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Background: Total knee arthroplasty (TKA) is an effective treatment for knee osteoarthritis; however, early readmissions due to complications are common. This study assessed the ability of the hemoglobin-to-red cell distribution width ratio (HRR), hemoglobin-to-monocyte ratio (HMR), and hemoglobin-to-leukocyte ratio (HLR) to predict readmission within 14 days after TKA., Methods: Data from the Chang Gung Medical Research Database (CGRD) from 2014 to 2022 were retrospectively analyzed. Patients ≥ 20 years old who underwent primary TKA were eligible for inclusion. Patients with incomplete data on the indices of interest or follow-up < 14 days were excluded. Patient demographic, clinical, and comorbidity data were collected. Logistic regression was utilized to determine the associations between HRR, HMR, and HLR and 14-day readmission., Results: Data from 1,137 patients were analyzed. Multivariable analysis revealed that a higher HMR was significantly associated with lower 14-day readmission risk (adjusted OR [aOR] = 0.72, 95% confidence interval [CI]: 0.51-0.997), an HMR ≥ 2.18 (optimal cutoff value) was predictive of a significantly lower 14-day readmission risk (aOR = 0.61, 95% CI: 0.39-0.96). The composite indicator, HRR-HMR-HLR score, derived from the 3 indices assessed, was significantly associated with a lower 14-day readmission risk (score 2 vs. score 0: aOR = 0.51, 95% CI: 0.27-0.98; score 3 vs. score 0: aOR = 0.37, 95% CI: 0.17-0.82)., Conclusions: High HMR and the HRR-HMR-HLR score are independently associated with a lower 14-day readmission risk after TKA. Implementing these indices into clinical practice may enhance postoperative management., (© 2024. The Author(s).)

Background: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis., Methods: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up., Results: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis., Conclusion: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis., (© 2024. The Author(s).)

Both morphological and metabolic imaging were used to determine how asymmetrical changes of thalamic subregions are involved in cognition in temporal lobe epilepsy (TLE). We retrospectively recruited 24 left-TLE and 15 right-TLE patients. Six thalamic subnuclei were segmented by magnetic resonance imaging, and then co-registered onto Positron emission tomography images. We calculated the asymmetrical indexes of the volumes and normalized standard uptake value ratio (SUVR) of the entire and individual thalamic subnuclei. The SUVR of ipsilateral subnuclei were extensively and prominently decreased compared with the volume loss. The posterior and medial subnuclei had persistently lower SUVR in both TLE cases. Processing speed is the cognitive function most related to the metabolic asymmetry. It negatively correlated with the metabolic asymmetrical indexes of subregions in left-TLE, while positively correlated with the subnuclei volume asymmetrical indexes in right-TLE. Epilepsy duration negatively correlated with the volume asymmetry of most thalamic subregions in left-TLE and the SUVR asymmetry of ventral and intralaminar subnuclei in right-TLE. Preserved metabolic activity of contralateral thalamic subregions is the key to maintain the processing speed in both TLEs. R-TLE had relatively preserved volume of the ipsilateral thalamic volume, while L-TLE had relatively decline of volume and metabolism in posterior subnucleus., (© 2023. The Author(s).)

Mineralization is a long-lasting method commonly used by biological materials to selectively strengthen in response to site specific mechanical stress. Achieving a similar form of toughening in synthetic polymer composites remains challenging. In previous work, we developed methods to promote chemical reactions via the piezoelectrochemical effect with mechanical responses of inorganic, ZnO nanoparticles. Herein, we report a distinct example of a mechanically-mediated reaction in which the spherical ZnO nanoparticles react themselves leading to the formation of microrods composed of a Zn/S mineral inside an organogel. The microrods can be used to selectively create mineral deposits within the material resulting in the strengthening of the overall resulting composite., (© 2023. The Author(s).)

The synthesis of well-defined cyclic polymers is crucial to exploring applications spanning engineering, energy, and biomedicine. These materials lack chain-ends and are therefore imbued with unique bulk properties. Despite recent advancements, the general methodology for controlled cyclic polymer synthesis via ring-expansion metathesis polymerization (REMP) remains challenging. Low initiator activity leads to high molar mass polymers at short reaction times that subsequently "evolve" to smaller polymeric products. In this work, we demonstrate that in situ addition of pyridine to the tethered ruthenium-benzylidene REMP initiator CB6 increases ancillary ligand lability to synthesize controlled and low dispersity cyclic poly(norbornene) on a short time scale without relying on molar mass evolution events.

Mid-infrared (MIR) flexible photodetectors (FPDs) constitute an essential element for wearable applications, including health-care monitoring and biomedical detection. Compared with organic materials, inorganic semiconductors are promising candidates for FPDs owing to their superior performance as well as optoelectronic properties. Herein, for the first time, we present the use of transfer-printing techniques to enable a cost-effective, nontoxic GeSn MIR resonant-cavity-enhanced FPDs (RCE-FPDs) with strain-amplified optical responses. A narrow bandgap nontoxic GeSn nanomembrane was employed as the active layer, which was grown on a silicon-on-insulator substrate and then transfer-printed onto a polyethylene terephthalate (PET) substrate, eliminating the unwanted defects and residual compressive strain, to yield the MIR RCE-FPDs. In addition, a vertical cavity was created for the GeSn active layer to enhance the optical responsivity. Under bending conditions, significant tensile strain up to 0.274% was introduced into the GeSn active layer to effectively modulate the band structure, extend the photodetection in the MIR region, and substantially enhance the optical responsivity to 0.292 A W -1 at λ = 1770 nm, corresponding to an enhancement of 323% compared with the device under flat conditions. Moreover, theoretical simulations were performed to confirm the strain effect on the device performance. The results demonstrated high-performance, nontoxic MIR RCE-FPDs for applications in flexible photodetection.

RNA interference (RNAi) has been developed and used as an emerging strategy for pest management. Here, an entomopathogen Bacillus thuringiensis ( Bt ) was used to express the dsRNA for the control of Plutella xylostella . A vector containing a 325-bp fragment of the conserved region of P. xylostella arginine kinase gene ( PxAK ) flanking in two ends with the promoter Pro3α was developed and transferred into Bt 8010 and BMB171, and consequently engineered Bt strains 8010AKi and BMB171AKi expressing dsRNA of PxAK were developed. The two engineered Bt strains were separately mixed with Bt 8010 in a series of ratios, and then fed to the P. xylostella larvae. We found that 8010:8010AKi of 9:1 and 8010:BMB171AKi of 7:3 caused a higher mortality than Bt 8010. PxAK expression levels in the individuals treated with the mixtures, 8010AKi and BMB171Aki, were lower than that in the control. The intrinsic rate of increase ( r ) and net reproductive rate ( R 0 ) of the population treated with 8010:8010AKi of 9:1 were lower than those of the population treated with Bt 8010 or 8010AKi. We developed a Bt -mediated insect RNAi for the control of P. xylostella and demonstrated a practical approach to integrating the entomopathogen with RNAi technique for the pest management.

Background: The formation of dental plaque and its involvement in the pathogenesis of periodontitis is a topic of intense interest given the high prevalence of periodontitis in humans. Even though calcium-based particles play an active role in both dental plaque formation and periodontitis, few publications describe the physical-chemical properties of these particles., Methods: Saliva samples were collected from healthy volunteers. From these samples, saliva-derived particles were isolated and stained for calcium using calcein or Fluo-4. The salivary particles were also subjected to characterization by flow cytometry and immunoblotting. Internalization of calcein-labeled salivary particles by gingival epithelial cells was visualized by confocal microscopy., Results: We found that calcium-based salivary particles from healthy volunteers varied greatly in size but were enriched in particles of sizes at or greater than 1.5 μm. Immunoblotting analysis of the salivary particles identified several proteins including albumin, fetuin-A, and statherin, which have been found in calcium phosphate particles from other tissues or are known to modulate calcium homeostasis in saliva. In addition, calcium particles were internalized by both gingival epithelial cells and monocyte-derived macrophages., Conclusion: Salivary calcium particles were enriched in the micrometer range, internalized by gingival epithelial cells, and contain albumin, fetuin-A and statherin, regulators of particle formation. These characteristics of the calcium-based salivary particles and their biological activities provide a basis for further studies to understand the molecular basis for pathogenesis of periodontitis., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Phthalates esters are widely used commercially and can leach from a food container or food packaging. Few studies have been conducted in Asia regarding food processed to varying levels and human phthalate exposure. This study aimed to evaluate the association between unprocessed and ultra-processed food intake and urinary phthalate metabolite levels in the Taiwanese adult population. Methods: A total of 516 participant data were extracted from the cross-sectional 1993-1996 and 2005-2008 Nutrition and Health Survey in Taiwan of those aged over 18 years, where urinary measures and one 24-h dietary recall were collected. Urinary concentrations of dimethyl phthalate, diethyl phthalate, dibutyl phthalate, butyl benzyl phthalate, and di-(2-ethylhexyl) phthalate metabolites including monomethyl phthalate, monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate, mono-(2-ethylhexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate were measured in spot urine samples. The NOVA food processing classification system was applied to divide all consumed foods into four mutually exclusive groups including unprocessed or minimally processed, processed culinary ingredients, processed and ultra-processed food. Generalized linear models were employed to examine the associations between the percentage quartiles (Qs) of unprocessed and ultra-processed foods in the total weight of food and the urinary phthalate metabolites. Results: Compared with participants in the lowest quartiles (Q1) of ultra-processed food intake, highest ultra-processed food intake (Q4) had 65.7% (95% confidence interval [CI]: 4.83, 162) higher urinary concentrations of MEP after adjusted for covariates. In contrast, the higher unprocessed food consumption was inversely associated with urinary concentrations of MEP and MBP ( P for trend = 0.03). When compared to the lowest unprocessed food consumers (Q1), higher consumers (Q4) presented 38.6% (95% CI: -61.3, -2.59) lower MEP concentrations and 23.1% (95% CI: -38.5, -3.71) lower MBP concentrations. Conclusion: Ultra-processed food consumption was associated with increased concentrations of urinary MEP. Conversely, consuming unprocessed food was associated with lower concentrations of MEP and MBP in the Asian Taiwanese adult population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Huang, Lo, Sun, Pan, Wang and Huang.)

Temperature-dependent characteristics of GeSn/Ge multiple-quantum-well (MQW) photoconductors (PCs) on silicon substrate were investigated. The high quality GeSn/Ge MQW epitaxial structure was grown on a silicon substrate using low temperature molecular beam epitaxy techniques with atomically precise thickness control. Surface-illuminated GeSn/Ge MQW PCs were fabricated using complementary metal-oxide-semiconductor-compatible processing and characterized in a wide temperature range of 55-320 K. The photodetection range was extended to λ =2235 n m at T =320 K due to bandgap shrinkage with Sn alloying. Measured spectral responsivity was enhanced at reduced temperatures. These results provide better understanding of GeSn/Ge MQW structures for efficient short-wave infrared photodetection.

In this study, by combining a large-area MoS 2 monolayer with silver plasmonic nanostructures in a deformable polydimethylsiloxane substrate, we theoretically and experimentally studied the photoluminescence (PL) enhancement of MoS 2 by surface lattice resonance (SLR) modes of different silver plasmonic nanostructures. We also observed the stable PL enhancement of MoS 2 by silver nanodisc arrays under differently applied stretching strains, caused by the mechanical holding effect of the MoS 2 monolayer. We believe the results presented herein can guarantee the possibility of stably enhancing the light emission of transition metal dichalcogenides using SLR modes in a deformable platform.

Ring-expansion metathesis polymerization (REMP) has shown potential as an efficient strategy to access cyclic macromolecules. Current approaches that utilize cyclic olefin feedstocks suffer from poor functional group tolerance, low initiator stability, and slow reaction kinetics. Improvements to current initiators will address these issues in order to develop more versatile and user-friendly technologies. Herein, we report a reinvigorated tethered ruthenium-benzylidene initiator, CB6 , that utilizes design features from ubiquitous Grubbs-type initiators that are regularly applied in linear polymerizations. We report the controlled synthesis of functionalized cyclic poly(norbornene)s and demonstrate that judicious ligand modifications not only greatly improve kinetics but also lead to enhanced initiator stability. Overall, CB6 is an adaptable platform for the study and application of cyclic macromolecules via REMP.

In this study, the double-layered nHA and PCL/nHA coatings were prepared on the substrate of Mg 66 Zn 28 Ca 6 amorphous alloy. The phase composition and morphological were analyzed by Scanning electron microscopy, Energy dispersive spectrometry and X-ray diffraction. The electrochemical properties of these samples were measured on electrochemical workstation. The degradation rate was evaluated by measuring the pH value and weight loss. Experiment results show that the outer composite PCL/nHA coating is a porous structure, where the porosity and pore size could be easily controlled by adding nHA. The combined properties of double-layered nHA and PCL/nHA coating can control the degradation of the Mg 66 Zn 28 Ca 6 amorphous alloy in the scheduled time. Moreover,the cell co-culture and cell adhesion tests show that the double-layered nHA and PCL/2%nHA coating possesses the best cytocompatibility with cell organization. The above experiments have demonstrated that the Mg 66 Zn 28 Ca 6 amorphous alloy which was coated with PCL/nHA composite coating have good mechanical properties, good corrosion resistance and perfect cytocompatibility. It can be used as a potential novel biomaterial for bone tissue engineering., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cytolethal distending toxins (Cdt) are a family of toxins produced by several human pathogens which infect mucocutaneous tissue and induce inflammatory disease. We have previously demonstrated that the Aggregatibacter actinomycetemcomitans Cdt induces a pro-inflammatory response from human macrophages which involves activation of the NLRP3 inflammasome. We now demonstrate that in addition to activating caspase-1 (canonical inflammasome), Cdt treatment leads to caspase-4 activation and involvement of the noncanonical inflammasome. Cdt-treated cells exhibit pyroptosis characterised by cleavage of gasdermin-D (GSDMD), release of HMGB1 at 24 hr and LDH at 48 hr. Inhibition of either the canonical (caspase-1) or noncanonical (caspase-4) inflammasome blocks both Cdt-induced release of IL-1β and induction of pyroptosis. Analysis of upstream events indicates that Cdt induces Syk phosphorylation (activation); furthermore, blockade of Syk expression and inhibition of pSyk activity inhibit both Cdt-induced cytokine release and pyroptosis. Finally, we demonstrate that increases in pSyk are dependent upon Cdt-induced activation of GSK3β. These studies advance our understanding of Cdt function and provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms such as A. actinomycetemcomitans., (© 2020 John Wiley & Sons Ltd.)

Background/purpose: Nonalcoholic fatty liver disease (NAFLD) is now a global liver disease. The fatty liver index (FLI), which is calculated by the equation comprising waist circumference, body mass index (BMI), triglyceride, and gamma glutamyl transpeptidase (GGT), is frequently used for hepatic steatosis evaluation. This study aimed to evaluate the optimal cut-off point of FLI to select subjects for abdominal ultrasonography (US) screening for NAFLD in the community., Methods: From August 2013 to August 2016, a community-based study was performed in the northeastern region of Taiwan. All subjects participated in a demographic survey, blood testing, and abdominal US. The formula for FLI is: FLI = [e 0.953×loge (TG)+0.139×BMI+0.718×loge (GGT) +0.053×waist circumference-15.745 ]/[1 + e 0.953×loge (TG)+0.139×BMI+0.718×loge (GGT)+0.053×waist circumference-15.745 ] × 100., Results: A total of 1371 subjects were included (746 in NAFLD group and 625 in the control group). The mean ages were 57.1 years in the control group and 56.3 years in the NAFLD group. The optimal cut-off points of FLI to discriminate fatty liver by abdominal US were 20 in male and 10 in female (sensitivity 80.3% and 76.1%; specificity 66.9% and 65.5%, respectively). FLI was correlated with the severity of fatty liver by abdominal US, predict fat component percent and NAFLD fibrosis score, especially in the female subjects., Conclusion: FLI could be a tool to select subjects for abdominal US in a large community survey. The cut-off point of FLI might be set to 10 for female and 20 for male subjects, to increase the sensitivity for selecting subjects to receive abdominal US., (Copyright © 2019. Published by Elsevier B.V.)

The A/B subfamily of heterogeneous nuclear ribonucleoproteins (hnRNPs A/B), which includes hnRNP A1, A2/B1, and A3, plays an important role in cell proliferation. The simultaneous suppression of hnRNP A1/A2, but not the suppression of hnRNP A1 or A2 alone, has been shown to inhibit cell proliferation and induce apoptosis in cancer cells, but not in mortal normal cells. However, the molecular basis for such a differential inhibition of cell proliferation remains unknown. Here, we show that the simultaneous suppression of hnRNP A1 and hnRNP A2 resulted in dysfunctional telomeres and induced DNA damage responses in cancer cells. The inhibition of apoptosis did not alleviate the inhibition of cell proliferation nor the formation of dysfunctional telomeres in cancer cells depleted of hnRNP A1/A2. Moreover, while proliferation of mortal normal fibroblasts was not sensitive to the depletion of hnRNP A1/A2, the ectopic expression of hTERT in normal fibroblasts rendered these cells sensitive to proliferation inhibition, which was associated with the production of dysfunctional telomeres. Our study demonstrates that hnRNP A1 and A2 function to maintain telomeres in telomerase-expressing cells only, suggesting that the maintenance of functional telomeres in telomerase-expressing cancer cells employs factors that differ from those used in the telomerase-negative normal cells.

NOD-like receptors (NLRs) play a large role in regulation of host innate immunity, yet their role in periodontitis remains to be defined. NLRX1, a member of the NLR family that localizes to mitochondria, enhances mitochondrial ROS (mROS) generation. mROS can activate the NLRP3 inflammasome, yet the role of NLRX1 in NLRP3 inflammasome activation has not been examined. In this study, we revealed the mechanism by which NLRX1 positively regulates ATP-induced NLRP3 inflammasome activation through mROS in gingival epithelial cells (GECs). We found that depletion of NLRX1 by shRNA attenuated ATP-induced mROS generation and redistribution of the NLRP3 inflammasome adaptor protein, ASC. Furthermore, depletion of NLRX1 inhibited Fusobacterium nucleatum infection-activated caspase-1, suggesting that it also inhibits the NLRP3 inflammasome. Conversely, NLRX1 also acted as a negative regulator of NF-κB signaling and IL-8 expression. Thus, NLRX1 stimulates detection of the pathogen F. nucleatum via the inflammasome, while dampening cytokine production. We expect that commensals should not activate the inflammasome, and NLRX1 should decrease their ability to stimulate expression of pro-inflammatory cytokines such as IL-8. Therefore, NLRX1 may act as a potential switch with regards to anti-microbial responses in healthy or diseased states in the oral cavity., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Chronic psychostimulant treatment in rodents readily produces behavioral sensitization, which reflects altered brain function in response to repeated drug exposure. Numerous morphological and biochemical investigations implicate altered neural plasticity in striatal medium spiny neurons (MSNs) as an essential component in behavioral sensitization. The mammalian target of the rapamycin (mTOR) signaling pathway, a key regulator of synaptic neuroplasticity, in the ventral striatum of methamphetamine (METH) -sensitized mice was investigated to determine if a link exists with the development of METH sensitization. Behaviorally, METH-sensitized mice possessed increased levels of phosphorylated mTOR/S2448 and its down-stream regulator p70S6K and pS6 in the ventral striatum. Systemic treatment with rapamycin, a specific mTOR inhibitor, coincident with a daily METH injection suppressed the induction of METH sensitization and reduced the number of dendritic spines in the shell and core of the nucleus accumbens. The infusion of lentivirus-expressing mTOR-shRNA into the shell region of the nucleus accumbens inhibited the induction of behavioral sensitization to METH, which was comparable to the effect of rapamycin. These results suggest that mTORC1-mediated signaling in the nucleus accumbens mediates the development of behavioral sensitization to METH., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To observe the effects of blocking and activating chloride channels on hemolysis induced by puerarin injection in rabbits and to investigate the roles of chloride channels in hemolytic reaction induced by puerarin injection., Methods: Rabbit erythrocyte suspension was incubated with different concentrations of puerarin injection(0.75, 1.5, 3, 6, 12 mg/ml) at 37 o C for 6 hours. The cell imaging system was employed to observe whether puerarin injection induced hemolysis. The hemolysis rate was detected by microplate reader and flow cytometry. Effects of activating and closing chloride channels on the hemolysis induced by puerarin injection were explored., Results: Puerarin injection could induce the hemolysis of rabbit erythrocytes in vitro . In the range of 1.5 mg/ml~12 mg/ml, puerarin injection could induce hemolysis in a concentration-dependent manner ( n =3, P <0.01). The chloride channel blockers tamoxifen (20 μmol/L) and ATP (10 mmol/L) significantly inhibited the hemolysis induced by puerarin injection ( n =3~5, P <0.01). Application of low concentration ATP (50 μmol/L) to activate the chloride channel significantly increased puerarin injection induced hemolysis ( n =4, P <0.01)., Conclusions: The hemolytic effect of puerarin injection is dose-dependent in vitro , and the activation of chloride channel is closely related to the hemolysis induced by puerarin injection.

Calcium phosphate-based mineralo-organic particles form spontaneously in the body and may represent precursors of ectopic calcification. We have shown earlier that these particles induce activation of caspase-1 and secretion of IL-1β by macrophages. However, whether the particles may produce other effects on immune cells is unclear. Here, we show that these particles induce the release of neutrophil extracellular traps (NETs) in a size-dependent manner by human neutrophils. Intracellular production of reactive oxygen species is required for particle-induced NET release by neutrophils. NETs contain the high-mobility group protein B1 (HMGB1), a DNA-binding protein capable of inducing secretion of TNF-α by a monocyte/macrophage cell line and primary macrophages. HMGB1 functions as a ligand of Toll-like receptors 2 and 4 on macrophages, leading to activation of the MyD88 pathway and TNF-α production. Furthermore, HMGB1 is critical to activate the particle-induced pro-inflammatory cascade in the peritoneum of mice. These results indicate that mineral particles promote pro-inflammatory responses by engaging neutrophils and macrophages via signaling of danger signals through NETs.

Although human blood is believed to be a sterile environment, recent studies suggest that pleomorphic bacteria exist in the blood of healthy humans. These studies have led to the development of "live-blood analysis," a technique used by alternative medicine practitioners to diagnose various human conditions, including allergies, cancer, cardiovascular disease and septicemia. We show here that bacteria-like vesicles and refringent particles form in healthy human blood observed under dark-field microscopy. These structures gradually increase in number during incubation and show morphologies reminiscent of cells undergoing division. Based on lipid analysis and Western blotting, we show that the bacteria-like entities consist of membrane vesicles containing serum and exosome proteins, including albumin, fetuin-A, apolipoprotein-A1, alkaline phosphatase, TNFR1 and CD63. In contrast, the refringent particles represent protein aggregates that contain several blood proteins. 16S rDNA PCR analysis reveals the presence of bacterial DNA in incubated blood samples but also in negative controls, indicating that the amplified sequences represent contaminants. These results suggest that the bacteria-like vesicles and refringent particles observed in human blood represent non-living membrane vesicles and protein aggregates derived from blood. The phenomena observed during live-blood analysis are therefore consistent with time-dependent decay of cells and body fluids during incubation ex vivo.

Fusobacterium nucleatum is an invasive anaerobic bacterium that is associated with periodontal disease. Previous studies have focused on virulence factors produced by F. nucleatum, but early recognition of the pathogen by the immune system remains poorly understood. Although an inflammasome in gingival epithelial cells (GECs) can be stimulated by danger-associated molecular patterns (DAMPs) (also known as danger signals) such as ATP, inflammasome activation by this periodontal pathogen has yet to be described in these cells. This study therefore examines the effects of F. nucleatum infection on pro-inflammatory cytokine expression and inflammasome activation in GECs. Our results indicate that infection induces translocation of NF-κB into the nucleus, resulting in cytokine gene expression. In addition, infection activates the NLRP3 inflammasome, which in turn activates caspase-1 and stimulates secretion of mature IL-1β. Unlike other pathogens studied until now, F. nucleatum activates the inflammasome in GECs in the absence of exogenous DAMPs such as ATP. Finally, infection promotes release of other DAMPs that mediate inflammation, such as high-mobility group box 1 protein and apoptosis-associated speck-like protein, with a similar time-course as caspase-1 activation. Thus, F. nucleatum expresses the pathogen-associated molecular patterns necessary to activate NF-κB and also provides an endogenous DAMP to stimulate the inflammasome and further amplify inflammation through secretion of secondary DAMPs., (© 2015 John Wiley & Sons Ltd.)

Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A one-step process for the synthesis of hydrophilic carbon nanofibers (CNFs) through CO2 hydrogenation on NiNa/Al2O3 was developed for the loading and targeted delivery of the anticancer drug doxorubicin (DOX). CNFs that were synthesized on NiNa/Al2O3 for 9 h at 500 °C exhibited an adequate magnetic response and a large content of hydrophilic oxygen-containing functional groups on the carbon surface, resulting in excellent colloidal solution. The CNF material exhibited a highly efficient capacity for DOX adsorption, particularly at pH 9.0. The loading and release of DOX was strongly pH dependent, possibly due to electrostatic and π-π stacking interactions between DOX and CNF sample. The Langmuir isotherm and pseudo second-order kinetics of DOX-loaded CNFs were well-modeled for the process of DOX adsorption. DOX-loaded CNF targeted cancer cells more selectively and effectively than free DOX and exhibited a marked tendency to kill HeLa cancer cells and reduced toxicity to normal human primary fibroblast (HPF) cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)

N-(1-pyrenyl) maleimide (NPM) is a fluorescent reagent that is frequently used as a derivatization agent for the detection of thio-containing compounds. NPM has been shown to display a great differential cytotoxicity against hematopoietic cancer cells. In this study, the molecular mechanism by which NPM induces apoptosis was examined. Here, we show that treatment of Jurkat cells with NPM leads to Bak oligomerization, loss of mitochondrial membrane potential (Δψm), and release of cytochrome C from mitochondria to cytosol. Induction of Bak oligomerization appears to play a critical role in NPM-induced apoptosis, as downregulation of Bak by shRNA significantly prevented NPM-induced apoptosis. Inhibition of caspase 8 by Z-IETD-FMK and/or depletion of Bid did not affect NPM-induced oligomerization of Bak. Taken together, these results suggest that NPM-induced apoptosis is mediated through a pathway that is independent of caspase-8 activation.

Band structure of transition metal oxides plays a critical role in many applications such as photo-catalysis, photovoltaics, and electroluminescent devices. In this work we report findings that the band structure of MoO3 can be significantly altered by a distortion in the octahedral coordination structure. We discovered that, in addition to epitaxial type of structural strain, chemical force such as hydrogen inclusion can also cause extended lattice distortion. The lattice distortion in hydrogenated MoO3 led to a significant reduction of the energy gap, overshadowing the Moss-Burstein effect of band filling. Charge doping simulations revealed that filling of conduction band drives the lattice distortion. This suggests that any charge transfer or n-type electron doping could lead to lattice distortion and consequentially a reduction in energy gap.

Several lines of evidence suggest that hnRNPs A/B (hnRNPs A1, A2/B1, and A3) play an important role in proliferation, although the functional overlap among members of hnRNPs A/B remains largely unknown. In this study, we have employed RNAi knockdown and proteomic approaches to investigate the biological functions of hnRNPs A/B. Depletion of hnRNP A2, but not A1 or A3, produced a significant inhibition of cellular proliferation in Jurkat cells. Analysis of the proteomes in the cells depleted for hnRNP A1, A2, or A3 has identified a total of 167 differentially expressed proteins in the depleted cells. Network analysis of the proteins altered in the cells depleted for hnRNP A2 revealed that the biological processes likely affected by these proteins are related to cell cycle, cytoskeleton rearrangement, and transcription regulation. Indeed, we have confirmed that the level of RhoA and CrkL was selectively reduced in the cells depleted of hnRNP A2, but not in the cells depleted for hnRNP A1 or A3. Therefore, we suggest that the reduced proliferation observed in the cells depleted of hnRNP A2 may result from its effects on cell adhesion processes in the Jurkat cells., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A Si quantum dot (QD)-embedded ZnO thin film is successfully fabricated on a p-type Si substrate using a ZnO/Si multilayer structure. Its optical transmittance is largely improved when increasing the annealing temperature, owing to the phase transformation from amorphous to nanocrystalline Si QDs embedded in the ZnO matrix. The sample annealed at 700°C exhibits not only high optical transmittance in the long-wavelength range but also better electrical properties including low resistivity, small turn-on voltage, and high rectification ratio. By using ZnO as the QDs' matrix, the carrier transport is dominated by the multistep tunneling mechanism, the same as in a n-ZnO/p-Si heterojunction diode, which clearly differs from that using the traditional matrix materials. Hence, the carriers transport mainly in the ZnO matrix, not through the Si QDs. The unusual transport mechanism using ZnO as matrix promises the great potential for optoelectronic devices integrating Si QDs.

A gradient Si-rich oxide multilayer (GSRO-ML) deposition structure is proposed to achieve super-high density Si quantum dot (QD) thin film formation while preserving QD size controllability for better photovoltaic properties. Our results indicate that the Si QD thin film using a GSRO-ML structure can efficiently increase the QD density and control the QD size. Its optical properties clearly promise the capability of effective bandgap engineering even though these QDs are closely formed. The Si QD thin film using a GSRO-ML structure obviously reveals better electro-optical properties than those using a [silicon dioxide/silicon-rich oxide] multilayer ([SiO2/SRO]-ML) structure owing to the better optical absorption and carrier transport properties. Therefore, we successfully demonstrate that our proposed GSRO-ML structure has great potential for application in solar cells integrating Si QD thin films.

Telomerase activity is repressed in normal human somatic cells, but is activated in most cancers, suggesting that telomerase may be an important target for cancer therapy. Agents that interact selectively with telomerase are anticipated to exert specific action on cancer cells. In this study, we evaluated maleimide derivatives for their potency and selectivity of telomerase inhibition. Among the several N-substituted derivatives of maleimide tested, N-(1-Pyrenyl) maleimide was shown to exert the greatest inhibition of telomerase in a cell free system, with an IC50 value of 0.25 μM. Importantly, we demonstrated that N-(1-pyrenyl) maleimide induces apoptosis in Jurkat T cells and displays the greatest differential cytotoxicity against hematopoietic cancer cells. These results suggest that N-(1-pyrenyl) maleimide is an attractive maleimide to be tested and developed as anti-cancer drug.

Our previous study has shown that genistein enhances apoptosis in A549 lung cancer cells induced by trichostatin A (TSA). The precise molecular mechanism underlying the effect of genistein, however, remains unclear. In the present study, we investigated whether genistein enhances the anti-cancer effect of TSA through up-regulation of TNF receptor-1 (TNFR-1) death receptor signaling. We incubated A549 cells with TSA (50 ng/mL) alone or in combination with genistein and then determined the mRNA and protein expression of TNFR-1 as well as the activation of downstream caspases. Genistein at 5 and 10 μM significantly enhanced the TSA-induced decrease in cell number and apoptosis in a dose-dependent manner. The combined treatment significantly increased mRNA and protein expression of TNFR-1 at 6 and 12h, respectively, compared with that of the control group; while TSA alone had no effect. TSA in combination with 10 μM of genistein increased TNFR-1 mRNA and protein expression by about 70% and 40%, respectively. The underlying mechanism for this effect of genistein may be partly associated with the estrogen receptor pathway. The combined treatment also increased the activation of caspase-3 and -10 as well as p53 protein expression in A549 cells. The enhancing effects of genistein on the TSA-induced decrease in cell number and on the expression of caspase-3 in A549 cells were suppressed by silencing TNFR-1 expression. These data demonstrated that the upregulation of TNFR-1 death receptor signaling plays an important role, at least in part, in the enhancing effect of genistein on TSA-induced apoptosis in A549 cells., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In this study, we fabricate ZnO thin films with nano-crystalline Si (nc-Si) quantum dots (QDs) using a ZnO/Si multilayer deposition structure and a post-annealing process, and the formation of high crystallinity of Si QDs embedded in the crystalline ZnO matrix is demonstrated. For optical properties, the essential features of ZnO material, high transmission in long-wavelength and high absorption in short-wavelength ranges, are preserved. We observe significantly enhanced light absorption and an unusual photoluminescence emission peak contributed from the nc-Si QDs in the middle-wavelength range. In addition, we confirm the formation of optical sub-bandgap and the obtained value is quite close to the unusual PL emission peak. We show that meaningful sub-bandgap can form in ZnO thin film by embedding nc-Si QDs while maintaining the advantageous properties of ZnO matrix. This newly developed composite material, nc-Si QD embedded ZnO thin films, can be useful for various electro-optical applications.

Inoculating common sterilized soil with different non-sterilized soils was used to investigate the potentials of altered microbial communities to change rate and temperature sensitivity of soil microbial respiration. Results showed that accumulative CO2 emission of sterilized Hailun black soils inoculated with non-sterilized Harbin black soil, Fengqiu fluvo-aquic soil and Qiyang red soil were 684.25, 753.97 and 644.91 microg, respectively, at 15 degrees C; were 963.06, 1 015.44 and 852.31 microg, respectively, at 25 degrees C; and were 1 252.55, 380.36 and 1 177.88 microg, respectively, at 35 degrees C. The soil accumulative CO2 emissions increased with pH of inoculant soils, but did not relate to organic content of and geographical distance from inoculant soils. Difference of microbial respiration rates among the three inoculant soils kept for 104, 277 and 1 177 h at 15 degrees C, 25 degrees C and 35 degrees C, respectively. Temperature sensitivity quotients (Q10) of microbial respiration of sterilized Hailun black soils inoculated with non-sterilized Harbin black soil, Fengqiu fluvo-aquic soil and Qiyang red soil were 1.63, 1.49 and 1.80, respectively, during 0-104 h; were 1.43, 1.39 and 1.46, respectively, during 0-277 h and were 1.35, 1.35 and 1.35, respectively, during 0-1 609 h. The Q10 decreased with pH of inoculant soils and incubation time. The results suggest that altered microbial community would change rate and temperature sensitivity of soil microbial respiration.

Telomeres are dynamic DNA-protein complexes that protect the ends of linear chromosome. Telomere-binding proteins play crucial role in the maintenance of telomeres. HnRNP A3 has been shown recently to bind specifically to single-stranded telomeric DNA in vitro, although its in vivo telomere function remains unknown. In this study, the DNA-binding properties of hnRNP A3 in vitro as well as its putative role of telomere maintenance in vivo were investigated. The minimal sequence for hnRNP A3 binding to DNA was determined as an undecamer with the following consensus sequence 5'-[T/C]AG[G/T]NN[T/C]AG[G/T]N-3'. Confocal microscopy and chromatin-immunoprecipitation (ChIP) analyses showed that hnRNP A3 is associated with telomere in vivo. Knocking-down the expression of hnRNP A3 had no effect on telomere length maintenance and did not affect cell proliferation. In contrast, overexpression of hnRNP A3 resulted in the production of steady-state short telomeres in OECM1 cells. These results suggest that hnRNP A3 is associated with telomere in vivo and acts as a negative regulator of telomere length maintenance., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Prion diseases such as Bovine Spongiform Encephalopathy (BSE) and new variant Creutzfeldt-Jakob disease (nvCJD) have caused a major safety concern in cell cultures using fetal calf serum (FCS). In this study, we found that screened and tested human plasma (HP) obtained from blood centers may be an ideal alternate nutrient substitute to FCS for culturing hybridoma. In addition to the inherent safety, a ten-fold increase in the fusion efficiency has been observed if the HP was used as the nutrient supplement instead of FCS. Subsequently, a broader antibody repertoire may be recovered. The HP supplement was found to promote the growth of hybridoma cells but no impact on antibody secretion. Interestingly, this effect of enrichment was only observed for HP, but not plasma from other animals. Unidentified murine hybridoma cloning factors other than IL-6 may specifically reside in human blood., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The inhibition of dihydrofolate reductase (DHFR) by antifolates is a common practice both in cell culture and in chemotherapy. Surprisingly, antifolate resistance was also observed in cultured murine myeloma cells (SP2/0) in the presence of human plasma (HP); thus, we used a proteomic approach to identify novel plasma biomarker(s) for this condition. In contrast to the in vitro antifolate response, metabolic enzymes and translation machinery proteins were found to be up-regulated in the presence of HP. The antifolate resistance inherent in HP may be explained by a simultaneous promotion of cell proliferation and the maintenance of DNA integrity. Furthermore, the factor(s) was found to be extrinsic, heat stable and very small in size. Adenine, a supplemented additive in erythrocyte preservation, was subsequently identified as the contributing factor and exogenous addition in cultures reversed the cytotoxicity induced by antifolates. Importantly, adenine-containing blood components, which may provide enhanced survival to otherwise sensitive antifolate-targeted cells, showed a dose-dependent adverse effect in transfusion recipients receiving antifolate (methotrexate) medications. These findings not only highlight a previously unnoticed role of adenine, but also emphasize a novel mechanistic link between transfusion and subsequently reduced survival in patients taking methotrexate.

Telomeres are dynamic DNA-protein complexes at the end of linear chromosomes. Maintenance of functional telomeres is required for chromosome stability, and to avoid the activation of DNA damage response pathway and cell cycle arrest. Telomere-binding proteins play crucial roles in the maintenance of functional telomeres. In this study, we employed affinity pull-down and proteomic approach to search for novel proteins that interact with the single-stranded telomeric DNA. The proteins identified by two-dimensional gel electrophoresis were further characterized by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and MALDI-TOF-TOF tandem MS. Among the five identified proteins, we report here the biochemical properties of a novel protein, hnRNP A3. The purified hnRNP A3 bound specifically to G-rich strand, but not to C-rich strand or double-stranded telomeric DNA. The RRM1 (RNA recognition motif 1) domain, but not RRM2, of hnRNP A3 is sufficient to confer specific binding to the telomeric sequence. In addition, we present evidence that hnRNP A3 can inhibit telomerase extension in vitro. These biochemical properties of hnRNP A3 suggest that hnRNP A3 can participate in telomere regulation in vivo.

Telomerase activity is repressed in normal human somatic cells, but is activated in most cancers, suggesting that telomerase may be an important target for cancer therapy. In this study, we report that U-73122, an amphiphilic alkylating agent that is commonly used as an inhibitor for phospholipase C, is also a potent and selective inhibitor of human telomerase. The inhibition of telomerase by U-73122 was attributed primarily to the pyrrole-2,5-dione group, since its structural analog U-73343 did not inhibit telomerase. In confirmation, we observed that telomerase was inhibited by N-ethylmaleimide, but not N-ethylsuccinimide. The IC(50) value of U-73122 for the in vitro inhibition of telomerase activity is 0.2 microM, which is comparable to or slightly more sensitive than that for phospholipase C. The inhibitory action of U-73122 on telomerase appears to be rather selective since the presence of externally added proteins did not protect the inhibition and the IC(50) values for the other enzymes tested in this study were at least an order of magnitude higher than that for telomerase. Furthermore, we demonstrate that U-73122 can inhibit telomerase in hematopoietic cancer cells. The potent and selective inhibition of telomerase by U-73122 raises the potential exploitation of this drug and other alkylating agents as telomerase inhibitor.

Telomerase activity is repressed in normal human somatic cells, but is activated in most cancers, suggesting that telomerase may be an important target for cancer therapy. Inhibition of telomerase in cancer cells has been shown to limit the growth of human cancer cells in culture. In this study, we report that helenalin, a natural sesquiterpene lactone, is a potent and selective inhibitor for human telomerase. In vitro studies indicate that this drug can inactivate telomerase directly in a manner that is dependent on concentration and time. The inhibitory action of this drug on telomerase is selective since the presence of excessive externally added proteins did not protect the inhibition and all of the other enzymes tested in this study were not inhibited by this drug. Furthermore, we demonstrated that helenalin can inhibit the expression of hTERT and telomerase in hematopoietic cancer cells. Therefore, the anti-tumor activity of helenalin is attributed, at least in part, to the inhibition of telomerase.