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The main pollution sources of heavy metals are the arbitrary discharge of industrial wastewater and waste residues, which cause serious harm to the water environment, soil environment, and human health. In this study, following the principle of waste utilization, a gel adsorbent (AA-SW-AMPS) was prepared by microwave-assisted chemical cross-linking using fir sawdust as raw material. A scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and swelling dynamic experiments were used to investigate the microstructure, reaction mechanism, and water absorption performance of AA-SW-AMPS. The N

Doublecortin-like kinase 2 (DCLK2) is a microtubule-associated protein kinase that participates in neural development and maturation; however, whether it is involved in tumour progression remains unclear.DCLK2 overexpression and knockdown clones were established by lentivirus transfection. Western blot, PCR assays and bioinformatics analyses were conducted to observe the expression of DCLK2. CCK8, colony formation, scratch migration and Transwell assays were used to detect cell proliferation, migration and invasion, respectively. Tumour metastasis was evaluated in vivo using a tail vein metastasis model. Bioinformatics analyses were performed to analyse the expression correlation between DCLK2 and TCF4, or EMT markers in breast cancer.Our data indicate that DCLK2 is highly expressed in breast cancer cells and is associated with poor prognosis. Silencing DCLK2 does not affect the proliferation rate of tumour cells, but significantly suppresses migration and invasion as well as lung metastasis processes. Overexpression of DCLK2 can enhance the migratory and invasive abilities of normal breast epithelial cells. Moreover, TCF4/β-catenin inhibitor LF3 downregulates the expression of DCLK2 and inhibits the migration and invasion of breast cancer cells. Furthermore, we found that the downregulation of DCLK2 blocks the epithelial-mesenchymal transition (EMT) process.Our study indicates that DCLK2 plays an important role in EMT, cell invasion and metastasis, suggesting that DCLK2 is a potential target for the treatment of metastatic breast cancer.

To test the hypothesis that elevated plasma levels of homocysteine (Hcy) and lipoprotein (a) (LPA) contribute to diabetic retinopathy (DR) associated with dysregulated lipid profile, dyslipidaemia, and kidney function.A total of 83 patients with type 2 diabetes mellitus (T2DM) were enrolled in this prospective case-control study. Patients were categorized into those with no DR (DM), non-proliferative DR (NPDR), and proliferative DR (PDR). Age and sex-matched individuals with no diabetes were included in the control group. Biochemical tests, including fasting blood glucose (FBG), glycated hemoglobin (HbA1c), Hcy, LPA, lipid profile, and urine microalbumin (UMA), were evaluated.Hcy was negatively correlated with high-density lipoprotein-cholesterol (HDL-C) (p 0.05), but positively correlated with [total cholesterol (TC)-HDL-C)/HDL-C] (p 0.05), low-density lipoprotein cholesterol (LDL-C)/HDL-C (p 0.05), and UMA (p 0.05). Traditional risk factors, Hcy, arteriosclerosis-associated plasma indices, and UMA, resulted as the independent risk factors for the occurrence of DM and DR. After controlling for age, sex, duration of DM, and FBG, a multiple ordinal logistic regression model showed that LPA [OR = 2.90, 95% confidence interval (95% CI) 1.16-7.23, p = 0.023)], LDL-C (OR = 4.28, 95% CI 1.24-14.79, p = 0.021), and (TC-HDL-C)/HDL-C (OR = 1.92, 95% CI 1.05-3.53, p = 0.035) were risk factors for DM and DR.Hcy and LPA contributed to DM and DR. Hcy was positively correlated with kidney dysfunction and the ratios of lipid profiles, and negatively with HDL-C, LPA, LDL-C, and (TC-HDL-C)/HDL-C resulted as predictors of the occurrence of DM and severity of DR.

Silicon (Si) is a widely recognized beneficial element in plants. The application of Si fertilizers has become a rather common agronomic practice for sustainable agricultural production. However, due to the vast diversity of Si fertilizers, no official method is currently available for estimating the availability of Si in different Si fertilizers to direct their field application. In this study, we evaluated the bio-available Si concentration in eight Si fertilizers differing in Si form and pH by using different extraction methods including HCl, NaOH, Amberlite resin, 3-morpholinopropane-1-sulfonic acid (MOPS), ammonium acetate, and citric acid. To test the effectiveness of these methods, we investigated the relationships between bio-available Si and plant growth and Si accumulation by conducting a pot experiment with rice. The results indicate that the Si fertilizers applied increased shoot biomass and grain weight, but no single extraction method could be used to assess the bioavailability of Si in all the Si fertilizers tested. Accordingly, based on Si sources and pH, we classified the tested fertilizers into three categories, i.e. alkaline, acid and amorphous Si fertilizers, to find out their suitable extractant. The correlation analyses clearly show that 1) 0.025 M ammonium acetate could accurately predict Si availability and shoot biomass for alkaline Si fertilizers (Slag and Fulibang), 2) the amount of Si extracted by 0.2 M NaOH from amorphous Si fertilizers (Elkem A, Elkem B and Tangshan) correlated well with Si availability and shoot biomass and 3) the amount of Si extracted by 0.5 M NaOH and citric from acid fertilizers (Shanjia 1, Shanjia 2 and Shanyin) could be used to assess Si availability and shoot biomass response, respectively. Furthermore, resin extraction was the best predictor of grain yield response for alkaline Si fertilizers (Slag and Fulibang) and acid fertilizers (Shanjia 1, Shanjia 2 and Shanyin), whereas the amount of Si extracted by 0.5 M NaOH could satisfactorily estimate the response of grain yield for amorphous Si fertilizers.

Several regulatory guidances on the use of physiologically based pharmacokinetic (PBPK) analyses and physiologically based biopharmaceutics model(s) (PBBM(s)) have been issued. Workshops are routinely held, demonstrating substantial interest in applying these modeling approaches to address scientific questions in drug development. PBPK models and PBBMs have remarkably contributed to model-informed drug development (MIDD) such as anticipating clinical PK outcomes affected by extrinsic and intrinsic factors in general and specific populations. In this review, we proposed practical considerations for a "base" PBPK model construction and development, summarized current status, challenges including model validation and gaps in system models, and future perspectives in PBPK evaluation to assess a) drug metabolizing enzyme(s)- or drug transporter(s)- mediated drug-drug interactions b) dosing regimen prediction, sampling timepoint selection and dose validation in pediatric patients from newborns to adolescents, c) drug exposure in patients with renal and/or and hepatic organ impairment, d) maternal-fetal drug disposition during pregnancy, and e) pH-mediated drug-drug interactions in patients treated with proton pump inhibitors/acid-reducing agents (PPIs/ARAs) intended for gastric protection. Since PBPK can simulate outcomes in clinical studies with enrollment challenges or ethical issues, the impact of PBPK models on waivers and how to strengthen study waiver is discussed.

In this study, hydrochars and biochars were prepared from rice husk (RH) and Zizania latifolia straw (ZL) at various pyrolysis temperatures as absorbents, for removing toxic ions from single and competitive solutions of cadmium (Cd) and/or lead (Pb). The adsorption efficiencies of Cd and Pb in both hydrochars and biochars were lower in the competitive solution than in the single solution, and the absorbents had a stronger affinity for Pb than for Cd. Compared to hydrochars, biochars showed more favorable Cd and Pb adsorption capacities in the single or competitive solutions, and the ZL biochars had the maximum adsorption capacity among them. The SEM and FTIR analyses suggest that the predominant adsorption mechanisms of biochars and hydrochars are surfaces monolayer adsorption, precipitation, complexation, and coordination with π electrons. However, hydrochars derived from ZL exhibited an optimal additional Pb adsorption capacity in the high-level (5 ~ 10 mg L

Background Mixed payment schemes have become one of the effective measures to balance medical costs and quality of medical services. However, altruism as an intrinsic motivation may influence the effect of switching from a pure payment system to mixed payment schemes. This study aimed to quantify physicians’ altruism and analyze the effect of changes of payment system on physicians’ altruism and thus proposed references for the reform of payment system. Methods We simulated an exogenous payment system in a controlled laboratory with five experimental groups and 150 medical student subjects. Physicians’ altruism was measured by estimating altruistic parameter and marginal rate of substitution. The non-parametric test and the least square regression analysis were used to analyze the differences of altruistic parameters between pure payment systems and mixed payment schemes. Finally, we analyzed the effect of changes in payment system accompanied by changes in trade-off range on physicians’ altruism. Results We find that the mean value of individual altruistic parameter is 0.78 and the marginal rate of substitution is 1.078. Their estimates at the individual level were significantly positively correlated (Spearman’s ρ = 0.715, p Conclusion The estimates of altruistic parameters are reliable. Physicians attach a higher weight to patients’ benefit than to their own profit. Mixed payment schemes improve physicians’ behavior and relate to lower altruistic parameters; physicians only need to sacrifice less personal profits to generate the same or even higher altruistic parameter as under the pure payment system. The design of mixed payment schemes that make the interests of physicians and patients close to each other by reducing the trade-off range can provide implication for the reform of payment system in which the physicians’ interest and the patients’ benefit are consistent.

The prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) in patients with hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aims to evaluate the prognostic role of AAPR in patients with HCC. The databases of Web of Science, Embase, Cochrane Library and PubMed were comprehensively searched from inception to April 25, 2022. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated with Stata 16.0 software for the assessment of the relationship between AAPR and overall survival (OS) as well as recurrence-free survival (RFS) in patients with HCC. A total of 2634 patients from 12 cohorts were included in this meta-analysis. The pooled results showed that lower AAPR predicted poorer OS (HR 2.02, 95% CI 1.78–2.30). Similarly, pooled results demonstrated that lower AAPR also predicted poorer RFS (HR 1.88, 95% CI 1.37–2.57). The heterogeneity for RFS by multivariate analytic results and the publication bias for OS existed, however, the subgroup analysis, meta-regression analysis as well as adjustment using trim-and-fill analysis confirmed an association between AAPR and OS as well as RFS. This meta-analysis proves that lower AAPR in patients with HCC predicted inferior survival outcomes, and AAPR might be a promising indicator for the prognosis of HCC.

Circular polarized light-dependent anomalous bulk photovoltaic effect - a steady anomalous photovoltaic current can be manipulated by changing the light helicity, is an increasingly interesting topic in contexts ranging from physics to chemistry. Herein, circular polarized light-dependent anomalous bulk photovoltaic effect is presented in achiral hybrid perovskites, (4-AMP)BiI5 (ABI, 4-AMP is 4-(aminomethyl)piperidinium), breaking conventional realization that it can only happen in chiral species. Achiral hybrid perovskite ABI crystallizes in chiroptical-active asymmetric point group m (Cs), showing an anomalous bulk photovoltaic effect with giant photovoltage of 25 V, as well as strong circular polarized light - sensitive properties. Significantly, conspicuous circular polarized light-dependent anomalous bulk photovoltaic effect is reflected in the large degree of dependence of anomalous bulk photovoltaic effect on left-and right-CPL helicity, which is associated with left and right-handed screw optical axes of ABI. Such degree of dependence is demonstrated by a large asymmetry factor of 0.24, which almost falls around the highest value of hybrid perovskites. These unprecedented results may provide a perspective to develop opto-spintronic functionalities in hybrid perovskites.

To explore the prognostic value of the systemic inflammation response index (SIRI) defined as neutrophil count × monocyte count/lymphocyte count in the patients with early stage hepatocellular carcinoma (HCC) within the Milan criteria after radiofrequency ablation (RFA). The prognostic value of SIRI was evaluated in a primary cohort (n = 403) and then further validated in an independent test cohort (n = 140). A novel preoperative prognostic nomogram was constructed from a multivariate analysis and validated in an external validation cohort. The optimal cutoff value of SIRI for patient stratification into a low SIRI group and a high SIRI group was 1.36. Survival analysis showed that the median overall survival (OS) and recurrence-free survival (RFS) were significantly higher in patients with a low SIRI compared to those with a high SIRI. The alpha-fetoprotein (AFP), SIRI, tumor number and size were independent predictors of RFS based on multivariate analysis. The nomogram including the SIRI, tumor number, tumor size, AFP could more accurately determine the prognosis of HCC patients than BCLC stage (0.74 vs. 0.62, P 75% had a better prognosis. Preoperative SIRI was an independent predictor for RFS in patients with early stage HCC within the Milan criteria. The comprehensive nomogram can objectively and reliably help clinicians identify high-risk patients and develop individualized treatment plans.

An ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) was blended with spiro-(1,10)-bipyrrolidinium tetrafluoroborate (SBPBF4) salt and propylene carbonate (PC) to obtain a liquid mixture electrolyte system. The thermodynamic properties of the mixture electrolyte with different molar compositions such as viscosity, density, and electrical conductivity were determined at different temperatures. Infrared spectroscopy and density functional theory (DFT) are used to calculate and describe the microscopic interactions in the mixture electrolyte system. Then, the IL-based mixture electrolyte was applied in supercapacitor with active carbon electrodes. The supercapacitor performances of the mixture electrolyte including the electrochemical window, the specific capacitance, and the energy density were tested and reckoned by cyclic voltammetry (CV), electrochemical impedance spectrum (EIS), and galvanostatic charge–discharge (GCD) methods, respectively. The interaction analysis and the electrochemical test results indicate that the appropriate addition of IL is a simple and effective way to improve the electrochemical performance of the electrolyte in supercapacitors.

Background Healthcare reforms in many countries have shown a movement from pure payment systems to mixed payment systems. However, there remains an insufficient understanding of how to design better mixed payment systems and how such systems, especially Diagnosis-Related-Group (DRG)-based systems, benefit patients. We therefore designed a controlled laboratory experiment to investigate the effects of fee-for-service (FFS), DRG, and mixed payment systems on physicians’ service provision. Methods A total of 210 medical students were recruited from Capital Medical University as subjects. They, in the role of physicians, were randomly divided into seven groups and chose the quantity of medical services for different patient types under pure FFS, pure DRG, or mixed payment schemes that included two FFS-based mixed payment schemes and three DRG-based mixed payment schemes. There were five rounds of each group of experiments, and each subject made 18 decisions per round. The quantity of medical services provided by subjects were collected. And relevant statistics were computed and analyzed by nonparametric tests and random effects model. Results The results showed that the physicians’ overprovision (underprovision) of services under FFS (DRG) schemes decreased under mixed payment schemes, resulting in higher benefit to patients under mixed payment schemes. Patients’ health conditions also affected physicians’ behavior but in different directions. Higher disease severity was associated with higher deviation of physicians’ quantity choices from the optimal quantity under DRG and DRG-based mixed payment schemes, while the opposite was found for FFS and FFS-based mixed payment schemes. Conclusions Mixed payment systems are a better way to balance physicians’ profit and patients’ benefit. The design of mixed payment systems should be adjusted according to the patient’s health conditions. When patients are in lower disease severity and resource consumption is relatively small, prospective payments or mixed systems based on prospective payments are more suitable. While for patients in higher disease severity, retrospective payments or mixed systems based predominantly on retrospective payments are better.

Clinical and epidemiological studies have shown that circulatory system diseases and nervous system disorders often co-occur in patients. However, genetic susceptibility factors shared between these disease categories remain largely unknown. Here, we characterized pleiotropy across 107 circulatory system and 40 nervous system traits using an ensemble of methods in the eMERGE Network and UK Biobank. Using a formal test of pleiotropy, five genomic loci demonstrated statistically significant evidence of pleiotropy. We observed region-specific patterns of direction of genetic effects for the two disease categories, suggesting potential antagonistic and synergistic pleiotropy. Our findings provide insights into the relationship between circulatory system diseases and nervous system disorders which can provide context for future prevention and treatment strategies.

Evaluating the biomechanics of soft tissues at depths well below their surface, and at high precision and in real time, would open up diagnostic opportunities. Here, we report the development and application of miniaturized electromagnetic devices, each integrating a vibratory actuator and a soft strain-sensing sheet, for dynamically measuring the Young’s modulus of skin and of other soft tissues at depths of approximately 1–8 mm, depending on the particular design of the sensor. We experimentally and computationally established the operational principles of the devices and evaluated their performance with a range of synthetic and biological materials and with human skin in healthy volunteers. Arrays of devices can be used to spatially map elastic moduli and to profile the modulus depth-wise. As an example of practical medical utility, we show that the devices can be used to accurately locate lesions associated with psoriasis. Compact electronic devices for the rapid and precise mechanical characterization of living tissues could be used to monitor and diagnose a range of health disorders. Electromagnetic devices involving a vibratory actuator and a soft strain-sensing sheet can dynamically measure the Young’s modulus of skin and of other soft biological tissues at depths of millimetres.

To investigate the prognostic value of pre-procedure neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and construct a nomogram to predict disease-free survival (DFS) in patients receiving radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within Milan criteria. The data of 515 patients of HCC within Milan criteria receiving RFA were retrospectively collected. The patients were divided into two groups: the training group (n = 382) and the validation group (n = 133). Several preprocedural variables were analyzed in the two groups to determine the prognostic factors. The median DFS time of the training and validation group was 28.4 months and 24.5 months, respectively. Multivariate analyses showed that number of lesions, alpha-feto protein levels, NLR and PLR were independent risk factors of DFS. According to the time-dependent receiver operating characteristic curve (t-ROC), the optimal cutoff value of the NLR and PLR was 1.55 and 75.30, respectively, with sensitivity of 0.737 and 0.648 and specificity of 0.541 and 0.508, respectively. The area under curve (AUC) of the t-ROC curves for the NLR was 0.662 and PLR was 0.597. The DFS was significantly higher in the NLR ≤ 1.55 group compared to NLR > 1.55 group and the PLR ≤ 75.30 group compared to PLR > 75.30 group in both training and validation datasets. Nomogram was developed based on the prognostic factors indicated by the Cox regression to predict 1-, 2-, 3- and 5-year DFS probabilities. The cutoff value of the NLR and PLR was 1.55 and 75.30. This new nomogram based on NLR and PLR may provide good and individualized prediction of recurrence for HCC patients within Milan criteria after RFA.

Based on low cost and earth abundance potassium resources, potassium-ion batteries have been regarded as the potential candidate for large-scale energy storage applications for renewable energy and smart grid. Although some earlier works have proposed reversible insertion/extraction of K+ ions in K cells, their cycle instability is insufficient for the further application of potassium-ion batteries. Herein, we report a symmetric potassium-ion battery with ultralong life employing a bipolar Cr/Ti based layered oxide, which contains two electrochemically active transition metals with the redox couples of Cr4+/Cr3+ and Ti4+/Ti3+ working on the cathode and anode side, respectively. Moreover, the (de)intercalation process in the structure and the in-situ electrochemical exchange process are investigated by ex-situ XRD. As a result, the symmetric cell based on the obtained K-based bipolar layered material exhibits a reversible capacity of 102 mA·h/g between 0.5 V and 3.5 V at 20 mA/g, an ultralong cycle life of 2000 cycles with a capacity retention of 80% and high rate capabilities. The outstanding cycling stability and rate performance endow this work with promising advantages for the future development of the novel energy storage system.

The objective of this study was to evaluate how erbium-doped yttrium aluminium garnet (Er:YAG) laser debonding treatment affects the optical and mechanical properties of dental ceramics. In total, 120 rectangular (22*5*1.2 mm) IPS E.max Press specimens were fabricated and divided into 4 groups: the control group, 3 W laser group, 4 W laser group, and 5 W laser group. For each group, 10 specimens were used for the colour test (colour difference (△E) and transparency parameter (TP)), 10 specimens were used for the flexural strength test, and 10 were used for the Vickers hardness test. One random sample from each colour test specimens was observed by scanning electron microscopy (SEM). The L*, a*, b*, △E, TP, flexural strength, and Vickers hardness values were measured and calculated. According to the Kruskal-Wallis test, the L*, a*, and b* values showed no significant variations (P > 0.05), except for the b* value in the 5 W laser group (P 0.05). Microcracks were detected during the SEM analysis of the 5 W laser group. Er:YAG laser debonding treatment did not affect the mechanical properties, but changed the optical properties of dental ceramics.

An intrauterine system (IUS) can be implanted in the uterus and deliver drug directly at the site of pharmacological action. Mirena was the first FDA-approved levonorgestrel (LNG) releasing IUS without an approved generic form. Its 5-year application duration presents challenges for bioequivalence (BE) assessment using the conventional in vivo studies with pharmacokinetic and/or comparative clinical endpoints. Conventionally, along with other conditions, BE could be established if the 90% confidence interval (CI) of the ratio of geometric means of residual LNG at the end of 5 years is within the BE limits of 80.00% and 125.00%. Modeling and simulation were conducted to identify a shortened BE study duration and its corresponding BE acceptance limit that can be used as a surrogate for the conventional limit for a 5-year study. Simulation results suggest that having the 90% CI of the residual LNG 12 months post insertion within 95.00-105.26% would ensure that residual LNG amount at 5 years to be within 80.00-125.00%. This modeling and simulation practice leads to the current BE recommendation: if a test IUS is made of the same material in the same concentration and has the same physical dimensions as the Mirena, its BE could be established by showing (1) comparative physicochemical and mechanical properties; (2) comparative in vitro drug release behavior for 5 years; and (3) performance in a comparative short-term in vivo study and BE based on 90% confidence interval of test and reference ratio of residual LNG to be within 95.00-105.26% at month 12.

Potassium-ion batteries (KIBs) are promising candidates for large-scale energy storage due to the abundance of potassium and its chemical similarity to lithium. Nevertheless, the performances of KIBs are still unsatisfactory for practical applications, mainly hindered by the lack of suitable cathode materials. Herein, combining the strong inductive effect of sulphate and the feasible preparation of Fe2+-containing compounds in oxalate system, a compound with novel architecture, K4Fe3(C2O4)3(SO4)2, has been identified as a low-cost and environmentally friendly cathode for stable potassium-ion storage. Its unique crystal structure possesses an unprecedented two-dimensional framework of triple layers, with 3.379 A interlayer distance and large intralayer rings in the size of 4.576×6.846 A. According to first-principles simulations, such a configuration is favorable for reversible K-ion migration with a very low volume change of 6.4%. Synchrotron X-ray absorption spectra and X-ray diffraction characterizations at different charging/discharging states and electrochemical performances based on its half and full cells further verify its excellent reversibility and structural stability. Although its performance needs to be improved via further composition tuning with multi-valent transition metals, doping, structural optimization, etc., this study clearly presents a stable structural model for K-ion cathodes with merits of low cost and environmental friendliness.

According to Lagrange’s equation, the governing equation for a base isolated structural system was presented, with a variable friction coefficient RFPS (the rolling friction pendulum system) bearing on arbitrary curves. Its solution was presented with software prepared from MATLAB language. Results show that the variable friction coefficient RFPS might result in complication of structural dynamic responses. It is noticed that seismic mitigation efficiency for the variable friction coefficient is close to that for the high friction coefficient, but with notable disadvantages to the lower friction coefficient. As RFPS slipper transits from the low- to the high-friction area, the structural system could exhibit noticeable whipping effect, which will amplify story accelerations. It is suggested that lower friction coefficient FPS bearings, instead of variable friction coefficient RFPS bearings, should be applied.

Objectives To utilize a deep learning model for automatic detection of abnormalities in chest CT images from COVID-19 patients and compare its quantitative determination performance with radiological residents. Methods A deep learning algorithm consisted of lesion detection, segmentation, and location was trained and validated in 14,435 participants with chest CT images and definite pathogen diagnosis. The algorithm was tested in a non-overlapping dataset of 96 confirmed COVID-19 patients in three hospitals across China during the outbreak. Quantitative detection performance of the model was compared with three radiological residents with two experienced radiologists’ reading reports as reference standard by assessing the accuracy, sensitivity, specificity, and F1 score. Results Of 96 patients, 88 had pneumonia lesions on CT images and 8 had no abnormities on CT images. For per-patient basis, the algorithm showed superior sensitivity of 1.00 (95% confidence interval (CI) 0.95, 1.00) and F1 score of 0.97 in detecting lesions from CT images of COVID-19 pneumonia patients. While for per-lung lobe basis, the algorithm achieved a sensitivity of 0.96 (95% CI 0.94, 0.98) and a slightly inferior F1 score of 0.86. The median volume of lesions calculated by algorithm was 40.10 cm3. An average running speed of 20.3 s ± 5.8 per case demonstrated the algorithm was much faster than the residents in assessing CT images (all p

Cavitation erosion on sedimentary rocks by addition of abrasive nanoparticles was evaluated through ultrasonic cavitation experiments. Two kinds of typical sedimentary rocks, sandstone and organic-rich shale, were eroded by pure water cavitation and nanoparticle cavitation, respectively. Aluminum alloy was employed as a blank control group for contrast. The erosion rates, microstructure changes, and surface roughness before and after treatments were obtained to understand the erosion mechanisms. The results demonstrate that abrasive nanoparticle is capable of enhancing erosion and creating volume fragmentation on sedimentary rocks. In detail, the erosion rate on rock materials reaches ten times that on aluminum alloy. Mass loss of rock materials of the early stage is much severe compared to the erosion of the later stage. Brittle failure mode always dominates the rock failure that creates the volume fragmentation behavior. Enhanced cavitation intensity and high-speed abrasive impacts are the two main mechanisms to explain the enhanced erosion phenomenon. This work supports that cavitation abrasive waterjet with nanoparticles is a potential novel drilling and fracturing technology.

Background Inconsistent associations between egg consumption and cardiovascular disease (CVD) risk have been observed in previous studies. This study aims to longitudinally investigate the association between egg consumption and altered risk of arterial stiffness, a major pre-clinical pathogenic change of CVD, which was assessed by brachial-ankle pulse wave velocity (baPWV). Methods A total of 7315 Chinese participants from the Kailuan Study, free of CVD and cancer were included in this study. Egg consumption was assessed by a semi-quantitative validated food frequency questionnaire in 2014. baPWV was repeatedly measured at baseline and during follow-up (mean follow-up: 3.41 years). General linear regression was used to calculate means of baPWV change rate across different egg consumption groups, adjusting for age, sex, baseline baPWV, healthy eating index, total energy, social-economic status, blood pressure, obesity, smoking, lipid profiles, and fasting glucose concentrations. Results Compared to the annual baPWV change rate in participants with 0–1.9 eggs/wk. (adjusted mean: 35.9 ± 11.2 cm/s/y), those consuming 3–3.9 eggs/wk. (adjusted mean: 0.2 ± 11.4 cm/s/y) had the lowest increase in baPWV during follow-up (P-difference = 0.002). Individuals with low (0–1.9 eggs/wk) vs. high (5+ eggs /wk) egg intake showed similar changes in baPWV. Conclusions In this large-scale longitudinal analysis, we did not find a significant difference in arterial stiffness, as assessed by baPWV level, between low and high egg consumption groups. However, moderate egg consumption (3–3.9 eggs/wk) appeared to have beneficial effects on arterial stiffness.

This study is the first multi-center non-inferiority study that aims to critically evaluate the effectiveness of HHUS/ABUS in China breast cancer detection. This was a multicenter hospital-based study. Five hospitals participated in this study. Women (30–69 years old) with defined criteria were invited for breast examination by HHUS, ABUS or/and mammography. For BI-RADS category 3, an additional magnetic resonance imaging (MRI) test was provided to distinguish the true negative results from false negative results. For women classified as BI-RADS category 4 or 5, either core aspiration biopsy or surgical biopsy was done to confirm the diagnosis. Between February 2016 and March 2017, 2844 women signed the informed consent form, and 1947 of them involved in final analysis (680 were 30 to 39 years old, 1267 were 40 to 69 years old).For all participants, ABUS sensitivity (91.81%) compared with HHUS sensitivity (94.70%) with non-inferior Z tests, P = 0.015. In the 40–69 age group, non-inferior Z tests showed that ABUS sensitivity (93.01%) was non-inferior to MG sensitivity (86.02%) with P P P P P P P P = 0.114 by superior test. The sensitivity of ABUS/HHUS is superior to that of MG. The specificity of ABUS/HHUS is non-inferior to that of MG. In China, for an experienced US radiologist, both HHUS and ABUS have better diagnostic efficacy than MG in symptomatic individuals.

To identify urodynamic factors associated with the mechanical stop test and immediate spontaneous voiding following transurethral resection of prostate (TURP). We identified 90 men who underwent TURP over a 12-month period. Forty-three (mean age 68 years) underwent urodynamic evaluation prior to TURP. Isovolumetric detrusor contractile pressure (Piso) was obtained using the mechanical stop test during the voiding phase, and used to calculate detrusor contractile reserve (Pres = Piso − Pdet@Qmax). Primary outcome was spontaneous voiding after TURP. Preoperative catheter-free spontaneous voiding was present in 63% of men (27/43) with a urodynamic (mean ± SD): Qmax 6.2 ± 2.7 mL/s, Pdet@Qmax 102 ± 47 cmH2O, Piso 124 ± 49 cmH2O, Pres 22 ± 16 cmH2O, bladder outlet obstruction index (BOOI) 90 ± 49, and bladder contractility index (BCI) 132 ± 44. The remaining 16 catheter-dependent men demonstrated a urodynamic (mean ± SD): Qmax 3.6 ± 3.3 mL/s, Pdet@Qmax 87 ± 38 cmH2O, Piso 99 ± 51 cmH2O, Pres 10 ± 18 cmH2O, BOOI 82 ± 36, and BCI 106 ± 48. Following TURP, 67% of men voided spontaneously with their first void trial, and in receiver operator analysis of urodynamic measures (Pdet@Qmax, Piso, Pres, BOOI and BCI), only Pres was significantly associated with immediate spontaneous voiding after TURP (threshold Pres ≥ 9 cmH2O, AUC = 0.681, p = 0.035). In men who underwent TURP, a Pres ≥ 9 cmH2O was associated with immediate spontaneous voiding and may be easily incorporated into the postoperative pathway.

The effects of different biotransformation temperatures (250, 550, and 850 °C) and different dose (0-1%) of biochar on the physiological characteristics of maize seedlings under the stress of atrazine were studied. The results show that atrazine significantly inhibits the growth of maize seedlings, while biochar can alleviate the toxicity of atrazine to seedlings. Compared with the low temperature of biochar, the addition of BC850, the germination rate of maize was significantly increased. The biochars prepared at higher temperatures and adding 1% dose could significantly increase the plant height, while the effect of biochar on root growth of maize seedlings was not significant. According to the data, with the increase of biochar application, the accumulation of atrazine in maize leaves and roots gradually decreased. At the maximum application rate of 1%, the content of atrazine in maize leaves decreased by 58.94%, 60.70%, and 62.75%. The content of atrazine in maize roots decreased by 52.93%, 54.57%, and 55.42%, respectively. Meanwhile, the addition of biochar could slightly increase the chlorophyll content, but the change was not significant statistically, while the content of chlorophyll b increases with the application amount. The content of malondialdehyde (MDA) in roots and leaves decreased first and the increased with the dose of biochar from 0 to 1%. Compared with the atrazine treatment, the content of MDA in leaves and roots decreased significantly, and the lipid peroxidation of maize significantly decreased. With the addition of three kinds of biochar, the soluble content of plant tissues increased gradually, BC550 biochar has the most noticeable remediation effect. Given the toxicity of atrazine in soil, the quality and yield of agricultural products, and the potential health risks to human beings, biochar can be the soil remediation product.

The flammability and droplet properties of thermoplastic polyurethane (TPU) have limited its wide application in many fields. In this article, isopropyl tris(dioctylphosphoryloxy) titanate was selected as synergism and compatilizer with oyster shell powder as flame retardant in TPU composites. And the influence of isopropyl tris(dioctylphosphoryloxy) titanate for flame-retardant TPU composites has been intensively investigated using the smoke density test, the cone calorimeter test, and the thermogravimetric analysis/infrared spectrometry, respectively. The test results show that isopropyl tris(dioctylphosphoryloxy) titanate can reduce the smoke production and heat release. And the total smoke production was reduced by 32% when the mass fraction of isopropyl tris(dioctylphosphoryloxy) titanate was 0.1%. The above results indicate that isopropyl tris(dioctylphosphoryloxy) titanate has a good application prospect in reducing the risk of TPU combustion.

In the present work, we report a simple two-step process to fabricate hierarchical porous carbon from biomass. The so-called two-step refers to hydrothermal carbonization of cypress coats followed by activation with KOH. The morphology and porous parameters of the resulting porous carbon can be controlled by adjusting KOH/carbon mass ratio during activating stage. The optimal sample (SHPC-2) has a hierarchically porous structure containing micropores and meso-/macropores, high specific surface areas (1325.9 m2 g− 1) with appropriate pore size and hydrophilous surface properties due to rich nitrogen and oxygen co-doping. The electrochemical measurements show the as-prepared SHPC-2 exhibits a high specific capacitance (345 and 330 F g− 1 at 1.0 A g− 1) and better rate capability (75.4% and 87.8% capacitance retention at 50 A g− 1) in 1 M H2SO4 and 6 M KOH, respectively. Furthermore, the assembled symmetric supercapacitor based on SHPC-2 and filled with 1 M Na2SO4 electrolyte delivers an outstanding energy storage performance (energy density of 30.5 W h kg− 1 at power density 900 W kg− 1) with good cycling stability (86.2% retention after 10000 cycles at 5 A g− 1). These results indicate that the eco-friendly carbon materials derived from biomass have a huge potential in the applications of high-performance electrode materials for supercapacitors.

In the present work, a new binary mixture system composed of the ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([Emim][CF3SO3]) and propylene carbonate (PC) was prepared. The densities, dynamic viscosities, and electrical conductivities of ([Emim][CF3SO3] + PC) were measured over the whole concentration range (mole fractions of IL from 0 to 1) for temperatures from 288.15 to 353.15 K. The excess molar volumes (VE) and viscosity deviations (Δη) of the binary systems were calculated to characterize the volume contraction and intermolecular interactions in the mixture system, and both were correlated with the Redlich–Kister polynomial equation. The Vogel–Fulcher–Tamman equation was used to describe the temperature dependences of the dynamic viscosities and the electrical conductivities of the binary system. Further, density functional theory calculations were employed to obtain the structure, energy, and COSMO charge distributions of the cation and anion of the IL and the PC molecule, and the intermolecular interactions in the binary mixture system were evaluated.

A facile one-step strategy is established to prepare nitrogen doped three-dimensional (3D) hierarchical porous carbon from buckwheat husk, in which the synchronous activation and nitrogen-doping is fulfilled via using KOH and urea. The obtained sample (BSCN-700) possesses an ultrahigh specific surface area of 2794.5 m2 g−1 with a unique carbon frame. The electrochemical measurements indicate that the resultant BSCN-700 exhibits a high specific capacitance of 326 F g−1 at current density of 1 A g−1, with good rate capability (78.4% capacitance retention at 100 A g−1) in 6 M KOH electrolyte. Furthermore, the as-prepared sample was used to assemble a symmetric supercapacitor filled with 6 M KOH electrolyte. As a result, the BSCN-700 symmetric supercapacitor displays a high energy density of 20.4 Wh kg−1 at a power density of 699 W kg−1 and good cycling stability which retains 95% of the initial capacitance at 5 A g−1 after 5000 cycles.

Background Whether mushroom consumption, which is rich in several bioactive compounds, including the crucial antioxidants ergothioneine and glutathione, is inversely associated with low all-cause and cause-specific mortality remains uncertain. This study aimed to prospectively investigate the association between mushroom consumption and all-cause and cause-specific mortality risk. Methods Longitudinal analyses of participants from the Third National Health and Nutrition Examination Survey (NHANES III) extant data (1988–1994). Mushroom intake was assessed by a single 24-h dietary recall using the US Department of Agriculture food codes for recipe foods. All-cause and cause-specific mortality were assessed in all participants linked to the National Death Index mortality data (1988–2015). We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cause-specific mortality. Results Among 15,546 participants included in the current analysis, the mean (SE) age was 44.3 (0.5) years. During a mean (SD) follow-up duration of 19.5 (7.4) years , a total of 5826 deaths were documented. Participants who reported consuming mushrooms had lower risk of all-cause mortality compared with those without mushroom intake (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.73–0.98) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors including total energy. When cause-specific mortality was examined, we did not observe any statistically significant associations with mushroom consumption. Consuming 1-serving of mushrooms per day instead of 1-serving of processed or red meats was associated with lower risk of all-cause mortality (adjusted HR = 0.65; 95% CI: 0.50–0.84). We also observed a dose-response relationship between higher mushroom consumption and lower risk of all-cause mortality (P-trend = 0.03). Conclusion Mushroom consumption was associated with a lower risk of total mortality in this nationally representative sample of US adults.

Background Studies regarding whether light to moderate alcohol consumption is associated with a lower risk of cardiovascular diseases (CVD) have generated mixed results. Further, few studies have examined the potential impact of alcohol consumption on diverse disease outcomes simultaneously. We aimed to prospectively study the dose-response association between alcohol consumption and risk of CVD, cancer, and mortality. Methods This study included 83,732 adult Chinese participants, free of CVD and cancer at baseline. Participants were categorized into 6 groups based on self-report alcohol consumption: 0, 1–25, 26–150, 151–350, 351–750, and > 750 g alcohol/wk. Incident cases of CVD, cancers, and mortality were confirmed by medical records. Hazard ratios (HRs) for the composite risk of these three outcomes, and each individual outcome, were calculated using Cox proportional hazard model. Results During a median follow-up of 10.0 years, there were 6411 incident cases of CVD, 2947 cancers and 6646 deaths. We observed a J-shaped relation between alcohol intake and risk of CVD, cancer, and mortality, with the lowest risk at 25 g/wk., which is equivalent to ~ 2 servings/wk. Compared to consuming 1–25 g/wk., the adjusted HR for composite outcomes was 1.38 (95% confidence interval (CI):1.29–1.49) for non-drinker, 1.15 (95% CI: 1.04–1.27) for 26–150 g/wk., 1.22 (95% CI: 1.10–1.34) for 151–350 g/wk., 1.33 (95% CI: 1.21–1.46) for 351–750 g/wk., and 1.57 (95% CI: 1.30–1.90) for > 750 g/wk., after adjusting for age, sex, lifestyle, social economic status, and medication use. Conclusions Light alcohol consumption at ~ 25 g/wk was associated with lower risk of CVD, cancer, and mortality than none or higher consumption in Chinese adults.

Many orally administered drugs with negative food effects (i.e., lower exposure under fed conditions) are often primarily or partially eliminated by biliary excretion. The aim of this study is to assess the potential correlation between a negative food effect and biliary excretion. Correlation analysis was conducted using a training dataset containing 27 drugs which met the following criteria: (1) immediate-release formulations, (2) shows a negative food effect, (3) > 10% biliary clearance, and (4) does not undergo extensive metabolism. A correlation between fed-state biliary clearance (CLb,fed) and fasted-state biliary clearance (CLb,fast) (y = 1.81*x, R2 = 0.68) was observed. The 1.8-fold increase in biliary clearance was then used as a correction factor to improve physiologically based pharmacokinetic (PBPK) prediction of food effects for 12 test drugs. The mean deviations of predicted fed/fasting AUC ratio and Cmax ratio from clinically observed values were reduced from 32.4 to 17.2% and from 63.3 to 54.3%, respectively. In contrast to the positive food effects on most biopharmaceutics classification system (BCS) class II drugs for which food-stimulated bile flow increases drug solubility and absorption, our results suggest that the elimination of biliary excreted drugs is increased by food-stimulated bile flow, resulting in negative food effects.

A novel ionic liquid (IL) 1-ethyl-2,3-dimethylimidazolium tetrafluoroborate ([Emmim][BF4]) with trialkyl substitution imidazolium cation was synthesized, and its binary system blended with acetonitrile (ACN) under different concentrations were prepared and investigated as possible electrolytes for supercapacitors. The physico-chemical properties such as density, viscosity, and electrical conductivity of the binary mixture system were measured from 288.15 to 333.15 K. The temperature dependences of density, viscosity, and electrical conductivity were illustrated and discussed by the Vogel-Fulcher-Tamman (VFT) equation and Arrhenius equation. It was found that the VFT equation was more suitable to [Emmim][BF4] + ACN system. Further, the important characteristics of this IL-based electrolyte for supercapacitors including the maximum operative voltage, the capacitance, the energy density, and power density were measured and calculated by cyclic voltammetry (CV), electrochemical impedance spectrum (EIS), and galvanostatic charge-discharge. The results show that the performance of the electrolyte can be improved with appropriate ratio of IL. When the concentration of the IL increased to 0.8 mol L−1, the maximum operative voltage increased to 5.9 V, and the specific capacitance achieves 142.6 F g−1. It shows the IL-based mixtures with excellent characteristics are applicable as high-voltage electrolytes for supercapacitors.

Streptococcus pneumoniae is a leading cause of infectious diseases in children under 5-year-old. Vaccine has been used as an indispensable strategy to prevent S. pneumoniae infection for more than 30 years. Our previous studies confirmed that mucosal immunization with live attenuated strain SPY1 can protect mice against nasopharyngeal colonization of S. pneumoniae and lethal pneumococcal infection, and the protective effects are comparable with those induced by commercially available 23-valent polysaccharide vaccine. However, live attenuated vaccine SPY1 needs four inoculations to get satisfactory protective effect, which may increase the risk of virulence recovery. It is reported that heterologous primeboost approach is more effective than homologous primeboost approach. In the present study, to decrease the doses of live SPY1 and improve the safety of SPY1 vaccine, we immunized mice with SPY1 and DnaJ protein alternately. Our results showed that heterologous prime-boost immunization with SPY1 and DnaJ protein could significantly reduce the colonization of S. pneumoniae in the respiratory tract of mice, and induce stronger Th1 and Th17 cellular immune responses than SPY1 alone. These results indicate heterologous prime-boost immunization method not only elicits better protective effect than SPY1 alone, but also reduces the doses of live SPY1 and decreases the risk of SPY1 vaccine. This work is the first time to study the protective efficiency with two different forms of S. pneumoniae candidate vaccine, and provides a new strategy for the development of S. pneumoniae vaccine.

Prasugrel HCl may convert to prasugrel base during manufacturing or storage. It was reported that formulations with different ratios of salt to base were bioequivalent in healthy subjects, but formulations with a higher extent of conversion were not bioequivalent in subjects taking proton pump inhibitor (PPI) whose stomach pH is elevated. The objective of this study was to assess the magnitude of impact of salt-to-base conversion on prasugrel HCl products BE evaluation in healthy subjects on PPI. A physiologically based pharmacokinetic (PBPK) absorption model was constructed to predict pharmacokinetic (PK) profiles of active metabolite after oral administration of prasugrel HCl products containing various fractions of base based on the prasugrel salt and base intrinsic solubility. The intrinsic solubility was obtained by deconvoluting the model against the observed active metabolite PK profiles with various fractions of base in healthy subjects with or without PPI. The developed PBPK absorption model accurately predicted the average active metabolite PK profiles in healthy subjects without PPI for the product containing 100% salt. A model based on assumptions of the fraction of a dose absorbed remaining unchanged for formulations containing different fractions of base over predicted the reduction of bioavailability upon conversion to the base. Therefore, this represented the conservative estimate with respect to the impact of free base in a product on BE evaluation. Virtual BE trial simulation predicted that less than 20% free base in prasugrel HCl product ensures in vivo BE of the generic product including in subjects that may be taking PPI.

This publication summarizes the proceedings of day 2 of a 3-day workshop on "Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development." Patient-centric drug product development from a drug product quality perspective necessitates the establishment of clinically relevant drug product specifications via an in vitro-in vivo link. Modeling and simulation offer a path to establish this link; in this regard, physiologically based modeling has been implemented successfully to support regulatory decision-making and drug product labeling. In this manuscript, case studies of physiologically based biopharmaceutics modeling (PBBM) applied to drug product quality are presented and summarized. These case studies exemplify a possible path to achieve an in vitro-in vivo link and encompass (a) development of biopredictive dissolution methods to support biowaivers, (b) model-informed formulation selection, (c) predicting clinical formulation performance, and (d) defining a safe space for regulatory flexibility via virtual bioequivalence (BE). Workflows for the development and verification of absorption models/PBBM and for the establishment of a safe space using dissolution as an input are described with examples. Breakout session discussions on topics, such as current challenges and some best practices in model development and verification, are included as part of the Supplementary material.

This study aimed to evaluate if macular autofluorescence (MAF) is a valuable, non-invasive follow-up parameter for cystoid macular edema. A total of 71 eyes (71 cases) with cystoid macular edema (CME) were included in the study. Macular pigment (MP) was evaluated using HRA2 (infrared) IF and FA models. The density of MP was graded into three categories: without, partial, and normal amount of MP. A comparison was made between the baseline (before the first administration) level and at the fourth month, following three consecutive intravitreal lucentis injections every month. The morphology and distribution of MAF, and the density and distribution of MP were regarded as the main outcome measures. At the baseline visit, all eyes with CME had petaloid/irregular-shaped MAF in the macular area (100%). No MAF was detected in the control eyes (0). There was significant difference in MAF between the CME and normal groups (P=0.000). At the fourth monthly visit, normal levels of MP density without MAF was detected in 68 eyes (95.8%) with the best corrected spectacular visual acuity increasing to at least 1 line accordingly. We conclude that macular MAF can be used as a follow-up parameter for patients with CME. MP and MAF can indirectly reflect the fovea cone function.

The (conditional) matching preclusion number of a graph is the minimum number of edges whose deletion leaves a resulting graph (with no isolated vertices) that has neither perfect matchings nor almost perfect matchings. In this paper, we find this number and classify all optimal sets for the augmented k -ary n-cubes with even k ⩾ 4.

In recent years, considerable progress has been made in the molecular mechanisms of epigenetics in disease development and progression, the reversible characteristics of epigenetic modification provide new insights for the treatment of such diseases. The pathogenesis of diabetic retinopathy (DR) has not yet been fully understood, treatment of refractory and recurrent diabetic macular edema remains a big change in clinical practice. This review emphasizes that reversibility of epigenetic modification could provide a new strategy for the prevention and treatment of diseases.