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Pesticide compounding technology for disease and pest control emerges as an effective way to increase the effectiveness of pesticides while reducing pesticides resistance. Nanomaterials and encapsulation technology have offered a new insight into preparing efficient pesticide formulations, especially constructing a co-delivery nanoparticle for synergistic pesticides. In this study, a dinotefuran/avermectin co-delivery nanoparticles (DACNPs) against pear tree pests with polylactic acid (PLA) as the wall material were constructed by double-emulsion method combined with high-pressure homogenization technique. The drug content of the DACNPs was 39.1% with an average size of 245.7 ± 4.2 nm and the mean polymer dispersity index (PDI) value was 0.123. The DACNPs showed high foliar retention and good spread performance on target leaves due to the nanoscale effect. The obtained DACNPs showed a better control effect on Grapholitha molesta Busck and Psylla chinensis Yang et Li compared with the commercial formulations, which could significantly prolong the effective duration and enhance the bioactivity with lower amounts and application frequency of pesticides. This study may provide new insights into developing novel pesticide formulations to improve the utilization rate of pesticides, reduce environmental pollution and minimize the cost of farming.

A visible-light-promoted alkylation/cyclization of active alkenes via radical cascade cyclization for the preparation of functionalized isoquinolinones by using Hantzsch esters as alkylation radical precursors.

The efficient transition-metal-free alkylation/cyclization of activated alkenes using Hantzsch ester derivatives as effective alkyl reagents was described.

Cellular senescence is a dynamic process driven by epigenetic and genetic changes. Although some transcriptomic signatures of senescent cells have been discovered, how these senescence-related signals change over time remains largely unclear. Here, we profiled the transcriptome dynamics of human dermal fibroblast (HDF) cells in successive stages of growth from proliferation to senescence. Based on time-series expression profile analysis, we discovered four trajectories (C1, C2, C3, C4) that are dynamically expressed as senescence progresses. While some genes were continuously up-regulated (C4) or down-regulated (C2) with aging, other genes did not change linearly with cell proliferation, but remained stable until entering the senescent state (C1, C3). Further analysis revealed that the four modes were enriched in different biological pathways, including regulation of cellular senescence. These findings provide a new perspective on understanding the dynamic regulatory mechanism of cellular senescence.

The CRISPR/Cas9 system enables precise, simple editing of genes in many animals and plants. However, this system has not been applied to rose (Rosa hybrida) due to the genomic complexity and lack of an efficient transformation technology for this plant. Here, we established a platform for screening single-guide RNAs with high editing efficiency for use in CRISPR/Cas9-mediated gene editing of rose suspension cells. We used the Arabidopsis thaliana U6-29 promoter, which showed high activity for driving sgRNA expression, to modify the CRISPR/Cas9 system. We used our highly efficient optimized CRISPR/Cas9 system to successfully edit RhEIN2, encoding an indispensable component of the ethylene signaling pathway, resulting in ethylene insensitivity in rose. Our optimized CRISPR/Cas9 system provides a powerful toolbox for functional genomics, molecular breeding, and synthetic biology in rose. This article is protected by copyright. All rights reserved.

Although chronic intermittent hypoxia- (IH-) induced myocardial apoptosis is an established pathophysiological process resulting in a poor prognosis for patients with obstructive sleep apnea syndrome, its underlying mechanism remains unclear. This study is aimed at exploring the role of makorin ring finger protein 1 (MKRN1) in IH-induced myocardial apoptosis and elucidating its molecular activity. First, the GSE2271 dataset was downloaded from the Gene Expression Omnibus database to identify the differentially expressed genes. Then, an SD rat model of IH, together with rat cardiomyocyte H9C2 and human cardiomyocyte AC16 IH models, was constructed. TUNEL, Western blot, and immunohistochemistry assays were used to detect cell apoptosis. Dihydroethidium staining was conducted to analyze the concentration of reactive oxygen species. In addition, RT-qPCR, Western blot, and immunohistochemistry were performed to measure the expression levels of MKRN1 and p21. The direct interaction between MKRN1 and p21 was determined using coimmunoprecipitation and ubiquitination analysis. MKRN1 expression was found to be downregulated in IH rat myocardial tissues as well as in H9C2 and AC16 cells. Upregulated expression of MKRN1 in H9C2 and AC16 cells alleviated the IH-induced reactive oxygen species production and cell apoptosis. Mechanistically, MKRN1 promoted p21 protein ubiquitination and the proteasome pathway degradation to negatively regulate p21 expression. Thus, MKRN1 regulates p21 ubiquitination to prevent IH-induced myocardial apoptosis.

The anaphase promoting complex/cyclosome (APC/C) is a large multi-subunit complex, regulating plant development and cell cycle. In plants, the APC/C gene family has been identified in Arabidopsis, rice, and maize. The APC/Cs in rose has not yet been reported. In this study, a total of 19 APC/C genes were identified in rose. Furthermore, we also investigated phylogenetic relationships, chromosomal distribution, gene structure, motif analysis, promoter sequence analysis and expression pattern of RhAPC/C genes. Synteny analysis indicated that AtAPC/Cs and RhAPC/Cs show a high degree of conservation. RhAPC/C promoters contains numerous cis-elements involved in plant morphogenesis, hormone response and stress response. Based on the transcription of RhAPC/Cs in different tissues and developmental stages, it appears that RhAPC/Cs may play a variety of roles in rose growth and development. RhAPC/Cs have limitations in the time and space during which they respond to hormones and abiotic stress. RhAPC5, RhAPC11d, RhAPC13a and RhAPC13c may play a role in rose responding to abiotic stress. The expression of RhAPC10 was altered by infection with fungal pathogen. Our study will serve as a basis for determining the functional role of APC/C genes in roses and help future research on woody plants.

As the first-line clinical drugs for tuberculosis (TB), isoniazid (INH), pyrazinamide (PZA), and rifampicin (RMP) are playing important roles for preventing the rapid spread of TB. Precise quantification of these drugs in biological samples is crucial to evaluate or improve the efficacy of advanced TB drug delivery systems, which are designed for reducing drug resistance, minimizing side effects, etc. Herein, a simple and sensitive method based on UPLC–UV was established and investigated for simultaneous quantification of PZA, INH, and RMP in human plasma and was applied to anti-TB drug therapeutic drug monitoring. The analytes were implemented on an HSS T3 C18 column at 40°C. The separation was performed with a gradient elution with methanol–acetonitrile–water (3:3:94) at 0.1 ml/min. The analysis only involved plasma with a small volume of 100 µL and a rapid one-step protein precipitation with methanol–acetonitrile (1:1). The results showed that the calibration curves for INH, PZA, and RMP were linear in a range of 0.5–20 μg/ml, 5–60 μg/ml, and 5–60 μg/ml, respectively. The intra- and inter-day precisions were both smaller than 15%, and the lower limit of quantitation (LLOQ) was identifiable and reproducible at 0.5 μg/ml for INH and 5 μg/ml for both PZA and RMP, respectively. The target drugs in plasma were stable after 21 days of storage at −80°C. The results indicated that our developed method is suitable for the simultaneous monitoring of INH, PZA, and RMP in human plasma.

Two-photon carbon-based nanoprobes hold great potential for biomedical applications as a result of their advantages of low fluorescence background, deep tissue imaging penetration and enhanced spatial resolution. However, the development of an activatable two-photon fluorescence carbon-based nanoprobe that simultaneously has the ability to target desired organs or cells is highly desired but remained a largely unsolved challenge. Herein, we developed boronate affinity BCNP@MnO2 nanocomposites, constructed by one step in situ growth of MnO2 nanosheets on the surface of aminophenylboronic acid-functionalized CNPs (BCNPs) via a redox reaction, which can feature efficient fluorescence energy transfer quenching to the BCNPs, allowing for tumor-specific affinity recognition and two-photon fluorescence activation imaging. By utilizing the inherent two-photon optical properties and sialic acid (SA) specific targeting ability of the BCNPs, good biocompatibility of the nanocomposites as well as highly sensitive and selective responses of MnO2 nanosheets towards GSH, the developed nanocomposites have demonstrated specific two-photon fluorescence activation imaging in target cancer cells and nude mouse tissues. Therefore, our proposed novel strategy could be used for monitoring GSH-triggered two-photon fluorescence activation events in SA-overexpressed cancer cells and has promising applications in both biological exploration and clinical diagnosis.

Background: Artemisinin is a sesquiterpene lactone compound with a special peroxide bridge that is tightly linked to the cytotoxicity involved in fighting malaria and cancer. Artemisinin and its derivatives (ARTs) are considered to be potential anticancer drugs that promote cancer cell apoptosis, induce cell cycle arrest and autophagy, inhibit cancer cell invasion and migration. Additionally, ARTs significantly increase intracellular Reactive Oxygen Species (ROS) in cancer cells, which result in ferroptosis, a new form of cell death, depending on the ferritin concentration. Ferroptosis is regarded as a cancer suppressor and as well as considered a new mechanism for cancer therapy. Methods: The anticancer activities of ARTs and reference molecules were compared by literature search and analysis. The latest research progress on ferroptosis was described, with a special focus on the molecular mechanism of artemisinin-induced ferroptosis. Results: Artemisinin derivatives, artemisinin-derived dimers, hybrids and artemisinin-transferrin conjugates, could significantly improve anticancer activity, and their IC50 values are lower than those of reference molecules such as doxorubicin and paclitaxel. The biological activities of linkers in dimers and hybrids are important in the drug design processes. ARTs induce ferroptosis mainly by triggering intracellular ROS production, promoting the lysosomal degradation of ferritin and regulating the System Xc-/Gpx4 axis. Interestingly, ARTs also stimulate the feedback inhibition pathway. Conclusion: Artemisinin and its derivatives could be used in the future as cancer therapies with broader applications due to their induction of ferroptosis. Meanwhile, more attention should be paid to the development of novel artemisinin-related drugs based on the mechanism of artemisinininduced ferroptosis.

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) is a nutritional crop, which has high rutin, and is good for health. Until now, plant genetic engineering is insufficient for Tartary buckwheat. Abscisic acid (ABA), as one of phytohormones, is involved in the regulation of plant growth and development, and responses to diverse environmental challenges. Although ABA receptors have been well characterized in Arabidopsis, it is little understood in Tartary buckwheat. In this study, we identified 12 ABA receptors, designated as FtRCAR1 through FtRCAR12 in Tartary buckwheat. FtRCARs are divided into three subfamily. Based on the similarity, we could predict that FtRCARs comprise of the monomeric (FtRCAR1, 3, 4, 5, 9, 10, 11 and 12) and the dimeric (FtRCAR2, 7 and 8) state in solution. The analysis of the transcript pattern indicated that most of FtRCARs were significantly variable among the root, stem, leaf, flower and seed, while FtRCAR4 transcript was undetectable under in all tissues. The transcript levels of FtRCARs under ABA treatment indicated that most FtRCARs transcripts were depressed, indicating a possible feedback regulation of ABA signaling. The analysis of rutin biosynthesis related-genes indicated that ABA up-graduated CHS, CHI, F3'H, F3H and FLS transcript levels, while transcripts of 4CL and PAL were down-regulated. In addition, the transcription factors that mediated the rutin biosynthesis related-genes were also regulated by exogenous ABA. Thus, the identification and the characterization of FtRCARs would enable us to further understand the role of ABA signal in Tartary buckwheat.

Bcr‐abl1 oncogene causes a shift in the transcription start site of the SMS1 gene (SGMS1) encoding the sphingomyelin (SM) synthesizing enzyme, sphingomyelin synthase 1 (SMS1). This results in an mRNA with a significantly shorter 5′‐UTR, called 7‐SGMS1, which is translated more efficiently than another transcript (IIb‐SGMS1) with a longer 5′UTR in Bcr‐abl1‐positive cells. Here, we determine the effects of these alternative 5′UTRs on SMS1 translation and investigate the key features underlying such regulation. First, the presence of the longer IIb 5′UTR is sufficient to greatly impair translation of a reporter gene. Deletion of the upstream open reading frame (−164 nt) or of the predicted stem‐loops in the 5′UTR of IIb‐SGMS1 has minimal effects on SGMS1 translation. Conversely, deletion of nucleotides −310 to −132 enhanced transcription of IIb‐SGMS1 to reach that of 7‐SGMS1. We thus suggest that regulatory features within nucleotides −310 and −132 modulate IIb‐SGMS1 translation efficiency.

Pyrethrins constitute a class of terpene derivatives with high insecticidal activity and are mainly synthesized in the capitula of the horticulturally important plant, Tanacetum cinerariifolium. Treatment of T. cinerariifolium with methyl jasmonate (MeJA) in the field induces pyrethrin biosynthesis, but the mechanism linking MeJA with pyrethrin biosynthesis remains unclear. In this study, we explored the transcription factors involved in regulating MeJA-induced pyrethrin biosynthesis. A single spray application of MeJA to T. cinerariifolium leaves rapidly upregulated the expression of most known pyrethrin biosynthesis genes and subsequently increased the total pyrethrin content in the leaf. A continuous 2-week MeJA treatment resulted in enhanced pyrethrin content and increased trichome density. TcMYC2, a key gene in jasmonate signaling, was screened at the transcriptome after MeJA treatment. TcMYC2 positively regulated expression of the pyrethrin biosynthesis genes TcCHS, TcAOC, and TcGLIP by directly binding to E-box/G-box motifs in the promoters. The stable overexpression of TcMYC2 in T. cinerariifolium hairy roots significantly increased the expression of TcAOC and TcGLIP. Further transient overexpression and viral-induced gene-silencing experiments demonstrated that TcMYC2 positively promoted pyrethrin biosynthesis. Collectively, the results reveal a novel molecular mechanism for MeJA-induced pyrethrin biosynthesis in T. cinerariifolium involving TcMYC2.

A simple but effective method for the detection of miRNAs was proposed by integrating exonuclease-III assisted target recycling amplification and repeated-fishing strategy. In the proposed method, exonuclease-III assisted target recycling amplification reaction is adopted to produce a large amount of DNA fragments with fluorescence group at its 5′ end in the presence of the target miRNA, which are then repeatedly fished out from the reaction mixture by a gold foil modified with a capture probe and transferred into a so-called ‘product tube’. The amount of the target miRNA can then be determined from the fluorescence measurement of the solution in the ‘product tube’. Application to the detection of miRNA-155 in samples of KH-2 and BRSA-2B cells revealed that the proposed method could achieve sensitive and accurate quantification of the target miRNA with a limit of detection of 36 fM and recovery rates in the range from 96.2% to 105%. Its simplicity, sensitivity and resistance to possible fluorescence interferences in complex biological samples make the proposed method a potentially competitive alternative for miRNAs detection in complex biological samples.

Hematopoietic gene delivery, such as hematopoietic stem/progenitor cells (HSPCs), is a promising treatment for both inherited and acquired diseases, such as hemophilia. Recently, a combined strategy to achieve more than 90% transduction efficiency was documented using recombinant adeno-associated virus serotype 6 (rAAV6) vectors. However, the mechanisms of enhanced vector transduction efficiency in hematopoietic cells are largely unknown. In this manuscript, we first reported that proteasome inhibitors, which are well-known to facilitate rAAV intracellular trafficking in various cell types, are not effective in hematopoietic cells. From the screening of small molecules derived from traditional Chinese medicine, we demonstrated that shikonin, a potential reactive oxygen species (ROS) generator, significantly increased the in vitro and ex vivo transgene expression mediated by rAAV6 vectors in hematopoietic cells, including human cord blood-derived CD34 + HSPCs. Shikonin mainly targeted vector intracellular trafficking, instead of host cell entry or endonuclear single to double strand vector DNA transition, in a vector serotype-dependent manner. Moreover, a ROS scavenger completely prevented the capability of shikonin to enhance rAAV6 vector-mediated transgene expression. Taken together, these studies expand our understanding of rAAV6-mediated transduction in hematopoietic cells and are informative for improving rAAV6-based treatment of blood diseases.

Luminescent nanoclusters (NCs) have attracted much attention because of their good photostability and low toxicity, however, the low quantum yield is still a deficiency, and many increasing efforts are being devoted to enhance the luminescence intensity of NCs. In this paper, a method of enhancing the fluorescent signal of gold-silver nanoclusters (AuAgNCs) by photonic crystals (PhCs) was proposed. The fluorescent intensity of AuAgNCs on PhCs can be enhanced 8.0-fold in comparison to the control sample without PhCs. Furthermore, a novel fluorescence sensor of AuAgNCs based on PhCs is used for the sensitive and selective detection of Hg2+ ion in the aqueous solution, the detection limit is 0.35 nM due to the PhCs enhancement effect for the fluorescence. This proposed method may not only develop a highly sensitive method for determination of Hg2+ ion, but also expand the application of AuAgNCs in ultra-trace analysis.

The aim of this study is to evaluate the enhanced ability of various choline based ionic liquids (ILs) for dermal delivery of hyaluronic acid (HA). Eight ILs were synthesized via neutralization reactions, which were characterized using Fourier transform infrared spectrometer and proton nuclear magnetic resonance. The enhanced capacity of ILs varied with organic acids. The IL formed by choline and citric acid ([Ch][Cit]) exerted the strongest ability to promote HA penetrating deep into the skin among all ILs. The enhanced ability of [Ch][Cit] were still maintained and even improved after diluted by water although it could be disassociated partially according to electricity. The moisture and transepidermal water loss (TEWL) were employed to evaluate the effect of attenuating skin dehydration. As expected, the IL of choline and malic acid ([Ch][Mala]) and [Ch][Cit] increased moisture and decreased TEWL significantly by improving the penetration of HA into skin. Meanwhile, no irritation was observed on skin of nude mice after treatment by the three ILs which showed optimal enhanced effect. In conclusion, ILs could be high potential biocompatible carriers for facilitating HA dermal delivery to resist skin dehydration for medical or cosmetic uses.

Pyricularia oryzae is the causal agent of blast disease on staple gramineous crops. Sulphur is an essential element for the biosynthesis of cysteine and methionine in fungi. Here, we targeted the P. oryzae PoMET3 encoding the enzyme ATP sulfurylase, and PoMET14 encoding the APS (adenosine-5'-phosphosulphate) kinase that are involved in sulfate assimilation and sulphur-containing amino acids biosynthesis. In P. oryzae, deletion of PoMET3 or PoMET14 separately results in defects of conidiophore formation, significant impairments in conidiation, methionine and cysteine auxotrophy, limited invasive hypha extension, and remarkably reduced virulence on rice and barley. Furthermore, the defects of the null mutants could be restored by supplementing with exogenous cysteine or methionine. Our study explored the biological functions of sulfur assimilation and sulphur-containing amino acids biosynthesis in P. oryzae.

Here, we report a novel fluorescence method for the highly selective and sensitive detection of RNase H by combining the use of a dual-pyrene-labeled DNA/RNA duplex with supramolecular inclusion-enhanced fluorescence. Initially, the probe is in the “off” state due to the rigidness of the double-stranded duplex, which separates the two pyrene units. In the presence of RNase H, the RNA strand of the DNA/RNA duplex will be hydrolyzed, and the DNA strand transforms into a hairpin structure, bringing close the two pyrene units which in turn enter the hydrophobic cavity of a γ-cyclodextrin. As a result, the pyrene excimer emission is greatly enhanced, thereby realizing the detection of RNase H activity. Under optimal conditions, RNase H detection can be achieved in the range from 0.08 to 4 U/mL, with a detection limit of 0.02 U/mL.

In this paper, in order to solve signal instability of high-performance liquid chromatography-diode array detection (HPLC-DAD) data and maintain the second-order advantage, this work proposed piecewise direct standardization (PDS) assisted with second-order calibration methods to analyze two different complex HPLC-DAD data with signal instability, including simulated HPLC-DAD data and the data of pesticide residues in saffron. Accurate quantitative results of target analytes can be obtained by PDS combined with alternating trilinear decomposition algorithm (ATLD) and alternating trilinear decomposition assisted multivariate curve resolution algorithm (ATLD-MCR) in the presence of signal instability with time shifts and changes of peak shape. Quantitative results of the model after calibration transfer are better than those of the model established by calibration sets and prediction sets with signal instability using ATLD algorithm and ATLD-MCR algorithm under different situations. Meanwhile, t-test was used to judge whether there are significant differences between these quantitative results of models. The performances of MCR-ALS algorithm were compared with that of PDS-ATLD method and PDS-ATLD-MCR method and the proposed methods have greater potential in dealing with the case of signal instability with time shifts and changes of peak shape. In a word, this methodology can reduce the number of calibration samples for recalibration and modeling, improve the efficiency of experiment, conform to the principle of green chemistry, and obtain satisfactory quantitative results in the presence of signal instability with time shifts and changes of peak shape.

This cross-sectional study aimed to investigate the current attention and intervention of oncologists on oxaliplatin (OXA)-induced adverse reactions (ADRs).In 31 provinces or administrative regions across China, 401 oncologists were surveyed through a self-designed questionnaire. The survey queried the basic information of respondents, clinical use of OXA, OXA-induced ADRs, and relative interventions. Chi-square tests and multiple logistic regression were used to explore the sociodemographic factors influencing the safety perception of OXA and the relevant interventions.The survey showed that the age of respondents was mainly distributed between 30 and 40 years and the working period for most oncologists was no more than 5 years. Oncologists with long working years were more willing to conduct patient education and inquire about ADRs than those with short working years. The rate of ADRs reported by oncologists with intermediate professional titles was significantly higher than that reported by oncologists with junior and senior professional titles.Our findings indicate that oncologists in mainland China are concerned about OXA-induced ADRs, but the reporting of ADRs still needs to be strengthened. Therefore, training and educational programs are urgently needed to improve the risk management of OXA-induced ADRs among oncologists.

Quantitation of protoberberine alkaloids is an essential guarantee for efficacy control and medication safety of Coptidis Rhizoma (CR) related medicines. Traditional univariate chromatography faced challenges with co-elution, unknown interferences, and retention time shift when analyzing isomeric analytes in varying sample matrices. We presented a chemometrics-enhanced high-performance liquid chromatography-diode array detection (HPLC-DAD) strategy for simultaneous quantification of six protoberberine alkaloids and processed multi-channels chromatographic-spectral data with four second-order calibration algorithms. Chromatographic conditions were firstly optimized. Four groups of predicted samples were modeled individually with the designed calibration set. Mathematical resolutions were then obtained, and pseudo-univariate regression gave the quantitative concentration of each analyte. Four models were scored on fit, linearity, recovery, and robustness, where alternating trilinear decomposition assisted multivariate curve resolution (ATLD-MCR) exhibited an optimal and stable performance. Besides, the resolved spectra presented high consistency with the actual spectra (r≥0.9993). Limits of quantification (LOQ) fully met the pharmacopoeia stipulation and were 0.17, 0.60, 0.19, 0.74, 0.15, and 0.38 µg mL

Severe haze hovered over Harbin during the heating season of 2019–2020, making it one of the ten most polluted Chinese cities in January of 2020. Here we focused on the optical properties and sources of brown carbon (BrC) during the extreme atmospheric pollution periods. Enhanced formation of secondary BrC (BrCsec) was evident as relative humidity (RH) became higher, accompanied with a decrease of ozone but concurrent increases of aerosol water content and secondary inorganic aerosols. These features were generally similar to the characteristics of haze chemistry observed during winter haze events in the North China Plain, and indicated that heterogeneous reactions involving aerosol water might be at play in the formation of BrCsec, despite the low temperatures in Harbin. Although BrCsec accounted for a substantial fraction of brown carbon mass, its contribution to BrC absorption was much smaller (6 vs. 28%), pointing to a lower mass absorption efficiency (MAE) of BrCsec compared to primary BrC. In addition, emissions of biomass burning BrC (BrCBB) were inferred to increase with increasing RH, coinciding with a large drop of temperature. Since both the less absorbing BrCsec and the more absorbing BrCBB increased as RH became higher, the MAE of total BrC were largely unchanged throughout the measurement period. This study unfolded the contrast in the source apportionment results of BrC mass and absorption, and could have implications for the simulation of radiative forcing by brown carbon.

The dysregulation of LncRNAs is related to the malignant progression of many cancers. The study aimed to investigate the expression and the biological role of LncSNHG3 in hepatocellular carcinoma (HCC). The TCGA data of the LncSNHG3 in HCC were analyzed. The expression in HCC cell lines was detected by qRT-PCR. Proliferation, migration, and invasion of HepG2 and Huh7 were examined by cell counting kit-8, colony formation, transwell assays, and wound healing assays. At the same time, the interactions among LncSNHG3, miR-152-3p, and JAK1 were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, subcellular distribution. Xenograft tumor-bearing mice models were used to measure the effect of LncSNHG3 on the growth of HCC in vivo. The apoptosis and epithelial mesenchymal transition (EMT)-associated proteins were checked by WB and IHC. LncSNHG3 was overexpressed in HCC tissues and cell lines. In addition, it is correlated with the tumor stage and survival time of HCC patients. Down-regulated LncSNHG3 could significantly suppress the EMT progression of HCC in vivo and in vitro. LncSNHG3 could promote the JAK1 expression by sponging miR-152-3p. LncSNHG3 acted as an oncogene and promoted the EMT procession in HCC by binding miR-152-3p and promoting JAK1 expression. Predictably, LncSNHG3 was used as a potential marker and will be used as a novel therapy target for HCC in the future.

Without the estimation of the intermediate parameters, the direct position determination (DPD) method can achieve higher localization accuracy than conventional two-step methods. However, multipath environments are still a key problem, and complex high-dimensional matrix operations are required in most DPD methods. In this paper, a time-difference-of-arrival-based (TDOA-based) DPD method is proposed based on the subspace orthogonality in the cross-spectra between the different sensors. Firstly, the cross-spectrum between the segmented received signal and reference signal is calculated and eigenvalue decomposition is performed to obtain the subspaces. Then, the cost functions are constructed by using the orthogonality of subspace. Finally, the location of the radiation source is obtained by searching the superposition of these cost functions in the target area. Compared with other DPD methods, our proposed DPD method leads to better localization accuracy with less complexity. The superiority of this method is verified by both simulated and real measured data when compared to other TDOA and DPD algorithms.

In this work, a simple and effective strategy for the determination of 12 active compounds of Atractylodes macrocephala Koidz. (AM) was proposed by using high performance liquid chromatography-diode array detection (HPLC-DAD) combined with alternating trilinear decomposition (ATLD) algorithm. Utilizing the "second-order advantage", three common problems in HPLC could be resolved, namely baseline drifts, peak overlaps, and unknown interferences. 12 compounds were rapidly eluted within 12.5 min, and the average spiked recoveries were 80.8-109.9%. The figures of merit reflected the feasibility of the proposed method. Compared with the results of the traditional univariate calibration method based on HPLC-UV technique, the proposed strategy further verified the reliability and simplicity of the mathematical separation. On this basis, partial least squares-discriminant analysis (PLS-DA) was applied to discriminate 113 AM samples from different geographical origins, and variable importance in projection (VIP) was used to further screen the main differential components that affect the regional division of AM. A series of results show that the AM samples from the three regions have obviously different clustering trends. Overall, the strategy is expected to provide a scientific basis for the modern research of medicinal materials, and it is also conducive to the clinical use and market supervision of AM.

In the current study, we sought to determine the roles of histone deacetylase 5 (HDAC5) on the promotion of intestinal sepsis in a mouse model. Dual luciferase reporter gene assay was used to determine the binding relationship between HDAC5 and Ghrelin. Cecal ligation and puncture (CLP) was used as an animal model of intestinal sepsis. The roles of HDAC5 on intestinal sepsis were determined by HDAC5 knockdown, overexpression, and inhibitor (LMK-235) in vivo. Mice intestinal permeability and intestinal epithelial damage were evaluated, and HE staining was used to evaluate the intestinal mucosal injury index. Lipopolysaccharide (LPS)-treated intestinal-derived macrophages served as a cell model of sepsis, followed by the loss-of-function and gain-of-function assays. ELISA was used to determine the levels of inflammatory factors, and TUNEL staining was used to detect intestinal cell apoptosis. HDAC5 was upregulated in the intestine of sepsis patients. This increased HDAC5 expression was positively correlated with the expression of inflammatory factors TNF-α, IL-1β, IL-6, and HMGB1, as well as the intestinal dysfunction-related factors IFABP. In sepsis mice, the expression of inflammatory factors was reduced by HDAC5 knockdown. HDAC5 knockdown also improved survival, morphology of intestinal tissue, intestinal permeability, and epithelial damage. Ghrelin was bound and inhibited by HDAC5, but E2F1 expression was increased by Ghrelin overexpression, leading to inhibition of the NF-κB pathway. Ghrelin and E2F1 expression were increased by the treatment with HDAC5 inhibitor LMK-235, which inhibited the NF-κB pathway to improve intestinal dysfunction in the sepsis model. In conclusion, HDAC5 inhibits Ghrelin to reduce E2F1 and thus activate the NF-κB pathway, thereby promoting intestinal sepsis.

Background Endometriosis is a refractory and recurrent disease and it affects nearly 10% of reproductive-aged women and 40% of infertile patients. The commonly accepted theory for endometriosis is retrograde menstruation where endometrial tissues invade into peritoneal cavity and fail to be cleared due to immune dysfunction. Therefore, the comprehensive understanding of immunologic microenvironment of peritoneal cavity deserves further investigation for the previous studies mainly focus on one or several immune cells. Results High-quality transcriptomes were from peritoneal fluid samples of patients with endometriosis and control, and firstly subjected to 10 × genomics single-cell RNA-sequencing. We acquired the single-cell transcriptomes of 10,280 cells from endometriosis sample and 7250 cells from control sample with an average of approximately 63,000 reads per cell. A comprehensive map of overall cells in peritoneal fluid was first exhibited. We unveiled the heterogeneity of immune cells and discovered new cell subtypes including T cell receptor positive (TCR+) macrophages, proliferating macrophages and natural killer dendritic cells in peritoneal fluid, which was further verified by double immunofluorescence staining and flow cytometry. Pseudo-time analysis showed that the response of macrophages to the menstrual debris might follow the certain differentiation trajectory after endometrial tissues invaded into the peritoneal cavity, that is, from antigen presentation to pro-inflammation, then to chemotaxis and phagocytosis. Our analyses also mirrored the dysfunctions of immune cells including decreased phagocytosis and cytotoxic activity and elevated pro-inflammatory and chemotactic effects in endometriosis. Conclusion TCR+ macrophages, proliferating macrophages and natural killer dendritic cells are firstly reported in human peritoneal fluid. Our results also revealed that immune dysfunction happens in peritoneal fluid of endometriosis, which may be responsible for the residues of invaded menstrual debris. It provided a large-scale and high-dimensional characterization of peritoneal microenvironment and offered a useful resource for future development of immunotherapy.

Glyphosate, the most commonly used herbicide in the world, controls a wide range of plant species, mainly because plants have little capacity to metabolize (detoxify) glyphosate. Massive glyphosate use has led to world-wide evolution of glyphosate-resistant (GR) weed species, including the economically damaging grass weed Echinochloa colona. An Australian population of E. colona has evolved resistance to glyphosate with unknown mechanisms that do not involve the glyphosate target enzyme 5-enolpyruvylshikimate-3-P synthase. GR and glyphosate-susceptible (S) lines were isolated from this population and used for resistance gene discovery. RNA sequencing analysis and phenotype/genotype validation experiments revealed that one aldo-keto reductase (AKR) contig had higher expression and higher resultant AKR activity in GR than S plants. Two full-length AKR (EcAKR4-1 and EcAKR4-2) complementary DNA transcripts were cloned with identical sequences between the GR and S plants but were upregulated in the GR plants. Rice (Oryza sativa) calli and seedlings overexpressing EcAKR4-1 and displaying increased AKR activity were resistant to glyphosate. EcAKR4-1 expressed in Escherichia coli can metabolize glyphosate to produce aminomethylphosphonic acid and glyoxylate. Consistent with these results, GR E. colona plants exhibited enhanced capacity for detoxifying glyphosate into aminomethylphosphonic acid and glyoxylate. Structural modeling predicted that glyphosate binds to EcAKR4-1 for oxidation, and metabolomics analysis of EcAKR4-1 transgenic rice seedlings revealed possible redox pathways involved in glyphosate metabolism. Our study provides direct experimental evidence of the evolution of a plant AKR that metabolizes glyphosate and thereby confers glyphosate resistance.

Dye molecules pre-anchored on titanium oxo clusters (dye-TOCs) are attractive as model compounds of dye-sensitized titanium oxide. To investigate the effects of the dye ligand structures of the dye-TOCs on photocurrent conversion, a series of dye-TOCs with the same Ti6 core structure and different antenna ligands (L) was synthesized and characterized crystallographically. The TOCs have the same structural formula of [Ti6 O4 L2 (O3 PPh)2 (OiPr)10 ]. Two types of dyes with para- or meta-substituted structures were designed and used as the ligands. The results show that charge transfer from the donor group to the TiO core of the TOCs with the para-substituted ligands is stronger than those with the meta-substituted ligands. The steric effect of the ligands also greatly influences the photocurrent density. Larger branched structures of the dye ligands reduce the coverage density of the dye-TOCs on TiO2 electrodes and also weaken the effective covalent bonding of the dye-TOCs on the electrode, and consequently, the photocurrent is decreased.

Objective To compare the diagnostic performance of the manual BACTEC™ Mycobacteria Growth Indicator Tube (MGIT™) system (M-MGIT) with the automated BACTEC™ MGIT™ 960 system (A-MGIT) and Löwenstein-Jensen (L-J) culture method in detecting mycobacteria in sputum specimens from patients with suspected pulmonary tuberculosis (TB). Methods For this cross-sectional study, sputum samples were taken from patients aged ≥18 years attending a TB clinic in Beijing, China between July 2015 and October 2016. Processed sputum samples were inoculated into the MGIT systems and L-J medium for up to 6 and 8 weeks, respectively. Results The M-MGIT and A-MGIT methods detected significantly more Mycobacterium tuberculosis complex (MTC) isolates than L-J culture from the 565 sputum samples (39%, 40% and 32%, respectively). Using a positive result from any of the three culture systems as reference, the sensitivity of M-MGIT, A-MGIT and L-J methods were 92%, 94%, and 74%, respectively. The time-to-detection of mycobacteria was 12.9±4.2 days for M-MGIT, 11.8±5.2 days for A-MGIT and 24.2±8.7 days for L-J. Conclusions M-MGIT has a similar diagnostic performance to A-MGIT, and is a fast and reliable alternative to conventional culture methods in the diagnosis of pulmonary TB in a developing country.

A novel and versatile platform is developed for single-step amplified fluorescence detection of antibodies via specific proximity-induced hybridization chain assembly.

Carbon dots with different emission fluorescence have a great number of potential applications for various areas from in vitro imaging and biotherapy, due to the good biosafety of red fluorescent CDs, to efficient ion detection and photocatalysis, due to the excellent photoluminescence properties of blue fluorescent carbon dots. Traditional methods for the synthesis of full-spectrum carbon dots require 24 h of synthesis and complex column chromatography. In this paper, a facile and efficient microfluidic method to continuously synthesize small and uniform carbon dots with full-spectrum emission fluorescence is developed for the first time. The synthesis process could be reduced to 20 minutes. Through XPS analysis and DFT calculations, it is quantitatively revealed that the number of primary amino groups determines the energy gap of the carbon dots and thus determines the fluorescence emission wavelength of the carbon dots. Applications for precise Fe3+ detection and in vitro bio-imaging were successfully implemented, showing great potential application value of the carbon dots.

Formaldehyde (FA), as a reactive carbonyl species, is endogenously generated in various biological processes. Abnormal levels of FA could lead to various cellular dysfunction and pathological conditions. Here, we develop a new activatable fluorescent probe for highly selective visualization of FA in living cells. Our probe (Naph-1) is designed using a naphthalene derivative as the fluorophore and hydrazone as a recognition site for FA. Naph-1 is essentially nonemissive. After reacting with FA, the amine moiety is converted into a Schiff base with electron-withdrawing ability and the fluorescence is simultaneously turned on due to synergetic intramolecular charge transfer and favoured excited state intramolecular proton transfer effects. Naph-1 exhibits a large Stokes shift upon reaction with FA. Furthermore, it possesses high selectivity and superior sensitivity toward FA with an estimated limit of detection of 0.35 μM. Moreover, Naph-1 is also successfully applied to image both endogenous and exogenous formaldehyde in living cells. These features demonstrate that Naph-1 holds great potential in the detection and imaging of formaldehyde in biological systems.

Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines. Superparamagnetic iron oxide nanoparticles (SPION) are effective carriers for targeted drug delivery. This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI) (SPION-PEI) designed for small interfering RNA (siRNA) delivery both in vitro and in vivo. SPION-PEI/siRNA complexes were prepared at different weight ratios. Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). Rats were divided into three groups: a control group, a normal-saline group and a SPION-PEI/siRNA group. After a single intravenous injection, in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart, liver, spleen, lung and kidney 8 h, 24 h, and 7 days after the injection. Their distribution was histologically studied at the three time points by measuring ironpositive areas (μm2) in organ sections stained with Prussian blue. The same organs were analyzed by H&E staining for any possible histopathological changes. Furthermore, biochemical indexes such as alanine amino transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN) and creatinine (CREA) were also assessed at all experimental time points. Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4. MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity. In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition. The iron content was significantly increased in the liver and spleen, peaking 24 h after intravenous injection and then declining gradually. No evidence was found of irreversible histopathological damage to any of the organs tested. These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen, which might be the target organs of SPION-PEI/siRNA complexes. SPIONPEI/siRNA may serve as in vivo carrier for biomedical medicines.

Background Decades of efforts have attempted to differentiate the pluripotent stem cells (PSCs) into truly functional hematopoietic stem cells (HSCs), yet the problems of low differentiation efficiency in vitro and poor hematopoiesis reconstitution in vivo still exist, mainly attributing to the lack of solid, reproduced, or pursued differentiation system. Methods In this study, we established an in vitro differentiation system yielding in vivo hematopoietic reconstitution hematopoietic cells from mouse PSCs through a 3D induction system followed by coculture with OP9 stromal cells. The in vivo hematopoietic reconstitution potential of c-kit+ cells derived from the mouse PSCs was evaluated via m-NSG transplantation assay. Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system. Results The c-kit+ cells from 3D self-assembling peptide induction system followed by the OP9 coculture system possessed apparently superiority in terms of in vivo repopulating activity than that of 3D induction system followed by the 0.1% gelatin culture. We interestingly found that our 3D+OP9 system enriched a higher percentage of CD201+c-kit+cells that showed more similar HSC-like features such as transcriptome level and CFU formation ability than CD201-c-kit+cells, which have not been reported in the field of mouse PSCs hematopoietic differentiation. Moreover, CD201+ hematopoietic cells remained in a relatively slow cycling state, consistent with high expression levels of P57 and Ccng2. Further, we innovatively demonstrated that notch signaling pathway is responsible for in vitro CD201+ hematopoietic cell induction from mouse PSCs. Conclusions Altogether, our findings lay a foundation for improving the efficiency of hematopoietic differentiation and generating in vivo functional HSC-like cells from mouse PSCs for clinical application.

Posterior reversible encephalopathy syndrome (PRES) can develop in patients following exposure to multiple triggers, including blood pressure fluctuations, kidney diseases, immunosuppressive agents, chemotherapy, or autoimmune disorders. However, to the best of our knowledge, the development of PRES secondary to food poisoning has not been previously reported, especially in a pediatric patient. Here, we report a 13-year-old boy who presented with PRES following the consumption of palmatum (a chicken feet dish). The patient presented with headache, vomiting, and altered consciousness. Neuroimaging findings revealed white matter hyperintensities in a bilateral, symmetrical, and parieto-occipital pattern. The patient was diagnosed with PRES and was managed with fluid expansion and a short-term mannitol regimen (1 g/kg every 12 hours for 3 days). Neuroimaging findings returned to normal at 8 days after admission. Food poisoning may therefore be a new possible trigger for PRES. A timely PRES diagnosis is recommended to prevent possible central nervous system complications.

ObjectiveThis study aimed to determine the relationship between serum testosterone levels and depressive symptoms in an adult male population.MethodsWe conducted a cross-sectional study of 1166 male participants from Zunyi, Guizhou, China. Each participant completed a questionnaire, a brief clinical exam, and had a fasting blood sample taken. We measured serum testosterone, sex hormone-binding globulin, and luteinizing hormone levels. Multiple linear regression was used to evaluate the effect of demographic factors on the relationship between the depressive symptom score and serum sex hormone levels.ResultsMean testosterone, sex hormone-binding globulin, and luteinizing hormone levels were significantly higher in the depressive symptom group than in the non-depressed group. The mean calculated free serum testosterone level and free testosterone index (FTI) were significantly lower in the depressive symptom group than in the non-depressed group. Additionally, the mean FTI was significantly negatively correlated with the Beck Depression Inventory scale score in the multiple linear regression model (95% confidence interval: −3.274 to −0.406).ConclusionsDecreased bioactive testosterone levels might be a contributing factor of depression in adult men. The FTI could be the most sensitive biomarker reflecting the level of bioavailable testosterone in patients with depression.

We report a novel DNA-programmed plasmonic enzyme-linked immunosorbent assay (ELISA) for the ultrasensitive detection of protein biomarkers with the naked eye. The DNA-programmed plasmonic assay was based on two enzyme-free and isothermal nucleic acid amplification methods: hybridization chain reaction (HCR) and catalyzed hairpin assembly (CHA). In this study, a biotin-labeled DNA probe was utilized insteand of an enzyme-label probe in well-developed ELISA method. The biotin-labeled DNA probe was able to trigger the HCR and CHA processes, and the products could hybridize with DNA-modified gold nanoparticles (AuNPs) to induce the aggregation of the AuNPs and a color change in the solution. The developed method was able to detect as low as 1 pg mL-1 PSA target with the naked eye. Clinical serum samples demonstrated satisfactory results, indicating that the method is useful for early diagnostics and monitoring curative effects after a medical treatment. The developed method presents a simple and portable platform for ultrasensitive protein detection and has potential for point-of-care (POC) diagnostics in less developed areas.

A novel soft strategy for combination and partition of mass spectra data recorded at different fragmentor voltages in full scan mode of a mass spectrometer was developed to generate abundant multi-way data. It is the first time that non-linear four-way and combined three-way LC-MS data have been obtained simultaneously in a single chromatographic run. This strategy ensures that each analyte can be ionized and detected at the most appropriate MS conditions (ionization modes, fragmentor voltages) and avoids a hard chromatographic segmentation in subsequent chemometric analysis. Two different experimental datasets were analyzed to validate the feasibility and applicability of this strategy. Some simple pretreatments were carried out before LC-MS analysis to prevent potential matrix effects. Proper chemometric tools were used to resolve three-way (partitioned data) and enhanced three-way LC-MS (combined data) data, respectively. The method was assessed by comparing the analytical results obtained from the same chemometric algorithm with both combined and partitioned datasets: (1) the combined data provided the best global overall resolution, higher sensitivity and more reliable results, (2) the partitioned data provided higher selectivity for some specific analytes. The results showed that the developed method could be a soft and ingenious tool to handle the unordered but information-rich raw LC-MS data. Moreover, the proposed strategy could take extra analytical advantages in terms of higher sensitivity and more reliable quantitative results when compared with LC-MS (with single fragmentor voltage) strategy and showed nearly the same capability in analytical quality as classic LC-MS/MS method.

The two-dimensional Ruddlesden–Popper (RP) phases are an important class of halide perovskites with versatile optoelectronic properties. So far, only organic–inorganic hybrid RP phases involving long organic spacers were reported in this class. Here, we report an all-inorganic RP phase lead halide perovskite, Cs2PbI2Cl2 (1, I4/mmm space group; a = 5.6385(8) A, c = 18.879(4) A), synthesized by a solid-state method. The compound exhibits a band gap of Eg ∼ 3.04 eV and photoconductivity. We find an anomalous band gap evolution in Cs2Pb1–xSnxI2Cl2 solid solutions. Our combined density functional theory and experimental study supports the thermodynamically stable nature of 1 as a unique ordered phase in the Cs2PbX4 (X = Cl, Br, I) system. The calculations suggest that 1 is a direct bandgap semiconductor with relatively small effective carrier mass along the in-plane direction, consistent with the experimentally observed in-plane UV-light photoresponse. We also demonstrate that 1 is promising for radiation dete...