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Molecular self-replication is a fundamental function of all living organisms with the capability of templating and catalyzing its own synthesis, and it plays important roles in prebiotic chemical evolution and effective synthetic machineries. However, the construction of the self-replication system in vitro remains a great challenge and its application for biosensing is rare. Here, we demonstrate for the first time the construction of an in vitro enzymatic nucleic acid self-replication system and its application for amplified sensing of human 8-oxoguanine DNA glycosylase (hOGG1) based on autocatalytic self-replication-driven cascaded recycling amplification. In this strategy, hOGG1 excises 8-oxoguanine (8-oxoG) to unfold the hairpin substrate, activating the autonomous biocatalytic process with molecular beacons (MBs) as both the fuels for producing nucleic acid templates and the generators for signal output, leading to the continuous replication of biocatalytic nucleic acid templates and the repeated cleavage of MBs for an enhanced fluorescence signal. This strategy exhibits an extremely low detection limit of 4.3 × 10

A series of acridines were designed and synthesized for the development of effective inhibitors for mild steel corrosion in 1 M HCl solution, in which the halogen-substituted acridines showed better inhibitive performance than the nonhalogen-substituted acridines. The corrosion protection properties of the halogen-substituted acridines, including 2-chloro-9-phenylacridine (CPA), 2-chloro-9-(2-fluorophenyl)acridine (CFPA), and 2-bromo-9-(2-fluorophenyl)acridine (BFPA), were further investigated using weight loss test and electrochemical techniques. The results indicated the halogen-substituted acridines have excellent inhibitiion performance, and these acridines act as mixed-type inhibitors with predominant cathodic effectiveness. Adsorption of acridines on a mild steel surface obeyed the Langmuir adsorption isotherm. The adsorption of the inhibitor molecules on the steel surface was further supported by scanning electron microscopy (SEM), scanning electrochemical microscopy (SECM), and FTIR spectroscopy. ...

The present work reported a simple, lable-free and sensitive electrochemical method for the detection of protein kinase A (PKA) activity. This method was based on the specific recognition of aptamer and the aptamer-induced hybridization chain reaction (HCR) amplification strategy. The aptasensor was constructed by immobilizing capture probe on a gold electrode via an Au–S bond. When adenosine triphosphate (ATP) aptamer was introduced, its one terminus hybridized with capture probe and the other hybridized with the complementary region of an auxiliary probe, which other region triggered HCR between two hairpin DNA (H1 and H2) to form a long DNA concatamer. At last a large number of electroactive methyle blue (MB) molecules were assembled on the dsDNA concatamer, which generated a significantly amplified electrochemical signal. In the presence of ATP, the HCR would not be performed because the aptamer specifically bond to ATP and the electrochemical response would decrease. However, when ATP and PKA coexisted, the electrochemical response would recovery because that ATP had been translated into ADP by PKA. So the activity of PKA could be effectively monitored according to the change of electrochemical signal. Based on the HCR amplification strategy, the aptasensor showed a wide linear range (4 − 4 ×105 U L−1) and a low detection limit (1.5 U L−1) for the detection of PKA. Furthermore, the method was applied to study the inhibitory effect of H-89 on PKA activity. The developed aptasensor was also used to the analysis of drug-induced PKA activity in cell lysates, indicating the potential application of the developed method in the fields of clinical diagnostics and discovery of new targeted drugs.

This study uses the national ambient air quality station data of Anyang City from 2014 to 2017 to analyze the characteristics and variation rules of ozone (O

Guided by bioisosterism and pharmacokinetic parameters, we designed and synthesized a series of novel benzamide derivatives. Preliminary in vitro studies indicated that compounds 10b and 10j show significant inhibitory bioactivity in HepG2 cells (IC50 values of 0.12 and 0.13 μM, respectively). Compounds 10b and 10j induced the expression of HIF-1α protein and downstream target gene p21, and upregulated the expression of cleaved caspase-3 to promote tumor cells apoptosis.

Gender confirmation surgery is increasingly common in persons with gender dysphoria. We describe changes seen in gonads from individuals seeking male-to-female physical adaptation. We studied 99 orchiectomies from 50 persons. The average age was 33 years (range, 21-63 years). Eighty-six (86.8%) of 99 testes were normal in size with an average size of 3.87 cm (range, 3.0-5.5 cm). Thirteen (13.1%) of 99 testes were hypotrophic and measured up to 2.5 cm. Seminiferous tubules were reduced in diameter compared with controls (0.137 mm versus 0.237 mm; P < .001) and showed peritubular fibrosis in 41 (82%) of 50 persons. In 40 (80%) of 50 persons, there was maturation arrest at the spermatogonia level. In 10 (20%) of 50 persons, the seminiferous tubules showed focal spermatids/spermatozoa up to 7 per 10 tubules mixed with partial maturation arrest at primary spermatocytes. Twenty-six (26%) of 99 testes showed seminiferous tubules with rare cells with large nuclei (3× size of Sertoli cells nuclei) and degenerative chromatin (cytomegaly). Leydig cells were absent in 50 (50%), markedly reduced in 30 (30%), and similar to controls (mean, 33/high-power field) in 20 (20%). A subset (20/99; 20%) of testes had epithelial hyperplasia of the proximal epididymis with stratification and micropapillae. There was no germ cell tumor, sex cord stromal tumors, or germ cell neoplasia in situ. In summary, the histologic changes include (1) decreased diameter of seminiferous tubules and expansion of the interstitium, (2) marked hypoplasia of germ cells, (3) rare cytomegaly, (4) hypoplasia or absence of Leydig cells, and (5) epididymal hyperplasia.

Synapse dysfunction is an early hallmark of Alzheimer's disease (AD), and was considered to be closely related to memory loss. The molecular mechanisms that trigger synapse loss and dysfunction remain poorly understood. Increasing evidence shows a link between Rho GTPases and synapse plasticity. Rho GTPases play a role in controlling synapse function by regulating actin cytoskeleton and dendritic spines. Observations have suggested that phytochemicals, such as flavonoids, alleviate cognition impairment in AD. However, to date, the link between the protective effect of flavonoids on AD and the activity of Rho GTPases remains uninvestigated. In this study, APP/PS1 mice were used as an AD model, and we found that synapse loss occurred in AD mice brain. Flavonoids extracted from leaves of Diospyros kaki (FLDK) were used to investigate whether its protective effects on synapse were related to Rho GTPases activity in AD mice. The Rho GTPases Activation Kit showed that Ras homologous member A (RhoA)-GTP was significantly higher and Ras-related C3 botulinum toxin substrate 1 (Rac1)-GTP was significantly lower in APP/PS1 mice than in normal mice, and RhoA-GTP activity was significantly inhibited by FLDK. We also found that FLDK improved learning and memory function, and antagonized the downregulation expressions of synapse-related proteins such as synaptophysin and drebrin. These findings suggest that FLDK is a potential therapeutic agent for AD, and modulation of Rho GTPases activity might contribute toward its protective effect.

Alumina ceramics sintered at 1350, 1450 and 1550 °C with different grain sizes were tested under dynamic load using a small-scale compressed air gun with sharpened tungsten carbide bullets impacting at a sub-ballistic velocity of 360 km/h. The deformation behavior and sub-surface cracks were recorded by visual examination. Cr3+fluorescence was used to measure the residual stress distribution on and beneath the impact site. The results show the alumina sintered at 1350 °C with a fine grain size of 1.7 μm and high hardness of 18.3 GPa is good at bulletproof due to the cone cracks can spread the dynamic stress effectively and consume much impact energy.

In the present work a highly sensitive and selective aptasensor was developed for the determination of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) based on the hybridization chain reaction (HCR) signal amplification. It was observed that the aptamer of 8-OH-dG could hybridize with the capture DNA immobilized on the gold electrode with a sticky tail left, which initiated the HCR and led to the formation of extended dsDNA structure on the electrode surface. Then the electroactive species ([Ru(NH3)6]3+, RuHex) intercalated into the dsDNA grooves to generate the amplified signal. However, in the presence of 8-OH-dG, the aptamer containing G-rich nucleic acid sequences would be induced to form a G-quadruplex structure, which made it impossible to continue the HCR. So the detection signal will significantly decrease. Under the optimal conditions, the peak current of RuHex was linear with the logarithm of 8-OH-dG concentration in the range from 10pM to 100μM with the detection limit of 2.5pM. By integrating the merits of enzyme-free amplification power of the HCR and the inherent high sensitivity of the electrochemical technique, the prepared aptasensor not only showed high sensitivity for the detection of 8-OH-dG, but also exhibited good selectivity against to the uric acid, an important interferent in the urine sample. Particularly, the aptasensor was applied to detect 8-OH-dG in urine samples with satisfactory results.

It was found that the expression level of miR-147a was significantly increased and the pathway of PI3K/AKT was dramatically inhibited after radiation. In view of the relationship between miRNA and target genes, we put forward the question, what is the relationship between PI3K/AKT and miR-147a? In order to find the answer to the question, we used bioinformatics techniques to analyze the relationship between miR- 147 (a or b) and PI3K/AKT signaling pathway. miR-147a overexpression plasmid and PDPK1 3′UTR luciferase reporter gene plasmid were constructed. Dual luciferase reporter gene system validation experiments were carried out on miR-147a and PDPK1 relationship. The verification experiments were also carried out. Bioinformatics analysis showed that there is a miR-147a binding site in the non-coding region (3′UTR) of PDPK1. In the experimental groups transfected with wild type PDPK1 gene of 3′UTR plasmid, the luciferase activity decreased (or increased) significantly in miR-147a (or inhibitor) group compared with miR-NC (or anti-miR-NC); There was no significant difference between the miR-147a group (or inhibitor) and the miR-NC group (or anti- miR-NC) in the transfection of PDPK1–3′UTR-Mut gene vector. PDPK1 was a target gene for direct regulation of miR-147a downstream. Verifying test results showed that the expression of PDPK1 mRNA and protein was reduced after overexpression of miR-147a, which was up-regulated after silencing miR-147a in TC, and V79 cells. These results suggest that miR-147a could be involved in the regulation of PDPK1 transcription by binding to the target site in PDPK1 mRNA 3′UTR, and then regulated AKT.

Specific and sensitive detection of DNA MTase activity can be achieved by a single-ribonucleotide repair-mediated ligation-dependent cycling signal amplification approach., DNA methylation is a predominant epigenetic modification that plays crucial roles in various cellular processes. DNA methyltransferase (MTase) is responsible for DNA methylation, and its dysregulation may induce aberrant methylation patterns that are closely related to cancers. Conventional methods for DNA MTase assay are usually cumbersome and laborious with poor sensitivity. Alternatively, some signal amplification strategies are employed to improve the sensitivity, but they suffer from poor specificity and consequently limited sensitivity due to the nonspecific amplification. Herein, we develop for the first time a new fluorescence method to specifically and sensitively detect DNA MTase activity on the basis of single-ribonucleotide repair-mediated ligation-dependent cycling signal amplification. In the presence of DNA MTase, the hairpin substrate is methylated and cleaved by endonuclease Dpn I, releasing a 24-nt cleavage product. The 24-nt cleavage product may function as a primer and adjacently hybridize with the ligation probes (LP1 and LP2) to form the template (LP1–LP2) for strand displacement amplification (SDA), initiating the single-ribonucleotide repair-mediated cyclic ligation-dependent SDA to produce a large number of reporter probes. The reporter probe can subsequently hybridize with the signal probe that is modified with FAM and BHQ1 to form a stable double-stranded DNA (dsDNA) duplex with a ribonucleotide mismatch. Ribonuclease HII (RNase HII) can excise the single ribonucleotide, resulting in the cyclic cleavage of signal probes and the generation of an enhanced fluorescence signal. Taking advantage of the high specificity of RNase HII-catalyzed single-ribonucleotide excision and the high amplification efficiency of cyclic ligation-dependent SDA, this assay exhibits the highest sensitivity reported so far with a detection limit of 4.8 × 10–6 U mL–1 and a large dynamic range of 5 orders of magnitude. Moreover, this method can be used for the discrimination of Dam MTase from other DNA MTases, the accurate quantification of Dam MTase activity in E. coli cells, and the screening of Dam MTase inhibitors, providing a new paradigm for biomedical research and clinical diagnosis.

Human T-lymphotropic virus type II (HTLV-II) is an important type-C retrovirus, closely related to a variety of human diseases. Here, we demonstrate for the first time the controllable fabrication of bio-bar codes for dendritically amplified sensing of low-abundant HTLV-II DNA by the integration of terminal deoxynucleotidyl transferase (TdT)-catalyzed template-free polymerization extension with bio-bar-code amplification (BCA). HTLV-II DNA hybridizes with magnetic microparticle (MMP)-modified capture probe 1, forming a stable DNA duplex with a protruding 3'-hydroxylated sequence which may function as a primer to initiate the TdT-catalyzed first-step polymerization extension for the generation of a poly-thymidine (T) sequence. The resultant poly-T products may hybridize with poly-adenine (A) capture probe 2, inducing the self-assembly of multiple capture probe 2-/reporter probe-functionalized Au nanoparticles (AuNPs) onto the MMP. Subsequently, the reporter probes may act as the primers to initiate the TdT-catalyzed second-step polymerization extension, producing large numbers of G-rich DNAzymes for the generation of an enhanced chemiluminescence signal. Taking advantage of the efficient polymerization extension reaction catalyzed by TdT, the high amplification efficiency of BCA, and the intrinsically high sensitivity of G-rich DNAzyme-driven chemiluminescence, this method exhibits ultrahigh sensitivity with a limit of detection of as low as 0.50 aM and a large dynamic range of 9 orders of magnitude from 1 aM to 1 nM. Moreover, this method can be applied for the discrimination of a single-base mismatch and the measurement of HTLV-II DNA in both human serum and human T-lymphocytic leukemia cells, holding great potential in biomedical research and clinical diagnosis.

Alkaline phosphatase (ALP) is an important diagnostic indicator for various human diseases including bone diseases, liver dysfunction, diabetes, breast and prostatic cancers. However, the conventional methods for ALP assay are usually cumbersome and time-consuming with low sensitivity. Here, we develop a new fluorescent method for ultrasensitive detection of ALP activity on the basis of primer dephosphorylation-initiated isothermal circular exponential amplification. We design two dual-functional hairpin probes (HP1 and HP2), which function as both the templates for exponential amplification reaction (EXPAR) and the generators for signal output. In the presence of ALP, the 3'-phosphorylated primer is dephosphorylated and subsequently hybridizes with the 3' protruding end of HP1 to initiate the first strand displacement amplification (SDA), producing trigger 1 and fluorescence signal. The released trigger 1 is complementary to the 3' protruding end of HP2 for the initiation of the second SDA, producing trigger 2 and fluorescence signal. Notably, trigger 2 is complementary to the 3' protruding end of HP1 and may subsequently initiate two consecutive SDAs, enabling circular EXPAR to generate an amplified fluorescence signal. This method exhibits high sensitivity with a detection limit of 2.0 × 10-10 U μL-1 and a large dynamic range of 5 orders of magnitude from 1.0 × 10-9 to 1.0 × 10-4 U μL-1, and it can measure ALP at the single-cell level. Importantly, this method can be applied for the measurement of kinetic parameters and the screening of potential inhibitors, providing a powerful tool for ALP-related biomedical research and clinical diagnosis.

The clinical significance of the sodium-potassium ATPase regulator FXYD domain-containing ion transport regulator 3 (FXYD3) has been demonstrated in a number of types of cancer. However, the role of this protein in human hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, 217 HCC tissue samples were analyzed to evaluate the expression and prognostic significance of FXYD3 in HCC. Reverse transcription-quantitative polymerase chain reaction was used to analyze the mRNA expression of FXYD3 in 80 primary HCC specimens and paired non-cancerous liver tissue samples, while western blotting was used to analyze the protein expression level of FXYD3 in another 24 pairs. These analyses demonstrated that the expression level of FXYD3 was significantly increasedb at the mRNA and protein levels in HCC tumor tissues compared with adjacent non-cancerous tissues. Immunohistochemical analysis of 137 paraffin-embedded HCC tissue samples indicated that the expression of FXYD3 was associated with HCC clinicopathological characteristics. Kaplan-Meier analysis demonstrated that patients with high FXYD3 protein expression (n=60) experienced significantly poorer overall survival time compared with patients with low FXYD3 protein expression (n=77) (P

Proton-conducting solid oxide fuel cells have the potential ability to simultaneously convert ethane to electrical energy and value-added ethylene with high selectivity and the absence of CO2 emissions. However, their development is impeded by a lack of efficient and stable anode materials. Herein, in-situ exsolved FeNi nanoparticles on (La0.6Sr0.4)0.95Fe0.8Ni0.1Mo0.1O3-δ (LSFNM) perovskite oxide are realised by controlling A-site deficiency and Mo-doping. The introduction of high-valence molybdenum ions in (La0.6Sr0.4)0.95Fe0.8Ni0.2O3-δ (LSFN) not only stabilises its cubic perovskite structure under a reducing atmosphere, but also facilities the exsolution of FeNi nanoparticles from the parent perovskite matrix. The power density of the BaZr0.1Ce0.7Y0.2O3−δ (BZCY) electrolyte-supported single cells with a LSFNM/BZCY/LSCF-SDC configuration reaches 172mW•cm−2 at 750°C in C2H6; meanwhile, the ethylene yield also reaches approximately 40.5%. The presented results extend the functionality and applicability of proton conducting fuel cells for carrying out efficient hydrocarbon-related electrochemical conversion for producing power and co-production of value-added chemicals.

Background When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis. Purpose The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (H2O2)-induced injury in SH-SY5Y cells in vitro. Methods SH-SY5Y cells were simultaneously treated with AU and H2O2 for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry. Results The results showed that AU can significantly increase the H2O2-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that H2O2 stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In H2O2-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways. Conclusion These results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways.

Well-ordered polyvinyl alcohol (PVA) parallel nanofiber arrays (PNAs) were fabricated by using electrospinning receiving board with clined gap. A three-dimensional (3D) copper phthalocyanine (CuPc) organic field effect transistor (OFET) sensor was obtained by evaporating CuPc on the PVA PNAs. This 3D structure is conducive to the multi angle adsorption and desorption of the target gas and active layers. The detection limit of the obtained sensors is lower, and the response and recovery time are also shorter. Compared with single CuPc films and CuPc films with disordered PVA nanofibers sensors, the minimum detection concentration is reduced by one third. The CuPc/PVA PNAs sensors have been successfully used in real-time monitoring of NO2 at 0.3 ppm. The response and recovery time of the CuPc/PVA PNAs sensors are both 0.02 min for 25 ppm NO2. The response and recovery time are 350 and 130 times faster than those of CuPc sensors with disordered PVA nanofibers, respectively. Humidity has little effect on the response of the sensor. This convenient and effective method to prepare high performance OFET sensors can be extended to other gas monitoring.

To estimate the pollution of As and Pb in the Songhua River which flows through the major rice-producing regions in China, the present study investigated the level and release of As and Pb in surficial sediments which collected from nine sites in Songhua River (M1–M9). The concentration of As and Pb was ranged as follows: As = 3.104~15.01 μg/g, Pb = 20.10~37.42 μg/g; the average concentration: As = 6.466 ± 3.077 μg/g, Pb = 28.88 ± 5.077 μg/g. By analysis vertically, the average concentration of As was 5.166 ± 1.496 μg/g in the upstream, 5.815 ± 1.793 μg/g in the midstream, and 9.716 ± 4.977 μg/g in the downstream. The average concentration of Pb was 27.83 ± 4.552 μg/g in the upstream, 28.66 ± 6.333 μg/g in the midstream, and 30.99 ± 4.837 μg/g in the downstream. It indicated that the concentration of As and Pb increased gradually from upstream to downstream. As existed mainly as insoluble state and Pb existed mainly as sulfide and organic combining state in surficial sediments, and the species of As and Pb could transform with the change of the circumstance. The release of quantity of As was higher than Pb. The pH of 6 was not conducive to the release of As and Pb. When the temperature was 35 and 6 °C, the release of As and Pb in surficial sediments were restrained, respectively. Fumaric acid and citric acid played an important role in promoting the release of As, but not conducive to Pb. Furthermore, the reasonable aeration rate was beneficial to the release process of As and Pb in surficial sediment. By kinetic analysis, the Elovich equation (Ct = 84.931–8.952lnt) could be used to describe the dynamic process of the release of As in a relatively short time. The Elovich equation (C t = 2.724 + 1.3724lnt) and double constant rate equation (lnC T = 1.4646 + 0.1522lnT) could well describe the dynamics process of the release of Pb.

Pulsed electric field (PEF) was applied to moisture-preconditioned canola seeds to evaluate the effect on oil yield. The effect of PEF on functional and structural properties of canola protein left over after oil extraction were also examined in albumin and globulin fractions obtained at optimal conditions for oil yield. Generally, PEF pretreatment significantly improved (P

AIM To investigate the underlying effect of Jianpi Qingchang decoction (JQD) regulating intestinal motility of dextran sulfate sodium (DSS)-induced colitis in mice. METHODS C57BL/6 mice were randomly divided into four groups: the control group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except for the control group, colitis was induced in other groups by giving distilled water containing 5% DSS. Seven days after modeling, the mice were administered corresponding drugs intragastrically. The mice were sacrificed on the 15th day. The disease activity index, macroscopic and histopathologic lesions, and ultrastructure of colon interstitial cells of Cajal (ICC) were observed. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-10 and interferon gamma (IFN-γ), the expression of nuclear factor-kappa B (NF-κB) p65, c-kit, microtubule-associated protein 1 light chain 3 (LC3-II) and Beclin-l mRNA, and the colonic smooth muscle tension were assessed. RESULTS Acute inflammation occurred in the mice administered DSS. Compared with the control group, the levels of IL-1β, TNF-α, IL-10 and IFN-γ, the expression of LC3-II, Beclin-1 and NF-κB p65 mRNA, and the contractile frequency increased (P < 0.05), the expression of c-kit mRNA and the colonic smooth muscle contractile amplitude decreased in the DSS group (P < 0.05). Compared with the DSS group, the levels of IL-10 and IFN-γ, the expression of c-kit mRNA, and the colonic smooth muscle contractile amplitude increased (P < 0.05), the levels of TNF-α and IL-1β, the expression of LC3-II, Beclin-1 and NF-κB p65 mRNA, and the contractile frequency decreased in the JQD group (P < 0.05). CONCLUSION JQD can regulate the intestinal motility of DSS-induced colitis in mice through suppressing intestinal inflammatory cascade reaction, reducing autophagy of ICC, and regulating the network path of ICC/smooth muscle cells.

5'-Polynucleotide kinase such as T4 polynucleotide kinase (T4 PNK) may catalyze the phosphorylation of 5'-hydroxyl termini in nucleic acids, playing a crucial role in DNA replication, DNA recombination, and DNA damage repair. Here, we demonstrate for the first time single-molecule detection of PNK based on phosphorylation-directed recovery of fluorescence quenched by Au nanoparticle (AuNP) in combination with lambda exonuclease-mediated cleavage reaction. In the presence of PNK, the γ-phosphate group from adenosine triphosphate (ATP) is transferred to 5'-hydroxyl terminus, resulting in 5'-phosphorylation of the hairpin probe. The phosphorylated hairpin probes may function as the substrates of lambda exonuclease and enable the removal of 5' mononucleotides from the stem, leading to the unfolding of hairpin structure and the formation of binding probes. The resultant binding probes may specifically hybridize with the AuNP-modified capture probes, forming double-strand DNA (dsDNA) duplexes with 5'-phosphate groups as the substrates of lambda exonuclease and subsequently leading to the cleavage of capture probes and the liberation of Cy5 molecules and the binding probes. The released binding probes may further hybridize with new capture probes, inducing cycles of digestion-release-hybridization and consequently the release of numerous Cy5 molecules. Through simply monitoring Cy5 molecules with total internal reflection fluorescence (TIRF)-based imaging, PNK activity can be quantitatively measured. This assay is very sensitive with a limit of detection of 9.77 × 10

The present study performed a meta-analysis of randomized controlled trials in multiple sclerosis (MS) patients to evaluate the efficacy and safety of anti-B-cell monoclonal antibodies (mAbs). To the best of our knowledge, no previous meta-analysis has evaluated this. Relevant studies published until March 2015 were retrieved from the PubMed, EMBASE and Cochrane Library using the following keywords: ‘Clinical trial’, ‘randomized’, ‘multiple sclerosis’ or ‘MS’ and ‘monoclonal antibodies’ or ‘mAbs’. Two authors independently selected the articles and extracted the data. The meta-analysis was performed using Review Manager version 5.3 software. Four randomized clinical trials comprising a total of 745 patients were selected. Anti-B-cell mAb treatment reduced the formation of gadolinium-enhancing lesions [mean difference (MD)=−5.62; 95% confidence interval (CI)=−8.00 to −3.24; P

The embryology of the genus Hemerocallis L. was studied to re-evaluate its current systematic position proposed by recent phylogenies based on molecular data. Using the improved carbol fuchsin–aniline blue staining method and conventional paraffin sectioning technique, we followed the development of anther and pollen grain, ovule and female gametophyte, and embryo and endosperm up to seed maturity. Our results showed that the (1) anther wall development is of the Monocot type, with a one cell-thick middle layer and a secretory tapetum, (2) microsporocytes cytokinesis is of the intermediate type, (3) microspore tetrads are tetragonal or decussate, (4) pollen grains are two-celled, (5) ovary is superior and trilocular, with axile placentas bearing two collateral ovules per locule, (6) ovules are anatropous, tenuinucellate, and bitegmic, with micropyle formed by the inner integument, (7) megaspore tetrads are linear, and only the chalazal one is functional, (8) embryo sac development is typically of Polygonum type, (9) embryogenesis is of Graminad type, and (10) endosperm development is of nuclear type. Overall, our study thus confirms that the embryological features of Hemerocallis support its exclusion from Liliaceae in Liliales, its inclusion in Asparagales, and its affinities with Asphodelaceae.

Routine histopathologic examination of hemorrhoidectomy specimens is controversial having been described as not useful and expensive with few of these common cases demonstrating incidental lesions. However, unexpected premalignant and malignant lesions have been detected on excised hemorrhoids. The high-risk human papillomavirus (HR-HPV) types associated with these incidentally identified high-grade lesions are presently unknown. We aimed to identify cases of incidental high-grade anal intraepithelial neoplasia (HG-AIN) and anal squamous cell carcinoma incidentally discovered on hemorrhoidectomy specimens, genotype HR-HPVs from these lesions, and assess p53 and p16 expression by immunohistochemistry to identify risk factors for their development. With institutional approval, cases with associated demographics from 1995 to 2015 were reviewed to identify and confirm incidental HG-AIN or squamous cell carcinoma in hemorrhoidectomy specimens. Genotyping for HR-HPV types and immunohistochemical staining for p53 and p16 was performed. Statistical analysis comparing HPV genotypes, p53 and p16 staining, and potential risk factors by the Fisher exact test was performed. In the largest series of incidental high-grade lesions on hemorrhoidectomy, HPV 16 was the most common HR-HPV detected though multiple-type infections were common including some HPV 16/18-negative cases. By genotyping, HPV 39 was significantly associated with IV-drug abuse history (P=0.0015) and HIV-positive status (P=0.037), whereas HPV 58 detection correlated with chemotherapy-induced immunosuppression (P=0.029). There was frequent overlap between p53 staining and HPV positivity, particularly when HPV 31 was detected. We also identified several mimickers of HG-AIN that may present diagnostic challenges in these specimens. Our data support continued routine examination of hemorrhoidectomy specimens and suggest that adjunctive studies such as immunohistochemistry for challenging cases may be useful.

A Gram-stain-negative, motile, non-spore-forming bacterium, designated strain Y4G10-17T, was isolated from the saline–alkali farmland top soil, Inner Mongolia, northern China. Strain Y4G10-17T could grow at 4–45 °C (with 30 °C as the optimal temperature), pH 6.0–12.0 (optimal at pH 9.0) and in the presence of 1.0–12.0 % (w/v) NaCl (optimal at 4.0–6.0 %). Phylogenetic analysis based on the eight different copies of the 16S rRNA gene sequences revealed that strain Y4G10-17T shared the highest sequence similarity with Aliidiomarina maris CF12-14T, 97.93–98.66 %, and lower than 97.0 % sequence similarity with all other type strains. Its major cellular fatty acids contained iso-C15 : 0, iso-C17 : 0, summed feature 9 (iso-C17 : 1ω9c and/or C16 : 0 10-methyl), iso-C15 : 1 F, iso-C11 : 0 3-OH and summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1ω7c). Q-8 was the predominantubiquinone. The major polar lipids of strain Y4G10-17T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unknown lipids and one unknown aminolipid. The genomic DNA G+C content was 49.3 mol%. DNA–DNA hybridization revealed that strain Y4G10-17T showed 20.2±5 % genomic DNA relatedness with its close relative A. maris CF12-14T. Based on the phenotypic, phylogenetic and genotypic characteristics, strain Y4G10-17T represents a novel species within the genus Aliidiomarina , for which the name Aliidiomarina soli sp. nov. is proposed. The type strain is Y4G10-17T (=CGMCC 1.15759T=KCTC 52381T).

We developed a simple and rapid method for terminal deoxynucleotidyl transferase (TdT) assay on the basis of the polymerization-directed exonuclease-assisted construction of a single quantum dot (QD)-based fluorescence resonance energy transfer (FRET) nanosensor. This method is very sensitive with a detection limit as low as 1 × 10-6 U μL-1, and it can be used for the screening of TDT inhibitors and accurate quantification of TdT activity even in 5 cancer cells.

Silicon carbide ceramics with different grain sizes were tested at high strain rate using a small-scale gas gun with sharpened tungsten carbide projectiles impacting at a sub-ballistic velocity of 100 m/s. The resistance of ceramics to fracture was recorded by visual examination of the cracking on the impacted surface and the damage in the sub-surface region. The crack pattern and impact crater region size observed in silicon carbide specimens are generally due to their mechanical properties. Silicon carbide samples had good capacity to defeat the projectiles but the low toughness led to early failure. Raman SiC mapping was used to examine the residual stress and plastic deformation induced in each material. The silicon carbide samples showed different dynamic behaviours due to the extent of stress relaxation.

A simple colorimetric sensing method for the detection of Hg2+ was developed by combining enzymatic catalysis with DNA-based hybridization chain reactions (HCRs). Firstly, thymine (T)-rich capture DNA (cDNA) was immobilized on a gold electrode via Au–S bonding. In the presence of Hg2+, thymine (T)-rich probe DNA (pDNA) hybridized with cDNA via T–Hg2+–T base pairs. Then the HCRs were realized using pDNA as an initiator and two biotin-labeled hairpin DNAs (H1 and H2) as fuel strands. Finally, numerous avidin-labeled horseradish peroxidase (HRP) enzymes were immobilized on long nicked ds-DNA strands, which can catalyze the H2O2-mediated oxidation of 3,3,5,5-tetramethylbenzidine dihydrochloride hydrate (TMB) to cause a dramatic color change. Under optimal conditions, the absorbance of TMB was linear with the logarithm of Hg2+ concentrations in the range of 1 fM to 1 pM, with a detection limit of 0.33 fM. This strategy exhibited good selectivity and high sensitivity, which might be a potential tool for the practical detection of Hg2+ in environmental monitoring.

We develop a new fluorescence method for real-time monitoring of thymine DNA glycosylase (TDG) activity through cyclic enzymatic repairing-mediated dual-signal amplification. This method exhibits excellent sensitivity with a detection limit of 5.6 × 10−7 U μL−1, and it can be used to determine kinetic parameters and quantify TDG activity from even single cancer cells.

Objective To observe the efficacy and safety of the Chinese medicine (CM) Compound Zhuye Shigao Granule (复方竹叶石膏颗粒, CZSG) on acute radiation-induced esophagitis (ARIE) in cancer patients.

The aim of the present study was to evaluate the effectiveness and safety of recombinant human interleukin-11 (IL-11) with glucocorticoids for treatment of adult idiopathic thrombocytopenic purpura (ITP) and the regulatory effect on immune mechanisms. A total of 80 patients with initial diagnosis of ITP admitted to our hospital were selected. Patients were randomly divided into the control group and observation group, with 40 cases each. The control group received glucocorticoids treatment, and the observation group received IL-11 and glucocorticoids. The treatment effects were compared. The total effective rate and effective degree of the observation group was higher than in the control group and the difference was statistically significant (P0.05). In the observation group, onset time was reduced, platelet recovery level increased and platelet antibody positive rate decreased, and the differences were statistically significant (P

We reviewed recent advances in telomerase assays including both in vitro detection and in vivo imaging., Telomerase is a ribonucleoprotein reverse transcriptase that is responsible for maintaining the telomere length in cells. Telomerase overexpresses in almost all malignant tumor cells, and it has become a promising biomarker and a potential therapy target for cancers. Consequently, accurate and efficient quantification of the telomerase is highly essential to medical diagnostics and therapeutics. Recently, a series of novel telomerase detection methods with excellent performance have been developed, but a overview of in vivo telomerase detection methods is lacking. In this Minireview, we summarize the emerging strategies for telomerase assays in the last five years, including both in vitro assays and in vivo imaging methods, and discuss their future directions as well.

There are few studies applying pulsed electric field (PEF) on solid foods in databases. Egg white protein (EWP) was subjected to PEF for elucidating mechanism of changes in molecular structure of enzymes and protein components for solid foods. Determination of free and total sulfhydryl groups, ultraviolet (UV) spectroscopy, infrared (IR) spectroscopy, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were used to compare EWP before and after PEF treatment. The results showed that the amount of free sulfhydryl increased while that of total sulfhydryl decreased after PEF exertion. PEF did not change the SDS-PAGE patterns visibly and no shift in maximum absorption wavelength but intensity could be observed in UV spectra of EWP. IR spectra of EWP were subjected to Gaussian multi-component peak modeling for molecular secondary structure analyses. Either the voltage of the PEF ( P P

BACKGROUND Worldwide, mortality from cervical cancer in women remains high. This study aimed to investigate the expression of long noncoding RNA (lncRNA) TP73-AS1, microRNA-329-3p (miRNA-329-3p), and the SMAD2 gene and their regulatory relationships in human cervical cancer tissue and cervical cancer cell lines. MATERIAL AND METHODS Cervical cancer tissue samples (n=30) and normal control cervical tissues were studied. Cell proliferation and migration were investigated in HeLa and SiHa human cervical cancer cells using the MTT assay, crystal violet staining, wound healing assay, and the transwell assay. Expression of lncRNA TP73-AS1 and the SMAD2 gene were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Enrichment of miR-329-3p was measured using the RNA immunoprecipitation assay (RIPA). Targeting relationships between TP73-AS1, miR-329-3p, and SMAD2 were identified using the dual-luciferase reporter assay. A subcutaneous xenograft model was established, tumor size was measured, and SMAD2 expression was detected using immunohistochemistry. RESULTS LncRNA TP73-AS1 was overexpressed in cervical cancer tissues and cells and was associated with reduced expression of miR-329-3p. Down-regulation of lncRNA TP73-AS1 inhibited cell proliferation, migration and invasion and increased miR-329-3p expression. Expression of SMAD2 down-regulated miR-329-3p and was associated with increased expression of TP73-AS1. LncRNA TP73-AS1 knockdown resulted in miR-329-3p silencing. In tumor xenografts, expression of TP73-AS1 reduced the tumor volume and down-regulated the expression levels of the SMAD2 gene. CONCLUSIONS LncRNA TP73-AS1 promoted proliferation of cervical cancer cell lines by targeting miR-329-3p to regulate the expression of the SMAD2 gene. A regulatory network was formed between lncRNA TP73-AS1, miR-329-3p, and SMAD2.

BackgroundCytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited.MethodsThis study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival.ResultsCK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P = 0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2% of Grade 1 cases were GATA3 negative (P ConclusionsThis is the first study to characterize CK7 negative breast tumors in the context of clinicopathology. Profiling the CK7 negative and GATA3 negative breast cancers helps to understand the biology of these specific tumor subgroups and may aid in their diagnosis.

We construct a self-directed replication system for label-free and real-time sensing of repair glycosylases with zero background., Genomic DNA damage and repair are involved in multiple fundamental biological processes, including metabolism, disease, and aging. Inspired by the natural repair mechanism in vivo, we demonstrate for the first time the construction of a self-directed replication system for label-free and real-time sensing of repair glycosylases with zero background. The presence of DNA glycosylase can catalyze the excision repair of the damaged base, successively autostarting the self-directed replication through recycling polymerization extension and strand-displacement DNA synthesis for the generation of exponentially amplified dsDNAs. The resultant dsDNA products can be label-free and real-time monitored with SYBR Green I as the fluorescent indicator. Owing to the high efficiency of self-directed exponential replication and the absolute zero background resulting from the efficient inhibition of nonspecific amplification induced by multiple primer-dependent amplification, this strategy exhibits high sensitivity with a detection limit of 1 × 10–8 U μL–1in vitro and 1 cell in vivo, and it can be further used to screen inhibitors, quantify DNA glycosylase from diverse cancer cells, and even monitor various repair enzymes by simply changing the specific damaged base in the DNA template. Importantly, this assay can be performed in a label-free, real-time and isothermal manner with the involvement of only a single type of polymerase, providing a simple, robust and universal platform for repair enzyme-related biomedical research and clinical therapeutics.

This study investigated the effects of taurine on bowel inflammation resulting from heat stress in broilers, with the intent of providing insight into potential improvement of the condition of broilers. A total of 300 healthy 1 day AA broilers were selected, fed normally until day 7, and allocated randomly to 5 treatment groups, namely, the control group(C), the heat stress group(HS), the low Tau (LTau) group, the middle Tau (MTau) group and the high Tau (HTau) group, which represent low, medium and high concentrations of taurine respectively. In the study, various concentrations of taurine were added to the drinking water. The Heat Stress model was produced by maintaining Broilers in a room at 34 °C.Heat stress persisted for 6 h, 12 h, 7 days, and 14 days. The results showed that the expression levels of TNF-α, IFN-γ, and IL-1β of the HTau group were significantly lower than that of the HS group at all time points examined (6 h, 12 h, 7 days, and 14 days) (P 0.05). Compared with the HS group subjected to 6 h, 12 h and 14 days of heat stress, the MTau group exhibited significantly lower degrees of TNF-α and IL-1β expression. Moreover, the expression of IFN-γ was higher in the HS group after 6 h, 12 h and 7 days of heat stress than that of the MTau group subjected to similar times of heat stress (P 0.05).There were no significant difference among the groups at other periods of heat stress (P 0.05).

MicroRNAs (miRNAs or miRs) play an important role in pathological processes in diabetic nephropathy (DN). This study aimed to explore whether miR‑379‑5p is associated with renal fibrosis in DN and to elucidate the underlying mechanisms. In vitro experiments indicated that miR‑379‑5p expression was downregulated by high glucose (HG) treatment in mouse mesangial cells (MMCs). Transfection with miR‑379‑5p mimics suppressed the proliferation and the accumulation of extracellular matrix (ECM) components, which were promoted by HG treatment. LIN28B was proven to be a direct target of miR‑379‑5p by luciferase report assay. In addition, the loss of expression of LIN28B, as well as the decrease in cell proliferation and in the accumulation of ECM components, which were induced by the knockdown of LIN28B, were attenuated in the MMCs following transfection with miR‑379‑5p inhibitors. Furthermore, type 2 diabetic db/db mice were used to examine the efficiency of miR‑379‑5p agomir in the alleviation of renal fibrosis. Consistent with the results of the in vitro experiments, miR‑379‑5p agomir suppressed mesangial cell proliferation and the accumulation of ECM components by regulating the LIN28B/let‑7 pathway. Taken together, the findings of this study suggest that miR‑379‑5p is highly involved in renal fibrosis in DN, and that it may be a potential effective therapeutic target for DN.

Among Chinese breast cancer survivors, treatment decision-making is different than that in western countries. Among Chinese women, family often plays an important role during the treatment period, and Chinese-specific cultural factors have negative influences on their psychological conditions. The aim of the present study was to explore the treatment decision making, family influences, and cultural influences of Chinese breast cancer survivors. This study used an expressive writing method to explore the experiences of breast cancer survivors who were diagnosed with stage 0 to III cancer. Participants were instructed to write 30 min per week over a period of 3 weeks. All writings were analyzed using a qualitative method. Three themes were identified: treatment decision making, family influences, and cultural influences. Treatment decision-making included the subthemes of preference for mastectomy, passive involvement, and active involvement. Family influences included the subthemes of financial burden, family expectations, and family support. Cultural influences included the subthemes of fatalism, barriers to expressing emotions, and stigma related to cancer. Information on breast cancer treatment and survivorship should be provided to patients through multiple methods to improve their knowledge of breast cancer. Family support should be maintained to ensure patients’ confidence and courage during the treatment period. Necessary and appropriate psychological interventions that consider cultural influences should be administered.

Epigenetic inheritance is a heritable change in gene function independent of alterations in nucleotide sequence. It regulates the normal cellular activities of the organisms by affecting gene expression and transcription, and its abnormal expression may lead to the developmental disorder, senile dementia, and carcinogenesis progression. Thus, epigenetic inheritance is recognized as an important biomarker, and the accurate quantification of epigenetic inheritance is crucial to clinical diagnosis, drug development and cancer treatment. Noncoding RNA, DNA methylation and histone modification are the most common epigenetic biomarkers. The conventional biosensors (e.g., northern blotting, radiometric, mass spectrometry and immunosorbent biosensors) for epigenetic biomarkers assay usually suffer from hazardous radiation, complicated manipulation, and time-consuming procedures. To facilitate the practical applications, some new biosensors including colorimetric, luminescent, Raman scattering spectroscopy, electrochemical and fluorescent biosensors have been developed for the detection of epigenetic biomarkers with simplicity, rapidity, high throughput and high sensitivity. In this review, we summarize the recent advances in epigenetic biomarkers assay. We classify the biosensors into the direct amplification-free and the nucleotide amplification-assisted ones, and describe the principles of various biosensors, and further compare their performance for epigenetic biomarkers detection. Moreover, we discuss the emerging trends and challenges in the future development of epigenetic biomarkers biosensors.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS). The present study explored the role of intestinal microbiota in the initiation and propagation of mice induced by experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. 48 C57BL/6 were randomly divided into control group and EAE group. The changes of body weight and the scores of neurological function were recorded. The mRNA expression of the receptor tyrosine kinase subfamily (AXL) was detected by real-time quantitative PCR. The levels of IL-17 and IFN-γ in blood samples were examined by ELISA. The intestinal microbial composition of mice at different time points during the EAE induction was analyzed by 16S rRNA gene-based sequencing. In EAE group, the body weight began to reduce at day 3 and neurological symptoms began to appear at day 7 after EAE induction. The levels of IL-17 and IFN-γ in EAE group reached the peak at day 21 and then decreased gradually. However, the expression of Axl and SOCS3 reached the lowest level at day 21 and then increased gradually. The microbiome analyses revealed that the abundances of Alistipes, Blautia, and Lachnospiraceae_NK4A136_group were significantly changed at day 14, whereas the abundances of Allobaculum, Eubacterium and Helicobacter were significantly changed at day 30 of EAE induction. The prevotellaceae_NK3B31_group may be key bacteria that contribute to the development of MS. Regulation of intestinal microbiota composition can become a new therapeutic target for the treatment of MS.

To evaluate the distribution by age and sex of serum high-sensitivity C-reactive protein (hsCRP) in an urban Chinese population and to provide a profile prediction for the risk of bacterial infection, inflammatory diseases, or tissue damages in the body.Serum hsCRP was determined using the Roche Tina-quant immuno-turbidimetric assay on a Hitachi 7600-010 automatic biochemical analyzer (Roche Diagnostics) in 1,572 males and 1,800 females, including 78 pregnant women, who were derived from the National Health and Nutrition Survey in 2010-2012.The average hsCRP concentration in urban China was 0.68 mg/L for males and 0.65 mg/L for females. Significant differences in hsCRP were found among different age groups (The distribution of the hsCRP status of residents in large cities in China was influenced by age and gender, and the hsCRP levels of both sexes increased gradually with age. In addition, hsCRP concentration was higher in healthy pregnant women than in non-pregnant women. Basing on our results, we recommend that this parameter be included in future national and international screening for early detection of various illnesses.

The specific functions and clinical significance of miR-940 in endometrial carcinoma (EC) have not been studied. First, we assessed the expression of miR-940 and MRVI1 in EC tissues collected from The Cancer Genome Atlas (TCGA) database and EC cell lines. miR-940 was significantly overexpressed in EC tissues and cell lines, particularly in RL95-2 cells. Correlation analysis showed that miR-940 expression level was remarkably associated with age, grade, and death. Moreover, the overall survival (OS) rate in the miR-940 low expression group was higher, compared with miR-940 high expression group. Univariate and multivariate models demonstrated that miR-940 expression, stage, and age were predictive indicators of OS. Moreover, there was no significance of the proliferation ability among the three EC cell lines (RL95-2, ISK, and KLE). To reveal the biological roles of miR-940, we respectively transfected RL95-2 cells with miR-940 mimics, miR-940 inhibitors, and control to further investigate the cell proliferation ability, and migration as well as invasion potential of RL95-2 cells. The transfection of miR-940 mimics significantly increased the proliferation and migration/invasion ability of RL95-2 cells. MRVI1 was predicted to be a potential target of miR-940 by means of in silico analysis followed by validation using luciferase reporter assays. MRVI1 was correlated with good prognosis. Moreover, forced expression of MRVI1 in miR-940 mimic transfected cells abolished the facilitation of miR-940 on cell proliferation, migration, and invasion of RL95-2 and KLE cells. In conclusion, our study demonstrates that miR-940 might function as a reliable diagnostic and prognostic signature in EC.

Chronic pancreatitis (CP) is characterized by persistent inflammation and fibrosis of the pancreas. To date, no clinical therapy is available to reverse the inflammatory damage or pancreatic fibrosis associated with CP. This study systematically investigated the effect of Dasatinib, a multiple tyrosine kinases (TKs) inhibitor, on pancreatic fibrosis and inflammation in vivo and in vitro. We found that Dasatinib notably ameliorated pancreatic fibrosis and infiltration of macrophages in a model of caerulein-induced murine CP. Further RNA-seq and phosphoproteomic analysis and in vitro validation assays indicated that Dasatinib exerted a marked inhibition on the proliferation and activation of PSCs, which may be resulted from increased GSK3β-mediated β-catenin cytosol retention by inhibiting upstream multiple TKs (such as PDGFR and Src) and MAPK cascades (including ERK1/2 and p38 MAPK). In addition, Dasatinib significantly restrained both the M1 and M2 polarization of macrophages, and impeded its recruitment and crosstalk with PSCs. Our findings indicated that Dasatinib is a potential anti-inflammatory and anti-fibrotic therapeutic strategy for CP.

Effective chimeric antigen receptor-modified T-cell (CAR-T) therapy for liver metastases (LM) will require innovative solutions to ensure efficient delivery and minimization of systemic toxicity. We previously demonstrated the safety of CAR-T hepatic artery infusions (HAI). We subsequently conducted the phase 1b HITM-SIR trial, in which six patients (pts) with CEA

We have previously demonstrated that anti-CD44s H4C4 or liposomal-delivered STAT3 inhibitor FLLL32 sensitized pancreatic cancer cells to radiotherapy through the elimination or inhibition of cancer stem cells (CSCs) and that HAb18G/CD147 promoted STAT3-mediated pancreatic tumor development by forming a signaling complex with CD44s. In this paper, we therefore explored whether anti-CD147 HAb18IgG sensitized pancreatic cancer cells to chemoradiotherapy via the targeting of CSCs. We tested the influence of HAb18IgG on the sensitivity of pancreatic cancer cells to chemoradiotherapy by clonogenic and MTT assays and on pancreatic CSCs by colony and sphere formation assays, flow cytometry, quantitative real-time RT-PCR (qRT-PCR) and stem cell transcription factors PCR array analysis. Changes in CD147 signaling were examined by immunoblot and reporter assays. We found that HAb18IgG sensitized pancreatic cancer cells to chemoradiotherapy by dose-dependently decreasing colony and sphere formation. Furthermore, HAb18IgG reduced the pancreatic CSC subpopulation and the expression of stem cell transcription factors OCT4, SOX2 and NANOG. Mechanistically, HAb18IgG inhibited CSCs by blocking CD44s-pSTAT3 signaling. The present findings indicated the promising therapeutic role of anti-CD147 HAb18IgG in suppressing pancreatic tumor initiation and overcoming post-chemoradiotherapy recurrence through the direct targeting of CSCs.

The study aimed to evaluate the effects of an expressive writing intervention on quality of life (QoL) among mainland Chinese breast cancer patients. A total of 118 Chinese breast cancer patients were randomly assigned to one of four groups: a cancer-facts writing condition (CTL group), an emotional disclosure writing condition (EMO group), a self-regulation writing condition (SR group), or a neutral control condition with no writing tasks (CON group). QoL was assessed by FACT-B at baseline, 3-, and 6-month follow-ups. A repeated measure analysis of variance revealed significant effects of time (F = 13.9, P

Purpose To perform a qualitative and quantitative analysis of catechin and quercetin in flavonoids extracted from Rosa roxburghii Tratt. Methods Total flavonoids were determined using ultraviolet spectrophotometry (UV) at 500 nm. The optimal gradient program started with 15 % methanol and was kept within a period of 0 – 20 min, while 25 % methanol was kept within 20 – 33 min. Subsequently, the concentration of methanol was reduced to 15 % and was held for 10 min until the next injection. Mass spectrometry spray voltage was 4,000 V, ionization temperature 350 °C, atomizer pressure 35 psi, nitrogen flow rate 8 L/min, and mass scan range 200 – 800 m/z. The detection wavelength used for catechin and quercetin was 270 and 368 nm, respectively. Results Based on the UV results, Rosa roxburghii Tratt content was 73.85 %, which is in agreement with the national standard. Liquid chromatography-mass spectrometry (LC-MS) results indicate that Rosa roxburghii Tratt flavonoids contained quercetin, 34.26 %, with relative standard deviation (RSD) of 2.88 % and catechin content of 2.97 % with RSD of 1.49 %. Conclusion The proposed measurement method for determining the content of flavonoids in Rosa roxburghii Tratt has the advantage of simplicity, feasibility, good repeatability, and rapid and accurate analysis.