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Much more attention has been paid to the contamination of Alternaria toxins because of food contamination and the threat to human health. In this study, an ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method was developed for the simultaneous detection of the prototypical alternariol, alternariol monomethylether, and the metabolites 4‐oxhydryl alternariol, and alternariol monomethylether 3‐sulfate ammonium salt of Alternaria toxins. The positive samples were used as matrix samples to optimize the different experimental conditions. 0.01% formic acid solution and acetonitrile were used as the mobile phase, and analytes were scanned in negative electron spray ionization under multiple reaction monitoring, and quantitative determination by isotope internal standard method. Application of this method to samples of human plasma and urine showed the detection of the above analytes. The results showed that the recoveries were from 80.40% to 116.4%, intra‐day accuracy was between 0.6% and 8.0%, and inter‐day accuracy was between 1.1% and 12.1%. The limit of detection of the four analytes ranged from 0.02 to 0.6 µg/L in urine, and 0.02 to 0.5 µg/L in plasma, respectively. Thus, the developed method was rapid and accurate for the simultaneous detection of analytes and provided a theoretical basis for the risk assessment of Alternaria toxins for human exposure. [ABSTRACT FROM AUTHOR]

In order to load fish oil for potential encapsulation of fat-soluble functional active substances, fish oil-loaded multicore submillimeter-sized capsules were prepared with a combination method of three strategies (monoaxial electrospraying, chitosan-tripolyphosphate ionotropic gelation, and Tween blending). The chitosan-tripolyphosphate/Tween (20, 40, 60, and 80) capsules had smaller and evener fish oil cores than the chitosan-tripolyphosphate capsules, which resulted from that Tween addition induced smaller and evener fish oil droplets in the emulsions. Tween addition decreased the water contents from 56.6 % to 35.0 %–43.4 %, increased the loading capacities from 10.4 % to 12.7 %–17.2 %, and increased encapsulation efficiencies from 97.4 % to 97.8 %–99.1 %. In addition, Tween addition also decreased the highest peroxide values from 417 meq/kg oil to 173–262 meq/kg oil. These properties' changes might result from the structural differences between the chitosan-tripolyphosphate and chitosan-tripolyphosphate/Tween capsules. All the results suggested that the obtained chitosan-tripolyphosphate/Tween capsules are promising carriers for fish oil encapsulation. This work also provided useful knowledge to understand the preparation, structural, and physicochemical properties of the chitosan-tripolyphosphate capsules. [ABSTRACT FROM AUTHOR]

• The defect-rich VS 4 nanosheets are obtained via microwave-induced fabrication method. • The sulfur vacancies promote the desorption of Mg2+. • V3+ self-doping maintains the structural stability of the active material. • Cation-anionic synergistic redox achieve a high specific capacity. Vanadium sulfide (VS 4) demonstrates the most prospect as the cathode materials for rechargeable magnesium battery due to its special one-dimensional linear crystal structure. However, VS 4 cathode still suffers from sluggish kinetics, irreversible structural change, short cycle life, and low capacity. Herein, a microwave-induced synthesis method is presented to fabricate VS 4 nanosheets with rich sulfur vacancies and high V3+/V4+ ratio. When serviced as the cathode material for rechargeable magnesium battery, the VS 4 nanosheets display excellent electrochemical performances with large specific capacity of 701 mAh/g at 200 mA g−1 current density. In addition, the VS 4 nanosheets cathodes also show long-term operating stability over 600 cycles at 1.0 A/g current density with only 0.3 % capacity decay per cycle. Our experimental results show that the improved electrochemical reaction kinetics is ascribed to the defect-rich structure and the reversible anionic redox reactions between S2−/S 2 2− of the VS 4 nanosheets. This work offers a meaningful way to design high-performance Mg2+ ion storage cathode materials with favorable diffusion kinetics. [ABSTRACT FROM AUTHOR]

The hierarchical carbon-encapsulated yolk-shell nickelic composites were fabricated by a general MOF-derived route via Ostwald ripening and anion exchange strategy. Benefitting from the unique yolk-shell carbon framework, synergistic effect and satisfied phys-chemical characters, the nickel phosphide displays superior sodium storage properties compared with sulfide and selenide counterparts. [Display omitted] Transition-metal compounds have attracted enormous attention as potential energy storage materials for their high theoretical capacity and energy density. However, the most present transition-metal compounds still suffer from severe capacity decay and limited rate capability due to the lack of robust architectures. Herein, a general metal–organic framework-derived route is reported to fabricate hierarchical carbon-encapsulated yolk-shell nickelic spheres as anode materials for sodium-ion batteries. The nickelic metal–organic framework (Ni-MOF) precursors can be in situ converted into hierarchical carbon-encapsulated Ni 2 P (Ni 2 P/C), NiS 2 (NiS 2 /C) and NiSe 2 (NiSe 2 /C) by phosphorization, sulfuration, and selenation reaction, respectively, and maintain their yolk-shell sphere-like morphology. The as-synthesized Ni 2 P/C sample can deliver much lower polarization and discharge platform, smaller voltage gap, and faster kinetics in comparison with that of the other two counterparts, and thus achieve higher initial specific capacity (3222.1/1979.3 mAh g−1) and reversible capacity of 765.4 mAh g−1 after 110 cycles. This work should provide new insights into the phase and structure engineering of carbon-encapsulated transition-metal compound electrodes via MOFs template for advanced battery systems. [ABSTRACT FROM AUTHOR]

Background: In light of the controversies regarding the surgical treatment of adult Chiari malformation type I (CM-I) with syringomyelia, a retrospective study was conducted to evaluate the safety and efficacy of tonsillectomy followed by modified reconstruction of the cisterna magna with or without craniectomy. Methods: Between 2008 and 2017, 78 adult CM-I patients (36 males and 42 females, mean age 40.6 years old) with syringomyelia were treated with posterior fossa decompression (PFD) with tonsillectomy and modified reconstruction of the cisterna magna. Patients were divided into two study groups: group A (n = 40) underwent cranioplasty with replacement of the bone flap; group B (n = 38) underwent suboccipital craniectomy. Neurological outcomes were evaluated by traditional physician assessment (improved, unchanged, and worsened) and the Chicago Chiari Outcome Scale (CCOS). Syringomyelia outcomes were assessed radiologically. Results: The procedure was successfully performed in all patients, and restoration of normal cerebrospinal fluid (CSF) flow was confirmed by intraoperative ultrasonography. The median postoperative follow-up was 20.3 months (range 18–60 months). Clinical improvement was evident in 66 (84.6%) patients, with no significant differences between the two groups (85.0% vs. 84.2%, P = 0.897). According to the CCOS, 36 patients (90.0%) in group A were labeled as "good" outcome, compared with that of 34 (86.8%) in group B (P = 0.734). Improvement of syringomyelia was also comparable between the groups, which was observed in 35 (87.5%) vs. 33 (86.8%) patients (P = 0.887). The postoperative overall (7.5% vs. 23.7%, P = 0.048) and CSF-related (2.5% vs. 18.4%, P = 0.027) complication rates were significantly lower in group A than group B. Conclusions: Tonsillectomy with modified reconstruction of the cisterna magna without craniectomy seems to be a safe and effective surgical option to treat adult CM-I patients with syringomyelia, though future well-powered prospective randomized studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

To evaluate the safety and efficacy of an enhanced recovery after surgery (ERAS) program for intraspinal tumors in a single-institutional prospective randomized controlled trial. A multimodal and multidisciplinary ERAS protocol for intraspinal tumor surgery was developed. A total of 94 enrolled patients were randomized into 2 groups: 48 were managed following the ERAS protocol (ERAS group), and 46 received conventional perioperative care (control group). The primary end point was postoperative length of stay (LOS). The secondary outcomes included postoperative pain score and pain medication use, urinary catheterization, ambulation, mortality, reoperation/readmission rates, complication rates, patient satisfaction, and overall cost. A significant reduction in LOS was achieved in patients undergoing ERAS protocol compared with the controls (5 vs. 8 days; P < 0.0001). Moreover, patients in the ERAS group had better postoperative pain scores (1.0 ± 1.3 vs. 1.9 ± 1.3; P = 0.007), decreased use of patient-controlled analgesia (4.2% vs. 19.6%; P = 0.020) and oral opioid (37.5% vs. 58.7%; P = 0.040), early urinary catheter removal (58.3% vs. 6.5%; P < 0.0001), greater ambulation (68.8% vs. 17.4%; P < 0.0001), and higher satisfaction scores (91.8 ± 4.4 vs. 88.2 ± 6.8; P = 0.022) than did the control group. There were no deaths or 30-day readmission/reoperation in both groups, nor did the postoperative complication rates differ between groups. The ERAS protocol for intraspinal tumor surgery seems to be feasible, effective, and safe in shortening postoperative LOS, improving postoperative pain control with reduced opioid use, and accelerating functional recovery without increasing rates of complications or reoperation/readmission. Adoption of spine ERAS programs could be encouraged in practice, although validation with larger-scale multicenter trials is warranted. [ABSTRACT FROM AUTHOR]

We sought to assess whether controlled, intraoperative lumbar drainage (LD) of cerebrospinal fluid (CSF) could facilitate resection of pituitary macroadenomas and reduce the rate of CSF leak. A retrospective cohort study from a prospective database was conducted on 189 patients with pituitary macroadenoma who received endoscopic transsphenoidal surgery between 2013 and 2017. Patients were classified into 2 groups: 119 patients received an intraoperative LD (LD group) and 70 patients underwent routine endoscopic surgery without LD (control group). In the LD group, lumbar catheters were placed preoperatively and CSF was drained intermittently during tumor resection. The rates of gross total resection (GTR) and CSF leaks were assessed both intraoperatively and postoperatively. Intraoperative LD was associated with a higher rate of GTR (92.4% in the LD group vs. 78.6% in the control group, P = 0.006), especially in macroadenomas with suprasellar extension (90.3% vs. 75.0%, P = 0.012). Both intraoperative and postoperative CSF leak rates were significantly decreased in the LD group (intraoperative: 10.1% vs. 31.4%, P < 0.001; postoperative: 3.4% vs. 11.4%, P = 0.035). In functioning adenomas, a better remission rate of excess-hormone secretion was observed in the LD group compared with the controls (89.1% vs. 60.6%, P = 0.001). Patients in the LD group also had an enhanced recovery with a shorter postoperative length of stay (7 days vs. 5 days, P = 0.020). Intraoperative LD may assist surgeons during endoscopic transsphenoidal resection of pituitary macroadenomas by achieving a higher rate of GTR and a lower rate of perioperative CSF leaks. Validation in prospective randomized controlled studies is needed. [ABSTRACT FROM AUTHOR]

Surrogate models have been widely adopted for reliability analysis. The common approach is to construct a series of surrogates based on a training set and then pick out the best one with the highest accuracy as an approximation of the time-consuming limit state function. However, the traditional method increases the risk of adopting an inappropriate model and does not take full advantage of the data devoted to constructing different surrogates. Furthermore, obtaining more samples is very expensive and sometimes even impossible. Therefore, to save the cost of constructing the surrogate and improve the prediction accuracy, an ensemble strategy is proposed in this paper for efficiently analyzing the structural reliability. The values of the weights are obtained by a recursive process and the leave-one-out technique, in which the values are updated in each iteration until a given prediction accuracy is achieved. Besides, a learning function is used to guide the selection of the next sampling candidate. Because the learning function utilizes the uncertainty estimator of the surrogate to guide the design of experiments (DoE), to accurately calculate the uncertainty estimator of the ensemble of surrogates, the concept of weighted mean square error is proposed. After the high-quality ensemble of surrogates of the limit state function is available, the Monte Carlo method is employed to calculate the failure probabilities. The proposed method is evaluated by three analytic problems and one engineering problem. The results show that the proposed ensemble of surrogates has better prediction accuracy and robustness than the stand-alone surrogates and the existing ensemble techniques. [ABSTRACT FROM AUTHOR]

To evaluate the health-related quality of life (HRQOL) in locally advanced cervical cancer (LACC) patients treated with neoadjuvant concurrent chemoradiation (CCRT) or radiation (RT) alone followed by radical surgery (RS). In a single-center retrospective study from a prospective database, 275 FIGO Stage IB2-IIIB patients who underwent CCRT/RT + RS were included. HRQOL was prospectively assessed by EORTC QLQ-C30 and EORTC QLQ-CX24 prior to any treatment (baseline) and 6 months after surgery, respectively. A statistically significant and clinically relevant improvement in physical functioning (P < 0.001) and role functioning (P = 0.002, P = 0.031) was observed in patients receiving either CCRT+RS or RT + RS at follow-up. In addition, quality of life (QoL), physical functioning, and social functioning were better in the RT + RS group than the CCRT+RS group after treatment (P = 0.028, P = 0.010, P = 0.014). Symptom scores of fatigue decreased in both groups over time (P < 0.001, P = 0.004) while insomnia decreased only in the RT + RS group (P = 0.042). Worsened menopausal symptoms were documented in both groups at follow-up (P = 0.001, P = 0.047), while lymphedema was deteriorated only in patients receiving CCRT + RS (P < 0.001). Sexuality scores did not differ between groups or over time with the exception of sexual worry, which was deteriorated in patients receiving RT + RS (P = 0.042). QLQ-C30 functioning and tumor-related symptoms scores improved while lymphedema and menopausal symptoms worsened 6 months after neoadjuvant CCRT or RT alone followed by RS in LACC patients. Patients treated with RT + RS had a generally better HRQOL compared with those receiving CCRT+RS, though further validation with prospective randomized clinical trials is warranted. • Physical/role functioning improved 6 months after concurrent chemoradiation (CCRT)/radiation (RT) + radical surgery (RS). • Tumor-related symptoms of fatigue and insomnia decreased 6 months after treatment. • Treatment-related symptoms of lymphedema and menopausal symptoms increased after treatment. • Sexuality was not impaired significantly except for a worsened sexual worry in the RT + RS group. • Generally RT + RS seems superior to CCRT+RS with greater improvement in functioning and less toxicity. [ABSTRACT FROM AUTHOR]

• Dark carbon fixation (DCF) is an important organic C source in intertidal wetlands. • Reductive sulfur in intertidal sediments was a key factor controlling DCF. • cbbM -harboring bacteria were the dominant DCF microbes in intertidal sediments. • DCF may play an important role in linking C-N-S cycles in intertidal wetlands. Dark carbon fixation (DCF) contributes approximately 0.77 Pg C y−1 to oceanic primary production and the global carbon budget. It is estimated that nearly half of the DCF in marine sediments occurs in estuarine and coastal regions, but the environmental factors controlling DCF and the microorganisms responsible for its production remain under exploration. In this study, we investigated DCF rates and the active chemoautotrophic microorganisms in intertidal sediments of the Yangtze Estuary, using 14C-labeling and DNA-stable isotope probing (DNA-SIP) techniques. The measured DCF rates ranged from 0.27 to 3.37 mmol C m−2 day−1 in intertidal surface sediments. The rates of DCF were closely related to sediment sulfide content, demonstrating that the availability of reductive substrates may be the dominant factor controlling DCF in the intertidal sediments. A significant positive correlation was also observed between the DCF rates and abundance of the cbbM gene. DNA-stable isotope probing (DNA-SIP) results further confirmed that cbbM -harboring bacteria, rather than cbbL -harboring bacteria, played a dominant role in DCF in intertidal sediments. Phylogenetic analysis showed that the predominant cbbM -harboring bacteria were affiliated with Burkholderia, including Sulfuricella denitrificans, Sulfuriferula, Acidihalobacter, Thiobacillus , and Sulfurivermis fontis. Moreover, metagenome analyses indicated that most of the potential dark-carbon-fixing bacteria detected in intertidal sediments also harbor genes for sulfur oxidation, denitrification, or dissimilatory nitrate reduction to ammonium (DNRA), indicating that these chemoautotrophic microorganisms may play important roles in coupled carbon, nitrogen, and sulfur cycles. These results shed light on the ecological importance and the underlying mechanisms of the DCF process driven by chemoautotrophic microorganisms in intertidal wetlands. [Display omitted] [ABSTRACT FROM AUTHOR]

The self-incompatibility (SI) reaction in the Solanaceae involves molecular recognition of stylar haplotypes by pollen and is mediated by the S-locus from which a stylar-localized S-RNase and several pollen-localized F-box proteins are expressed. S-RNase activity has been previously shown to be essential for the SI reaction, leading to the hypothesis that pollen rejection in incompatible crosses is due to degradation of pollen RNA. We used pollen expressing the fluorescent marker GFP, driven by the LAT52 promoter, to monitor the accumulation of mRNA and protein in pollen after compatible and incompatible pollinations. We find that GFP mRNA and protein gradually accumulate in pollen tubes until at least 18-h post-pollination and, up to this time, are only slightly more abundant in compatible compared with incompatible crosses. However, between 18- and 24-h post-pollination, pollen tube GFP mRNA and protein levels show a dramatic increase in compatible crosses and either remain constant or decrease in incompatible crosses. In contrast to these molecular correlates, the growth rates of compatible and incompatible pollen tubes begin to differ after 6-h post-pollination. We interpret the changes in growth rate at 6-h post-pollination as the previously described transition from autotrophic to heterotrophic growth. Thus, while pollen rejection is generally considered to result from the cytotoxic effects of S-RNase activity, this time course reveals that a difference in the growth rate of compatible and incompatible pollen appears prior to any marked effects on at least some types of pollen RNA. [ABSTRACT FROM AUTHOR]

A direct competitive fluorescence immunoassay (dc-FIA) and a direct competitive enzyme-linked immunosorbent assay (dc-ELISA) for the screening of dimethyl phthalate (DMP) in water samples were developed. The immunoassays utilise polyclonal antibodies against DMP raised in rabbits. The anti-DMP antibodies were linked to horseradish peroxidase (HRP) and fluorescein isothiocyanate (FITC). Under the optimal experimental conditions, the dc-ELISA has a linear working range of 0.1–2000 ng/ml (R 2=0.993) with a limit of detection of 0.09 ng/ml. In the dc-FIA, the linear working range was 0.05–30 ng/ml (R 2=0.996), and the limit of detection was 0.02 ng/ml, which is approximately four-fold more sensitive than the dc-ELISA using the same antibody and coating antigen. The results show low cross-reactivity with other structurally related compounds. The proposed methods are successfully applied to determine the DMP contaminants with a simple extraction procedure, and good recoveries were obtained. [ABSTRACT FROM AUTHOR]

Abstract: Flower-like ZnO particles were fabricated from zinc nitrate and urea via the microwave-induced combustion technique (MICT). The structure and morphology of the products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). The effects of growth conditions such as microwave power, radiation time, and molar ratio of urea/Zn2+ were investigated. Results show that the morphologies and particle sizes of the final products depend on the molar ratio of urea/Zn2+. The SEM images of ZnO flowers grown in different periods were employed to explain the formation mechanism. This study provides a simple and efficient approach for synthesizing flower-like ZnO heterostructures. [ABSTRACT FROM AUTHOR]

Gametophytic self-incompatibility (GSI) allows plants to block fertilization by haploid pollen whose S-allele constitution matches one of the two S-alleles in the diploid styles. GSI in Solanum chacoense requires a stylar S-RNase, first secreted from cells of the transmitting tract then imported into incompatible (self) pollen tubes. However, the molecular mechanisms allowing compatible pollen to evade S-RNase attack are less clear, as compatible pollen tubes also import S-RNase. Using styles of the same age and size in order to lower the degree of inter-style variability in S-RNase levels, we observe reduction of up to 30% of the total non-self stylar S-RNase in vivo during compatible crosses, whereas no degradation of self S-RNases is detected. This marked difference in stylar S-RNase levels dovetails with measurements of pollen-specific Lat52 mRNA, which decreases four-fold in incompatible compared to compatible crosses. Unexpectedly, we also find evidence for a reciprocal signaling mechanism from compatible pollen to the cells of the transmitting tract that results in a roughly threefold decrease in S-RNase transcript levels. These findings reveal a previously unsuspected feedback loop that may help reinforce the compatible reaction. [ABSTRACT FROM AUTHOR]

A method for the quantification of S-RNase levels in single styles of self-incompatible Solanum chacoense was developed and applied toward an experimental determination of the S-RNase threshold required for pollen rejection. It was found that, when single style values are averaged, accumulated levels of the S11- and S12-RNases can differ up to 10-fold within a genotype, while accumulated levels of the S12-RNase can differ by over 3-fold when different genotypes are compared. Surprisingly, the amount of S12-RNase accumulated in different styles of the same plant can differ by over 20-fold. A low level of 160 ng S-RNase in individual styles of fully incompatible plants, and a high value of 68 ng in a sporadic self-compatible (SSC) line during a bout of complete compatibility was measured, suggesting that these values bracket the threshold level of S-RNase needed for pollen rejection. Remarkably, correlations of S-RNase values to average fruit sets in different plant lines displaying sporadic self-compatibility (SSC) to different extents as well as to fruit set in immature flowers, are all consistent with a threshold value of 80 ng S12-RNase. Taken together, these results suggest that S-RNase levels alone are the principal determinant of the incompatibility phenotype. Interestingly, while the S-RNase threshold required for rejection of S12-pollen from a given genetic background is the same in styles of different genetic backgrounds, it is different when pollen donors of different genetic backgrounds are used. These results reveal a previously unsuspected level of complexity in the incompatibility reaction. [ABSTRACT FROM AUTHOR]

We previously reported that the anti-epidermal growth factor (EGF) receptor monoclonal antibody (mAb) 225 induces DiFi colon cancer cells to undergo apoptosis, and this apoptosis was accompanied by activation of the two apoptosis initiation caspases, caspase-8 and caspase-9. In the current study, we found that pretreatment of DiFi cells with the caspase-8-specific inhibitor z-IETD-fmk but not pretreatment with the caspase-9-specific inhibitor z-LEHD-fmk inhibited mAb 225-induced apoptosis, indicating that caspase-8 plays an essential role in initiating mAb 225-induced apoptosis. Because caspase-8 is activated primarily by the members of the tumor necrosis factor (TNF) receptor family, such as Fas, TNF receptor-1 (TNFR1), or receptors for TNF-related apoptosis-inducing ligand (TRAIL), we investigated whether mAb 225 activated caspase-8 by regulating one or more of these known pathways. Exposure of DiFi cells to TNFα or TRAIL activated caspase-8 and induced apoptosis in the cells. A TNFR1-antagonistic mAb or a TRAIL decoy receptor inhibited the activation of caspase-8 and the subsequent apoptosis induced by TNFα or TRAIL, respectively, in the cells. However, neither the TNFR1-antagonistic mAb nor the TRAIL decoy receptor inhibited mAb 225-induced activation of caspase-8 and apoptosis in DiFi cells. DiFi cells express detectable level of Fas but are not sensitive to the treatment by the Fas-agonistic mAb CH-11. A Fas-antagonistic mAb (ZB-4) inhibited the Fas-agonistic mAb CH-11-induced caspase-8 activation and apoptosis in Jurkat T-leukemic cells (used as positive control), but had no effect on mAb 225-induced activation of caspase-8 and apoptosis in DiFi cells. Taken together, our results suggest that mAb 225 does not interact with or regulate these known death receptor pathways. An exploration is therefore warranted for a novel mechanism by which mAb 225 activates caspase-8 and triggers apoptosis in DiFi cells. Oncogene (2001) 20, 3726–3734. [ABSTRACT FROM AUTHOR]

DiFi human colon carcinoma cells are stimulated by the transforming growth factor-α (TGF-α)/epidermal growth factor (EGF) receptor autocrine loop. Exposure of DiFi cells to monoclonal antibody (mAb) 225, which blocks ligand-induced activation of the EGF receptor, induces G1 arrest and subsequent cell death via apoptosis. We investigated the signal pathways by which basic fibroblast growth factor (bFGF) and insulin-like growth factor-1 (IGF-1) modulate mAb 225-induced G1 arrest and apoptosis in DiFi cells. Both bFGF and IGF-1 activated the mitogen-activated protein kinase (MAPK) kinase (MEK) pathway in DiFi cells. Additionally, IGF-1 activated the phosphoinositide 3-kinase (PI-3K)/Akt pathway. Both bFGF and IGF-1 inhibited mAb 225-induced apoptosis; however, bFGF provided sustained protection against apoptosis, while the protection by IGF-1 was only temporary. Also, bFGF reversed the mAb 225-induced increase in the p27Kip1 level, inhibition of cyclin-dependent kinase-2 (CDK-2) activity, dephosphorylation of the retinoblastoma (Rb) protein and the resultant G1 arrest of the cells. In contrast, IGF-1 did not reverse such effects by mAb 225. The prevention of mAb 225-induced G1 arrest and apoptosis in DiFi cells by bFGF was sensitive to the MEK/MAPK inhibitor PD98059 but not to the PI-3K inhibitor LY294002. In contrast, inhibition of apoptosis by IGF-1 in DiFi cells was sensitive only to LY294002 and not to PD98059. These results further our understanding of how mAb 225 induces apoptosis in DiFi cells. Oncogene (2001) 20, 1913–1922. [ABSTRACT FROM AUTHOR]

Focuses on increased expression of a multidrug gene-encoded P-glycoprotein as a major cause of tumor cell multidrug resistance. Function as a drug-efflux pump; Cross reaction of a widely used monoclonal antibody; Results of immunoprecipitation experiments.

We recently found that overexpression of p185c-erbB2 in c-erbB2 transfected MDA-MB-435 breast cancer cells (435.eB transfectants) confers a 5–9-fold increase in Taxol resistance. To examine whether Taxol resistance is a common phenomenon in other c-erbB2 overexpressing breast cancer cell lines, we tested a panel of human breast cancer cell lines established from different patients and expressing p185c-erbB2 at different levels for their sensitivity to Taxol and Taxotere, a synthetic taxoid. Higher expression of p185c-erbB2 in these breast cancer cell lines indeed correlated well with resistance to Taxol and Taxotere, and the degree of resistance was about 100-fold that in c-erbB2-overexpressing 435.eB transfectants, demonstrating that these breast cancer cells are highly resistant to Taxol. Since mdr-1-encoded p-glycoprotein (p170mdr-1) has been implicated in Taxol resistance, we next examined the p170mdr-1 levels in these breast cancer cell lines that are highly resistant to Taxol. Higher levels of p170mdr-1 expression were found in several breast cancer cell lines that are highly resistant to Taxol. Since these same breast cancer cell lines also expressed higher levels of p185c-erbB2, we sought to determine the relative contribution of p185c-erbB2 and p170mdr-1 overexpression to Taxol resistance. We first specifically down-regulated cell surface p185c-erbB2 using anti-p185c-erbB2 monoclonal antibodies and assayed sensitivity of these cells to Taxol. We next specifically inactivated p170mdr-1 function using p170mdr-1 blockers (thioridazine or verapamil) and again assayed Taxol sensitivity. Both p185c-erbB2 down-regulation and p170mdr-1 blockade significantly sensitized the breast cancer cell lines to Taxol. The results indicate that overexpression of either p185c-erbB2 or... [ABSTRACT FROM AUTHOR]

The Kriging-based reliability method with a sequential design of experiments (DoE) has been developed in recent years for implicit limit state functions. Such methods include the efficient global reliability analysis, the active learning reliability method combining Kriging and MCS Simulations. In this research, a novel local approximation method based on the most probable failure point (MPFP) is proposed to improve such methods. In this method, the MPFP calculated in the last iteration is the center of the next sampling region. The size of the local region depends on the reliability index obtained by the First Order Reliability Method (FORM) and the deviation distance of the standard deviation. The proposed algorithm, which approximates the limit state function accurately near MPFP rather than in the whole design space, can avoid selecting samples in regions that have negligible effects on the reliability analysis results. In addition, a multi-point enrichment technique is also introduced to select multiple sample points in each iteration. After the high-quality approximation of limit state function is obtained, the failure probability is calculated by the Monte Carlo method. Four numerical examples are used to validate the accuracy and efficiency of the proposed method. Results show that the proposed method is very effective for an accurate evaluation of the failure probability. [ABSTRACT FROM AUTHOR]

Natural proteins display organized hierarchical structures and tailored functionalities that cannot be achieved by synthetic approaches, highlighting the increased interest in developing protein‐based materials. Protein self‐assembly allows fabricating sophisticated supramolecular structures from relatively simple building blocks, a strategy naturally employed by amyloid proteins and intrinsically disordered proteins. However, the design of self‐assembled bioinspired materials with multi functionalities is still challenging. Inspired by the natural self‐assembly proteins (such as mussel foot proteins and amyloid proteins), a temperature‐inducible engineering programable hydrogel‐like amyloid nanostructure is developed by using a genetically modular fusion approach. The resulting hydrogel‐like assemblies display outstanding adhesive capacity, high stability, and broad substrate universality. The employed SpyCatcher/SpyTag system allows modifying the hydrogel‐like assemblies with any functional proteins of interest. Owing to their strong adhesive capacity and functional flexibility, such amyloid fibril‐based hydrogel shows advantages in the immobilization of diverse enzymes for highly efficient biocatalysis, fabrication of multi‐layered functional coatings, and construction of functionalized 3D scaffold for cell culture. Overall, a modular and straightforward approach is established to obtain a genetically programable nanostructure platform. The novel hydrogel‐like assemblies described here may be potentially applied to but not limited to synthetic biology, surface/interface engineering, and tissue engineering. [ABSTRACT FROM AUTHOR]

Estrogen receptor (ER) α expression and associated signaling is a major driver of over two-thirds of all breast cancers (BC). ER targeting strategies are typically used as a first-line therapy in patients with steroid receptor positive (SR+) disease. Secondary resistance to anti-estrogenic agents may occur with clonal expansion and disease progression. Mechanisms underlying hormone resistance are an expanding field of significant translational importance. Cross-talk with other nuclear hormones, receptors, and signaling pathways, including thyroid hormones (TH) and their receptors (THRs), have been shown to promote endocrine therapy resistance in some studies. We have shown that TH replacement therapy (THRT) was independently and significantly associated with higher rates of relapse and mortality in SR positive (+), node-negative (LN-) BC patients, whereas it showed no association with outcomes in SR negative (-) patients. LN-, SR+ patients receiving THRT and tamoxifen had the worst outcomes, suggesting a pro-carcinogenic interaction that significantly and independently shortened survival and increased mortality. Using in vivo and in vitro models, we previously showed hormonal cross-talk, altered gene signaling, target gene activation, and resistance to tamoxifen in the presence of TH. In this report, we show TH ± E2 ± tamoxifen inhibits cell cycle control signaling, reduces apoptosis, and enhances cell proliferation, tumor growth, tamoxifen resistance, and clonal expansion. Mechanistically these changes involve numerous genes and pathways, including critical cell cycle regulatory proteins and genes identified using various molecular methods. These studies facilitate a greater mechanistic understanding of the biological and molecular impact of TH on SR+ BC. [ABSTRACT FROM AUTHOR]

Background: Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease. Methods: Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. Specific shRNA was used to knockdown HER3 expression. IncuCyte system was utilized to monitor cell growth and migration. LIVE/DEAD Cell Imaging was to detect live and dead cells. HER3 recognition by our anti-HER3 monoclonal antibody (mAb) 4A7 was verified by ELISA, flow cytometry, and co-immunoprecipitation assays. Orthotopic tumor models were established in nude mice to determine the capability of TNBC cells forming tumors and to test if our mAb 4A7 could potentiate the antitumor activity of paclitaxel in vivo. Results: Elevated expression of HER3 was observed in approximately half of the TNBC specimens and cell lines tested. Analyses of TCGA databases found that the TNBC patients with high HER3 mRNA expression in the tumors showed significantly worse overall survival (OS) and relapse-free survival (RFS) than those with low HER3 expression. Specific knockdown of HER3 markedly inhibited TNBC cell proliferation and mammosphere formation in vitro and tumor growth in vivo. Our mAb 4A7 abrogated heregulin (a ligand for HER3), but not SDF-1 (a ligand for CXCR4)-induced enhancement of TNBC cell migration. Combinations of 4A7 and the EGFR-tyrosine kinase inhibitor (TKI) gefitinib dramatically decreased the levels of phosphorylated HER3, EGFR, Akt, and ERK1/2 in TNBC cells and potently induced growth inhibition and cell death. Moreover, 4A7 in combination with paclitaxel exerted significant antitumor activity against TNBC in vitro and in vivo. Conclusions: Our data demonstrate that increased HER3 is an effective therapeutic target for TNBC and our anti-HER3 mAb (4A7) may enhance the efficacy of gefitinib or paclitaxel in TNBC. [ABSTRACT FROM AUTHOR]

Dark carbon fixation (DCF), through which chemoautotrophs convert inorganic carbon to organic carbon, is recognized as a vital process of global carbon biogeochemical cycle. However, little is known about the response of DCF processes in estuarine and coastal waters to global warming. Using radiocarbon labelling method, the effects of temperature on the activity of chemoautotrophs were investigated in benthic water of the Yangtze estuarine and coastal areas. A dome‐shaped thermal response pattern was observed for DCF rates (i.e., reduced rates at lower or higher temperatures), with the optimum temperature (Topt) varying from about 21.9 to 32.0°C. Offshore sites showed lower Topt values and were more vulnerable to global warming compared with nearshore sites. Based on temperature seasonality of the study area, it was estimated that warming would accelerate DCF rate in winter and spring but inhibit DCF activity in summer and fall. However, at an annual scale, warming showed an overall promoting effect on DCF rates. Metagenomic analysis revealed that the dominant chemoautotrophic carbon fixation pathways in the nearshore area were Calvin‐Benson‐Bassham (CBB) cycle, while the offshore sites were co‐dominated by CBB and 3‐hydroxypropionate/4‐hydroxybutyrate cycles, which may explain the differential temperature response of DCF along the estuarine and coastal gradients. Our findings highlight the importance of incorporating DCF thermal response into biogeochemical models to accurately estimate the carbon sink potential of estuarine and coastal ecosystems in the context of global warming. [ABSTRACT FROM AUTHOR]

Background: Resistance to HER2-targeted therapies, including the monoclonal antibody trastuzumab and tyrosine kinase inhibitor lapatinib, frequently occurs and currently represents a significant clinical challenge in the management of HER2-positive breast cancer. We previously showed that the trastuzumab-resistant SKBR3-pool2 and BT474-HR20 sublines were refractory to lapatinib in vitro as compared to the parental SKBR3 and BT474 cells, respectively. The in vivo efficacy of lapatinib against trastuzumab-resistant breast cancer remained unclear. Results: In tumor xenograft models, both SKBR3-pool2- and BT474-HR20-derived tumors retained their resistance phenotype to trastuzumab; however, those tumors responded differently to the treatment with lapatinib. While lapatinib markedly suppressed growth of SKBR3-pool2-derived tumors, it slightly attenuated BT474-HR20 tumor growth. Immunohistochemistry analyses revealed that lapatinib neither affected the expression of HER3, nor altered the levels of phosphorylated HER3 and FOXO3a in vivo. Interestingly, lapatinib treatment significantly increased the levels of phosphorylated Akt and upregulated the expression of insulin receptor substrate-1 (IRS1) in the tumors-derived from BT474-HR20, but not SKBR3-pool2 cells. Conclusions: Our data indicated that SKBR3-pool2-derived tumors were highly sensitive to lapatinib treatment, whereas BT474-HR20 tumors exhibited resistance to lapatinib. It seemed that the inefficacy of lapatinib against BT474-HR20 tumors in vivo was attributed to lapatinib-induced upregulation of IRS1 and activation of Akt. Thus, the tumor xenograft models-derived from SKBR3-pool2 and BT474-HR20 cells serve as an excellent in vivo system to test the efficacy of other HER2-targeted therapies and novel agents to overcome trastuzumab resistance against HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Carbon dots as new nanomaterials, have been widely used in rapid detection because of their nondestructive, real-time detection characteristics. Improving the sensitivity and selectivity of the method in complex real samples is new challenge and requirement for sensing technology. Here, we report an ultrasensitive fluorescence immunoassay (FIA) for trace diethyl phthalate (DEP) using red carbon dots@SiO2 (R-CDs@SiO2) as tags. SiO2 as a nanocarrier can effectively improve the bio-functionalization and utilization rate of carbon dots. Moreover, several R-CDs embedded in SiO2 nanospheres can magnify the fluorescence signal and improve sensitivity. R-CDs@SiO2 conjugate anti-DEP antibody (Ab) as fluorescent immunosensor, which can specifically recognize DEP. Under optimization conditions, the detection limit (LOD) of this FIA was calculated as 0.0011 ng/mL. In addition, the recoveries of this established FIA ranged from 96.8 to 108.5%, showing satisfactory accuracy. Compared with GC-MS/MS (LOD µg/mL), the sensitivity of the FIA was significantly improved. As a result, the FIA developed using R-CDs@SiO2 as tags has a high potential for determining trace DEP. [ABSTRACT FROM AUTHOR]

Three types of tilapia scale gelatins (hot water-pretreated gelatin, HWG; acetic acid-pretreated gelatin, AAG; and pepsin enzyme-pretreated gelatin, PEG) were extracted and their gel strength, foaming properties, and emulsifying properties were analyzed. They had different gel strength values: AAG (370 ± 10 g Bloom) > HWG (320 ± 10 g Bloom) > PEG (280 ± 10 g Bloom). The creaming index values of tilapia scale gelatin-stabilized fish oil-loaded emulsions were dependent on gelatin type (HWG ≈ AAG > PEG) at low gelatin concentration (2 mg/mL), whereas they were similar and low (8–10 %) at high gelatin concentration (10 mg/mL). Extraction methods had no consistently significant effects on the gelatin foaming properties. In summary, tilapia scale gelatins had better gel strength and foaming properties and similar or even better emulsifying properties than mammalian gelatins. Therefore, tilapia scales could be a potential source of gelatins to replace mammalian gelatins. • Tilapia scale gelatins were extracted using three different pretreatment methods. • Hot water- and pepsin-pretreated gels were the finest and coarsest, respectively. • These gelatins had better or comparable gel strength than commercial mammalian ones. • These gelatins had better foaming properties than some reported mammalian ones. • These gelatins had comparable emulsifying properties to some reported mammalian ones. [ABSTRACT FROM AUTHOR]

Growth factor receptor-mediated signal transduction has been implicated in conferring resistance to conventional chemotherapy on cancer cells. In this study, we delineated a pathway that involves HER2/PI-3K/Akt in mediating multidrug resistance in human breast cancer cells. We found that the cell lines that express both HER2 and HER3 appear to have a higher phosphorylation level of Akt (activated Akt). Transfection of HER2 in MCF7 breast cancer cells that express HER3 caused a phosphoinoside-3 kinase (PI-3K)-dependent activation of Akt, and was associated with an increased resistance of the cells to multiple chemotherapeutic agents (paclitaxel, doxorubicin, 5-fluorouracil, etoposide, and camptothecin). Selective inhibition of PI-3K or Akt activity with their respective dominant-negative expression vectors sensitized the cells to the induction of apoptosis by the chemotherapeutic agents. We further demonstrated that MCF7 cells expressing a constitutively active Akt, in which the phospholipid-interactive PH domain of Akt was replaced by a farnesylation sequence for constitutive membrane anchorage (?PH-Akt1-farn), showed a similar increased resistance to the chemotherapeutic agents. Our results suggest that activation of Akt1 by HER2/PI-3K plays an important role in conferring a broad-spectrum chemoresistance on breast cancer cells and that Akt may therefore be a novel molecular target for therapies that would improve the outcome of patients with breast cancer.Oncogene (2003) 22, 3205-3212. doi:10.1038/sj.onc.1206394 [ABSTRACT FROM AUTHOR]

The impact of the cyclin dependent kinase (CDK) inhibitors p21Waf1 and p27Kip1 on paclitaxel-mediated cytotoxicity was investigated in RKO human colon adenocarcinoma cells with the ecdysone-inducible expression of p21Waf1 or p27Kip1. Ectopic expression of p27Kip1 arrested cells at G1 phase, whereas p21Waf1 expression arrested cells at G1 and G2. Expression of p21Waf1 after paclitaxel treatment produced much greater resistance to paclitaxel than did expression of p27Kip1. We attributed this difference to the additional block at G2 induced by p21Waf1, which prevented cells from entering M phase and becoming paclitaxel susceptible. Expression of p21Waf1 inhibited p34cdc2 activity and markedly reduced paclitaxel-mediated mitotic arrest, from 87.5 to 23%. In contrast, p27Kip1 expression also inhibited p34cdc2 but reduced mitotic arrest only slightly, from 87.4 to 74.5%. We concluded that the G2 block produced by p21Waf1, but not by p27Kip1, contributed to their unequal modulation of sensitivity to paclitaxel-mediated apoptosis in RKO cells, and there is no causal relationship between paclitaxel-mediated cytotoxicity and elevation of p34cdc2 activity. Oncogene (2000) 19, 2423–2429 [ABSTRACT FROM AUTHOR]

A multifunctional trastuzumab-nanoparticle-fluorocarbon system was developed to maximize the diagnostic effects in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The mesoporous silica nanoparticle shape (e.g. amorphous, spherical, and tubular) was altered to optimize the ultrasound contrast potential. Fluorocarbon conjugated mesoporous silica nanoparticles produced higher mean pixel intensities. At lower non-toxic concentrations, tubular shaped nanoparticles produced a higher mean pixel intensity compared to amorphous and spherical particles. All systems displayed a clear binding preference towards HER2-positive breast cancer cells. Increased incubation times and conjugation of fluorocarbon to mesoporous nanoparticles increased binding preference to HER2-positive breast cancer cells. The highest binding affinity was seen with tubular shaped nanoparticles as compared to amorphous and spherical particles. The trastuzumab-nanoparticlefluorocarbon system of each morphology displayed functionality of enhancing contrast in ultrasound. [ABSTRACT FROM AUTHOR]

Background: Infratentorial craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). Enhanced Recovery After Surgery (ERAS) protocols have been shown in multiple surgical disciplines to improve outcomes, including reduced PONV. However, very few studies have described the application of ERAS to infratentorial craniotomy. The aim of this study was to examine whether our ERAS protocol for infratentorial craniotomy could improve PONV. Methods: We implemented an evidence-based, multimodal ERAS protocol for patients undergoing infratentorial craniotomy. A total of 105 patients who underwent infratentorial craniotomy were randomized into either the ERAS group (n = 50) or the control group (n = 55). Primary outcomes were the incidence of vomiting, nausea score, and use of rescue antiemetic during the first 72 h after surgery. Secondary outcomes included postoperative anxiety level, sleep quality, and complications. Results: Over the entire 72 h post-craniotomy observation period, the cumulative incidence of vomiting was significantly lower in the ERAS group than in the control group. Meanwhile, the incidence of vomiting was significantly lower in the ERAS group on postoperative days (PODs) 2 and 3. Notably, the proportion of patients with mild nausea (VAS 0–4) was higher in the ERAS group as compared to the control group on PODs 2 or 3. Additionally, the postoperative anxiety level and quality of sleep were significantly better in the ERAS group. Conclusion: Successful implementation of our ERAS protocol in infratentorial craniotomy patients could attenuate postoperative anxiety, improve sleep quality, and reduce the incidence of PONV, without increasing the rate of postoperative complications. Trial registration: ChiCTR-INR-16009662, 27 Oct 2016, Clinical study on the development and efficacy evaluation of Enhanced Recovery After Surgery (ERAS) in Neurosurgery. [ABSTRACT FROM AUTHOR]

Endoscopic endonasal transsphenoidal resection has been accepted as a routine therapy for pituitary adenoma, but the postoperative hospital stay is typically several days long. With the advantages of reduced cost and improved patient satisfaction, the application of ambulatory surgery (AS) has developed rapidly. However, AS was still rarely adopted in neurosurgery. Here we designed an AS treatment protocol for pituitary adenoma with the endoscopic endonasal approach (EEA), and reported our initial experiences regarding the safety and efficacy of the AS protocol. 63 patients who presented with pituitary adenoma were screened at the Department of Neurosurgery, Tangdu Hospital from July to September, 2017. A total of 20 pituitary adenoma patients who met the inclusion criteria underwent EEA surgery using this evidence-based AS protocol, which emphasized adequate assessment for eligibility, full preparation to minimize invasiveness, enhanced recovery, and active perioperative patient education. Of the 20 patients enrolled, 18 were discharged on the afternoon of the operation day with a median total length of stay (LOS) of 31 hours (range, 29–32) hours. The median LOS after surgery was 6.5 (range, 5–8) hours. Two patients were transferred from the AS protocol to conventional care due to intraoperative cerebrospinal fluid leakage (one case) and an unsatisfying post-anesthetic discharge score (one case). Complications included transient and reversible mild postoperative nausea and vomiting [visual analog scale (VAS) score <3], headache (VAS score <3) after the operation or early after discharge. No patient was readmitted. Our results supported the safety and efficacy of the AS protocol for pituitary adenoma patients undergoing EEA resection among eligible patients, and further evaluation of this protocol in controlled studies with a larger sample size is warranted. [ABSTRACT FROM AUTHOR]

In this paper, a visual detection method by a UAV (unmanned aerial vehicle) was proposed to detect green mangoes on the surface of the tree crown rapidly and meet the need of estimating the number of mango fruits in orchards. The YOLOv2 model was used for quick detection of mango images captured by a UAV. First, mango images were collected by a UAV. These images were marked manually and used to build a training set and a test set. The parameters of the model were determined by experiments. The resolution of the images was 544 × 544 pixels. The batch size was 64, and the initial learning rate was 0.01. The mAP (mean average precision) of the trained model on the training set was 86.4%. Good detection results were achieved on images containing different fruit numbers and different lighting conditions with a precision of 96.1% and a recall rate of 89.0%. Finally, an experiment was conducted to estimate the actual number of green mango fruits. A method of generating an image of the whole mango tree was designed. The fruit numbers estimation model for green mango was obtained by linear fitting between the actual number and the detected number of mangoes. From the comparison of the fruit numbers of 10 mango trees determined by manual calculation and model prediction, an estimation error rate of 1.1% was achieved. The result demonstrated that the algorithm was effective for green mango detection and provided a methodological reference for quick estimation of the number of green mango fruits in orchards. • A UAV-based technique was developed to detect mango fruit in commercial orchards. • A method for estimating the number of mango fruits per tree was developed. • The algorithm proposed in this paper had a detection accuracy of 96.1%. [ABSTRACT FROM AUTHOR]

Background: Infratentorial craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). Enhanced Recovery After Surgery (ERAS) protocols have been shown in multiple surgical disciplines to improve outcomes, including reduced PONV. However, very few studies have described the application of ERAS to infratentorial craniotomy. The aim of this study was to examine whether our ERAS protocol for infratentorial craniotomy could improve PONV.Methods: We implemented an evidence-based, multimodal ERAS protocol for patients undergoing infratentorial craniotomy. A total of 105 patients who underwent infratentorial craniotomy were randomized into either the ERAS group (n = 50) or the control group (n = 55). Primary outcomes were the incidence of vomiting, nausea score, and use of rescue antiemetic during the first 72 h after surgery. Secondary outcomes included postoperative anxiety level, sleep quality, and complications.Results: Over the entire 72 h post-craniotomy observation period, the cumulative incidence of vomiting was significantly lower in the ERAS group than in the control group. Meanwhile, the incidence of vomiting was significantly lower in the ERAS group on postoperative days (PODs) 2 and 3. Notably, the proportion of patients with mild nausea (VAS 0-4) was higher in the ERAS group as compared to the control group on PODs 2 or 3. Additionally, the postoperative anxiety level and quality of sleep were significantly better in the ERAS group.Conclusion: Successful implementation of our ERAS protocol in infratentorial craniotomy patients could attenuate postoperative anxiety, improve sleep quality, and reduce the incidence of PONV, without increasing the rate of postoperative complications.Trial Registration: ChiCTR-INR-16009662, 27 Oct 2016, Clinical study on the development and efficacy evaluation of Enhanced Recovery After Surgery (ERAS) in Neurosurgery. [ABSTRACT FROM AUTHOR]

Background. Nosocomial EVD-related ventriculitis is a major complication and a significant cause of morbidity and mortality in critically ill neurological patients. Questions remain about best management of EVDs. The purpose of this study is to compare our incidence of ventriculitis to studies using different catheters and/or antibiotic coverage schemes and determine whether c-EVD with prolonged antibiotics given for the duration of drain placement is inferior to ac-EVD with pp-abx or ac-EVD with prolonged antibiotics for prevention of ventriculitis. Methods. A retrospective chart review of all patients who had EVDs placed from January 2010 through December 2015 at home institution was performed. Statistical analysis was performed using Fisher’s exact test to compare incidence of ventriculitis identified in other studies with that of home institution. Results. The study included 107 patients, 66 (61.7%) males and 41 (38.3%) females. Average age was 56 years ranging from 18 to 95 years. Average length of drain placement was 7.8 days ranging from 2 to 23 days. Average length of drain placement in infected drains was 13.3 days ranging from 11 to 15 days. There were 3 cases with positive CSF cultures (Staphylococcus haemolyticus and Staphylococcus epidermidis x 2). There were 2 cases with a CSF having a positive gram stain but failed to yield any bacterial growth on culture and did not meet predefined criteria. Conclusions. The c-EVD with prolonged antibiotics given for the duration of drain placement is not inferior to ac-EVD with pp-abx or ac-EVD with prolonged antibiotics for prevention of ventriculitis. The c-EVD with prolonged antibiotics is superior to c-EVD with pp-abx and conventional EVD without antibiotics for prevention of ventriculitis. Selection should include considerations for antibiotic stewardship and cost effectiveness. Future studies should also utilize clinical and CSF profile criteria in addition to positive CSF cultures for identifying ventriculitis to prevent line colonization from classification as ventriculitis in analysis. [ABSTRACT FROM AUTHOR]

Elevated expression of HER3, which interacts with HER2 in breast cancer cells, confers chemoresistance via phosphoinositide 3-kinase (PI-3K)/Akt-dependent upregulation of Survivin. However, the underlying mechanism is not clear. Ectopic expression or specific knockdown of HER3 in HER2-overexpressing breast cancer cells did not alter Survivin mRNA levels and Survivin protein stability, supporting the notion that HER3 signaling may regulate specific miRNAs that target Survivin to alter its protein translation. Here we showed that overexpression and specific knockdown of HER3 reduced and enhanced expression of two Survivin-targeting miRNAs, miR-203 and miR-542-3p, in breast cancer cells, respectively. While the specific inhibitor of either miR-203 or miR-542-3p attenuated an anti-HER3 antibody-induced downregulation of Survivin, inhibition of miR-542-3p exhibited a better efficacy than miR-203 inhibition did. Consistently, miR-542-3p mimic was much more effective than miR-203 mimic not only in inhibition of Survivin, but also in enhancement of paclitaxel-induced apoptosis in HER2-overexpressing breast cancer cells. Moreover, the combination of miR-542-3p mimic and paclitaxel, as compared with either agent alone, significantly inhibited in vivo tumor growth of HER2-overexpressing breast cancer cells. Collectively, our data indicated that the HER3/PI-3K/Akt signaling upregulates Survivin via suppression of miR-203 and miR-542-3p. Because miR-542-3p has three binding sites on the 3'-UTR of Survivin mRNA, its mimic was able to effectively downregulate Survivin in vitro and in vivo. Thus, miR-542-3p-replacement therapy is an excellent approach to overcome HER3-mediated paclitaxel resistance and significantly enhances the antitumor activity of paclitaxel against HER2-overexpressing breast cancer. [ABSTRACT FROM AUTHOR]

Coastal wetlands are hotspots for nitrogen (N) cycling and a significant natural source of the potent greenhouse gas nitrous oxide (N 2 O). Burrowing benthos are known to transform N in intertidal marsh soils, but their contribution to N 2 O emissions and the underlying molecular mechanisms remain unclear. Here, the effects of crab bioturbation on N 2 O emissions in coastal marshes, where Chiromantes dehaani and Helice tridens tientsinensis were the dominant crab species, were investigated in field and indoor experiments. The N 2 O emissions increased significantly in the presence of crabs, being positively correlated with the intensity of crab bioturbation but differing among crab species. Natural-abundance isotope analyses indicated that crab bioturbation greatly promoted the contribution of hydroxylamine oxidation to N 2 O production; nevertheless, bacterial denitrification (including heterotrophic denitrification and nitrifier denitrification) remained the dominant pathway. Molecular analyses suggested that the increased N 2 O emissions in crab-disturbed habitats might be driven by underlying changes to microbial communities, especially by the disproportionate stimulation of nitric oxide reductase-carrying microbes over nitrous oxide reductase-carrying microbes. This study highlights the importance of considering the burrowing activity, density, and species of benthos when evaluating the N cycle in coastal wetlands. [Display omitted] • Crab bioturbation greatly accelerates N 2 O emission in intertidal marsh soils. • Increase of N 2 O emission is closely related to reshaped microbial community by crab. • Different species of crabs exhibit different promoting effects on N 2 O emission. • Crab bioturbation affects N 2 O production pathways based on N 2 O isotopic signatures. • Activity and species of crabs should be considered when restoring coastal wetlands. [ABSTRACT FROM AUTHOR]

Overexpression of survivin is observed in various hematological malignancies, including acute myeloid leukemia (AML). Studies show that elevated expression of survivin correlates with a worse clinic outcome in AML patients. It remains unclear whether inhibition of survivin may alter the efficacy of chemotherapy against AML. Here, we evaluate the effects of specific knockdown of survivin on AML cells' sensitivity to chemotherapy, and investigate the therapeutic potential of the transcription inhibitor of survivin YM155 either alone or in combination with chemotherapeutic agents. We found Kasumi-1 and HL-60 cells had relatively higher expression levels of survivin among all AML cell lines tested. Specific knockdown of survivin in Kasumi-1 and HL-60 cells resulted in: inhibition of cell proliferation; cell cycle G2/M arrest; induction of DNA damage response and apoptosis. Downregulation of survivin enhanced etoposide- or doxorubicin-induced anti-proliferative/anti-survival activity in AML cells. The small molecule inhibitor YM155 reduced survivin in a dose- and time-dependent manner and trigged apoptosis in Kasumi-1 and HL-60 cells. The combinatorial effects of YM155 and chemotherapeutics were either synergetic or antagonistic, depending upon the drugs used for combination and the type of AML cells being treated. Collectively, our data demonstrate that survivin plays an important role in the maintenance and proliferation of AML cells. While specific knockdown of survivin enhances chemosensitivity, the combinations of YM155 and chemotherapeutic agents exhibit synergetic or antagonistic effects on AML cells. Our findings provide a rationale for further assessment of survivin-targeted therapy in the treatment of patients with AML. [ABSTRACT FROM AUTHOR]

"Turn on" fluorescence immunoassay of endocrine diethyl phthalate. [Display omitted] • Fluorescence turn-on immunoassay of endocrine diethyl phthalate. • Red carbon dots can reduce interference of autofluorescence. • Red carbon dots as tags can improve the sensitivity of immunoassay. • "Turn-on" probe can reduce the interference of actual sample medium. Diethyl phthalate (DEP), as the environmental endocrine, would interfere with people's endocrine system and has greatly harm in health. Here a sensitivity, eco-friendly fluorescence immunoassay technique was established based on "turn-on" red carbon dots (R-CDs) conjugated anti-DEP antibody (Ab) as the immunoprobe for the detection of DEP in daily supplies. The R-CDs will "turn-on" fluorescence when it in formamide solution, due to the change of the electron distribution on the surface and electronic charge transfer of the red carbon dots. The use of "turn-on" R-CDs as immunoprobe effectively increased the sensitivity of the immunoassay. Moreover, the R-CDs conjugated anti-DEP Ab without any additional embellishment. Under the optimal conditions, a good linear was established with the DEP concentration range of 5 × 10−2 ng/mL–10 ng/mL, the low limit of detection (LOD) of the proposed method was 0.0056 ng/mL. This project has satisfactory accuracy with recoveries ranging from 96.0% to 115.1%. Our research provides an accurately, simply and sensitivity strategy to detect the content of environmental endocrine DEP in daily supplies. [ABSTRACT FROM AUTHOR]

The highly structured (64% GC) covalently closed circular (CCC) RNA (220 nt) of the virusoid associated with rice yellow mottle virus codes for a 16-kDa highly basic protein using novel modalities for coding, translation, and gene expression. This CCC RNA is the smallest among all known viroids and virusoids and the only one that codes proteins. Its sequence possesses an internal ribo-some entry site and is directly translated through two (or three) completely overlapping ORFs (shifting to a new reading frame at the end of each round). The initiation and termination codons overlap UGAUGA (underline highlights the initiation codon AUG within the combined initiation-termination sequence). Termination codons can be ignored to obtain larger read-through proteins. This circular RNA with no noncoding sequences is a unique natural supercompact "nanogenome." [ABSTRACT FROM AUTHOR]

The defect-rich unconventional phase Cu 7.2 S 4 Nanotubes are fabricated by a facile microwave-induced selective etching method. Benefitting from the unique one-dimensional crystal structure and lattice defect-rich hollow structure, the Cu 7.2 S 4 nanotubes exhibit high reversible capacity and remarkable cycling stability. [Display omitted] • The defect-rich Cu 7.2 S 4 nanotubes are fabricated for the first time. • The unique microwave-induced selective etching method is demonstrated. • The record cycling stability is achieved over the Cu 7.2 S 4 nanotube cathode. • The multistep reaction kinetics of the Cu 7.2 S 4 nanotube cathode are confirmed. Copper sulfide is promising great potential for capable cathode in rechargeable magnesium batteries. However, divalent Mg2+ diffusion in its host lattice is subject to high lattice strain and mechanical stress mainly due to strong Coulombic interaction. Herein, a microwave-induced selective etching strategy is reported to construct non-stoichiometric-phase robust Cu 7.2 S 4 nanotubes with rich lattice defects, which can proceed with ultra-long-cycling stability over 1600 cycles with ultra-low capacity decay of 0.0109 % per cycle at 1.0 A g−1. Furthermore, the Cu 7.2 S 4 nanotube cathode can also exhibit a large specific capacity of 314 mAh g−1 at 0.1 A g−1 as well as an excellent rate capability of 91.7 mAh g−1 at 1.0 A g−1. The present electrochemical performances greatly surpass those of Cu 7.2 S 4 nanowire, Cu 7.2 S 4 nanoparticle, and conventional phase CuS nanotubes and at least are comparable to the conversion-type cathode materials reported so far. The generated lattice defect combined with the optimized robust nanotube structure can effectively buffer lattice strain and mechanical stress to provide a favorable diffusion kinetic. Our designed microwave-induced selective etching system demonstrates significant superiority in morphology, phase, and defect engineering of Cu 7.2 S 4 nanotubes to accommodate reversible Mg2+ storage for high-performance rechargeable magnesium batteries. [ABSTRACT FROM AUTHOR]

Abstract: Ultrasound (US) is used widely in the context of breast cancer. While it is advantageous for a number of reasons, it has low specificity and requires the use of a contrast agent. Its use as a standalone diagnostic and real-time imaging modality could be achieved by development of a tumor-targeted ultrasound contrast agent (UCA); functionalizing the UCA with a tumor-targeting agent would also allow the targeted administration of anti-cancer drugs at the tumor site. In this article, clinical US techniques are used to show that mesoporous silica nanoparticles (MSNs), functionalized with the monoclonal antibody Herceptin®, can be used as an effective UCA by increasing US image contrast. Furthermore, in vitro assays show the successful localization and binding of the MSN-Herceptin conjugate to HER2+ cancer cells, resulting in tumor-specific cytotoxicity. These results demonstrate the potential of MSNs as a stable, biocompatible, and effective therapeutic and diagnostic (“theranostic”) agent for US-based breast cancer imaging, diagnosis, and treatment. [Copyright &y& Elsevier]

Abstract: Bendamustine, a hybrid molecule of purine analog and alkylator, induces cell death by activation of apoptosis, DNA damage response, and mitotic catastrophe. Entinostat, a selective class I inhibitor of histone deacetylase (HDAC), exerts anti-tumor activity in various cancer types, including multiple myeloma (MM). We sought to determine the combinatorial effects of bendamustine and entinostat on MM cells. Cell growth assays showed that bendamustine or entinostat inhibited proliferation in a dose-dependent manner, and their combinations synergistically induced growth inhibition in all MM cells tested. An apoptotic-ELISA and western blot assays on PARP cleavage and caspase-8 and caspase-3 revealed that bendamustine in combination with entinostat exhibited a much more potent activity than either agent alone to promote the MM cells undergoing apoptosis in a dose-dependent manner. Flow cytometric analysis found that entinostat exhibited distinct effects on cell cycle progression in different lines and bendamustine mainly arrested the cells at S phase, whereas their combinations dramatically blocked the S cells entering G2/M phase. Furthermore, studies on DNA damage response indicated that phospho-histone H2A.X (P-H2A.X), a hall marker of DNA double strand break, along with phosphorylated CHK2 (P-CHK2) was significantly enhanced by the combinations of bendamustine and entinostat as compared to either agent alone. These molecular changes were correlated with the increases in mitotic catastrophe. Collectively, our data demonstrate that bendamustine in combination with entinostat exhibit potent anti-proliferative/anti-survival activity in MM cells via induction of apoptosis and DNA damage response. Regimens consisting of bendamustine and/or entinostat may represent novel therapeutic strategies against MM. [Copyright &y& Elsevier]

A highly sensitive and specific direct competitive enzyme-linked immunosorbent assay has been developed for the detection of dipropyl phthalate (DPrP) based on antibody-coating format. The specific polyclonal antibodies against DPrP raised in rabbits. The conjugates of the antigen with horseradish peroxidase (HRP) were used as the detectable probe. Under the optimal conditions, the limit of detection of the method was 0.01 ng/mL, and a good quantitative working range of 0.01–16 ng/mL (R2=0.995) was obtained. The cross-reactivities of four structurally related phthalate esters were below 12% and did not interfere significantly the analysis of DPrP. The accuracy of the immunoassay has been evaluated and validated by analyzing real and spiked leachate from plastic food contact materials. The recoveries of DPrP ranged from 85.9% to 109.4%. This developed dc-ELISA was reliable, accurate and highly sensitive. [ABSTRACT FROM PUBLISHER]