Dental caries is a disease that results from microbiome dysbiosis with the involvement of multiple cariogenic species, including mutans streptococci (MS), lactobacilli, Scardovia wiggsiae, and ...several Actinomyces species that have the cariogenic traits of acid production and acid tolerance. Sugar consumption also plays an important role interacting with microbiome dysbiosis, determining the fate of caries development. In addition, the MS transmission that encompasses multiple sources can have long-term impacts on the oral microbiome and caries development in children. Intervention in MS transmission in early childhood may promote effective long-term caries prevention. Anticaries regimens aimed against the above mechanisms will be important for successful caries management. Xylitol and erythritol may serve as good components of anticaries regimens as oral microbiome modifiers, sugar substitutes, and agents to prevent MS transmission in early childhood with both oral and systemic benefits. Further studies are needed to elucidate the mechanism of the anticaries effects of xylitol and erythritol with consideration of their impacts on the microbiome and bacterial virulence, in addition to cariogenic bacteria levels as well as their benefits for overall health. On the other hand, the anticaries agent C16G2, specifically targeting Streptococcus mutans, the most common cariogenic bacterial species, has shown good safety for short-term oral topical use and promising effects in reducing S. mutans in vitro and in vivo with the promotion of oral commensal bacteria. Future study on its anticaries effect will need to include its long-term impact on the oral microbiome and effects on other important cariogenic bacteria.
Radium-223 dichloride (radium-223), a first-in-class α-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer ...(CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P).
Analyses were conducted to determine treatment effects of radium-223 plus standard of care (SOC) versus placebo plus SOC on QOL using FACT-P and EQ-5D. Outcomes assessed were percentage of patients experiencing improvement, percentage of patients experiencing worsening, and mean QOL scores during the study.
Analyses were carried out on the intent-to-treat population of patients randomized to receive radium-223 (n = 614) or placebo (n = 307). The mean baseline EQ-5D utility and FACT-P total scores were similar between treatment groups. A significantly higher percentage of patients receiving radium-223 experienced meaningful improvement in EQ-5D utility score on treatment versus placebo {29.2% versus 18.5%, respectively; P = 0.004; odds ratio (OR) = 1.82 95% confidence interval (CI) 1.21–2.74}. Findings were similar for FACT-P total score 24.6% versus 16.1%, respectively; P = 0.020; OR = 1.70 (95% CI 1.08–2.65). A lower percentage of patients receiving radium-223 experienced meaningful worsening versus placebo measured by EQ-5D utility score and FACT-P total score. Prior docetaxel use and current bisphosphonate use did not affect these findings. Treatment was a significant predictor of EQ-5D utility score, with radium-223 associated with higher scores versus placebo (0.56 versus 0.50, respectively; P = 0.002). Findings were similar for FACT-P total score (99.08 versus 95.22, respectively; P = 0.004).
QOL data from ALSYMPCA demonstrated that improved survival with radium-223 is accompanied by significant QOL benefits, including a higher percentage of patients with meaningful QOL improvement and a slower decline in QOL over time in patients with CRPC.
In this study, low-carbon martensite steel was obtained by rapid quenching and was then subjected to cold rolling and electroplastic rolling with different deformation amounts. The mechanical ...properties and microstructures of the steel after rolling deformation were compared and analyzed. The results showed that with the increase in the deformation amount, the material strength and hardness of the steel subjected to cold rolling and electroplastic rolling increased, while the elongation decreased. Under the same rolling thickness-reduction amount, the strength (hardness) of the electroplastic-rolled material was slightly lower than that of the cold-rolled specimen, and the elongation was significantly improved. Owing to the various angles between the lath direction and rolling direction, the deformed laths featured different characteristics. Regarding the lath morphology, there were no significant differences between the electroplastic rolling deformation and cold rolling deformation. During the plastic deformation process, the texture exhibited significant rotation; the texture transformed to a relatively more stable {112} , and the steel showed strong ɑ texture and weak γ texture. The {111} texture was the strongest in the γ direction; it is stronger than the {111} texture. The {111} plane of the electroplastic-rolled specimen was significantly higher than that of the cold-rolled specimen. The positive relationship between texture and plasticity was obtained.
Salmonella, a major foodborne pathogen, causes severe gastrointestinal disease in people and animals worldwide. Plasmid-borne mcr-1, which confers colistin resistance in Salmonella, has significant ...epidemiological interest for public health safety. Here, we report the first evidence of mcr-1-mediated colistin resistance in one multidrug-resistant strain, 16062, from 355 Salmonella isolates collected for Jiaxing foodborne pathogen monitoring in Zhejiang Province from 2015 to 2019. In addition to colistin, 16062 displayed multidrug resistance to various antimicrobials (β-lactams, quinolone, sulfonamide, florfenicol, ampicillin, streptomycin, nalidixic acid, aminoglycoside, and trimethoprim-sulfamethoxazole). The mcr-1-carrying IncX4 plasmid (p16062-MCR) in this study shares a conserved structure with other mcr-IncX4 plasmids. We found that other antimicrobial-resistance genes (aac(6')-Ib-cr, aadA1, aadA2, aph(3')-Ia, oqxA, oqxB, sul1, and cmlA1) are located on p16062-cmlA, an atypical IncHI2 plasmid, in isolate 16062. This is the first identification of transferable colistin resistance in a foodborne Salmonella isolate collected in Jiaxing City, the 5-year monitoring of which revealed limited dissemination. By determining the genetic features of the plasmid vehicle, the characteristics of transferable mcr genes circulating in isolates from Jiaxing are now clearer.
The fly ash treated by H
2SO
4 was used as a low-cost adsorbent for the removal of a typical dye, methylene blue, from aqueous solution. An increase in the specific surface area and dye-adsorption ...capacity was observed after the acid treatment. The adsorption isotherm and kinetics of the treated fly ash were studied. The experimental results were fitted using Langmuir and Freundlich isotherms. It shows that the Freundlich isotherm is better in describing the adsorption process. Two kinetic models, pseudo-first order and pseudo-second order, were employed to analyze the kinetic data. It was found that the pseudo-second-order model is the better choice to describe the adsorption behavior. The thermodynamic study reveals that the enthalpy (Δ
H
0) value is positive (5.63
kJ/mol), suggesting an endothermic nature of the adsorption.
Smad and STAT proteins are critical signal transducers and transcription factors in controlling cell growth and tumorigenesis. Here we report that the STAT3 signaling pathway attenuates transforming ...growth factor-β (TGF-β)-induced responses through a direct Smad3–STAT3 interplay. Activated STAT3 blunts TGF-β-mediated signaling. Depletion of STAT3 promotes TGF-β-mediated transcriptional and physiological responses, including cell cycle arrest, apoptosis and epithelial-to-mesenchymal transition. STAT3 directly interacts with Smad3 in vivo and in vitro, resulting in attenuation of the Smad3–Smad4 complex formation and suppression of DNA-binding ability of Smad3. The N-terminal region of DNA-binding domain of STAT3 is responsible for the STAT3–Smad3 interaction and also indispensable for STAT3-mediated inhibition of TGF-β signaling. Thus, our finding illustrates a direct crosstalk between the STAT3 and Smad3 signaling pathways that may contribute to tumor development and inflammation.
•A formula of steel slag and bentonite mixtures (SBM) to construct a hydraulic barrier.•The saturated hydraulic conductivity (ks) and microstructure of SBM was studied.•A better steel slag gradation ...reduces ks significantly due to less macropores.•Compact SBM at water content 1–2% wetter than the optimum value reduces ks a lot.•Water washing treatment of steel slag reduces ks of SBM by one order of magnitude.
The feasibility of using steel slag and bentonite mixtures to construct the hydraulic barrier of a landfill cover was explored in the present study. Fine-grained steel slag (SS; particle diameter < 1 mm) and sodium-activated calcium bentonite (SACB) were used to prepare compacted specimens, and the saturated hydraulic conductivity (ks) was measured using a flexible-wall permeameter. Influential factors including SACB content (BC), SS gradation, water-washing treatment of SS and compaction water content (ωcomp) were investigated. The hydraulic conductivity results were interpreted in microscopic scale through mercury intrusion porosimetry (MIP) and scanning electron microscope (SEM). It was found that when BC was below 10%, the ks value of the specimens prepared with well graded SS was about one order of magnitude lower than that of the specimens prepared with poorly graded SS. This was due to less macropores caused by better SS gradation. Yet, the effects of SS gradation on ks diminished as BC further increased to 15%, suggesting the dominant role of BC on ks at high BC. Water-washing treatment of SS helped reduce ks significantly to 1.2 × 10−10 m/s at BC of 10%, owing to less multivalent cations and hence lower osmotic swelling reduction caused by cations. Controlling ωcomp 1–2% wetter than the optimum water content (ωopt) also helped reduce ks significantly, owing to the reduction of macropores. Accordingly, it is suggested to use well-graded SS mixed with 10% SACB and then compact at ωcomp slightly wetter than ωopt to the degree of compaction greater than 90% in engineering practice.
The apolipoprotein E (APOE) ε4 allele is the best characterized genetic risk factor for Alzheimer's disease to date. Older APOE ε4 carriers (aged 60 + years) are known to have disrupted structural ...and functional connectivity, but less is known about APOE-associated network integrity in middle age. The goal of this study was to characterize APOE-related differences in network topology in middle age, as disentangling the early effects of healthy versus pathological aging may aid early detection of Alzheimer's disease and inform treatments. We performed resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) in healthy, cognitively normal, middle-aged adults (age 40–60; N = 76, 38 APOE ε4 carriers). Graph theoretical analysis was used to calculate local and global efficiency of 1) a whole brain rs-fMRI network; 2) a whole brain DTI network; and 3) the resting state structural connectome (rsSC), an integrated functional-structural network derived using functional-by-structural hierarchical (FSH) mapping. Our results indicated no APOE ε4-associated differences in network topology of the rs-fMRI or DTI networks alone. However, ε4 carriers had significantly lower global and local efficiency of the integrated rsSC compared to non-carriers. Furthermore, ε4 carriers were less resilient to targeted node failure of the rsSC, which mimics the neuropathological process of Alzheimer's disease. Collectively, these findings suggest that integrating multiple neuroimaging modalities and employing graph theoretical analysis may reveal network-level vulnerabilities that may serve as biomarkers of age-related cognitive decline in middle age, decades before the onset of overt cognitive impairment.
The expansion of a municipal solid waste (MSW) landfill requires the ability to predict settlement behavior of the existing landfill. The practice of using a single compressibility value when ...performing a settlement analysis may lead to inaccurate predictions. This paper gives consideration to changes in the mechanical compressibility of MSW as a function of the fill age of MSW as well as the embedding depth of MSW. Borehole samples representative of various fill ages were obtained from five boreholes drilled to the bottom of the Qizhishan landfill in Suzhou, China. Thirty-one borehole samples were used to perform confined compression tests. Waste composition and volume-mass properties (i.e., unit weight, void ratio, and water content) were measured on all the samples. The test results showed that the compressible components of the MSW (i.e., organics, plastics, paper, wood and textiles) decreased with an increase in the fill age. The
in situ void ratio of the MSW was shown to decrease with depth into the landfill. The compression index,
C
c, was observed to decrease from 1.0 to 0.3 with depth into the landfill. Settlement analyses were performed on the existing landfill, demonstrating that the variation of MSW compressibility with fill age or depth should be taken into account in the settlement prediction.
AbstractThis study developed a new method to simultaneously measure gas dispersion coefficient and gas coefficient of permeability (GCP) of an unsaturated soils with due theoretical consideration of ...steady-state gas transport mechanisms. Correspondingly, a soil column apparatus was developed. Based on the proposed method, gas mixture containing air (with a volumetric concentration >90%) and tracer gas were applied to the column base. The gas dispersion coefficient was estimated based on a measured steady-state tracer gas concentration gradient and a dispersive flux of the tracer gas, the latter of which was determined based on mass conservation of the tracer gas. On the other hand, the GCP was determined based on the total flux of gas mixture and gas pressure gradient following Darcy’s law. The new method has the following advantages over existing methods: (1) has an ability to determine gas dispersion coefficient and GCP at any soil depth rather than an average value of a test region; (2) measures the two transport properties at varying soil moisture conditions rather than being limited by uniform moisture distribution; and (3) requires only a simple hand-calculation method to estimate the gas dispersion coefficient without the need to apply nonlinear regression on a gas breakthrough curve. The proposed method to determine GCP and gas dispersion coefficient of a silty sand was verified by independent element tests.
PDF
