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Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increasing in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

As the most commonly used antipyretic and analgesic drug, paracetamol (PA) coexists with neurotransmitter dopamine (DA) in real biological samples. Their simultaneous determination is extremely important for human health, but puzzled by their mutual interference. In order to improve the conductivity, adsorption affinity, sensitivity and selectivity of TiO2-based electrochemical sensor, N-doped carbon@TiO2 double-shelled hollow sphere (H–C/N@TiO2) is designed and synthesized by simple alcoholic and hydrothermal method, using polystyrene sphere (PS) as a template. Meanwhile, TiO2 hollow spheres (H–TiO2) or N-doped carbon hollow spheres (H–C/N) are prepared by the same method. H–C/N@TiO2 hollow spheres have good conductivity, charge separation, and the highly enhanced and stable current responses for the detection of PA and DA. The detection limit and linear range are 50.0 nmol/L and 0.3–50 μmol/L for PA, 40.0 nmol/L and 0.3–50 μmol/L for DA, respectively, which are better than those of carbon-based sensors. Moreover, this electrochemical sensor with high selectivity, strong anti-interference, high reliability, and long time durability, can be used for the simultaneous detection of PA and DA in human blood serum and saliva. The high electrochemical performance of H–C/N@TiO2 is attributed to the multi-functional combination of different layers, because of good conductivity, absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO2.

Rutin, a flavonoid found in fruits and vegetables, is a potential anticancer compound with strong anticancer activity. Therefore, electrochemical sensor was developed for the detection of rutin. In this study, CoWO4 nanosheets were synthesized via a hydrothermal method, and porous carbon (PC) was prepared via high-temperature pyrolysis. Successful preparation of the materials was confirmed, and characterization was performed by transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin. The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability. PC has a high surface-to-volume ratio and superior conductivity. Moreover, the hydrophobicity of PC allows large amounts of rutin to be adsorbed, there by increasing the concentration of rutin at the electrode surface. Owing to the synergistic effect of the 3D CoWO4 nanosheets and PC, the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity. The sensor showed a good linear range (5–5000 ng/mL) with a detection limit of 0.45 ng/mL. The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Previous work showed that the copper oxide nanoparticles confined in titania nanotubes (Cu-in-TiO2NT) can effectively enhance the water–gas shift (WGS) activity. The WGS activity is directly related to the concentration of active copper species and oxygen vacancies (Ov). The addition of potassium is found to enhance WGS activity of copper catalysts to some extent. Herein, the K-promoted copper oxide (2 wt% Cu) nanoparticles confined in TiO2 nanotubes catalysts (Cu-in-K/TiO2NT) with different potassium contents were synthesized and investigated for the WGS reaction. The K-promoted catalysts exhibit the enhanced WGS activity. Especially, the Cu-in-K20/TiO2NT with the molar ratio of K/Cu = 20 displays twofold higher WGS activity compared with the Cu-in-TiO2NT. XRD, Raman, XPS, H2-TPR and in situ DRIFTS have verified that the addition of appropriate potassium can make active copper species bound with oxygen of the TiO2, leading to a partial reduction of TiO2 to TiO2-x, which is beneficial to form Cu–Ov–Ti site for the WGS reaction.

The rhamnogalacturonan acetylesterase gene (named pp1113), encoding a novel cold-adapted rhamnogalacturonan acetylesterase, was cloned from Paenibacillus polymyxa. pp1113 was functionally expressed in Escherichia coli by inducing expression at 20 °C for 16 h. The pH and temperature optimums for the recombinant enzyme were 8.5 and 30 °C, respectively. As an SGNH-type acetylesterase, pp1113 demonstrated high activity against acetyl ester substrates and could maintain approximately 60 % activity at 0 °C.The specific activity of purified pp1113 was 65.95 U/mg (C2). The Km and Vmax values of purified pp1113 were 3.89 mM and 81.07 μmol/min, respectively. We obtained an R232L variant with improved thermal stability and catalytic activity through site-directed mutagenesis. T1/2 of R232L at 50 °C increased from less than 30 min to 6 h when compared to wild-type pp1113, and T1/2 extended to 8 h after immobilization. The R232L mutant improved the conversion rate of 0.1 M cinnamyl alcohol at 40 °C to 94 % in the reaction of synthesis of cinnamyl acetate. After purification, the R232L mutant was immobilized (pH 8.0 phosphate buffer 0.5 M, 20 h at 20 °C, protein loading reached 17 mg/g). This was the first report of the rhamnogalacturonan acetylesterase gene obtained from Paenibacillus polymyxa with detailed enzymatic properties.

Existence of cuticle wax layer not only reduces the drying rate of blueberries but also causes the fruit to burst during drying. Such a phenomenon results in undesirable appearance as well as in losses of bioactive compounds responsible for health benefits and in sugars adhering to the surface and hence increased moisture adsorption capability of the dried fruit. In this study, uses of CO2 laser perforation, ultrasound and freezing–thawing as skin pretreatments prior to infrared freeze drying and their effects on drying characteristics as well as selected properties, i.e., shrinkage, color, rehydration capacity, as well as total anthocyanins and phenolics contents, of blueberries were investigated. Fourier transform infrared (FTIR) spectra of the dried fruit were also determined. Pretreatments increased drying rate and rehydration capacity of blueberries; shrinkage reduced from around 57 to 25%. Laser perforation and freezing–thawing but not ultrasonic pretreatments exhibited no significant effects on color of blueberries. Laser perforation and ultrasonic pretreatments exerted positive effects on the total phenolic and anthocyanin contents of the dried samples, respectively. FTIR spectra illustrated that all pretreatments did not alter the chemical fingerprints of the dried fruit powder.

A one-pot, base-mediated approach to Acanthus ilicifolius Linn alkaloid 2-benzoxazolinone derivatives is developed. Starting from trichloroacetic acid, o-aminophenol, substituted benzaldehydes and alkyl isocyanides, the desired 2-benzoxazolinone derivatives are obtained in good yields via a tandem Ugi condensation and intramolecular haloform cyclization at room temperature in the presence of Et3N.

Purpose Based on DNase I and reduced graphene oxide (rGO)-magnetic silicon microspheres (MNPS), a highly sensitive and selective fluorescent probe for the detection of PD-L1 was developed. Design/methodology/approach Here °C we present a feasibility of biosensor to detection of PD-L1 in lung tumors plasma. In the absence of PD-L1°C the PD-L1 aptamer is absorbed on the surface of graphene oxide modified magnetic nanoparticles °8rGO-MNPS°9 and leading to effective fluorescence quenching. Upon adding PD-L1°C the aptamer sequences could be specifically recognized by PD-L1 and the aptamer/PD-L1 complex is formed°C resulting in the recovery of quenched fluorescence. Findings This sensor can detect PD-L1 with a linear range from 100 pg mL−1 to 100 ng mL−1, and a detection limit of 10 pg•m−1 was achieved. Originality/value This method provides an easy and sensitive method for the detection of PD-L1 and will be beneficial to the early diagnosis and prognosis of tumors.

The methane bubble plume attracts interest because it offers direct evidence of seafloor gas leakage and plays an indirect role in the exploration and identification of natural gas hydrate. In this study, based on established plume models and their migration sections, three amplitude-class attributes were extracted from three formations for the migration sections of five plumes, and the correlation between the gas content and seismic attribute was obtained. As the gas content increases, the amplitude attribute correspondingly increases, and the linear correlation is relatively good. Moreover, correlation coefficients between gas content and amplitude attributes are close to 1.0. By using linear fitting, the relation model between the gas content of the plume and the seismic attribute was obtained. The relation model was subsequently used to invert the gas content from a real data-bearing plume. Comparison of the gas content section of the plume with the attribute section and real seismic section reveals common distribution characteristics, namely, the color of the section in the lower right corner is dark. If the amplitude value is large in the seismic section of the real plume, the amplitude attribute value is also large in the corresponding attribute section, and the inverted value of the gas content is also large (because gas content and amplitude are linearly correlated), which indicates that the plume bubbles of the section in the lower right corner is intensively distributed. Finally, the obtained gas content section of the plume can reflect the distribution of the plume bubble content more simply and intuitively, from which the distribution law of seafloor bubbles can be deduced, and this lays a foundation for the further estimation of the gas content of the plume and hydrate reserves.

Ketoprofen, a non-steroidal anti-inflammatory drug, can effectively relieve pain associated with arthritis, and microRNA-124 (miR-124) can inhibit the progression of the disease. In this study, poly (cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) nanoparticles (NPs) co-loaded with ketoprofen and miR-124 were successfully prepared using an emulsified solvent evaporation method. The co-loaded NPs exhibited a mean particle diameter of 160 nm. The acid sensitivity of the NPs was determined through in vitro release experiments. An adjuvant-induced arthritis rat model of arthritis was established for evaluating the pharmacodynamics of the NPs through clinical scoring and degree of swelling. The PCADK NPs exhibited more potent pharmacodynamic effects owing to the acid-sensitive properties of the carrier materials, compared with Poly (lactic-co-glycolic acid) (PLGA) NPs. Furthermore, PCADK co-loaded NPs exhibited superior anti-inflammatory effects compared to NPs loaded with either miR-124 or ketoprofen alone. In conclusion, co-delivery of ketoprofen and miR-124 through NPs is a promising strategy for the treatment of arthritis.

Yunning Huang,1,* Yuanyuan Yang,2,* Yuanyi Xu,2,* Qian Ma,3,4,* Fengying Guo,2 Yuan Zhao,2 Yuejia Tao,2 Mengqi Li,2 Jiaxin Guo2 1Department of Gastrointestinal Surgery, The Affiliated People’s Hospital of Ningxia Medical University, Yinchuan City, Ningxia Province, 750001, People’s Republic of China; 2Department of Pathology, Ningxia Medical University, Yinchuan City, Ningxia Province, 750004, People’s Republic of China; 3College of Life Sciences, Ningxia University, Yinchuan City, Ningxia Province, 750021, People’s Republic of China; 4College of Basic Medicine, Ningxia Medical University, Yinchuan City, Ningxia Province, 750004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunning Huang; Yuanyi Xu Email nxhyncc@126.com; nxxyy@hotmail.comPurpose: Gastric cancer (GC) is one of the most fatal digestive tumors worldwide. Abnormal activation or accumulation of the nuclear factor-erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) axis is a malignant event in numerous solid tumors. However, its involvement in angiogenesis of GC remains unknown. This study investigated the role of the Nrf2/HO-1 axis in angiogenesis of GC.Methods: The expression of Nrf2, HO-1, and vascular endothelial growth factor (VEGF) in BGC-823 cells under hypoxia was analyzed using immunocytochemistry, immunofluorescence, Western blotting, and quantitative polymerase chain reaction. The effects of brusatol (Nrf2 inhibitor) and tert-butylhydroquinone (Nrf2 inducer) on these factors and angiogenesis were examined using immunofluorescence, Western blotting, quantitative polymerase chain reaction, and tube formation assay. Moreover, immunohistochemistry and Western blotting were used to determine these factors and microvessel density in tumor and normal tissues of tumor-bearing and tumor-free mice, respectively. Immunohistochemistry and Western blotting were employed to examine these factors and microvessel density in human paracancerous tissues, well-differentiated GC, and poorly differentiated GC. The correlations between Nrf2, HO-1, and VEGF gene expression in 375 patients with GC from The Cancer Genome Atlas cohort were analyzed.Results: The expression of Nrf2, HO-1, and VEGF was increased in hypoxic BGC-823 cells (P< 0.05). Although brusatol decreased their expression and angiogenesis (P< 0.05), tert-butylhydroquinone had the opposite effect (P< 0.05). Moreover, the expression of Nrf2, HO-1, and VEGF, and microvessel density in tumor tissues was higher than that recorded in normal tissues of nude mice (P< 0.05). Similarly, these parameters were low in paracancerous tissues, but high in GC tissues (P< 0.05). Also, they were weak in well-differentiated GC, but strong in poorly differentiated GC (P< 0.05). In addition, there was a significant correlation between Nrf2, HO-1, and VEGF (P< 0.05).Conclusion: The Nrf2/HO-1 axis may regulate the angiogenesis of GC via targeting VEGF. These findings provide a promising biomarker and potential treatment target for GC.Keywords: gastric cancer, angiogenesis, Nrf2, HO-1, VEGF

The in situ glycan profiling of a single tumor cell plays an important role in personalized cancer treatment. Herein, an integrated microfluidic system was designed for living single-cell trapping and real-time monitoring of galactosyl expression on the surface, combining closed bipolar electrode (BPE) arrays and electrofluorochromic (EFC) imaging. Galactosyl groups on human liver cancer HepG2 cells were used as the model analysts, galactose oxidase (GAO) could selectively oxidize hydroxyl sites of galactosyl groups on the cell surface to aldehydes, and then biotin hydrazide (BH) was used to label the aldehydes by aniline-catalyzed hydrazone ligation. With the biotin-avidin system, nanoprobes were finally introduced to the galactosyl groups on the cell surface with avidin as a bridge, which was prepared by simultaneously assembling ferrocene-DNA (Fc-DNA) and biotin-DNA (Bio-DNA) on gold nanoparticles (AuNPs) due to their large surface area and excellent electrical conductivity. After a labeled single cell was captured in the anodic microchannel, the Fc groups attached on the cell surface were oxidized under suitable potential, and the nonfluorescent resazurin on the cathode was correspondingly reduced to produce highly fluorescent resorufin, collected by fluorescence confocal microscope. The combination of EFC imaging and BPE realized monitoring galactosyl group expression of 5.0 × 108 molecules per cell. Furthermore, the proposed platform had the ability to distinguish a single cancer cell from a normal cell according to the expression level of galactosyl groups and to dynamically monitor the galactosyl group variation on the cell surface, providing a simple and accessible method for the single-cell analysis.

Medicinally significant 3-monosubstituted tetrahydroquinolines and 1,2-dihydroquinolines were controllably constructed via redox-neutral vinylogous cascade condensation/[1,5]-hydride transfer/cyclization in EtOH from readily available starting materials with alkenyl and coumarin moieties being introduced facilely, which have the features of green solvent, novel hydride acceptor, metal-free conditions, controllable syntheses of hydroquinoline derivatives and with water as the only by-product. In addition, the electrophilicity and nucleophilicity of α,α-dicyanoalkenes have been consecutively employed as hydride acceptors and γ-exclusive nucleophiles.

A Zr-based MOF with UiO-66 topology, which was defined as Py-UiO-66, has been synthesized by modifying the ligand of p-phthalic acid with a pyridine group. Py-UiO-66 possesses excellent chemical stability in aqueous solutions of pH = 0-13, especially when the pore structure is functionalized by hanging bare Lewis basic pyridine groups. Results of gas adsorption experiment show that Py-UiO-66 has the ability to selectively absorb C2H2 and CO2 rather than CH4. More importantly, Py-UiO-66 has an efficient catalytic effect in CO2 cycloaddition.

The hydrophobic polymer driven crystallization of self-assembled micelles is usually sufficient for their purposes in materials chemistry studies. However, with the state of smart drug delivery research, micelles alone are not enough. The principles of the self assembly driven by hydrophilic dextran brushes together with charged poly(3-acrylamidophenyl boronic acid) (PPBA) are uncovered in this study. A series of poly(e-caprolactone)-block-poly(3-acrylamidophenyl boronic acid)-dextran (PCL-b-PPBA-Dex) micelles and vesicles are investigated as potential Alzheimer's disease (AD) treatments. Three inflammatory microenvironment responsive micelles, including celecoxib drug-loaded micelles (CEL), ibuprofen drug-loaded micelles (IBU) and telmisartan drug-loaded micelles (TEL), are developed. In vivo, CEL/IBU (mixture of CEL and IBU) and CEL/TEL (mixture of CEL and TEL) suppress the activation of glia and reduce the levels of inflammatory mediators through eliminating cyclooxygenase 2 (COX-2) signals. The CEL/TEL combination nanosystem is better at correcting neuroinflammation and improving the spatial memory ability of a senescence-accelerated mouse prone 8 model (SAMP8). We consider that the inflammation responsive combination nanosystem provides a new potential treatment for AD clinical patients.

Metal- and nitrogen-doped carbon materials (Me–N–C) have received intensive scientific interest as single-atom catalysts (SACs) for electro- and thermocatalytic reactions. In this work, the potenti...

Antimony chalcogenide Sb2(S, Se)3 is attracting a lot of attention as photovoltaic absorber owing to its rewarding photoelectric properties, low toxicity, and earth abundance. However, its device efficiency is still limited by the absorber material quality and device interface recombination. In this work, a fluorine-doped tin oxide (FTO) substrate with ultra-thin SnO2 layer and a low-cost stabilized carbon paste are introduced as a front and back contact layer respectively in Sb2(S, Se)3 based planar solar cells. Over 5.2 % efficiency is demonstrated in the structure of FTO/SnO2/CdS/Sb2(S, Se)3/Carbon/Ag, where the Sb2(S, Se)3 is prepared by hydrothermal technique. The complementary device physics characterizations reveal that the interfacial recombination between TCO and CdS is significantly suppressed by the introduction of ultra-thin SnO2 layer, which is profited from the leakage protection and bandgap offset engineering by its high resistivity and suitable conduction band minimum. Meanwhile, the successful adoption of the low-cost stabilized carbon as a back contact here shows an enormous potential to replace the conventional organic hole transport materials and noble metal. We hope this work can provide positive guidance to optimize Sb2(S, Se)3 based planar solar cells in the future.

This paper aimed to analyze the composition and pollution sources of particulate matter (PM) in the Beijing-Tianjin-Hebei region and its surrounding areas (henceforth the BTH region) during the heating season to support the mitigation and control of regional air pollution. Manual monitoring data from the China National Environmental Monitoring Network for Atmospheric PM in the BTH region were collected and analyzed during the 2016 and 2018 heating seasons. The positive definite matrix factor analysis (PMF) model was used to analyze the PM sources in BTH cities during the heating season. The main PM components were organic matter (OM), nitrate (NO3−), sulfate (SO42−) and ammonium salt (NH4+). Direct emission sources have decreased since 2016, indicating the effectiveness of governmental controls on these sources; however, secondary pollution showed an increasing trend, suggesting control measures should be strengthened. Daily regional average concentrations of OM, SO42−, NH4+, elemental carbon (EC), chloride (Cl−) and trace elements all showed similar trends. When air quality worsened, the concentrations of the main PM components increased, but trends of change varied among components. In 2018, concentrations of OM and chloride were highest in the Taihang Mountains, and NO3 concentrations were highest in Anyang, Hebi, Jiaozuo and Xinxiang. The SO42− concentration was highest in the southern section of the Taihang Mountains. The NH4+ and EC concentrations were generally highest in the central and southern regions. The concentration of crustal substances was highest in some cities in the north and central parts of the BTH region. In the 2018 heating season, the pollution level of five transmission channels showed an increasing trend in the Northwest, Southeast, Yanshan, South and Taihang Mountain channels. These findings provide a scientific basis for the continued management of atmospheric PM pollution.

This paper investigates the self-assembly of a flexible porphyrin derivative called 1,3-isophthalic acid-5-ether-4-tetraphenyl porphyrin at the interface of 1-heptanoic acid/highly oriented pyrolyt...

The aim of this study was to assess the spatial variation in the concentrations of total arsenic (Astotal), arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMAs(V)), and dimethylarsinic acid (DMAs(V)) in fine particulate matter (PM2.5) and to explore the influence of local emission sources based on the monitoring data from 18 sampling sites in Nanjing, China. The results showed that the average concentration of Astotal in the PM2.5 was 6.81 ng/m3 in Nanjing, which exceeded the standard limit of 6 ng/m3 in China. As(V) was the dominant species and varied between 71 and 81% of water-extractible As in the PM2.5. The results of the spatial variation coefficients (CVs) showed that Astotal, As(III), and As(V) displayed moderate levels of spatial heterogeneity (CV = 0.23), while DMAs(V) a considerably high level (CV = 0.60). The concentrations of Astotal and As species can be arranged in the following order: urban background ~ urban street < suburban < rural < industrial sampling sites. This pattern was connected to the influence of three local emission sources (industrial source, road traffic, and biovolatilization), which were quantified by multiple linear regression. Results showed that local road traffic sources had the smallest value of standardized regression coefficient (0.26) among these three sources, indicating that local road traffic sources contributed less to the concentration of As in PM2.5 than industrial source emissions and biovolatilization. Our findings indicate that the spatial heterogeneity of As species should be considered in exposure assessments and As biovolatilization is linked to the high heterogeneity.

Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy, while the mechanism was not very clear. Here, the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3, the liver transporters OATP1B1 and OATP1B3, and the intestine transporter OATP2B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation (YHP) comprising Corydalis yanhusuo (CYH) and Angelica dahurica (AD), which could relieve pain by restraining the central system. The results show that tetrahydropalmatine (TDE), the major component of CYH, could be transported by OAT3 into kidney, OATP1B1 and OATP1B3 into liver, while imperatorin (IPT) and isoimperatorin (ISP), the two key components of AD, and AD extract showed strong inhibition to OAT1 and OAT3. What's more, AD extract also exerted strongly inhibition to human transporters OATP1B1 and OATP1B3. It was also detected that IPT, ISP, and AD extract significantly downregulated the expression of Oatp1a1, Oatp1a4, and Oatp1b2 of liver in mice. The in vivo results show that the concentration of TDE in liver and kidney significantly decreased, while the TDE concentration in blood and brain were both significantly enhanced in the presence of IPT, ISP, and AD extract. These results suggest that the ingredients in AD with pungent taste could enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and kidney. That is to say, TDE with bitter taste could “flood up” into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within AD. This paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3, OATP1B1, and OATP1B3, but also illustrates how to improve the efficacy of CYH by reasonable compatibility with AD. This study may offer a valuable clue to illustrate the mechanism of compatibility theory., Graphical abstract Image 1The compatibility mechanism of Yuanhuzhitong preparation is that the ingredients in Angelica dahurica (AD) could enhance the exposure of tetrahydropalmatine (TDE) in blood and brain due to reduce the liver intake and renal excretion by inhibiting the uptake of TDE by liver transporters OATP1B1, OATP1B3 and kidney transporter OAT3.

Introduction To explore serum zinc-α2-glycoprotein (ZAG) and adiponectin in metabolically healthy non-obese (MHNO), metabolically healthy obesity (MHO), metabolically abnormal obesity (MAO) and metabolically abnormal diabetic obese (MADO) subjects and the relationship with metabolically phenotypes of obesity. Methods Two hundred twenty-five subjects including 32 with MHNO, 40 with MHO, 104 with MAO and 49 with MADO were enrolled. Baseline clinical data and biochemical variables were collected. Serum ZAG and adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Metabolically healthy (

In acute aristolochic acid nephropathy (AAN), aristolochic acid (AA) induces renal injury and tubulointerstitial fibrosis. However, the roles of microRNAs (miRNAs/miRs) and mRNAs involved in AAN are not clearly understood. The aim of the present study was to examine AA‑induced genome‑wide differentially expressed (DE) miRNAs and DE mRNAs using deep sequencing in mouse kidneys, and to analyze their regulatory networks. In the present self‑controlled study, mice were treated with 5 mg/kg/day AA for 5 days, following unilateral nephrectomy. AA‑induced renal injury and tubulointerstitial fibrosis were detected using hematoxylin and eosin staining and Masson's trichrome staining in the mouse kidneys. A total of 82 DE miRNAs and 4,605 DE mRNAs were identified between the AA‑treated group and the self‑control group. Of these DE miRNAs and mRNAs, some were validated using reverse transcription‑quantitative PCR. Expression levels of the profibrotic miR‑21, miR‑433 and miR‑132 families were significantly increased, whereas expression levels of the anti‑fibrotic miR‑122‑5p and let‑7a‑1‑3p were significantly decreased. Functions and signaling pathways associated with the DE miRNAs and mRNAs were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 767 DE pairs (in opposing directions) of miRNAs and their mRNA targets were identified. Among these, regulatory networks of miRNAs and mRNAs were analyzed using KEGG to identify enriched signaling pathways and extracellular matrix‑associated pathways. In conclusion, the present study identified genome‑wide DE miRNAs and mRNAs in the kidneys of AA‑treated mice, as well as their regulatory pairs and signaling networks. The present results may improve the understanding of the role of DE miRNAs and their mRNA targets in the pathophysiology of acute AAN.

In this paper, based on the evolution characteristics of the stress field of coal and rock masses during the mining process of the 2 + 3# coal seam of the Sichuan Coal Group, a three-way loading an...

In this study, a novel 0D/2D WS2/BiOBr heterostructured photocatalyst with rich oxygen vacancies was fabricated by a hydrothermal method. The WS2 QDs/BiOBr-10 heterostructures exhibited a maximum removal rate of 92% towards ciprofloxacin (CIP) within 100 min under visible-light irradiation, which was 2.63- and 2.02- folds higher activity than that of pristine BiOBr and WS2 QDs/BiOBr-10 with poor oxygen vacancies, respectively. In addition, the removal efficiencies of this photocatalyst towards various pollutants were 99% (Lanasol Red 5B), 95% (Rhodamine B), 85% (metronidazole), 96% (tetracycline) and 41% (Bisphenol A), respectively. Besides, the simultaneous photocatalytic degradation showed the competitive interactions between these organic contaminants for the active species, decreasing the removal efficiency for CIP. However, the simultaneous photocatalytic oxidation of CIP and reduction of Cr(VI) improved the utilization efficiency of photo-induced electrons and holes, resulting in high removal efficiencies for both CIP and Cr(VI). Three-dimensional excitation-emission matrix fluorescence spectra (3D EEMs) were used to investigate the degradation of CIP molecules. The synergistic effect of heterostructure and oxygen vacancies greatly assisted in the removal of organic pollutants, attributing to the enhanced visible-light harvesting and effective separation of photo-induced electron–hole pairs. Furthermore, trapping experiments and ESR results demonstrated that the CIP removal was dominated by the direct oxidation of holes (h+), whereas the hydroxyl radicals ( OH) and superoxide radicals ( O2−) acted as auxiliary active species. This study provides a new way to rationally design and construct active 0D/2D pattern heterojunction photocatalysts for environmental remediation.

Purpose Hepatocellular carcinoma (HCC) is one of the most malignant cancers around the world. HCC is less sensitive to conventional cytotoxic agents and easily develops into systemic metastases. However, the molecular mechanisms of the metastasis of HCC are poorly understood and need elucidation. Materials and methods Transwell system of the chemotherapy-challenged and unchallenged HepG2 cells was established. Adhesion assay and scratch-wound assay were utilized to analyze the adhesion and migration of HepG2 cells. iPLA2 and LOX-5 expression were analyzed by Western blot. LTB4 level was analyzed by ELISA. Results Chemotherapeutics are traditionally regarded as a way of killing tumor cells; on the other hand, we proved that the chemotherapeutics-induced tumor cell apoptosis can also change the tumor microenvironment by activating the LOX pathway and subsequently release inflammatory factors such as LTB4 which can stimulate the adhesion and migration of the small number of surviving cells. Berberine can reverse the adhesion and migration of HepG2 cells by inhibiting the expression of LOX-5 and reducing the LTB4 production in the tumor microenvironment. Conclusion Our study sheds light on a novel anti-metastasis strategy that the combination of Berberine and chemotherapy may prevent the chemotherapy-induced metastasis in HCC.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality among military service members and civilians in the United States. Despite significant advances in the understanding of TBI pathophysiology, several clinical reports indicate that multiple genetic and epigenetic factors can influence outcome. Homocysteine (HCY) is a non-proteinogenic amino acid, the catabolism of which can be dysregulated by stress, lifestyle, aging, or genetic abnormalities leading to hyperhomocysteinemia (HHCY). HHCY is a neurotoxic condition and a risk factor for multiple neurological and cardiovascular disorders that occurs when HCY levels is clinically > 15 µM. Although the deleterious impact of HHCY has been studied in human and animal models of neurological disorders such as stroke, Alzheimer’s disease and Parkinson's disease, it has not been addressed in TBI models. This study tested the hypothesis that HHCY has detrimental effects on TBI pathophysiology. Moderate HHCY was induced in adult male Sprague Dawley rats via daily administration of methionine followed by impact-induced traumatic brain injury. In this model, HHCY increased oxidative stress, upregulated expression of proteins that promote blood coagulation, exacerbated TBI-associated blood–brain barrier dysfunction and promoted the infiltration of inflammatory cells into the cortex. We also observed an increase of brain injury-induced lesion size and aggravated anxiety-like behavior. These findings show that moderate HHCY exacerbates TBI outcomes and suggest that HCY catabolic dysregulation may be a significant biological variable that could contribute to TBI pathophysiology heterogeneity.

Tumor microenvironment (TME)-responsive nanoformulations that catalyze a cascade of intracellular redox reactions showed promise for tumor treatment with high specificity and efficiency. In this study, we report Cu2+-doped zeolitic imidazolate frameworks-coated polydopamine nanoparticles (PDA@Cu/ZIF-8 NPs) for glutathione-triggered and photothermal-reinforced sequential catalytic therapy against breast cancer. In the TME, the PDA@Cu/ZIF-8 NPs could initially react with antioxidant glutathione (GSH), inducing GSH depletion and Cu+ generation. Whereafter, the generated Cu+ would catalyze local H2O2 to produce highly toxic hydroxyl radicals (·OH) through an efficient Fenton-like reaction even in weakly acidity. Importantly, the PDA could exert excellent photothermal conversion effect to simultaneously accelerate GSH consumption and improve the Fenton-like reaction for further expanding the intracellular oxidative stress, which innovatively achieves a synergistic photothermal-chemodynamic therapy for highly efficient anticancer treatment.

Cinnamyl acetate has a wide application in food industries. This work focuses on cinnamyl acetate synthesis with a novel esterase. estGUZ753, an esterase gene from Geobacillus uzenensis DSMZ 13551, was first cloned and expressed in Pichia pastoris KM71. The optimal activity of EstGUZ753 towards p-NP caprylate was at pH 8.0 and 70 °C, and the half-life at 70 °C was 28 h. Furthermore, EstGUZ753 showed marked tolerance in methanol. The activity of EstGUZ753 increased up to 1.16-fold in 90% methanol after 72 h, and the half-life in it was 336 h. The crude fermentation broth of EstGUZ753 was immobilized directly onto the epoxy resin (Lx-105s), and the immobilized EstGUZ753 exhibited a 99% conversion for cinnamyl acetate synthesis at a high cinnamyl alcohol concentration in 6 h (cinnamyl alcohol: 1.0 M, enzyme dosage: 3%). These characteristics of EstGUZ753 indicated its great potential for organic synthesis. A novel esterase gene from Geobacillus uzenensis DSMZ 13551 was first cloned and expressed in Pichia pastoris KM71. Esterase EstGUZ753 showed marked thermostability at high temperature and tolerance in methanol. Furthermore, the crude fermentation broth of EstGUZ753 was immobilized directly onto the epoxy resin, and immobilized EstGUZ753 exhibited a 99% conversion for cinnamyl acetate synthesis.

Enzyme-assisted aqueous extraction residue (REAE) has a lower utilization rate as it is the “waste” produced after the enzyme-assisted aqueous extraction (EAE), but its nutritional value is high. To improve the development and utilization of REAE, in this study, cookies were made by adding REAE (0%, 10%, 20%, 30%, 40%, 50%) as a food additive to a small amount of flour. The AOAC method was used to identify the basic components of REAE, analyze its physical and chemical properties, and characterize the cookie structure change in terms of texture, disulfide bond, and thiol content. An in vitro simulation system and sensory evaluation mechanism were established to analyze the bioavailability and impact of quality. The results show that REAE is a potential food additive. With an increase in the REAE content, the cookies become lighter in color, the sweetness and fat content are reduced, the hardness is increased, and the digestibility and glycerin index are reduced. The change in texture is caused by the reduction of disulfide bonds in the dough. The cookies were ‘well accepted’ with up to 30% REAE. Therefore, the use of the appropriate amount of REAE as a new food additive will reduce the amount of starch added.

Background Neonatal pneumonia (NP) has a high fatality rate in neonatal illness. This research investigated the functions of emodin on lipopolysaccharide (LPS)-evoked inflammatory injury in WI-38 cells. Methods Cell counting kit-8 (CCK-8) assay and flow cytometry were utilized for examining the impacts of LPS and emodin on viability and apoptosis, respectively. Taurine up-regulated gene 1 (TUG1) level was altered through cell transfection and investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, RT-qPCR, western blot and enzyme-linked immunosorbent assay (ELISA) were utilized for investigating expressions of monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6. Western blot was carried out for investigating the levels of Bcl-2, Bax, pro-Caspase-3, cleaved-Caspase-3 and NF-κB and p38MAPK pathway-related proteins. Results LPS treatment restrained cell viability, enhanced apoptosis, and expressions of inflammation-related IL-6 and MCP-1. Emodin alleviated LPS-evoked inflammatory injury and restrained the NF-κB and p38MAPK pathways. Furthermore, emodin positively regulated TUG1 expression and TUG1 silencing could reverse the efficacy of emodin on IL-6 and MCP-1 expressions. Finally, TUG1 regulates the expression of inflammatory factors through NF-κB and p38MAPK pathways. Conclusion Emodin alleviated LPS-evoked inflammatory injury by raising TUG1 expression via NF-κB and p38MAPK pathways in WI-38 cells.

Alkaline-earth metal Ca2+ modified CdS nanocrystals have been designed for the first time for highly efficient H2 evolution from hydrogen sulfide (H2S) with Na2SO3 as a favourable reaction medium. The advantage of Na2SO3 was revealed by an electrochemical test, and the conversion of Na2SO3 during the reaction was carefully studied. Particularly, most of Na2SO3 was converted into Na2S2O3. Highly value-added utilization of waste H2S is therefore achieved via photocatalysis.

The rigorous reaction conditions (sufficient H2O2 and a low pH value) of an efficient Fenton reaction limit its further biomedical translation. Therefore, it is urgent to improve the efficacy of the Fenton reaction at the tumor site for efficient ferroptotic therapy. Herein, a hypoxia-responsive-Azo-BSA functionalized biomimetic nanoreactor (Fe(iii)-GA/GOx@ZIF-Azo), encapsulating ultrasmall ferric-gallic acid coordination polymer nanoparticles (Fe(iii)-GA) and glucose oxidase (GOx) into a zeolitic imidazolate framework (ZIF), was constructed for tumor ablation through an intensive Fenton reaction accelerated by not only sustained Fe2+ and H2O2 supply but also low pH and photothermal stimulation. Moreover, Azo achieved charge reversal in a hypoxia microenvironment caused by the sustained oxygen consumption by GOx, which resulted in selective and enhanced tumor accumulation based on the hypoxia-activated positive feedback cellular uptake. This rationally designed biomimetic nanoreactor might lay a foundation for the clinical translation of ferroptotic therapy.

A chalcone, which is composed of two aromatic rings bridged by an alpha,beta-unsaturated carbonyl group, exhibits a variety of biological activities. With an objective to develop a novel chalcone-based functional dye, we have synthesized a chalcone diol CLN1, bearing two OH groups at the 2-positions on both phenyl rings, as well as reference compounds CLN2-6, and found that it serves as color indicators for pH and fluoride ions. CLN1showed a vivid color change from colorless to yellow (halochromism) in water at pH >= 10. Furthermore, it presented a selective color change from colorless to red upon the addition of TBAF in an organic solvent such as CH3CN. CLN1provided a strong red-shifted absorption band in the visible region under alkaline conditions in water and upon the addition of TBAF in CH3CN. The absorption spectral study together with TD-DFT calculations and X-ray crystallographic analysis revealed that the characteristic pi-resonant structures of CLN1caused by the ionization or OH-F(-)interactions and the planar conformation due to its intramolecular hydrogen bonding may provide a strong charge transfer (CT) absorption in the visible region.

The dual alkylation of the C(sp3)–H bond of cyclic α-methyl-N-sulfonyl imines has been achieved through the piperidine-promoted cascade condensation/[1,5]-hydride transfer/cyclization sequence from cyclic α-methyl-N-sulfonyl imines and o-aminobenzaldehydes in trifluoroethanol, providing structurally diverse 3-cyclic N-sulfonyl imine substituted tetrahydroquinolines in good yields with excellent diastereoselectivities.

Excess glucocorticoid (GC) production is known to induce obesity and insulin resistance through increased activation of the glucocorticoid receptor (GR). The molecular mechanism for the non-genomic effects of excessive circulating GC on the insulin-signalling pathway in skeletal muscle is unknown. The plant alkaloid berberine has been shown to attenuate insulin resistance and inhibit gluconeogenesis in type 2 diabetic animals. A highly bioavailable berberine formulation termed Huang-Gui solid dispersion (HGSD), is a preparation of berberine coupled to sodium caprate and this markedly improving berberines bioavailability. Here we examined how HGSD treatment attenuated GR-mediated alteration in PI3K signalling and insulin resistance in diabetic rats, dexamethasone-treated mice and in insulin resistant C2C12 skeletal muscle cells. Blood glucose and skeletal muscle GC levels were increased and insulin signalling impaired in skeletal muscle of type 2 diabetic rats compared to controls. Treatment of these animals with HGSD restored blood glucose and skeletal muscle GC levels to that of controls. Insulin resistant C2C12 skeletal muscle cells exhibited impaired insulin signalling compared to controls and treatment of HGSD and RU486, an antagonist of GR, restored insulin signalling to that of control cells. Administration of dexamethasone to mice increased GR/GRα-associated PI3K and reduced IRS1-associated PI3K, phosphorylated-AKT, and membrane GLUT4 translocation resulting in a higher blood glucose concentration compared to controls. HGSD treatment of these mice improved insulin resistance by reducing the association of GR/GRα with PI3K. Excess GC-induced insulin resistance is mediated by increased association of GR with PI3K and treatment with HGSD attenuates these effects. We hypothesize that HGSD may be a promising candidate drug for the treatment of type 2 diabetes by reducing the association of GR with PI3K in skeletal muscle.

Ovarian cancer is one of the leading causes of cancer-related death among women worldwide and accounts for 4% of all cancer cases in female patients. To date, ovarian cancer has the poorest prognosis among all types of gynecological cancer; thus, it is necessary to identify prospective therapeutic options. Previous studies have demonstrated the involvement of reactive oxygen species (ROS) in the cytotoxicity of various anticancer drugs against several types of carcinoma, including ovarian cancer. The present study aimed to investigate the anticancer effects of Siomycin A, a thiopeptide antibiotic, on the ovarian cancer cell lines PA1 and OVCAR3. To determine the viability of these cells following exposure to Siomycin A, the MTT assay was used, and apoptosis was determined by ELISA. In addition, mitochondrial membrane potential was determined by JC1 staining, and cellular ROS levels were assessed by dichlorodihydrofluorescein diacetate staining in the presence and absence of antioxidant NAC. The subsequent levels of antioxidant enzymes and glutathione were also determined following Siomycin A treatment in the two cell lines. A combination study with Siomycin A and cisplatin indicated enhanced efficiency of the drugs on ovarian cancer cell viability. The results of the present study also demonstrated that Siomycin A induced ROS production, inhibited the major antioxidant enzymes, including catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and intracellular GSH in PA1 and OVCAR3 cells, and inhibited the cell viability with an IC50 of ~5.0 and 2.5 µM after 72 h respectively compared with the untreated controls. Additionally, the Siomycin A-induced ROS production further targeted apoptotic cell death by impairing the mitochondrial membrane potential and modulating the levels of pro- and antiapoptotic proteins compared with those in the corresponding control groups. The administration of the antioxidant N-acetylcysteine significantly abrogated the cytotoxic effects of Siomycin A. In conclusion, the results of the present study demonstrated the role of ROS in Siomycin A-mediated cytotoxicity in ovarian cancer cells.

In this study, we cloned the complementary (c)DNA sequences of tumour necrosis factor receptor (TNFR)-associated factor 3 (traf3) in Nile tilapia, Oreochromis niloticus. The expression patterns of the traf3 gene were investigated and preliminary functional analyses were performed. In healthy fish, traf3 transcript was broadly expressed in all examined tissues, with the highest expression level in the blood and the lowest in the liver. The traf3 gene reached its highest expression at 8 days post-fertilisation (dpf) during embryonic development. Moreover, we found that expression of traf3 was clearly altered following stimulation with Streptococcus agalactiae in vivo and that traf3 could be induced by lipopolysaccharides (LPS), Poly I: C and S. agalactiae WC1535 in Nile tilapia macrophages. Overexpression in 293T cells showed that Traf3 protein was mainly distributed in the cytoplasm and could significantly increase nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Taken together, these results implied that traf3 could play important roles in the immune response to pathogen invasion.

Graphical abstract, Highlights • Ultrasound technology was used to modify rice bran protein. • Chlorogenic acid was combined with rice bran protein to prepare functional complex. • By ultrasonic treatment, the properties of the complex were improved. • The emulsification performance of the complex was better at 200 W 10 min conditions., Ultrasound technology was used to treat rice bran protein (RBP), and the structural and functional properties of ultrasonically treated RBP (URBP) and its chlorogenic acid (CA) complex were studied. When ultrasonic power of 200 W was applied for 10 min, the maximum emission peak λmax of the URBP-CA complex in the fluorescence spectrum was red-shifted by 3.6 nm compared to that of the untreated complex. The atomic force microscope (AFM) analysis indicated that the surface roughness of the complex was minimized (3.89 nm) at the ultrasonic power of 200 W and treatment time of 10 min. Under these conditions, the surface hydrophobicity (H0) was 1730, the contents of the α-helix and β-sheet in the complex were 2.97% and 6.17% lower than those in the untreated sample, respectively, the particle size decreased from 106 nm to 18.2 nm, and the absolute value of the zeta-potential increased by 11.0 mV. Therefore, ultrasonic treatment and the addition of CA changed the structural and functional properties of RBP. Moreover, when ultrasonic power of 200 W was applied for 10 min, the solubility, emulsifying activity index (EAI), and emulsion stability index (ESI) were 68%, 126 m2/g, and 37 min, respectively.

Osteoarthritis is a common multifactorial chronic disease that occurs in articular cartilage, subchondral bone, and periarticular tissue. The pathogenesis of OA is still unclear. To investigate the differences in serum metabolites between OA and the control group, liquid chromatography/mass spectrometry (LC/MS)-based metabolomics was used. To reveal the pathogenesis of OA, 12 SD male rats were randomly divided into control and OA groups using collagenase to induce OA for modeling, and serum was collected 7 days after modeling for testing. The OA group was distinguished from the control group by principal component analysis and orthogonal partial least squares-discriminant analysis, and six biomarkers were finally identified. These biomarkers were metabolized through tryptophan metabolism, glutamate metabolism, nitrogen metabolism, spermidine metabolism, and fatty acid metabolism pathways. The study identified metabolites that may be altered in OA, suggesting a role in OA through relevant metabolic pathways. Metabolomics, as an important tool for studying disease mechanisms, provides useful information for studying the metabolic mechanisms of OA.

Aim: This study explored whether abnormality in the inner mitochondrial membrane fusion protein optic atrophy 1 (Opa1) causes hepatic insulin resistance and whether berberine (BBR) can prevent hepatic insulin resistance through the SIRT1/Opa1 pathway. Method: High-fat diet (HFD)-fed mice and db/db mice were used as animal models to study hepatic insulin resistance in vivo . Insulin resistance, morphological changes, and mitochondrial injury of the liver were examined to explore the effects of BBR. SIRT1/Opa1 protein expressions were determined to confirm whether the signalling pathway was damaged in the model animals and involved in BBR treatment. A palmitate (PA)-induced hepatocyte insulin resistance model was established in HepG2 cells in vitro . Opa1 silencing and SIRT1 overexpression were induced to verify whether Opa1 abnormality causes hepatocyte insulin resistance and whether SIRT1 could improve this dysfunction. BBR treatment and SIRT1 silencing were employed to prove that BBR can prevent hepatic insulin resistance by activating the SIRT1/Opa1 pathway. Results: We found that Opa1 deficiency caused imbalance in mitochondrial fusion/fission and impaired insulin signalling in the HepG2 cells. SIRT1 and BBR overexpression ameliorated PA-induced insulin resistance, increased Opa1, and improved mitochondrial function. SIRT1 silencing could partly reverse the effects of BBR in the HepG2 cells. SIRT1 and Opa1 were downregulated in the animal models. BBR attenuated hepatic insulin resistance and enhanced SIRT1/Opa1 signalling in the the db/db mice. Conclusion: Opa1 silencing-mediated mitochondrial fusion/fission imbalance could lead to hepatocyte insulin resistance. BBR may improve hepatic insulin resistance by regulating the SIRT1/Opa1 pathway, and thus, it may be used to treat type 2 diabetes.

Nitrosative stress, as an important oxygen metabolism disorder, has been shown to be closely associated with cardiovascular diseases, such as myocardial ischemia/reperfusion injury, aortic aneurysm, heart failure, hypertension, and atherosclerosis. Nitrosative stress refers to the joint biochemical reactions of nitric oxide (NO) and superoxide (O2–) when an oxygen metabolism disorder occurs in the body. The peroxynitrite anion (ONOO–) produced during this process can nitrate several biomolecules, such as proteins, lipids, and DNA, to generate 3-nitrotyrosine (3-NT), which further induces cell death. Among these, protein tyrosine nitration and polyunsaturated fatty acid nitration are the most studied types to date. Accordingly, an in-depth study of the relationship between nitrosative stress and cell death has important practical significance for revealing the pathogenesis and strategies for prevention and treatment of various diseases, particularly cardiovascular diseases. Here, we review the latest research progress on the mechanisms of nitrosative stress-mediated cell death, primarily involving several regulated cell death processes, including apoptosis, autophagy, ferroptosis, pyroptosis, NETosis, and parthanatos, highlighting nitrosative stress as a unique mechanism in cardiovascular diseases.

Simple Summary Genomic selection is a promising approach to select superior wheat lines with better resistance to Fusarium head blight. The accuracy of genomic selection is determined by many factors. In this study, we found a training population with large size, genomic selection models incorporating biological information, and multi-environment modelling led to considerably better predictabilities. A training population designed by the coefficient of determination (CDmean) could increase accuracy of prediction. Relatedness between training population (TP) and testing population is the key for accuracies of genomic selection across populations. Abstract Fusarium head blight (FHB) resistance is quantitatively inherited, controlled by multiple minor effect genes, and highly affected by the interaction of genotype and environment. This makes genomic selection (GS) that uses genome-wide molecular marker data to predict the genetic breeding value as a promising approach to select superior lines with better resistance. However, various factors can affect accuracies of GS and better understanding how these factors affect GS accuracies could ensure the success of applying GS to improve FHB resistance in wheat. In this study, we performed a comprehensive evaluation of factors that affect GS accuracies with a multi-parental population designed for FHB resistance. We found larger sample sizes could get better accuracies. Training population designed by CDmean based optimization algorithms significantly increased accuracies than random sampling approach, while mean of predictor error variance (PEVmean) had the poorest performance. Different genomic selection models performed similarly for accuracies. Including prior known large effect quantitative trait loci (QTL) as fixed effect into the GS model considerably improved the predictability. Multi-traits models had almost no effects, while the multi-environment model outperformed the single environment model for prediction across different environments. By comparing within and across family prediction, better accuracies were obtained with the training population more closely related to the testing population. However, achieving good accuracies for GS prediction across populations is still a challenging issue for GS application.

The epigenetic modifications of histones are essential markers related to the development and pathogenesis of diseases, including human cancers. Mapping histone modification has emerged as the widely used tool for studying epigenetic regulation. However, existing approaches are limited by fragmentation and short-read sequencing represent the average chromatin status in samples and cannot provide information about the long-range chromatin states. We leveraged the advantage of long read sequencing to develop a method “BIND&MODIFY” for profiling the histone modification of individual DNA fibers. Our approach is based on the recombinant fused protein A-M.EcoGII, which tethers the methyltransferase M.EcoGII to the protein binding sites and locally labels the neighboring DNA regions through artificial methylations. We demonstrated that the aggregated BIND&MODIFY signal matches the bulk-level ChIP-seq and CUT&TAG, verify the single-molecule heterogenous histone modification status, and quantify the correlation between distal elements. This method could be an essential tool in future third-generation sequencing ages.

Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)–dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.

Carbonate esters are utilized as solvents and reagents for C1 building blocks in organic synthesis. This study reports a novel photo-on-demand in situ synthesis of carbonate esters with CHCl3 solutions containing a mixture of an aromatic or haloalkyl alcohol having relatively high acidity, and an organic base. We found that the acid-base interaction of the alcohol and base in the CHCl3 solution plays a key role in enabling the photochemical reaction. This reaction allows practical syntheses of diphenyl carbonate derivatives, haloalkyl carbonates, and polycarbonates, which are important chemicals and materials in industry.

Purpose Age-related macular degeneration is a multifactorial disease involving inflammation and choroidal neovascularization. Vascular endothelial growth factor (VEGF) has been regarded as a potential therapeutic target to treat choroidal neovascularization. Dexamethasone can interfere with the expression or action of VEGF while bevacizumab targets and combines with VEGF. We propose electrostatically-conjugated bevacizumab-bearing dexamethasone-loaded poly (D,L-lactide-co-glycolide)/polyethylenimine nanoparticles (eBev-DPPNs) for angiogenic combination treatment of ocular diseases. Methods We prepared a novel nanoparticle composed of poly (D, L-lactide-co-glycolide) and polyethylenimine and loaded the nanoparticles with dexamethasone. Bevacizumab was adsorbed onto the surfaces of the nanoparticles by electrostatic interactions. The eBev-DPPNs were evaluated according to their size, polydispersity index, zeta potential, morphology, drug loading, release behavior, and stability. The structural stability of bevacizumab on the surface of the nanoparticles was also analyzed. Subsequently, angiogenesis was investigated in the presence of the eBev-DPPNs using cell apoptosis, wound healing, Transwell invasion, and tube formation assays on the human umbilical vein endothelial cells (HUVECs) in vitro and chick embryo chorioallantoic membrane assay in vivo. The eBev-DPPNs intravitreal injection was applied in the laser-induced rabbit choroidal neovascularization (CNV) model to confirm the role for potential intravitreal applications. Results The eBev-DPPNs was about 200 nm in diameter, with a narrow diameter distribution, and the surface charge was neutral (0.85 ± 0.37mV), which made the eBev-DPPNs stable under physiological conditions. The apoptosis, migration, invasion, and tube formation assays showed that the eBev-DPPNs had a good anti-angiogenic effect on HUVECs. The eBev-DPPNs also provided a strong inhibitory effect on VEGF secretion from HUVECs. Moreover, in vivo chick embryo chorioallantoic membrane assay showed eBev-DPPNs greatly reduced the amount of blood vessels. The leakage area of CNV decreased in the eBev-DPPNs group on rabbit CNV model. Conclusion The eBev-DPPNs are a promising novel anti-angiogenesis therapeutic for potential intravitreal applications such as age-related macular degeneration.