reduction and oxidation when successively treated with ascorbic acid (AA) and hypochlorite (ClO

Sedimentary nitrogen isotope (δ15Nsed) in Santa Barbara Basin (SBB) has been mostly interpreted as the record of the eastern tropical North Pacific (ETNP) intermediate water denitrification process. Nevertheless, debate remains regarding sources and control mechanisms of δ15Nsed signal in SBB. Multi-proxy analyses including δ15Nsed, total organic carbon (TOC), total nitrogen (TN), C/N ratio, and marine biomarkers were performed on a 46-cm sediment core (SBB-190629) collected from SBB in 2019. The core was dated with varve counting and 210Pb dating method, showing a depositional history of 1938–2019 CE with a sedimentation rate of 0.564 cm/year. The findings show that the δ15Nsed record (at ~0.25-year resolution) ranges from 6.24‰ to 7.43‰, which was affected by both local and remote forcing. The long-term variations of the SBB δ15Nsed signature show a general decreasing trend from 1940 to the late 1980s, low values during 1980~2000, and an increase afterward, which is thought to reflect changes in ETNP denitrification induced by the strength of tropical trade winds. Our results also reveal a series of abrupt annual to multiannual changes, superimposed on the long-term variation mentioned above. The SBB local δ15N signal (Δδ15NSBB) is accessed by using the deviation from the mean δ15N (Δδ15N) of SBB-190629 to subtract the Δδ15N of the ETNP. The Δδ15NSBB record compares well with redox-sensitive proxies (Re/Mo ratio and C29 stanol/stenol ratio) from the SBB bottom water and with the OCmarine content calculated based on the C/N ratio mixing model, indicating that the Δδ15NSBB is mainly controlled by bottom water denitrification, which was induced by the change of upwelling intensity and marine productivity. Since various climatic factors (e.g., El Niño–Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), and North Pacific Gyre Oscillation (NPGO)) have different impacts on the upwelling intensity (hence the marine productivity and denitrification) in SBB on different timescales, the influence of combined climatic factors on SBB denitrification is time dependent.

Endothelial progenitor cells (EPCs) are immature endothelial cells (ECs) capable of proliferating and differentiating into mature ECs. These progenitor cells migrate from bone marrow (BM) after vascular injury to ischemic areas, where they participate in the repair of injured endothelium and new blood vessel formation. EPCs also secrete a series of protective cytokines and growth factors that support cell survival and tissue regeneration. Thus, EPCs provide novel and promising potential therapies to treat vascular disease, including ischemic stroke. However, EPCs are tightly regulated during the process of vascular repair and regeneration by numerous endogenous cytokines that are associated closely with the therapeutic efficacy of the progenitor cells. The regenerative capacity of EPCs also is affected by a range of exogenous factors and drugs as well as vascular risk factors. Understanding the functional properties of EPCs and the factors related to their regenerative capacity will facilitate better use of these progenitor cells in treating vascular disease. Here, we review the current knowledge of EPCs in cerebral neovascularization and tissue regeneration after cerebral ischemia and the factors associated with their regenerative function to better understand the underlying mechanisms and provide more effective strategies for the use of EPCs in treating ischemic stroke.

Reactivation of T-cell immunity by blocking the PD-1/PD-L1 immune checkpoint has been considered a promising strategy for cancer treatment. However, the recognition of PD-L1 by antibodies is usually suppressed due to the N-linked glycosylation of PD-L1. In this study, we present an effective PD-L1-blocking strategy based on a sialidase-conjugated "NanoNiche" to improve the antitumor effect via T-cell reactivation. Molecularly imprinted by PD-L1 N-glycans, NanoNiche can specifically recognize glycosylated PD-L1 on the tumor cell surface, thereby resulting in more efficient PD-L1 blockade. Moreover, sialidase modified on the surface of NanoNiche can selectively strip sialoglycans from tumor cells, enhancing immune cell infiltration. In vitro studies confirmed that NanoNiche can specifically bind with PD-L1 while also desialylate the tumor cell surface. The proliferation of PD-L1-positive MDA-MB-231 human breast cancer cells under T-cell killing was significantly inhibited after NanoNiche treatment. In vivo experiments in solid tumors show enhanced therapeutic efficacy. Thus, the NanoNiche-sialidase conjugate represents a promising approach for immune checkpoint blockade therapy.

Slides are commonly used to present information and tell stories. In academic and research communities, slides are typically used to summarize findings in accepted papers for presentation in meetings and conferences. These slides for academic papers usually contain common and essential topics such as major contributions, model design, experiment details and future work. In this paper, we aim to automatically generate slides for academic papers. We first conducted an in-depth analysis of how humans create slides. We then mined frequently used slide topics. Given a topic, our approach extracts relevant sentences in the paper to provide the draft slides. Due to the lack of labeling data, we integrate prior knowledge of ground truth sentences into a log-linear model to create an initial pseudo-target distribution. Two sentence extractors are learned collaboratively and bootstrap the performance of each other. Evaluation results on a labeled test set show that our model can extract more relevant sentences than baseline methods. Human evaluation also shows slides generated by our model can serve as a good basis for preparing the final presentations.

Constructing optical nanoprobes with superior performance is highly desirable for sensitive and accurate assays. Herein, we develop a facile room-temperature strategy for the fabrication of green emissive carbon nanoclusters (CNCs) with dual-exciting centers for the dual-channel sensing of hemin. The formation of the CNCs is attributed to the crosslinking polymerization of the precursors driven by the Schiff base reaction between ethylenediamine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. Most importantly, the proposed CNCs have a unique excitation-independent green emission (518 nm) with two excitation centers at 260 nm (channel 1) and 410 nm (channel 2). The dual-exciting central emission can serve as dual-channel fluorescence (FL) signals for highly sensitive and reliable detection of hemin based on the inner filter effect. Because of the great spectral overlap difference between the absorption spectrum of hemin and the excitation lights of the CNCs in the two channels, hemin has a different quenching effect on FL emission from different channels. The dual-channel signals of the CNCs can detect hemin in the range of 0.075–10 μM (channel 1) and 0.25–10 μM (channel 2), respectively. These findings not only offer new guidance for the facile synthesis of dual-exciting central CNCs but also establish a reliable sensing platform for the analysis of hemin in complex matrixes.

Gambierdiscus spp. is mainly responsible for the ciguatera fish poisoning (CFP) around the world. The gambiertoxin produced by Gambierdiscus can be passed through the food chain to form ciguatoxins (CTXs) that cause ciguatoxins poisoning. However, the toxic effects of Gambierdiscus on fish through the food chain and related mechanism remains unclear. In this study, the toxicity of Gambierdiscus caribaeus on the marine medaka (Oryzias melastigma) was investigated, where the simulated food chain toxic algae-food organism-fish (G. caribaeus-Artemia metanauplii-O. melastigma) was set. The results showed that direct or indirect exposure through the food chain of G. caribaeus could affect the swimming behaviour of O. melastigma, manifested as decreased swimming performance and spontaneous abnormal swimming behaviours. Histological observation showed that direct or indirect exposure of G. caribaeus caused different degrees of pathological damage to the gills, intestine and liver tissues of O. melastigma. Transcriptome sequencing and RT-qPCR demonstrated that G. caribaeus exposure could trigger a series of physiological and biochemical responses, mainly reflected in energy metabolism, reproductive system, neural activity, immune stress and drug metabolism in marine medaka. Our finding may provide novel insight into the toxicity of Gambierdiscus on fish.

Open relation extraction (ORE) aims to assign semantic relationships among arguments, essential to the automatic construction of knowledge graphs (KG). The previous ORE methods and some benchmark datasets consider a relation between two arguments as definitely existing and in a simple single-span form, neglecting possible non-existent relationships and flexible, expressive multi-span relations. However, detecting non-existent relations is necessary for a pipelined information extraction system (first performing named entity recognition then relation extraction), and multi-span relationships contribute to the diversity of connections in KGs. To fulfill the practical demands of ORE, we design a novel Query-based Multi-head Open Relation Extractor (QuORE) to extract single/multi-span relations and detect non-existent relationships effectively. Moreover, we re-construct some public datasets covering English and Chinese to derive augmented and multi-span relation tuples. Extensive experiment results show that our method outperforms the state-of-the-art ORE model LOREM in the extraction of existing single/multi-span relations and the overall performances on four datasets with non-existent relationships.

Previous researches have reported the association between air pollution and various diseases. However, few researches have investigated whether air pollutants are associated with the economic loss resulting from patients' hospitalization, especially the economic loss of hospitalization due to acute cardiovascular events. The purpose of our research was to explore the association between the levels of carbon monoxide (CO), taken as an index of pollution, and the hospitalization costs of myocardial infarction (MI), and the potential effect modification by the ABO blood group. A total of 3237 MI inpatients were included in this study. A multiple linear regression model was used to evaluate the association between ambient CO levels and hospitalization costs of MI patients. Moreover, we performed stratified analyses by age, gender, body mass index (BMI), season, hypertension, and ABO blood types. There was a positive association between the levels of CO in the air and the costs of hospitalization caused by MI. Furthermore, such association was stronger in males, BMI ≥25,65 years, with hypertension, and non-O blood group. Interestingly, we found the association was particularly significant in patients with blood group B. Overall, our study first found that ambient CO levels could have an impact on the hospitalization costs for MI patients, and those with blood group B can be more sensitive.

DNA methylation is an important feature of gene epigenetics that affects the metabolic process of organisms. Although surface-enhanced Raman spectroscopy (SERS) has demonstrated great potential in label-free DNA detection, discriminating the various processes involved in DNA methylation remains a challenge. DNA molecules fold themselves, wrapping the hydrophobic bases, thus making it difficult for traditional methods to detect single-base signals. In this study, we develop a SERS platform for detecting DNA via modifying silver nanoparticles by zirconium ions to obtain the DNA fingerprint information of base methylations (N6-methylated adenine and 5-methylated cytosine). Zirconium ions open the folded DNA molecules, enabling SERS signals of the four DNA bases (A, C, G, T) to be obtained as well as identification of the subtle differences between normal and methylated DNA with single base-level sensitivity. Moreover, the identifying information of DNA methylation was obtained by combining principal component analysis (PCA) with 2D correlation spectroscopy analysis. The findings of this study provide a substantial progress for current platforms for DNA sequencing, genetic testing, and gene-disease treatment.

Archaeal ammonia oxidation is the most important intermediate pathway in regulating the oceanic nitrogen cycle; however, the study of its specific role on a geological time scale is restricted to a specific part of marginal seas; thus far, only in the southern South China Sea (SCS). To explore the spatial pattern of the role of archaeal ammonia oxidation in the SCS, the GDGT-[2]/[3] ratio (Glycerol Dialkyl Glycerol Tetraether), an indicator of the archaeal ammonia oxidation rate, was analyzed and examined from the collected data profiles since the last glacial period in the northern SCS. The results showed that the GDGT-[2]/[3] ratio in the northern SCS was opposite to that in the southern SCS, with higher GDGT-[2]/[3] values during the Holocene compared to the last glacial period. Based on existing published depths of thermocline (DOT) data in the northern SCS since 30 ka, we believe that hydrological structural variations induced by mesoscale eddies caused this difference. Therefore, physical processes are very important factors that control the nitrogen cycle over a long-time scale. This study may provide new insights into the understanding of the role of archaeal ammonia oxidation within the marine nitrogen cycle over geological time scale.

To explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next‐generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction chemotherapy were associated with a lower number of mutations. NPM1 mutation was closely related to DNMT3A and FLT3‐internal tandem duplication (FLT3‐ITD) mutations, but mutually exclusive with ASXL1 mutation and CEBPA double mutation. In univariate analysis, ASXL1 or TET2 mutation predicted shorter overall survival (OS) or relapse‐free survival (RFS), DNMT3A, FLT3‐ITD, or RUNX1 mutation predicted a higher likelihood of remission‐induction failure, whereas NRAS mutation or CEBPA double mutation predicted longer OS. Concurrent DNMT3A, FLT3‐ITD, and NPM1 mutations predicted shorter OS. Hypomethylation agents could improve the OS in patients with DNA methylation‐related mutations. According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next‐generation sequencing screening., Genetic mutations can predict favorable or unfavorable prognosis of AML patients. Allo stem cell transplantation can provide benefits for AML patients with bad genetic mutations.

The single machine parallel-batch scheduling with deteriorating jobs and rejection is considered in this paper. A job is either rejected, in which a rejection penalty should be paid, or accepted and processed on the machine. Each job’s processing time is an increasing linear function of its starting time. The machine can process any number of jobs simultaneously as a batch. The processing time of a batch is equal to the largest processing time of the jobs in the batch. The objectives are to minimize the makespan and the total weighted completion time, respectively, under the condition that the total rejection penalty cannot exceed a given upper bound Q. We show that both problems are NP-complete and present dynamic programming algorithms and fully polynomial time approximation schemes (FPTASs) for the considered problems.

Solid-state high-resolution13C/7Li nuclear magnetic resonance (NMR) study was performed on the phase structure and chain dynamics of PEG-PPG-PEGn/LiCF3SO3(n=3, 6, 12) copolymer electrolytes. PEG repeating units and Li+form PEG3:LiCF3SO3crystalline complex and PE3/Li+amorphous complex in all the samples. PPG repeating units and Li+form different complexes with respect to O:Li+feed ratio (denoted as PP/Li+-3/6/12). The13C chemical shifts and half widths of the signals from PP/Li+-3/6/12 remain unchanged, which implies the structures of PP/Li+-3/6/12 are similar at least in a very short range. The half width of the7Li signals from PP/Li+-3/6/12 becomes narrower and narrower as the Li+concentration decreases. This indicates the chain mobility of the amorphous phase increases with the decrease of ionic concentration. Moreover, neat crystalline PEG, neat amorphous PEG and neat amorphous PPG start to appear when O:Li+is greater than 3:1 and their contents increase with the increase of O:Li+. Overall, solid-state high-resolution NMR is a powerful and unique method for understanding the phase structure and chain dynamics of solid polymer electrolytes (SPEs), more applications of this technique to studies on SPEs is expecting.

The Huanghe (Yellow River) supplies large amount of sediments and terrestrial organic carbon (OC) to the eastern Chinese marginal seas. A relocation of the Huanghe outlet from the southern Yellow Sea (YS) to the Bohai Sea occurred in 1855 AD, however, detailed knowledge about the impact of this relocation on sedimentary source and OC burial in Chinese marginal seas is still critically lacking. In this study, we present total OC content and its isotope (δ13C), along with bulk total organic carbon (TOC)/total nitrogen (TN) molar ratio and lipid biomarker contents, in a sediment core HH12 from the southern YS with sediment age spanning the last 300 years. We find that TOC and terrestrial lipid biomarker mass accumulation rates were lower between 1855 AD and 1950 AD than that prior to 1855 AD in core HH12; and in accordance, both TOC/TN ratio and δ13C records indicate a gradual decrease of terrigenous source contributions to sedimentary OC. This suggests that the relocation of the Huanghe outlet reduced the transport of terrestrial OC to the southern YS. However, the δ13C record also indicates a relative increase of terrestrial OC contribution to sedimentary OC after 1950 AD, and the most likely explanation is increased contributions from the old Huanghe delta erosion and Korean rivers. Future studies should focus on better constraining the variations of terrestrial and marine endmembers with δ13C and Δ14C analyses of specific biomarkers to examine these linkages.

Background: The disorders of endometrial receptivity and ovulatory dysfunction are both important causes of infertility of patients with Polycystic Ovary Syndrome(PCOS) .The study aimed to investigate the expression profile and functional analysis of circRNAs in the endometrial receptivity of mice with PCOS. Methods: Twenty-four 4-week-old female C57BL/6 mice were randomly divided into two groups(PCOS group and Normal control group,n=12) and PCOS group was subcutaneously with DHEA 6mg/kg for 20 days.The circRNA expression profile in the endometrium tissue of two groups on the 4th day of gestation was screened by gene chip technique.Bioinformatics analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to preliminary understand the functions of circRNAs. The expression of selected circRNA was verified by RT-PCR and and circRNA–microRNA(miRNA)–messenger RNA (mRNA) negative correlation network analyses was construct by Cytoscape.Result: Compared with mice in NC group,there are 205 differentially expressed circRNAs significantly in mice of PCOS group,including 147 up-regulated and 58 down-regulated circRNAs(fold change [FC]≥1.5 and p value < 0.05). GO analysis demonstrated that the host genes of differentially regulated circRNAs were mainly related to protein binding,cellular process and cellular anatomical entity.KEGG analysis revealed that these source genes were engaged in the Proteoglycans in cancer,Cell junctions (focal adheren and gap junction) ,Pathways in cancer,Ras signaling pathway,Chemokine signaling pathway，autophagy and PI3K-Akt signaling pathway.qRT-PCR results showed that the expression levels of circRNA_38548 (PConclusions: The circRNAs were aberrantly expressed in the implantation window of PCOS mice,suggesting that differentially expressed circRNA may play a role in the endometrial receptivity of PCOS. We validated four circRNAs(circRNA_38548, circRNA_38550, circRNA_001686 and circRNA_27938),which may contribute to the abnormal endometrial receptivity of PCOS by regulating the expression of Lifr, FOXK1, FOXO1, HOXA10 and other genes through targeting mir-214-3p, mir-532-5p, mir-423 and other miRNAs. These four circRNAs are worthy targets for further study of the related mechanisms.

There is a critical need to accurately diagnose, prevent, and treat biofilms in humans. The biofilm forming P. aeruginosa bacteria can cause acute and chronic infections, which are difficult to treat due to their ability to evade host defenses along with an inherent antibiotic-tolerance. Using an untargeted NMR-based metabolomics approach, we identified statistically significant differences in 52 metabolites between P. aeruginosa grown in the planktonic and lawn biofilm states. Among them, the metabolites of the cadaverine branch of the lysine degradation pathway were systematically decreased in biofilm. Exogenous supplementation of cadaverine caused significantly increased planktonic growth, decreased biofilm accumulation by 49% and led to altered biofilm morphology, converting to a pellicle biofilm at the air-liquid interface. Our findings show how metabolic pathway differences directly affect the growth mode in P. aeruginosa and could support interventional strategies to control biofilm formation.

Zearalenone (ZEN) is a potent oestrogenic mycotoxin that is mainly produced by Fusarium species and is a serious environmental pollutant in animal feeds. Apiotrichum mycotoxinivorans has been widely used as a feed additive to detoxify ZEN. However, the effects of ZEN on A. mycotoxinivorans and its detoxification mechanisms remain unclear. In this study, transcriptomic and bioinformatic analyses were used to investigate the molecular responses of A. mycotoxinivorans to ZEN exposure and the genetic basis of ZEN detoxification. We detected 1424 significantly differentially expressed genes (DEGs), of which 446 were upregulated and 978 were downregulated. Functional and enrichment analyses showed that ZEN-induced genes were significantly associated with xenobiotic metabolism, oxidative stress response, and active transport systems. However, ZEN-inhibited genes were mainly related to cell division, cell cycle, and fungal development. Subsequently, bioinformatic analysis identified candidate ZEN-detoxification enzymes. The Baeyer-Villiger monooxygenases and carboxylesterases, which are responsible for the formation and subsequent hydrolysis of a new ZEN lactone, respectively, were significantly upregulated. In addition, the expression levels of genes related to conjugation and transport involved in the xenobiotic detoxification pathway were significantly upregulated. Moreover, the expression levels of genes encoding enzymatic antioxidants and those related to growth and apoptosis were significantly upregulated and downregulated, respectively, which made it possible for A. mycotoxinivorans to survive in a highly toxic environment and efficiently detoxify ZEN. This is the first systematic report of ZEN tolerance and detoxification in A. mycotoxinivorans. We identified the metabolic enzymes that were potentially involved in detoxifying ZEN in the GMU1709 strain and found that ZEN-induced transcriptional regulation of genes is key to withstanding highly toxic environments. Hence, our results provide valuable information for developing enzymatic detoxification systems or engineering this detoxification pathway in other species.