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Dapagliflozin (DAPA) exerts cardioprotective effects in non-diabetic patients. Nonetheless, the protective mechanism remains unknown. This study aims to evaluate the performance of DAPA on cardiac function and remodeling as well as its potential mechanism in mice with myocardial infarction (MI). Here, a MI mice model was established. One week after MI, mice were treated with saline or DAPA (1.5 mg/kg/day) for 4 weeks. At the end of this study, echocardiography was performed to assess cardiac structure and function. Myocardial apoptosis was analyzed by Western blot and immunofluorescence. Inflammatory cytokines and cardiac fibrosis were analyzed by real-time PCR and Masson's trichrome stain, respectively. Results showed that DAPA improved cardiac structure and function, attenuated cardiac fibrosis, and inhibited inflammatory cytokines and myocardial apoptosis. Moreover, the inhibition of PI3K/AKT/mTOR pathway might be related to the cardioprotective role of DAPA. These findings reveal that dapagliflozin is a potential therapeutic agent for MI patients without diabetes.

Nanomaterials are threatening the environment and human health, but there has been little discussion about the stability and mobility of nanoparticles (NPs) in saturated porous media at environmentally relevant concentrations of surfactants, which is a knowledge gap in exploring the fate of engineered NPs in groundwater. Therefore, the influences of the anionic surfactant (sodium dodecylbenzene sulfonate, SDBS), the cationic surfactant (cetyltrimethylammonium bromide, CTAB), and the nonionic surfactant (Tween-80) with environmentally relevant concentrations of 0, 5, 10, and 20 mg/L on nano-TiO2 (nTiO2, negatively charged) and nano-CeO2 (nCeO2, positively charged) transport through saturated porous media were examined by column experiments. On the whole, with increasing SDBS concentration from 0 to 20 mg/L, the concentration peak of nTiO2 and nCeO2 in effluents increased by approximately 0.2 and 0.3 (dimensionless concentration, C/C0), respectively, because of enhanced stability and reduced aggregate size resulting from enhanced electrostatic and steric repulsions. By contrast, the transportability of NPs significantly decreased with increasing CTAB concentration due to the attachment of positive charges, which was opposite to the charge on the medium surface and facilitated the NP deposition. On the other hand, the addition of Tween-80 had no significant influence on the stability and mobility of nTiO2 and nCeO2. The results were also demonstrated by the colloid filtration theory (CFT) modeling and the Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction calculations; it might promote the assessment and remediation of NP pollution in subsurface environments.

Three Gracilariopsis lemaneiformis strains, including wild type and high-temperature-resistant cultivars 981 and 2007, were studied with the changes in their photosynthetic pigment contents and related gene transcription levels under different light intensities (10, 60, 100, and 200 µmol m−2 s−1). The three G. lemaneiformis strains had the following photosynthetic pigments with high-to-low contents: phycoerythrin (PE), phycocyanin (PC), allophycocyanin (APC), and chlorophyll a (Chl a). Among the three strains, cultivar 981 had the highest PE content, followed by cultivar 2007. The PC and APC contents were similar among the three strains, but they were higher in cultivars 981 and 2007 than in the wild type. The Chl a contents in the three G. lemaneiformis strains were equal. A low light intensity (10 µmol m−2 s−1) promoted photosynthetic pigment accumulation in G. lemaneiformis and improved the relative PE gene transcription (peA and peB) in a short period (≤ 6 d). A high light intensity decreased the PE content. PebA and PebB, which catalyzed phycoerythrobilin synthesis, showed no compensatory upregulation at a low light intensity among the strains except for the wild type. At a high light intensity, transcription levels of pebA and pebB in the three strains were upregulated. This study provided an experimental basis for elucidating the photosynthesis of G. lemaneiformis. As key genes of algal growth, photosynthesis-related genes served as useful gene markers for screening elite varieties with good traits in breeding. Cultivar 2007 was superior to cultivar 981 in terms of maintaining high pigment levels in a wide range of light intensities, which is the most suitable for aquaculture.

A facile and green approach to the preparation of peroxidase-like nanozymes by reducing and functionalizing graphene oxide (rGO) with Ganoderma polysaccharide (GP) has been achieved in this work. Our results showed that the as-fabricated nanozyme, namely rGO-GP, possessed the excellent property of simulating peroxidase with higher catalytic activity compared with GO or rGO obtained by using chitosan, which may be due to the better dispersion of rGO-GP in the solution. Steady-state kinetics studies further showed that the catalytic process conformed to Michaelis-Menten equation and ping-pong mechanism. Benefiting from the excellent peroxidase property of rGO-GP, we have also successfully established a highly sensitive and selective colorimetric detection approach to trace detection of L-cysteine (L-Cys). The limit of detection (LOD) of L-cysteine is 0.1 μM and the linear detection range is 2-30 μM. Furthermore, the nanozyme was successfully applied for detecting L-cysteine in serum. This work therefore demonstrates the advantages of rGO-GP as an effective nanozyme in both its green synthesis and detecting application.

Bufadienolides are the main active ingredients of Venenum Bufonis, which is a widely used traditional Chinese medicine secreted from parotoid gland and skin glands of Bufo bufo gargarizans. According to the transcriptome analysis, “cholesterol-bile acid-bufadienolidies pathway” was proposed as animal-derived bufadienolides biosynthesis pathway by us previously. In this pathway 3β-hydroxysteroid dehydrogenase (3βHSD) and steroid 5β-reductase (SRD5β) might be the key enzymes to convert the A/B ring to cis-configuration. Therefore, as the second report of our group, here we report the cloning of the full length of SRD5β cDNA of B. bufo gargarizans (Bbg-SRD5β) from the parotoid gland of B. bufo gargarizans for the first time, and site-directed mutagenesis was used to explored the character of Bbg-SRD5β. Bbg-SRD5β had an open reading frame of 981 bp and encoded 326 amino acids residues. The expression conditions of the recombinant Bbg-SRD5β in E. coli BL21 (DE3) harbored with pCold-Bbg-SRD5β was optimized as induction for 10 h at 15 °C with 0.1 mM IPTG. With NADPH as a cofactor, Bbg-SRD5β can reduce the Δ4,5 double bonds of progesterone to generate dihydroprogesterone owithout substrate inhibition effect. The catalytic rate of mutant type Bbg-SRD5β-Y132G was 1.8 times higher than that of wild type Bbg-SRD5β. Although Bbg-SRD5β was almost unable to reduce the progesterone to dihydroprogesterone after mutation of V309, the affinity of enzyme with NADPH changed significantly. Bbg-SRD5β is the key enzymes to convert the A/B ring of steroid to cis-configuration, and V309 is a key site affecting the binding affinity of enzyme with NADPH, and the mutation of Y132 can adjust the catalytic rate of Bbg-SRD5β.

Cu–ZnO catalysts are widely studied for the direct hydrogenation of CO2 to methanol for high activity. However, despite the widespread research, promoting the intrinsic activity of active sites rem...

An efficient copper-catalyzed addition of arylboronic esters to (Boc)2O was developed. The reaction can be conducted under exceedingly mild conditions and is compatible with a variety of synthetically relevant functional groups. It therefore represents a useful alternative route for the synthesis of methyl arylcarboxylates. A preliminary mechanistic study indicated the involvement of an addition–elimination mechanism.

Metallic oxide based catalysts have received much attention in CO2 hydrogenation to methanol because of their high methanol selectivity and long-term stability. But the relatively weak hydrogenation ability leads to low methanol activity. Here, we introduce a small amount of Cu (molar fraction

It is imminent to develop a new type of rapid COVID-19 detection method with high sensitivity. Here, we used novel red emission-enhanced carbon dot (CD)-based silica (RCS) spheres as the signals of lateral flow immunochromatography (LFI) to ultrasensitively detect novel severe acute respiratory syndrome coronavirus 2 nucleocapsid proteins (SARS-CoV-2 NPs). The red emission of CDs can be enhanced and enriched in silica spheres by a simple way. The amino ends of the N-β-(aminoethyl)-γ-aminopropyltrimethoxy anchor carboxyl-rich CDs and enhance the red emission, while the other end is embedded in the silica carrier. Then, the composite silica spheres werecoated with 3-(triethylsilyl) propylamine to protect the CDs, promote bioconjugation and obtain RCS spheres. The optimal emission peaks of the aqueous solution and the solid state of RCS spheres were at 634 nm and 638 nm, respectively, with quantum yields (QYs) of 48.5% and 35.7%, respectively. Their red emission has a wide excitation range (from the ultraviolet region to the red region), and the best excitation wavelength is about 580 nm. Two fluorescence detection modes of the RCS-LFI technology for the SARS-CoV-2 NP assay are available: the simple mode of observation under ultraviolet light has a sensitivity of 100 pg mL-1; the advanced mode of detection under a fluorescence microscope has a sensitivity of 10 pg mL-1. This assay also exhibits the advantages of fast detection speed, high specificity, and simple operation. In addition, the feasibility of this method in actual sample detection was verified in human serum by the standard-addition method, and the results show that the method has excellent practicability. We believe that this method will be a valuable supplement for the diagnosis of COVID-19.

Background: Some literature has studied the relationship between lignans intake and its metabolite, enterolactone, and breast cancer survival, but the results are far from consistent and conclusive. Therefore, we conducted a systematic review and meta-analysis in this situation. Methods: From its inception to August 2020, we conducted a comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library databases. This study reported the correlation between lignans intake and serum enterolactone concentrations and prognosis of breast carcinoma. The total hazard ratios (HRs) and 95% confidence interval (95% CI) were estimated, comparing the highest versus the lowest category of lignans intake and serum enterolactone concentrations, using a fixed or random-effects effect model. Results: A total of 6 articles were included in reporting the all-cause mortality (ACM), breast cancer-specific mortality (BCSM), and recurrence of 2668, 1516, and 474 breast cancer patients in 18053 breast cancer patients. In postmenopausal women with breast cancer, lignans intake or enterolactone concentrations were associated with a reduced risk of all-cause mortality (maximum and minimum) (pooled HR = 0.73, 95% CI, 0.58-0.91), as was the association with breast cancer-specific mortality (maximum and minimum) (pooled HR = 0.72, 95% CI, 0.60, 0.87). Stratified analysis showed that exposure type and diagnosis time might be the sources of heterogeneity. In premenopausal women, the relationship seemed to be the opposite, showing an increased risk of all-cause mortality (maximum and minimum) in breast cancer patients (pooled HR = 1.57, 95% CI, 1.11-2.23). No significant association was found between lignans intake or enterolactone concentrations and breast cancer recurrence (pooled HR = 0.91, 95% CI, 0.69, 1.20). Conclusion: This study provides limited evidence that lignans intake and higher serum enterolactone concentrations in postmenopausal women are beneficial to breast cancer patients' prognosis. In premenopausal women, however, the relationship may be reversed.

Ginseng is usually consumed as a dietary supplement for health care in the normal state or prescribed as a herbal medicine in pathologic conditions. Although metabolic studies of ginseng are commonly performed on healthy organisms, the metabolic characteristics in pathologic organisms remain unexplored. This study aimed to uncover the difference in intestinal metabolism of ginseng between normal and cyclophosphamide-induced immunosuppressed rats and further discuss the potential mechanisms involved. Twelve Sprague-Dawley rats (6–8 weeks old) were randomly divided into two groups: the normal group (NG) and immunosuppressed group (ISG). Rats in the NG and ISG groups were intraperitoneally administered normal saline and cyclophosphamide injections (40 mg/kg) on the 1st, 2nd, 3rd and 10th days; on the 12th day, all rats were intragastrically administered ginseng water extract (900 mg/kg). The difference in intestinal metabolism of ginseng was compared using an ultra-high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry-based metabolomics approach, and the diversities of gut microbiota were analyzed by 16S rRNA gene sequencing between the two groups. The intestinal metabolomic characteristics of ginseng were significantly different between the normal and immunosuppressed rats, with the ginsenoside F2 (F2), 20S-ginsenoside Rg3 (20(S)-Rg3), pseudo-ginsenoside Rt5 (Pseudo-Rt5), ginsenoside Rd (Rd), ginsenoside Rh1 (Rh1), 20S-ginsenoside Rg1 (20(S)-Rg1), ginsenoside compound K (CK), ginsenoside Rg2 (Rg2) and 20S-panaxatriol (S-PPT) more abundant in immunosuppressed ones (P

Development of low-cost and eco-friendly approaches to fight bacterial pathogens is especially needed in aquaculture. We previously showed that exogenous malate reprograms zebrafish’s metabolome to potentiate zebrafish survival against Vibrio alginolyticus infection. However, the underlying mechanism is unknown. Here, we use GC-MS based metabolomics to identify the malate-triggered metabolic shift. An activated TCA cycle and elevated taurine are identified as the key metabolic pathways and the most crucial biomarker of the reprogrammed metabolome, respectively. Taurine elevation is attributed to the activated TCA cycle, which is further supported by the increased expression of genes in the metabolic pathway of taurine biosynthesis from the isocitrate of the TCA cycle to taurine. Exogenous taurine increases the survival of zebrafish against V. alginolyticus infection as malate did. Moreover, exogenous taurine and malate regulate the expression of innate immunity genes and promote the generation of reactive oxygen species and nitrogen oxide in a similar way. The two metabolites can alleviate the excessive immune response to bacterial challenge, which protects fish from bacterial infection. These results indicate that malate enhances the survival of zebrafish to V. alginolyticus infection via taurine. Thus, our study highlights a metabolic approach to enhance a host’s ability to fight bacterial infection.

Higher alcohol (C2+) synthesis (HAS) from direct CO2 hydrogenation is a promising way to realize the fixation of CO2 to high-value chemicals; however, the identification of active catalysts to give...

The nitrile groups in the tetrafluoroterephthalonitrile-crosslinked β-cyclodextrin (β-CD) were modified by (1) the reaction with the diethanolamine resulting in the hydroxyalkylaminoalkylamide groups or the hydroxyalkylaminoimide groups (2) the reduction of the borane-tetrahydrofuran complex resulting in the amide groups to form two novel β-CD based polymers (CDPs), namely the CDP-DEA and the CDP-NH2, correspondingly. Furthermore, the dye adsorption abilities of these two CDPs in the aqueous solution were investigated using the anionic dyes including the Congo red (CR) and the orange G (OG). For both the CDP-DEA and the CDP-NH2, the pseudo second-order model fitted well with their adsorption dynamics and their equilibrium adsorption process followed the Langmuir isotherm model. The maximum adsorption capacities of the CDP-DEA for CR at pH = 5 and OG at pH = 3 were 813 mg/g and 442 mg/g, respectively, while the corresponding values of the CDP-NH2 were 40 mg/g and 446 mg/g, respectively. It was found that the electrostatic attraction played an important role in the anionic dye adsorption of the CDP-DEA and the CDP-NH2.

Tea consumption has been found to be associated with low incidence of inflammatory bowel disease in Asian countries. However, there is very limited knowledge of such potential protection and its underlying mechanism. Ripened Pu-erh tea (RPT) belongs to the variety of microbial fermented tea, but its function regarding anti-inflammation remains unclear. In the present study, we investigated the effects of RPT on dextran sulfate sodium (DSS)-induced colitis in mice. The results demonstrated that RPT significantly relieved the loss of body weight, disease severity and shortening of colon length, and remarkably inhibited the secretion of pro-inflammatory cytokines by lessening the infiltration of inflammatory cells. Furthermore, we found that RPT suppressed the activation of the NF-κB pathway and down-regulated the expression of HIF-1α. Thus, it was concluded that RPT attenuated the progress of colitis via suppressing the HIF-1α/NF-κB signaling pathways thus reducing inflammation. This suggests that RPT may be a potential anti-inflammatory nutraceutical for the prevention and treatment of colonic colitis.

International audience; Dielectric nanomaterials offer great promise for diverse technological applications such as capacitors, actuators, and sensors. Unfortunately, the exploitation of desirable dielectric properties in polymer nanocomposites is a great challenge due to lack of efficient routes to achieve uniform dispersion of nanoparticles and good compatibility of interfaces at high nanoparticle loadings. A dilemma between the nanofiller loading and dispersion as well as interfacial compatibility makes it impossible to fully exploit the intrinsic polarization of the nanoparticles. Herein, we solve such a dilemma and fabricate highly filled barium titanate/silicone rubber (BT/SR) nanocomposites through chemically bonding BT nanoparticles with SR by “thiol–ene click” and isostatic pressing techniques. BT loading varies from 88 wt% to 97 wt% without compromising the uniform dispersion quality and good interfacial adhesion with the SR matrix. The 90 wt% BT nanocomposite shows an optimum dielectric constant as high as 55, while its loss tangent can be kept as low as 0.019 at 103 Hz. Meanwhile, it displays good stability of dielectric properties from room temperature up to 100 °C. In addition, the breakdown strength just decreases slightly compared to neat SR (97 MV m−1) but is still beyond 75 MV m−1. The present work provides a facile strategy towards superior dielectric polymer nanocomposites.

In the present study, the hypoglycemic effects of glucomannan (AGM) and its enzyme-degraded products from Amorphophallus albus were investigated. Four degraded products were prepared through ultrafiltration of β-glucanase-degraded products of AGM. The hypoglycemic activities were evaluated in HFD-STZ-induced type 2 diabetes mellitus (T2DM) mice, and the diversity of gut bacteria was analyzed by 16S rRNA gene sequencing; the fecal short chain fatty acids (SCFAs) and endogenous metabolites were determined by UPLC-QTOF-MS/MS. It was found that AGM and its enzyme-degraded products, though with different molecular weights, had similar β-glycosidic bonds and monosaccharide compositions, exerted similar strength of hypoglycemic effects, and reinstated with a similar extent the disordered gut microbiota and the contents of SCFAs and endogenous metabolites. It was speculated that the hypoglycemic activity of AGM is decided by not the molecular weight but the glycosidic bonds/monosaccharide composition of AGM, which might be structurally specific to the gut bacteria, and thus certain SCFAs and endogenous metabolites that are related to the occurrence and therapy of T2DM. This study provides a scientific basis for using AGM as potential prebiotics beneficial for prevention or therapeutic treatment of T2DM.

Rhubarb is a widely used herbal medicine. To achieve different effects, rhubarb is usually steamed with rice wine (steamed rhubarb). This steaming treatment increases the blood-activating and stasis-removing effects of rhubarb. A specific and accurate ultra high performance liquid chromatography with tandem mass spectrometry method was established for simultaneous determination of anthraquinone glycosides, aglycones, and glucuronic acid metabolites in plasma and tissues after administration of raw rhubarb and steamed rhubarb in blood stasis rats. Chromatographic separation was performed on ACQUITY UPLC BEH Shield RP 18 column using the mobile phase consisting of water and acetonitrile both containing 0.1% formic acid. Satisfactory linearity, precision, accuracy, extraction recovery, and matrix effect have been achieved. From pharmacokinetic study, it showed that glucuronic acid metabolites were found abundantly in plasma as bioactive components. The lower area under concentration-time curve, maximum concentration, and higher apparent volume of distribution (P

One of the major challenges in treating Alzheimer's disease (AD) is its early diagnosis. Increasing data from clinical and animal research indicate that the retina may facilitate an early diagnosis of AD. However, a previous study on the 5xFAD (a fast AD model), showing retinal changes before those in the brain, has been questioned because of the involvement of the retinal degeneration allele Pde6brd1. Here, we tested in parallel, at 4 and 6 months of age, both the retinal and the brain structure and function in a 5xFAD mouse line that carries no mutation of rd1. In the three tested regions of the 5xFAD brain (hippocampus, visual cortex, and olfactory bulb), the Aβ plaques were more numerous than in wild-type (WT) littermates already at 4 months, but deterioration in the cognitive behavioral test and long-term potentiation (LTP) lagged behind, showing significant deterioration only at 6 months. Similarly in the retina, structural changes preceded functional decay. At 4 months, the retina was generally normal except for a thicker outer nuclear layer in the middle region than WT. At 6 months, the visual behavior (as seen by an optomotor test) was clearly impaired. While the full-field and pattern electroretinogram (ERG) responses were relatively normal, the light responses of the retinal ganglion cells (measured with multielectrode-array recording) were decreased. Structurally, the retina became abnormally thick with few more Aβ plaques and activated glia cells. In conclusion, the timeline of the degenerative processes in the retina and the brain is similar, supporting the use of non-invasive methods to test the retinal structure and function to reflect changes in the brain for early AD diagnosis.

The present study hypothesized that fumaric acid and succinic acid may exhibit therapeutic effects on gestational hypertension. During pregnancy, estrogen upregulates ten-eleven translocation 1 (TET1) expression, which subsequently increases calcium-activated potassium channel subunit β1 (KCNMB1) expression. KCNMB1 is associated with hypertension. Fumaric acid and succinic acid are understood to inhibit TET. Therefore, the present study investigated whether fumaric acid and succinic acid exhibit therapeutic effects on gestational hypertension and whether these effects are mediated by TET1 and KCNMB1. Nω-Nitro-L-arginine methyl ester hydrochloride was injected into rats to establish a gestational hypertension model. Dimethyl fumarate (DMF) and succinic acid were administrated into rats to treat gestational hypertension. Rats were divided into five groups: i) Control; ii) model; iii) DMF; iv) succinic acid; and v) DMF + succinic acid. Blood pressure was monitored by a noninvasive meter and urinary protein was determined using a urinary protein kit. Placenta pathology was examined by hematoxylin-eosin staining. Compared with the control group, urinary protein and blood pressure in the model group increased significantly. The placental cells in the control group were arranged orderly. However, in the model group, decidual cellular edema of placenta and vacuolar degeneration were observed, and the intervascular membrane was markedly thicker with plenty of fibrin deposition. These results indicate successful establishment of a gestational hypertension model. However, compared with the model group, urinary protein, blood pressure, edema, vacuoles and fibrin deposition were markedly reduced in the DMF, succinic acid and DMF + succinic acid groups. mRNA and protein levels of TET1 and KCNMB1 in placenta were evaluated by immunohistochemical analysis, reverse transcription-quantitative polymerase chain reaction and western blotting. The TET1 and KCNMB1 levels in the model group were markedly increased compared with those in the control group. However, compared with the model group, the expression levels were markedly downregulated in the DMF, succinic acid and DMF + succinic acid groups. In conclusion, fumaric acid and succinic acid may treat gestational hypertension by downregulating the expression of KCNMB1 and TET1.

The separation and chemical analysis of mixtures in an emergency situation represent major challenges, especially in remote or poverty-stricken areas. A novel method was developed for the rapid separation and detection of multiple components via paper centrifugal chromatography, which costs as little as $2.26 US. The method was realized based on the combination of portable paper centrifugal chromatography and surface-enhanced Raman scattering (SERS) detection. This coupled technique was successfully implemented for the separation and qualitative analysis of a rhodamine 6G-crystal violet mixture and a colorless aniline-pyrocatechol-benzidine mixture. A chromatographic mobile phase was collected using absorbent cotton, which was demonstrated to have no effect on the SERS results. The optimized device achieved rapid and effective separation of the colorless aniline-pyrocatechol-benzidine mixture with a high centrifugal force (0.3303π2 N). The newly developed method involving multicomponent paper centrifugal chromatography-SERS detection will be of great value for emergency-related substance separation and analysis in remote and poor areas.

Glycogen synthase (GS) and glycogen phosphorylase (GP) are two key enzymes in the glycogen synthesis pathway, which catalyze trehalose and glucose transformation in insects. GS and GP can be regulated by trehalose metabolism, which plays an important role in insect growth. However, it is not known whether these genes can be targeted for pest control through regulation of chitin metabolism. We studied the function of Nilaparvata lugens GS and GP (NLGS and NLGP, respectively) using RNA interference, and reported that trehalose and the chitin biosynthesis pathways are regulated by GP and GS, especially TPS3, TRE1-1, and G6PI1, which decreased following knockdown of these two genes. The expression levels of TPS1, TPS2, and several chitin synthesis pathway family genes were significantly increased following dsNlGP injection. Additionally, despite there being no apparent change to the chitin content, an abnormal molting phenotype and wing deformity appeared, and close to 25% insects died. These results demonstrate that silencing of NLGP or NLGS can lead to molting deformities and an elevated mortality rate through the regulation of chitin pathway genes and chitinase genes. NLGP may play a key role in chitin synthesis due to the number of genes regulated, and higher deformity and mortality rates resulting from its knockdown.

A highly regioselective Mg-catalyzed alkylation of 3-substituted pyrazoles has been developed to provide N2-alkylated regioisomers. Using α-bromoacetates and acetamides as alkylating agents, this new method was applied to a variety of 3-substituted and 3,4-disubstituted pyrazoles to produce the N2-alkylated products with high regioselectivities ranging from 76:24 to 99:1 and 44–90% yields.

An early and rapid diagnosis of acute myocardial infraction (MI) by serum biomarker quantification is vital for boosting up treatment efficacy and survival rate; however, it still remains challenging due to ultralow biomarkers content and the emergent nature of the disease. In view of these challenges, a single-step target capturing method for cardiac Troponin I (cTnI), the major cardiac biomarker of MI, was developed. The detection of target cTnI was performed by coupling the capture antibody modified magnetic silica nanoparticle (mSiO2) and an aptamer-based DNA nanostructure produced by hybridization chain reaction (aptHCR). cTnI in sample was first directly captured by mSiO2 and aptHCR in 30 min. The as formed nanocomplex was then labelled by a customized DNA turn on fluorescent dye SPM. By reading the strengthened fluorescent signal using total internal reflection fluorescence microscope (TIRFM), the detection platform has accomplished an impressive LOD of 8.5 fM with high specificity towards cTnI. The advantages of the short immunoreaction time (30 min) and the pre-treatment free property of the method have addressed the urgent diagnostic requirements of MI. The detection platform offers a potential solution to tackle insufficient sensitivity and tedious turnaround time of clinically approved assays for cTnI detection.

Water deficit is one of the main limiting factors for apple growth and production. Root architecture plays an important role in drought tolerance of plants. However, little is known about the molecular basis of root system in apple trees under drought. In this study, we compared root morphology of two widely used rootstocks of apple (R3 and Malus sieversii) under drought. Our results suggested that M. sieversii is more tolerant to drought than R3, since M. sieversii had a higher ratio of root to shoot as well as root hydraulic conductivity under long-term drought conditions. We then performed whole-genome transcriptomic analysis to figure out the molecular basis of root responses in M. sieversii under drought. It was found that genes involved in transcription regulation, signaling or biosynthesis of hormones, and oxidative stress were differentially expressed under drought. Consistent with the gene expression profile, roots of M. sieversii had higher activities of peroxidase (POD) and superoxide dismutase (SOD) under drought, as well as higher content of abscisic acid (ABA) and lower content of auxin. Taken together, our results revealed the physiological and transcriptomic analyses of M. sieversii roots in response to drought.

Corona and chemical treatment worked cooperatively for increasing and stabilizing the polyethylene film surface energy. Gentle and varied corona discharge treatment conditions were applied for each polyethylene film to reach 40 dynes/cm. A rather low blending amount of additive could stabilize the film surface energy obviously. Compared with neat PE film, of which the surface energy decreased to 36 dynes/cm at the 12th day, films blended with 1000 ppm A7-OH or PE-PEG4k-PE showed stable surface energy (36–38 dynes/cm) over 150 days. The influence of industrial applied slipping agent was investigated as well. Morphological and chemical changes were studied by X-ray photoelectron spectroscopy (XPS) and Atomic Force Microscope (AFM). The surface energy was determined by the dyne pens. Mechanism investigation of hydrophilization and hydrophobic recovery processes showed that proper crystallization behavior and enough C O groups on the film surface guarantee satisfactory stability of the surface energy.

Water kefir is a fermented beverage, which is traditionally prepared from sucrose, kefir grains, dried or fresh fruits, and water. L. hordei and S. cerevisiae are isolated as predominant and stable species of lactic acid bacteria and yeasts, respectively. In this study we demonstrate that label free quantitative proteomics is useful to study microbial interaction along the response of co-cultivated L. hordei TMW 1.1822 in the presence of S. cerevisiae TMW 3.221 as compared with their single cultures in a water kefir model. It is shown and L. hordei responds to S. cerevisiae in many respects revealing a mutualistic relationship. The data suggest that L. hordei responds to the presence of S. cerevisiae with adjustment of intracellular redox reactions controlled of proteins, which are part of Rex regulons and proteins involved in the glycolytic pathway and energy fermentation. An NADH, H+-driven metabolic switch to preferential production of butanediol instead of acetate or lactate, and up-regulation of arginine deiminase, alleviated acid stress and concomitantly protected S. cerevisiae against an acidic environment, which L. hordei generated in single culture. Moreover, the data suggest that the presence of S. cerevisiae in the nitrogen and fatty acids limited environment of the water kefir facilitated and improved the growth of L. hordei by delivering gluconate, fructose, amino acids, fatty acids or substrates for their biosynthesis. Up-regulation of the OppABCDF peptide transport and enzymes involved in amino acid metabolism indicates enhanced peptide uptake, as well as cross-feeding of L. hordei by glutamine, glutamate, histidine, tryptophan, methionine, proline, tryptophan delivered by S. cerevisiae.

In metabolomics studies, metabolic pathway recognition (MPR) is performed by software tools to screen out the significant pathways disturbed by diseases or reinstated by drugs. To achieve MPR, the significantly changed metabolites determined in different biospecimens (e.g. plasma and urine) are analyzed either independently (metabolites from each biospecimen as a dataset) or integratively (metabolites from all biospecimens as a dataset). However, whether the choice of these two processing approaches affects the results of MPR remains unknown. In this study, this issue was addressed by selecting evaluation of the effects of the herbal medicine Rehmanniae Radix (RR) on anemia and adrenal fatigue by UPLC-QTOF-MS/MS-based metabolomics as an example. The significant pathways disturbed by the modeling of anemia and adrenal fatigue and those reinstated by treatments with raw and processed RR were recognized using MetPA software tool (MetaboAnalyst 3.0), and compared by independent and integrative processing of the significantly changed metabolites determined in plasma and urine. The results showed that the two processing approaches could yield different impact values of pathways and thereby recognize different significant pathways. The differences appear to happen more easily when metabolites from different biospecimens shared the same metabolic pathway. Such pathway could be recognized as a significant pathway by integrative processing but could be excluded by independent processing due to the converged and dispersed importance contributions of the involved metabolites to MPR in the two processing approaches. This issue should concern researchers because MPR is crucial not only to understanding metabolomics data but also to guiding subsequent mechanistic research.

Water kefir is a traditional fermented beverage made from sucrose, water, kefir granules, dried or fresh fruits. In our water kefir granules, Lactobacillus (L.) hordei is one of the predominant lactic acid bacteria (LAB) species of this presumed symbiotic consortium. It faces abundant sucrose versus limitation of amino- and fatty acids in an acidic environment. Sequencing of the genome of L. hordei TMW 1.1822 revealed one chromosome plus three plasmids. The size of the chromosome was 2.42 Mbp with a GC content of 35% GC and 2461 predicted coding sequences. Furthermore, we identified 1474 proteins upon growth on water kefir medium. Metabolic prediction revealed all enzymes required for the glycolytic Embden-Meyerhof (EMP) and phosphoketolase (PKP) pathways. Genes encoding all enzymes involved in citrate, pyruvate and mannitol metabolism are present. Moreover, it was confirmed that L. hordei is prototrophic for 11 amino acids and auxotrophic for 6 amino acids when combining putative biosynthesis pathways for amino acids with physiological characterization. Still, for glycine, serine and methionine no sure auxotype could be determined. The OppABCDF peptide transport system is complete, and 13 genes encoding peptidases are present. The arginine deiminase system, was predicted to be complete except for carbamate kinase, thus enabling neutralization reactions via ammonium formation but no additional energy generation. Taken together our findings enable prediction of the L. hordei lifestyle in water kefir: Abundant sucrose is consumed directly via parallel EMP and PK pathways and is also extracellularly converted to dextran and fructose by a glucansucrase, leaving fructose as additional carbon source. Essential amino acids (in the form of peptides) and citrate are acquired from fruits. In the lack of FabB unsaturated fatty acids are synthesized by predicted alternative enzymes. Formation of acetoin and diacetyl as well as arginine conversion reactions enable acidification limitation. Other members of the water kefir consortium (yeasts, acetic acid bacteria) likely facilitate or support growth of L. hordei by delivering gluconate, mannitol, amino- and fatty acids and vitamins.

Methanol synthesis from CO2 hydrogenation is an important reaction for future fuel and chemical production as the so-called “methanol economy” in the 21st century. Pd–ZnO catalysts are known to be active for this reaction, but the fabrication of ultrasmall PdZn alloy nanoparticles (NPs) on an oxygen defective ZnO surface as selective and efficient catalysts remains a challenge. Here, we report an epitaxial growth of a thin zeolitic imidazolate framework-8 (ZIF-8) overcoat on ZnO nanorods as a support to confine the synthesis of subnanometric Pd NPs at a ZnO/ZIF-8 interface for CO2 hydrogenation. The thickness of the ZIF-8 overcoat can be tuned by the etching time and the etching process enables the creation of oxygen defects on the ZnO surface. It is also found that increasing the ZIF-8 thickness disfavors the formation of the PdZn alloy upon H2 reduction due to the spatial isolation effect. In CO2 hydrogenation, the optimized Pd-Z@Z8-1 catalyst shows the best performance, with a methanol selectivity of 66–78% and a methanol yield of 12.1–19.8 g gPd−1 h−1 at 523–563 K and 4.5 MPa, which are ranked among the top values over Pd based catalysts reported in the literature under comparable conditions. Interestingly, we obtain a volcanic relationship between the methanol yield and ZIF-8 thickness. It thus appears to require a proper balance to optimize the activity between decreasing PdZn alloy sites and increasing ZnO defects with the increase in ZIF-8 thickness. From this study, we propose a synergetic catalysis mechanism between the PdZn alloy and surface defect enriched ZnO. It is believed that this work provides a novel “killing two birds with one stone” strategy to fabricate noble metal–metal oxide/MOF hybrid materials for catalytic applications.

In this study, a monoclonal antibody (mAb)-based enzyme-linked immunosorbent assay (ELISA) for the determination of chloramphenicol (CAP) in shrimp, feed and milk samples was developed and validated by LC-MS/MS coupled with immunoaffinity clean-up (LC-MS/MS-IAC). Three immunogens were synthesized and used to immunize mice. Spleen cells from the immunized mice with the highest titer were selected for cell fusion. Two lines of hybridoma cells (1B1 and 2D2) secreting specific antibodies against CAP were successfully screened. Under optimal conditions, the values of the 50% inhibitory concentration (IC50) and limit of detection (LOD) of the ELISA in phosphate-buffered saline (PBS) based on 2D2 mAb for the detection of CAP were 0.46 ng mL−1 and 0.06 ng mL−1, respectively. There was no cross-reactivity (CR) of the ELISA with other antibiotics (florfenicol, thiamphenicol, etc.). Shrimp, feed and milk samples were spiked with different contents of CAP and detected by ELISA. The recoveries and coefficients of variation (CVs) of the ELISA for CAP from three spiked samples were 80.6–116.0% and 5.5–15.4% (n = 3), 96.2–111.0% and 7.0–13.5% (n = 3), and 79.7–109.8% and 5.8–13.3% (n = 3), respectively. As the CAP concentrations in spiked samples measured by LC-MS/MS coupled with solid phase extraction (LC-MS/MS-SPE) were significantly lower than those measured by ELISA, we established an immunoaffinity clean-up (IAC) for CAP by covalently immobilizing our mAb against CAP on the CNBr-activated Sepharose-4B gel and directly mixing the mAb-immobilized gel with the spiked samples sufficiently. The recoveries of CAP from the spiked samples measured by LC-MS/MS-IAC were 78.6–106.7% with the CV less than 11.1% (n = 3).

Thermodynamic analysis for an integrated solar thermochemical energy storage system was conducted to examine its energy and chemical conversion performances. Detailed mathematical description for the transportation process of radiation energy was given to obtain the input solar power to the solar receiver/reactor. Plug-flow model was used to determine the species concentrations and temperature distributions of the solar reactor combined with kinetic models. Then concentrations of species and temperature at outlet of solar reactor were used in the overall thermodynamic model to investigate the effects of key parameters on thermal performance of the system. The results shown that each of the key parameters (initial molar flow rate, diameter and length of reactor, initial molar ratio of CH4/CO2, and absorption coefficient) produced both of positive and negative influences on energy and chemical conversion performances. In order to fully utilize the input energy and feed gas, mass transfer/heat transfer and chemical reaction rate should match with each other. So in both single factor analysis and transient operation condition analysis, the operation parameters were optimized which significantly improved the cycle work efficiency ηcycle (from 17.72% to 34.04% on 12:00 of Summer Solstice, and from 19.53% to 33.37% on 12:00 of Winter Solstice).

Macrophages play a fundamental role in human chronic diseases such as rheumatoid arthritis, atherosclerosis, and cancer. In the present study, we demonstrated that dual-specificity phosphatase 6 (DUSP6) was upregulated by lipopolysaccharide (LPS) treatment of macrophages. (E/Z)-BCI hydrochloride (BCI) functions as a small molecule inhibitor of DUSP6, and BCI treatment inhibited DUSP6 expression in LPS-activated macrophages. BCI treatment inhibited LPS-triggered inflammatory cytokine production, including IL-1β and IL-6, but not TNF-α, and also affected macrophage polarization to an M1 phenotype. In addition, BCI treatment decreased reactive oxygen species (ROS) production and significantly elevated the levels of Nrf2. Interestingly, pharmacological inhibition of DUSP6 attenuated LPS-induced inflammatory responses was independent of extracellular signal-regulated kinase (ERK) signaling. Furthermore, BCI treatment inhibited phosphorylation of P65 and nuclear P65 expression in LPS-activated macrophages. These results demonstrated that pharmacological inhibition of DUSP6 attenuated LPS-induced inflammatory mediators and ROS production in macrophage cells via activating the Nrf2 signaling axis and inhibiting the NF-κB pathway. These anti-inflammatory effects indicated that BCI may be considered as a therapeutic agent for blocking inflammatory disorders.

Background and aims Limited data is available on the efficacy of direct acting anti-viral drugs on hepatitis C in drug users. The aim of this meta-analysis was to comprehensively analyze the efficacy and safety of LDV/SOF in drug users infected with the hepatitis C virus (HCV). Methods The PubMed, Cochrane library, Embase and Web of Science databases were searched for articles published till April 2021 on HCV-positive drug users who were treated with ledipasvir/sofosbuvir (LDV/SOF). The primary endpoint was pooled sustained virological response at 12 weeks (SVR12) with 95% confidence interval (95% CI). Funnel plots and Egger’s test were used to assess the publication bias. Results A total of 12 studies and 711 subjects treated with LDV/SOF-based regimen for HCV were included, and the pooled SVR12 rate was 89.8% (95% CI 85.9–92.7). The pooled SVR12 rate of genotype 1 drug users was 92.4% (95% CI 88.6–95.0). Subgroup analysis showed that pooled SVR12 rates of patients treated with LDV/SOF and LDV/SOF ± RBV were 89.2% (95% CI 83.4–93.1), 90.4% (95% CI 83.6–94.5) respectively. In addition, the SVR12 rates were 88% (95% CI 70.7–95.7) for 8 weeks, 89.9% (95% CI 81.0–94.9) for 12 weeks and 82.2% (95% CI 24.9–98.5) for 24 weeks of treatment. Conclusion LDV/SOF is a safe and relatively effective treatment for hepatitis C in drug users.

International audience; Integrating high-loading dielectric nanoparticles into polar polymer matrices potentially can profit the intrinsic polarization of each phase and allow for greatly enhanced dielectric properties in polymer nanocomposites. It is however challenging to achieve desirable highly filled polar polymer composites because of the lack of efficient approaches to disperse nanoparticles and maintain interfacial compatibility. Here, we report a versatile route to fabricate highly filled barium titanate/fluorinated silicone rubber (BT/FSR) nanocomposites by ''thiol-ene click'' and isostatic pressing techniques. The loaded BT nanoparticles (from 82 wt.% to 90 wt.%) are chemically bonded with FSR in the nanocomposites. The existence of the polar group (-CH2CF3) of the polymer matrix does not affect the uniform dispersion of the nanoparticles and the good interfacial compatibility as well. 90 wt.% BT/FSR nanocomposite shows the highest dielectric constant of 57.8 at 10 3 Hz, while the loss tangent can be kept below 0.03. Besides, BT/FSR nanocomposites display the higher breakdown strength than BT/SR nanocomposites, respectively. This work offers a facile strategy towards superior dielectric properties of polymer nanocomposites.

Nilaparvata lugens (Stål) (Hemiptera: Delphacidae) is one of the pests that harm rice. In this paper, a new trehalose-6-phosphate synthase gene, TPS3, was identified by transcriptome sequencing and gene cloning. To explore its role in the energy metabolism of N. lugens we examined the carbohydrate contents at different stages of development, the tissue expression of TPS, and some physiological and biochemical indicators by injecting dsTPS3 and dsTPSs (a proportional mixture of dsTPS1, dsTPS2, and dsTPS3). The glucose content at the fifth instar was significantly higher than that in the fourth instar and the adult stages. The trehalose and glycogen contents before molting were higher than those after molting. TPS1, TPS2, and TPS3 were expressed in the head, leg, wing bud, and cuticle, with the highest expression in the wing bud. In addition, compared with the control group, the glucose content increased significantly at 48 h after RNA interference, and the trehalose content decreased significantly after 72 h. qRT-PCR showed that the expression level of UGPase decreased significantly at 48 h after injection, whereas GS expression increased significantly at 48 h after injecting dsTPS3. After dsTPS injection, the expression levels of PPGM2, UGPase, GP, and GS increased significantly at 72 h. After interfering with the expression of TPS3 gene alone, UGPase expression decreased significantly at 48 h, and GS expression increased significantly at 72 h. Finally, combined with the digital gene expression and pathway analysis, 1439 and 1346 genes were upregulated, and 2127 and 1927 genes were downregulated in the dsTPS3 and dsTPSs groups, respectively. The function of most differential genes was concentrated in sugar metabolism, lipid metabolism, and amino acid metabolism. The results indicated that TPS3 plays a key role in the energy metabolism of N. lugens and confirmed that TPS3 is a feasible target gene for RNA interference in N. lugens. Simultaneously, they provide a theoretical basis for the development and utilization of TPS3 to control pests.

Cicadae Periostracum (CP), the cast-off shell of Cryptotympana atrata, is specified in Chinese Pharmacopoeia for relieving fever and eliminating ulcer. N-acetyldopamine oligomers are the major characteristic bioactive components with antioxidant and anti-inflammatory activities that may be responsible for the efficacy of CP. However, the exposed components and metabolites of N-acetyldopamine oligomers of CP (NOCP) in vivo are still unknown. In present study, the metabolic profile of total NOCP and N-acetyldopamine dimer B in rats were systematically investigated by ultra-high liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). In biosamples of NOCP group, 34 prototypes and 15 metabolites were identified or tentatively characterized, including 5 metabolites in plasma, 3 prototype and 9 metabolites in urine, 2 metabolites in bile, 34 prototypes and 8 metabolites in feces, respectively. In dimer B group, the prototype and 8 metabolites were identified, including 2 metabolites in plasma, 4 metabolites in urine, 1 metabolite in bile and 5 metabolites in feces, respectively. Oxidation, and hydrogenation were supposed to be the major phase I reactions, while methylation, sulfation, and glucuronidation were the main phase II reactions of NOCP and dimer B. M10 and M13 might undergo enterohepatic circulation in rats. It is concluded that NOCP and dimer B were mainly absorbed in the form of metabolites, and metabolites are probably the major bioactive forms of NOCP and dimer B. The outcomes of this study provided helpful information for extensively elucidating biological and pharmacological mechanisms of NOCP.

The greening of etiolated seedlings is crucial for the growth and survival of plants. After reaching the soil surface and sunlight, etiolated seedlings integrate numerous environmental signals and internal cues to control the initiation and rate of greening thus to improve their survival and adaption. However, the underlying regulatory mechanisms by which light and phytohormones, such as abscisic acid (ABA), coordinately regulate greening of the etiolated seedlings is still unknown. In this study, we showed that Arabidopsis (Arabidopsis thaliana) DE-ETIOLATED1 (DET1), a key negative regulator of photomorphogenesis, positively regulated light-induced greening by repressing ABA responses. Upon irradiating etiolated seedlings with light, DET1 physically interacts with FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and subsequently associates to the promoter region of the FHY3 direct downstream target ABA INSENSITIVE5 (ABI5). Further, DET1 recruits HISTONE DEACETYLASE6 to the locus of the ABI5 promoter and reduces the enrichments of H3K27ac and H3K4me3 modification, thus subsequently repressing ABI5 expression and promoting the greening of etiolated seedlings. This study reveals the physiological and molecular function of DET1 and FHY3 in the greening of seedlings and provides insights into the regulatory mechanism by which plants integrate light and ABA signals to fine-tune early seedling establishment.

Background A sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism. Methods The SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, western blotting, and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro. Results In this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons. Conclusions Our study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI and suggests that its inhibition may be a new treatment strategy for this traumatic condition.

Phosphoglucomutase (PGM) is a key enzyme in glycolysis and gluconeogenesis, regulating both glycogen and trehalose metabolism in insects. In this study, we explored the potential function of phosphoglucomutase (PGM) using RNA interference technology in Nilaparvata lugens, the brown planthopper. PGM1 and PGM2 were found highly expressed in the midgut of brown planthoppers, with different expression levels in different instar nymphs. The glycogen, glucose, and trehalose levels were also significantly increased after brown planthoppers were injected with dsRNA targeting PGM1 (dsPGM1) or PGM2 (dsPGM2). In addition, injection of dsPGM1 or dsPGM2 resulted in increased membrane-bound trehalase activity but not soluble trehalase activity. Furthermore, the expression of genes related to trehalose and glycogen metabolism decreased significantly after injection with dsPGM1 and dsPGM2. The expression levels of genes involved in chitin metabolism in the brown planthopper were also significantly decreased and the insects showed wing deformities and difficulty molting following RNAi. We suggest that silencing of PGM1 and PGM2 expression directly inhibits trehalose metabolism, leading to impaired chitin synthesis. Electronic supplementary material The online version of this article (10.1007/s13205-020-2053-5) contains supplementary material, which is available to authorized users.

Structural design and optimization are important for improving the overall performance of solar reactors. In this study, a coupled optics-CFD model was established to simulate the complex processes of radiation absorption, mass and heat transfer, and chemical reactions in a solar methane dry reforming reactor. The effects of structural parameters on the photothermal chemical conversion process were mainly discussed. It is found that slight changes of structural parameters, such as inclined angle and length of transition section, and cut-off ratio and acceptance half-angle of compound parabolic concentrator, could affect the radiation heat flux density distributions greatly and thus leading to significant variation of the chemical reaction. Therefore, special attention should be paid to the coupled analysis of optics and fluid dynamics when designing and optimizing the solar-type reactor. The proposed model and the obtained results are of guiding significance for the study of various solar-thermochemical and photochemical reactors.

Enterococcus faecium WEFA23 is a potential probiotic strain from Chinese infants with the ability to decrease cholesterol levels. Aiming to explore the mechanism of E. faecium WEFA23 in lowering cholesterol in vivo, we examined the gene transcriptions related to cholesterol metabolism, the composition of bile acids in feces, the synthesis of trimethylamine N-oxide (TMAO) in liver, and the composition of the gut microbiota of rats. We found that E. faecium WEFA23 enhanced the synthesis of bile acids by promoting cholesterol excretion, upregulating the genes transcript level relevant to cholesterol decomposition and transportation, and downregulating the genes involved in cholesterol synthesis. In addition, E. faecium WEFA23 not only downregulated the transcript levels of farnesoid X receptor and fibroblast growth factor 15 as well as flavin-containing monooxygenase 3, but also decreased the TMAO production followed by increasing the CYP7A1 transcript level. Furthermore, when orally administered to rats for 35 d, E. faecium WEFA23 improved the gut microbiota diversity of rats fed a high-fat diet. Therein, the ratio of Bacteroidetes to Firmicutes and the abundance of Rikenellaceae increased, whereas the number of Veillonellaceae decreased. These results suggest that reduction of cholesterol level by E. faecium WEFA23 might be related to the changes in the gut microbiota. Our finding provides important information on lowering cholesterol by E. faecium and reveals that Enterococcus spp. might have the potential to decrease the TMAO level.

Water kefir granules are supposed to mainly consist of dextrans produced by Lactobacillus (L.) hilgardii. Still, other microorganisms such as L. hordei, L. nagelii, Leuconostoc (Lc.) citreum and Saccharomyces (S.) cerevisiae are commonly isolated from water kefir granules, while their contribution to the granule formation remains unknown. We studied putative functions of these microbes in granule formation, upon development of a simplified model system containing hydrophilic object slides, which mimics the hydrophilic surface of a growing kefir granule. We found that all tested lactic acid bacteria produced glucans, while solely those isolated from the four different L. hordei strains induced yeast aggregation on the hydrophilic slides. Therefore, structural differences between these glucans were investigated with respect to their size distributions and their linkage types. Beyond the finding that all glucans were identified as dextrans, those of the four L. hordei strains were highly similar among each other regarding portions of linkage types and size distributions. Thus, our study suggests the specific size and structural organization of the dextran produced by L. hordei as the main cause for inducing S. cerevisiae aggregation and network formation on hydrophilic surfaces and thus as crucial initiation of the stepwise water kefir granule growth.

We report herein an investigation of carbazole-based cyanine, (E)-4-(2-(9-(2-(2-methoxyethoxy)ethyl)-9H-carbazol-3-yl)-vinyl)-1-methyl-quinolin-1-iumiodide (SLM), as an effective theranostic agent for Alzheimer’s disease (AD). This cyanine exhibited desirable multifunctional and biological properties, including amyloid-β (Aβ)-oligomerization inhibition, blood–brain barrier permeability, low neurotoxicity, neuroprotective effect against Aβ-induced toxicities, high selectivity and strong binding interactions with Aβ peptide/species, good biostability, as well as strong fluorescence enhancement upon binding to Aβ species for diagnosis and therapy of AD. This cyanine has been successfully applied to perform near-infrared in vivo imaging of Aβ species in transgenic AD mouse model. The triple transgenic AD mice intraperitoneally treated with SLM showed significant recovery of cognitive deficits. Furthermore, those SLM-treated mice exhibited a substantial decrease in both of oligomeric Aβ contents and tau proteins in their brain, which was attributed to the induction of autophagic flux. These findings demonstrated for the first time that SLM is an effective theranostic agent with in vivo efficacy for diagnosis and treatment of AD in mouse models.

In this work, a novel photothermal agent based on methionine (Met) was synthesized, which shows strong absorbance in the near infrared ray (NIR) region and is available for NIR imaging and in vivo photothermal therapy in a mouse model. Comparing to free IR-782, the obtained Met modified fluorescent dye (Met-IR-782) exhibited excellent fluorescence stability, preferable photothermal conversion efficiency under 780 nm laser irradiation and specific targeting to MCF7 (human breast adenocarcinoma cell line) cells. The fluorescence imaging ability enabled in situ monitoring of the tumor accumulation of Met-IR-782. The photothermal cytotoxicity assays in vitro and photothermal therapy treatments in vivo indicated that Met-IR-782 could efficiently target and suppress the growth of MCF7 xenograft tumors. Hence, Met-IR-782 is a potential fluorescent agent for NIR imaging-guided cancer photothermal therapy in clinical application. This work highlights the prospect of using light absorbing agents for NIR imaging-guided photothermal therapy.

Early cancer diagnosis is critically important for early intervention and it can significantly enhance the treatment efficacy and the chance of cure. Herein, for the first time, the cyanine fluorophore namely, SLSO3, was synthesized and found to possess a high binding affinity towards a typical biomarker, carcinoembryonic antigen (CEA) in which it served as an excellent turn-on labelling fluorophore for the detection of CEA. On this basis, the target CEA antigen is captured by a primary antibody conjugated on magnetic silica coated iron oxide nanoparticles and then followed by secondary antibody-loaded SiO2 nanoparticles, which provide more binding sites for the labelling dyes resulting in 6-fold increase in fluorescence and thus heightened sensitivity. The immunosensor is capable of differentiating target analyte from other cancer-associated proteins and has been applied to quantify CEA in human serum sample and the result was consistent to that obtained from a commercial ELISA kit. This simple and direct detection assay has achieved a low limit of detection in the pg mL−1 regime with small sample consumption (only 10 μL) and without any sample pre-treatment and purification.

Wenting Jiang,1,* Han Wang,1,* Yongmei Cui,1,* Yiyan Lei,2 Yuefeng Wang,1 Di Xu,3 Neng Jiang,1 Yangshan Chen,1 Yu Sun,1 Yang Zhang,4 Jessica Cao,5 Zunfu Ke1 1Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; 2Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; 3Department of Thoracic Surgery, The Central Hospital of Wuhan, Jiang’an District, Wuhan, Hubei, China; 4Biomedical Engineering, The University of Texas at El Paso, El Paso, TX, USA; 5Cumming School of Medicine, University of Calgary, Calgary, AB, Canada *These authors contributed equally tothis work Background: Circulating tumor cells (CTCs) detection, an approach considered to be “liquid biopsy”, is a potential alternative method in clinical use for early diagnosis of solid tumor progression.Methods: In this study, we developed a poly (lactic-co-glycolic acid) (PLGA) – nanofiber (PN)-NanoVelcro chip as an efficient device for simple and rapid capture of CTCs from peripheral blood. We evaluated the device performance by assessing the capture efficiency and purity. Single CTC was isolated via laser microdissection system for subsequent genetic analysis, with an aim to find the concordance of epidermal growth factor receptor (EGFR) mutations between tumor tissue and CTCs. Results: PN-NanoVelcro chip exhibits great performance in capture efficiency and high purity. The genetic analysis results showed that most EGFR mutation in tumor tissue could also be detected in CTCs.Conclusion: Compared to computed tomography image results, CTC detection can be implemented throughout the course of diseases and provides an accurate and earlier diagnosis of tumor progression, which make it possible for patients to acquire suitable and timely treatment. Keywords: PN-NanoVelcro chip, CTCs, EGFR mutation, prognosis, lung adenocarcinoma

Human respiratory syncytial virus (RSV) can cause severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths in the infant and elderly populations worldwide, while no vaccine or effective drug is available for RSV infections. In the present study, truncated G protein was successfully expressed both in prokaryotic and eukaryotic system, and high levels of serum IgG in response to truncated G protein were observed both in GD-protein group (intramuscularly with purified GD protein) and GD-VNP20009 group (challenged via the oral route with 1 × 109 CFU of pLIVE-RSV-GD-VNP20009 strains) since 21th day, and GD-VNP20009 significantly reduced the productions of IL-1β, IL-6, and TNF-α, histamine and pathological features caused by the RSV Long strain (P

This study investigated the protective effects of astaxanthin on diabetic cardiomyopathy in rats. The rat diabetes mellitus model was treated with astaxanthin. Compared with the model group, in the 20 mg/kg astaxanthin group the LVSP (92.03 ± 11.96 mmHg), + dp/dtmax (6045.36 ± 52.74 mmHg/s) and -dp/dtmax (4956.33 ± 448.21 mmHg/s), myocardial superoxide dismutase (163.41 ± 17.42 U/mg) and glutathione peroxidase activity (148.39 ± 19.28 nmol/mg) were significantly increased (P