Excretion of hazardous pharmaceutical residues causes the emergence of toxic potential to the environment. Nanomedicine is commonly associated with nanoparticulate drug delivery to offer the improved ...therapeutic effects at a lower dose for disease treatments. Green chemistry aims to reduce or exclude the utilisation or generation of toxic substances in the design, manufacture and application of chemical products. The use of non-toxic and biodegradable materials in pharmaceutical formulations could minimize the adverse effects of pharmaceutical residues entering the environment in the first place. In our study, bovine serum albumin, a non-toxic, biodegradable and biocompatible protein, was used in the formation of nanoparticulate drug delivery systems. Glucose was used instead of glutaraldehyde to modify albumin nanoparticles for berberine delivery in order to prevent the potential toxicity to humans and the environment. These nanoparticles highly inhibited LX-2 cell growth and exhibited stronger caspase 3 activation at a lower dose when compared with free drug
in vitro
. Nanoparticles with berberine at doses of 1 and 2 μg g
−1
could rescue mice from CCl
4
-induced hepatotoxicity
in vivo
. Green glucose-bovine serum albumin nanoparticles could be safe and effective to deliver berberine at low doses in liver fibrosis treatment.
Use of non-hazardous materials in pharmaceutical formulation avoids the emergence of toxic potential to the environment.
Antimicrobial resistance remains a serious problem that results in high mortality and increased healthcare costs globally. One of the major issues is that resistant pathogens decrease the efficacy of ...conventional antimicrobials. Accordingly, development of novel antimicrobial agents and therapeutic strategies is urgently needed to overcome the challenge of antimicrobial resistance. A potential strategy is to kill pathogenic microorganisms via the formation of reactive oxygen species (ROS). ROS are defined as a number of highly reactive molecules that comprise molecular oxygen (O2), superoxide anion (O2•−), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). ROS exhibit antimicrobial actions against a broad range of pathogens through the induction of oxidative stress, which is an imbalance between ROS and the ability of the antioxidant defence system to detoxify ROS. ROS-dependent oxidative stress can damage cellular macromolecules, including DNA, lipids and proteins. This article reviews the antimicrobial action of ROS, challenges to ROS hypothesis, work to solidify ROS-mediated antimicrobial lethality hypothesis, recent developments in antimicrobial agents using ROS as an antimicrobial strategy, safety concerns related to ROS, and future directions in ROS research.
•Reactive oxygen species (ROS) could combat antimicrobial resistance.•ROS are used as an antimicrobial strategy because of their toxicity to a broad range of microbial pathogens.•ROS exert antimicrobial activity via an induction of oxidative stress in microbial cells.•Oxidative stress caused by ROS leads to microbial DNA damage, and ultimately inducing cell death.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A series of ruthenium(II) bis(2,2'-bipyridyl) complexes containing N-phenyl-substituted diazafluorenes (Ru-C1, Ru-C6, Ru-C7 and Ru-F) was synthesized and their potential antibacterial activity ...against methicillin resistant Staphylococcus aureus (MRSA) was investigated. The Ru-C7 complex showed significant improvement in both minimum inhibitory concentration (MIC, 6.25 μg mL(-1)) and minimum bactericidal concentration (MBC, 25 μg mL(-1)) towards MRSA when compared with those of methicillin (positive control) (MIC = 25 μg mL(-1) and MBC = 100 μg mL(-1)). The Ru-C7 complex possessed much stronger antibacterial effects than the Ru-C6 complex (MIC, 25 μg mL(-1), MBC, >100 μg mL(-1)). Both Ru-C6 and Ru-C7 complexes were also demonstrated to be biologically safe when tested on normal human skin keratinocytes.
Summary Background Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality in China, where the population is also exposed to high levels of passive smoking, yet little ...information exists on the effects of such exposure on COPD. We examined the relation between passive smoking and COPD and respiratory symptoms in an adult Chinese population. Methods We used baseline data from the Guangzhou Biobank Cohort Study. Of 20 430 men and women over the age of 50 recruited in 2003–06, 15 379 never smokers (6497 with valid spirometry) were included in this cross-sectional analysis. We measured passive smoking exposure at home and work by two self-reported measures (density and duration of exposure). Diagnosis of COPD was based on spirometry and defined according to the GOLD guidelines. Findings There was an association between risk of COPD and self-reported exposure to passive smoking at home and work (adjusted odds ratio 1·48, 95% CI 1·18–1·85 for high level exposure; equivalent to 40 h a week for more than 5 years). There were significant associations between reported respiratory symptoms and increasing passive smoking exposure (1·16, 1·07–1·25 for any symptom). Interpretation Exposure to passive smoking is associated with an increased prevalence of COPD and respiratory symptoms. If this association is causal, we estimate that 1·9 million excess deaths from COPD among never smokers could be attributable to passive smoking in the current population in China. Our findings provide strong evidence for urgent measures against passive smoking in China.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This paper presents the stability analysis of polynomial fuzzy-model-based (PFMB) control systems using the sum-of-squares (SOS) approach. The PFMB control system under consideration requires that ...the polynomial fuzzy model and polynomial fuzzy controller share neither the same premise membership functions nor the same number of fuzzy rules. This class of PFMB control systems offers a greater design flexibility to the polynomial fuzzy controller. However, due to the imperfectly matched membership functions, it usually produces more conservative stability conditions by following the traditional stability-analysis approach for the FMB control systems. To facilitate the stability analysis, piecewise-linear membership functions (PLMFs) are proposed, which offer a nice property that the grades of membership are governed by a finite number of sample points. Thus, it allows the PLMFs to be brought to the SOS-based stability conditions, which are applied to the PFMB control systems with the specified PLMFs rather than any shapes. The system stability can be examined by checking only the PFMB control system at the sample points. It is worth mentioning that the PLMFs, which are not necessarily implemented physically, are a mathematical tool to carry out the stability analysis. To verify the stability-analysis result, a simulation example is given to demonstrate the effectiveness of the proposed approach.
Plastic waste are introduced into the environment inevitably and their exposure in the environment causes deterioration in mechanical and physicochemical properties and leads to the formation of ...plastic fragments, which are considered as microplastics when their size is < 5 mm. In recent years, microplastic pollution has been reported in all kinds of environments worldwide and is considered a potential threat to the health of ecosystems and humans. However, knowledge on the environmental degradation of plastics and the formation of microplastics is still limited. In this review, potential hotspots for the accumulation of plastic waste were identified, major mechanisms and characterization methods of plastic degradation were summarized, and studies on the environmental degradation of plastics were evaluated. Future research works should further identify the key environmental parameters and properties of plastics affecting the degradation in order to predict the fate of plastics in different environments and facilitate the development of technologies for reducing plastic pollution. Formation and degradation of microplastics, including nanoplastics, should receive more research attention to assess their fate and ecological risks in the environment more comprehensively.
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F0B7Large amount of plastic waste enters the environment due to inappropriate disposal.F0B7Ocean gyres, farmlands, reservoirs, beaches are potential hotspots for plastic wastes.F0B7Plastics degrade in the environment due to chemical, biological and mechanic processes.F0B7Physicochemical and mechanical properties alter due to oxidation and chain scission.F0B7Microplastics are generated as a result of the fragmentation of plastics.
Degradation of plastics and formation of microplastics in the environment should be better understood to assess their fate and risks more comprehensively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
► Mixed network design problem (MNDP) can be formulated as a mixed-integer linear programming problem (MILP) with the link-based formulation which helps avoiding the path enumeration. ► The global ...optimality of the approximated MNDP can then be guaranteed following the property of the MILP. ► The proposed algorithm performed well with the tests with small and medium sized networks compared to other existing solution algorithms in the literature.
This paper proposes a global optimization algorithm for solving a mixed (continuous/discrete) transportation network design problem (MNDP), which is generally expressed as a mathematical programming with equilibrium constraint (MPEC). The upper level of the MNDP aims to optimize the network performance via both expansion of existing links and addition of new candidate links, whereas the lower level is a traditional Wardrop user equilibrium (UE) problem. In this paper, we first formulate the UE condition as a variational inequality (VI) problem, which is defined from a finite number of extreme points of a link-flow feasible region. The MNDP is approximated as a piecewise-linear programming (P-LP) problem, which is then transformed into a mixed-integer linear programming (MILP) problem. A global optimization algorithm based on a cutting constraint method is developed for solving the MILP problem. Numerical examples are given to demonstrate the efficiency of the proposed method and to compare the results with alternative algorithms reported in the literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
After curative radiotherapy (RT) or chemoradiation (CRT), there is no validated tool to accurately identify patients for adjuvant therapy in nasopharyngeal carcinoma (NPC). Post-RT circulating plasma ...Epstein–Barr virus (EBV) DNA can detect minimal residual disease and is associated with recurrence and survival independent of TNM (tumor–lymph node–metastasis) stage. We aimed to develop and validate a risk model for stratification of NPC patients after completion of RT/CRT to observation or adjuvant therapy.
The prospective multicenter 0502 EBV DNA screening cohort (Hong Kong NPC Study Group 0502 trial) enrolled from 2006 to 2015 (n = 745) was used for model development. For internal validation, we pooled independent patient cohorts from prospective clinical studies enrolled from 1997 to 2006 (n = 340). For external validation, we used retrospective cohort of NPC patients treated at Sun Yat-sen University Cancer Center from 2009 to 2012 (n = 837). Eligible patients had histologically confirmed NPC of Union for International Cancer Control (UICC) 7th Edition stage II–IVB who completed curative RT/CRT with or without neoadjuvant chemotherapy, had post-RT EBV DNA tested within 120 days after RT and received no adjuvant therapy. The primary end point was overall survival (OS). We used recursive-partitioning analysis (RPA) to classify patients into groups of low, intermediate, and high risk of death.
Combining post-RT EBV DNA level (0, 1–49, 50–499, and ≥500 copies/ml) and TNM stage (II, III, IVAB), RPA model classified patients into low-, intermediate-, and high-risk groups with 5-year OS of 89.4%, 78.5% and 37.2%, respectively. The RPA low-risk group had comparable OS to TNM stage II (5-year OS 88.5%) but identified more patients (64.8% versus stage II 28.1%) that could potentially be spared adjuvant therapy toxicity. The RPA model (c-index 0.712) showed better risk discrimination than either the TNM stage (0.604) or post-RT EBV DNA alone (0.675) with improved calibration and consistence. These results were validated in both internal and external cohorts.
Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC.
•Integrating postradiotherapy plasma Epstein–Barr virus (EBV) DNA and tumor–lymph node–metastasis (TNM) stage improves the risk stratification of nasopharyngeal carcinoma.•Postradiotherapy plasma EBV DNA is a better predictor of early death in nasopharyngeal carcinoma than TNM stage.•The low-risk group by recursive partitioning model can spare more patients from unnecessary toxicity of adjuvant therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Otomycosis is a superficial infection of the ear caused by fungi. The disease may occur in the pinna, external auditory canal and tympanic membrane of humans and animals.
Aspergillus niger
and
...Candida albicans
are the most prevalent fungal species responsible for otomycosis. In our study, the potential antifungal properties of a series of Schiff bases was examined. The synthesized compounds (
1-14
) were investigated for their minimum inhibitory concentration, minimum fungicidal concentration and zone of clearance against
Aspergillus niger
and
Candida albicans
. Compounds
5
and
6
with alkyl chain containing 6 or 7 carbon atoms exhibited an obvious fungicidal activity with the MIC/MFC ratio of 2. Zone of clearance study also demonstrated that both compounds
5
and
6
produced noticeable clear zones against the tested fungi as compared to fluconazole. The time-kill kinetic study showed that
Candida albicans
colonies were reduced by more than 3 logs after 24 h exposure to compound
5
at 4 and 8 × MIC levels. Both compounds
5
and
6
at a concentration of 50 μg mL
−1
exhibited satisfactory cell viability towards human skin keratinocytes. Our results suggest that these compounds may be considered as potential drug candidates for the treatment of
Aspergillus niger
and
Candida albicans
ear infections.
Two substituted 4-pyridylmethylene-4′-aniline Schiff bases showed antifungal activity against.
Aspergillus niger
and
Candida albicans
. They may be useful for the development of safe drug candidates for
A. niger
and
C. albicans
cases of otomycosis.
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IJS, KILJ, NUK, UL, UM, UPUK
► Bus arrival time prediction at bus stop with multiple routes. ► Integrating the information of single route and multiple routes. ► Performance comparison of the SVM, ANN, KNN and LR models. ► ...Observation surveys to collect bus running and arrival time data for validation in Hong Kong.
Provision of accurate bus arrival information is vital to passengers for reducing their anxieties and waiting times at bus stop. This paper proposes models to predict bus arrival times at the same bus stop but with different routes. In the proposed models, bus running times of multiple routes are used for predicting the bus arrival time of each of these bus routes. Several methods, which include support vector machine (SVM), artificial neural network (ANN),
k nearest neighbours algorithm (
k-NN) and linear regression (LR), are adopted for the bus arrival time prediction. Observation surveys are conducted to collect bus running and arrival time data for validation of the proposed models. The results show that the proposed models are more accurate than the models based on the bus running times of single route. Moreover, it is found that the SVM model performs the best among the four proposed models for predicting the bus arrival times at bus stop with multiple routes.
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