Synthesis, Characterization, Cytotoxicity, Cellular Imaging, Molecular Docking, and ADMET Studies of Piperazine-Linked 1,8-Naphthalimide-Arylsulfonyl Derivatives.

To reduce the mortality and morbidity associated with cancer, new cancer theranostics are in high demand and are an emerging area of research. To achieve this goal, we report the synthesis and characterization of piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives (SA1-SA7). These compounds were synthesized in good yields following a two-step protocol and characterized using multiple analytical techniques. In vitro cytotoxicity and fluorescent cellular imaging of the compounds were assessed against non-cancerous fibroblast (3T3) and breast cancer (4T1) cell lines. Although the former study indicated the safe nature of the compounds (viability = 82-95% at 1 µg/mL), imaging studies revealed that the designed probes had good membrane permeability and could disperse in the whole cell cytoplasm. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and ADME/Tox results, indicated that the compounds had the ability to target CAIX-expressing cancers. These findings suggest that piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives are potential candidates for cancer theranostics and a valuable backbone for future research.

Temporal decline in diarrhea episodes and mortality in Kiribati children two years following rotavirus vaccine introduction, despite high malnutrition rates: a retrospective review.

BACKGROUND: Kiribati introduced rotavirus vaccine in 2015. To estimate the impact of rotavirus vaccine on acute gastroenteritis (AGE) and severe acute malnutrition (SAM) among children under 5 in Kiribati, a retrospective review of inpatient and outpatient AGE and hospitalized SAM was undertaken. METHODS: Inpatient data for admissions and hospital deaths due to AGE, SAM and all-causes were collected for children under 5 from all hospitals on the main island, Tarawa, from January 2010-December 2013 (pre-rotavirus vaccine) and January 2016-September 2017 (post-rotavirus vaccine). National outpatient diarrhea data were collected from January 2010 to August 2017 for under 5. An interrupted time-series analysis was undertaken to estimate the effect of rotavirus vaccine on the rates of inpatient and outpatient AGE, inpatient SAM; and inpatient case fatality rates for AGE and SAM, were calculated pre- and post-rotavirus vaccine introduction. RESULTS: The incidence rate of AGE admissions from Tarawa and national AGE outpatient presentations significantly declined by 37 and 44%, respectively, 2 years following rotavirus vaccine introduction. There was a significant decline in the percentage of AGE contributing to all-cause under 5 admissions (12·8% vs. 7·2%, p < 0·001) and all-cause under-five mortality (15·9% vs. 5·7%, p = 0·006) pre- and post-rotavirus vaccine introduction. The estimated incidence rate of inpatient SAM decreased by 24% in under 5 s, 2 years following rotavirus vaccine introduction. CONCLUSIONS: AGE morbidity and mortality and hospitalized SAM rates have declined following rotavirus vaccine introduction in Kiribati children.

Gas chromatography coupled with mass spectrometric characterization of Curcuma longa: Protection against pathogenic microbes and lipid peroxidation in rat's tissue homogenate.

The present study was designed to investigate the mineral content and antimicrobial activity of Curcuma Longa extracts and its essential oil. We also determined the lipid peroxidation inhibition activity of the ethanolic extract against sodium nitroprusside (SNP) induced thiobarbituric acid reactive species (TBARS) formation in rat's brain, kidney and liver homogenates. Major constituents of essential oil identified by gas chromatography and mass spectrometry (GCMS) were beta-sesquiphellandrene (38.69%), alpha-curcumene (18.44%) and p-mentha-1,4 (8)-diene (16.29%). Atomic absorption spectroscopy (AAS) was used for the quantitative estimation of Calcium (Ca), Magnesium (Mg), Iron (Fe), Copper (Cu), Zinc (Zn), Chromium (Cr), Nickel (Ni) and Manganese (Mn). The extract showed highest Mg (49.4 mg/l) concentration followed by Ca (35.42 mg/l) and Fe (1.27 mg/l). Our data revealed that the ethanolic extract of Curcuma Longa at 1-10 mg/kg significantly inhibited TBARS production in all tested homogenates. Crude extracts and essential oil were tested against three gram positive bacteria i.e. Bacillus subtilis, Bacillus atrophoeus, Staphylococcus aureus, six gram negative bacteria i.e. Escherichia coli, Klebsiella pneumonias, Salmonella typhi, Pseudomonas aeruginosa, Erwinia carotovora, Agrobacterium tumefaciens and one fungal strain namely Candida albicans by disc diffusion assay. Essential oil showed highest anti-microbial activity as compared to the crude extracts. The present study confirms the significant antimicrobial and antioxidant potential of the studied plant, which can be considered as a diet supplement for a variety of oxidative stress induced or infectious diseases.

Ethanolic extract of Nigella sativa protects Fe(II) induced lipid peroxidation in rat's brain, kidney and liver homogenates.

The study describes the effect of ethanolic extract of Nigella sativa against Fe(II) induced lipid peroxidation. Basal and Fe(II) induced thiobarbituric acid reactive species (TBARS) production was significantly inhibited by the ethanolic extract of Nigella sativa at 25-200 µg/ml. Our data revealed that the extract has high DPPH radical scavenging activity at highest tested concentrations. The extract significantly chelated Fe(II) and scavenged hydroxyl (OH) radical at 25-200µg/ml concentration. The nutritional analysis was performed and carbohydrate, fats, fiber, protein, moisture and ash content were measured in the studied extract. The phytochemical analysis confirmed the presence of alkaloid, carbohydrate & sugar, glycosides, phenolic compounds, flavonoids, protein and amino acid, phytosterols, tannins, gum and mucilage. The extract also showed significant antimicrobial activities against 10 bacterial strains i.e. Salmonella typhi, Bacillus subtilis, Bacillus cereus, Klebsiella pneumonia, Escheria coli, Xanthomonas, Salmonella heidelberg, Staphylococcus aureus, Clostridium and Escheria coli (human) and 5 fungal strains i.e. Aspergillus niger, Entomola, Aspergillus flavus, Alternaria alternata and Penicillium. This study confirms the potential antioxidant and antimicrobial activities of ethanolic extract of Nigella sativa which can be considered not only as a diet supplement but can be used against a variety of free radical induced damage diseases.

Modeling of a lot scale rainwater tank system in XP-SWMM: a case study in Western Sydney, Australia.

Lot scale rainwater tank system modeling is often used in sustainable urban storm water management, particularly to estimate the reduction in the storm water run-off and pollutant wash-off at the lot scale. These rainwater tank models often cannot be adequately calibrated and validated due to limited availability of observed rainwater tank quantity and quality data. This paper presents calibration and validation of a lot scale rainwater tank system model using XP-SWMM utilizing data collected from two rainwater tank systems located in Western Sydney, Australia. The modeling considers run-off peak and volume in and out of the rainwater tank system and also a number of water quality parameters (Total Phosphorus (TP), Total Nitrogen (TN) and Total Solids (TS)). It has been found that XP-SWMM can be used successfully to develop a lot scale rainwater system model within an acceptable error margin. It has been shown that TP and TS can be predicted more accurately than TN using the developed model. In addition, it was found that a significant reduction in storm water run-off discharge can be achieved as a result of the rainwater tank up to about one year average recurrence interval rainfall event. The model parameter set assembled in this study can be used for developing lot scale rainwater tank system models at other locations in the Western Sydney region and in other parts of Australia with necessary adjustments for the local site characteristics.

Long-term dissolved organic carbon changes in Woronora drinking water system in Australia.

Assessing historical records of DOC concentrations (DOC) in drinking water sources is important for water utilities to understand long-term planning for infrastructure needs. This study investigates 15-20 years of historical data of the Woronora water supply catchment in Australia inclusive of the water filtration plant (WFP), the lake from where the water was drawn for WFP supply, and the two primary river inputs. The DOC at each site ranged from 0.8 mg L-1 to 13.9 mg L-1, with the highest and lowest concentrations observed in Waratah Rivulet. The DOC in the lake and WFP significantly (p < 0.001) increased at annual change rates of 0.192 and 0.180 mg L-1 yr-1. However, Woronora River showed a ∼50% lower rate of DOC increase at 0.096 mg L-1 yr-1 (p < 0.001), while Waratah Rivulet showed no trend (p > 0.05). UV254 also showed increasing trends at Woronora River, Lake Woronora, and Woronora WFP, indicating an increase in aromatic DOC compounds in all three sites. Waratah Rivulet, however, transported more than 60% of the total DOC load into Lake Woronora due to high flow volumes (more than 65% of total annual system flow). Annual DOC load to the lake is positively correlated with annual rainfall (R2 > 0.92; p < 0.001). The higher percentage (>73%) of the samples had SUVA254 greater than 2 L mg -1 m-1 in all four sites indicating a dominance of hydrophobic DOC. The terrestrial plant-derived DOC has increased in Lake Woronora, predominantly influenced by historical rainfall magnitude. The results underscore the importance of considering the impact of increased DOC at the treatment plant intake for the planning and operation of the Woronora water supply system.

Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools.

The Dolichol kinase (DOLK) gene encodes the polytopic DOLK protein associated with the endoplasmic reticulum (ER) N-glycosylation pathway catalyzing the final step in the biosynthesis of dolichol phosphate. Dolichol phosphate is an oligosaccharide carrier required for N-glycosylation of DOLK protein, with its deficiency leading to a severe hypo glycosylation phenotype in humans which can cause congenital disorders of glycosylation and death in early infancy. The aim of the present study is to identify the phylogenetic relationship between human and ortholog species based on their conserved sequences in DOLK gene. Sequence alignment of DOLK was carried out in this study and the evolutionarily conserved regulatory sequences were identified using bioinformatics. Promoter sequence of human DOLK was compared with orthologous sequences from different organisms. Conserved non-coding sequences (CNS) and motifs in promoter regions were found by analyzing upstream promoter sequences of Homo sapiens DOLK and its orthologous genes in other organisms. Conserved sequences were predicted in the promoter regions in CNS1 and CNS2. Conserved protein sequences were also identified by alignment of the orthologous sequences. Organisms with similar gene sequences are assumed to be closely related and the ER N-glycosylation pathway is conserved in them.

Investigation of tetrasubstituted heterocycles reveals hydantoins as a promising scaffold for development of novel antimicrobials with membranolytic properties.

Mimics of antimicrobial peptides (AMPs) have been proposed as a promising class of antimicrobial agents. We report the analysis of five tetrasubstituted, cationic, amphipathic heterocycles as potential AMP mimics. The analysis showed that the heterocyclic scaffold had a strong influence on the haemolytic activity of the compounds, and the hydantoin scaffold was identified as a promising template for drug lead development. Subsequently, a total of 20 hydantoin derivatives were studied for their antimicrobial potency and haemolytic activity. We found 19 of these derivatives to have very low haemolytic toxicity and identified three lead structures, 2dA, 6cG, and 6dG with very promising broad-spectrum antimicrobial activity. Lead structure 6dG displayed minimum inhibitory concentration (MIC) values as low as 1 µg/mL against Gram-positive bacteria and 4-16 µg/mL against Gram-negative bacteria. Initial mode of action (MoA) studies performed on the amine derivative 6cG, utilizing a luciferase-based biosensor assay, suggested a strong membrane disrupting effect on the outer and inner membrane of Escherichia coli. Our findings show that the physical properties and structural arrangement induced by the heterocyclic scaffolds are important factors in the design of AMP mimics.

Effects of environmental and spatial gradients on Quercus-dominated Mountain forest communities in the Hindu-Kush ranges of Pakistan.

Quercus-dominated forests are among the most important broad-leaved evergreen forests of the Hindu Kush ranges and are currently prone to drastic anthropogenic and climatic changes. The aim of this study was to provide basic data for the development of a regional oak forest ecosystem framework for ecological restoration and management plan development to maintain local peoples' livelihoods. Hence, we analyzed distribution patterns and environmental factors that affect regional oak forests' species composition and diversity. Ward's Agglomerative clustering divided oak-dominated forest communities into three groups: i.e., Group I, dominated by Quercus baloot had an importance value index (IVI) of 89.87 ± 4.31, Group II, dominated by Quercus dilatata had an IVI of 32.16 ± 15.01, and Group III, dominated by Quercus oblongata had an IVI of 83.14 ± 4.67, respectively. The environmental factors which vary significantly within these communities were latitude, elevation, clay content and bulk density of the soil. Wilting point, saturation point, and electrical conductivity were also considered as ecosystem structural variables. Canonical correspondence analysis (CCA) indicated that community structure was affected by various environmental factors including precipitation, slope angle, elevation, clay content, and relative humidity.

A concise SAR-analysis of antimicrobial cationic amphipathic barbiturates for an improved activity-toxicity profile.

An amphipathic barbiturate mimic of the marine eusynstyelamides is reported as a promising class of antimicrobial agents. We hereby report a detailed analysis of the structure-activity relationship for cationic amphipathic N,N'-dialkylated-5,5-disubstituted barbiturates. The influence of various cationic groups, hydrocarbon linkers and lipophilic side chains on the compounds' antimicrobial potency and haemolytic activity was studied. A comprehensive library of 58 compounds was prepared using a concise synthetic strategy. We found cationic amine and guanidyl groups to yield the highest broad-spectrum activity and cationic trimethylated quaternary amine groups to exert narrow-spectrum activity against Gram-positive bacteria. n-Propyl hydrocarbon linkers proved to be the best compromise between potency and haemolytic activity. The combination of two different lipophilic side chains allowed for further fine-tuning of the biological properties. Using these insights, we were able to prepare both, the potent narrow-spectrum barbiturate 8a and the broad-spectrum barbiturates 11lG, 13jA and 13jG, all having low or no haemolytic activity. The guanidine derivative 11lG demonstrated a strong membrane disrupting effect in luciferase-based assays. We believe that these results may be valuable in further development of antimicrobial lead structures.

Birth and Death Notifications for Improving Civil Registration and Vital Statistics in Bangladesh: Pilot Exploratory Study.

BACKGROUND: Effective health policy formulation requires sound information of the numerical data and causes of deaths in a population. Currently, in Bangladesh, neither births nor deaths are fully and promptly registered. Birth registration in Bangladesh is around 54% nationally. Although the legal requirements are to register within 45 days of an event, only 4.5% of births and 35.9% of deaths were reported within the required time frame in 2020. This study adopted an innovative digital notification approach to improve the coverage of registration of these events at the community level. OBJECTIVE: Our primary objective was to assess (1) the proportion of events identified by the new notification systems (success rate) and the contribution of the different notifiers individually and in combination (completeness) and (2) the proportion of events notified within specific time limits (timeliness of notifications) after introducing the innovative approach. METHODS: We conducted a pilot study in 2016 in 2 subdistricts of Bangladesh to understand whether accurate, timely, and complete information on births and deaths can be collected and notified by facility-based service providers; community health workers, including those who routinely visit households; local government authorities; and key informants from the community. We designed a mobile technology-based platform, an app, and a call center through which the notifications were recorded. All notifications were verified through the confirmation of events by family members during visits to the concerned households. We undertook a household survey-based assessment at the end of the notification period. RESULTS: Our innovative system gathered 13,377 notifications for births and deaths from all channels, including duplicate reports from multiple sources. Project workers were able to verify 92% of the births and 93% of the deaths through household visits. The household survey conducted among a subsample of the project population identified 1204 births and 341 deaths. After matching the notifications with the household survey, we found that the system was able to capture over 87% of the births in the survey areas. Health assistants and family welfare assistants were the primary sources of information. Notifications from facilities were very low for both events. CONCLUSIONS: The Global Civil Registration and Vital Statistics: Scaling Up Investment Plan 2015-2024 and the World Health Organization reiterated the importance of building an evidence base for improving civil registration and vital statistics. Our pilot innovation revealed that it is possible to coordinate with the routine health information system to note births and deaths as the first step to ensure registration. Health assistants could capture more than half of the notifications as a stand-alone source.

Distance associated with marriage migration in a northern and a southern region of Bangladesh: an empirical study.

This paper investigates the distribution of distance associated with marriage migration in the northern region of Rajshahi and the southern region of Khulna in Bangladesh. The study was conducted in 2007 on 2250 respondents who had migrated due to marriage. Of the wide variety of curves that fitted the distance-marriage/contact data, three are discussed: Pareto, exponential, and Pareto-exponential. Logistic regression models were used to identify the covariates of marriage distance migration. In general, the three functions work better for marriages, whereas Pareto-exponential functions are a superior fit for migrations and marriage distance. The models disclose that the distribution of distance is significantly associated with marriage migration (p<0.001). The Pareto-exponential model was 100% stable and its shrinkage was 0.000000125. The main covariates associated with short-distance marriage migration were respondent's education, father's education and religion, whereas age at the time of marriage did not play a significant role in marriage migration. The risk of short-distance migration was greater in higher- than lower-educated Muslim families.

Sea outfall disposal of stormwater in Doha Bay: Risk assessment based on dispersion modelling.

A 3D numerical hydrodynamic and dispersion study was carried out using the MIKE3 Hydrodynamic model to assess the dispersion of stormwater effluents discharged from the four sea outfalls into Doha bay area in Qatar. Dispersion simulations were carried out for three scenarios: dry weather, representative storm event and first flush. Input parameters (such as temperature, salinity, total suspended solids, total Nitrogen and Faecal coliform) for the dispersion simulation were defined from measurements obtained during representative events for each scenario of interest. Results show that variation of temperature and salinity mostly occurred at the vicinity of disposal point. The net sedimentation of solids was observed above 25 g/m2 within about 250 m from the outfalls. Concentration of Faecal coliform was found >500 count/100 mL >90% of the simulation time within 50 m from one of the outfalls, which reduced to 250-500 count/100 mL at 100 m distance. Simulation of exceedance for total N of 0.2 mg/L shows that during the dry weather flow condition, overall in the Southern Doha Bay, total N exceeded from 70% to >90% of the time. However, when exceedance of 0.6 mg/L of total N was modelled, the vicinity of only one outfall showed exceedance >90% of the simulation period. A risk assessment was carried out using results of the numerical dispersion modelling based on negligible, minor, moderate and major risk categories. Criteria for risk assessment were developed based on field observation of local ambient sea water condition. Risk of eutrophication, impact on swimming water quality and sedimentation of hazardous contaminants was evaluated. The developed risk criteria are applicable for similar bays in Qatar and in other GCC countries near Arabian Gulf.

First flush analysis using a rainfall simulator on a micro catchment in an arid climate.

Urban runoff water from simulated rainfall for three different land uses (residential, industrial, commercial) at six different locations of Doha, Qatar was analysed for physico-chemical parameters such as, trace metals, pH, total suspended solids (TSS), total organic carbon (TOC), total phosphorus (TP), total kjeldahl nitrogen (TKN) and polyaromatic hydrocarbons (PAHs). Rainfall events with two different intensities (40 mm/h and 20 mm/h) were simulated in a micro catchment area (4.55 × 4.55 m2) using a specially designed portable rainfall simulator. Out of six sites, runoff samples were collected from five sites with paved surfaces. The study results demonstrated significant concentration of TSS, Cu, Fe, Mn and Zn in the urban runoff exceeding the Qatar Ministry of Municipality and Environment (MME) and Tropical Australian Standards. The first flush effect was also investigated during the experiment which exhibited first flush effect of selected pollutants (TSS, TKN, TP, TOC and heavy metals) at five study sites with impervious surfaces. The magnitude of the first flush varies across the study sites and was found to be affected by the surface texture of the sites. Analysis of variance revealed that, rainfall intensity has limited effect on the first flush in the studied scenarios, however, first flush effects showed relation with the event mean runoff concentration. Furthermore, strong positive correlations were observed between analysed water quality parameters, particularly between TSS, TOC and metals. This study is the first study investigating first flush in Qatar's capital, Doha which will provide a ground for future researcher to design appropriate stormwater treatment devices that will capture and treat the first flush for significant reduction of urban stormwater pollution.

Structural insights into biosynthesis of resorcinolic lipids by a type III polyketide synthase in Neurospora crassa.

Microbial type III polyketide synthases (PKSs) have revealed remarkable mechanistic as well as functional versatility. Recently, a type III PKS homolog from Azotobacter has been implicated in the biosynthesis of resorcinolic lipids, thus adding a new functional significance to this class of proteins. Here, we report the structural and mutational investigations of a novel type III PKS protein from Neurospora crassa involved in the biosynthesis of resorcinolic metabolites by utilizing long chain fatty acyl-CoAs. The structure revealed a long hydrophobic tunnel responsible for its fatty acyl chain length specificity resembling that of PKS18, a mycobacterial type III PKS. Structure-based mutational studies to block the tunnel not only altered the fatty acyl chain specificity but also resulted in change of cyclization pattern affecting the product profile. This first structural characterization of a resorcinolic lipid synthase provides insights into the coordinated functioning of cyclization and a substrate-binding pocket, which shows mechanistic intricacy underlying type III PKS catalysis.

The knowledge, awareness, attitude and motivational analysis of plastic waste and household perspective in Malaysia.

The focus of this study is to analyze the level of knowledge, awareness, and attitude toward plastic waste and to distinguish the key drivers that encourage the households in Kuala Lumpur, Malaysia, to participate in "No plastic campaign," This study used the logistic regression model to explain the factors that may affect the willingness to participate (WTP) of households in the campaign. In this study, it is found that 35 % of households are willing to participate in the campaign. The results of the study also indicate that people who are more informed and more convinced of their knowledge have a more positive attitude toward recycling than their counterparts do. Furthermore, this study provides additional evidence of the level and classification of importance of motivating factors for plastic recycling, using the modified average and coefficient of variation of the models. From the analysis, the factor "helps reduce landfill use" is found as the most important factor and the factor of "raising money for charity" is found as the least important factor that motivates households to participate in recycling. The determinations of the study suggest some strategies that could hold implications for government and households to boost them to participate in the campaign "No Plastic Bag."

Urban rainwater harvesting systems: Research, implementation and future perspectives.

While the practice of rainwater harvesting (RWH) can be traced back millennia, the degree of its modern implementation varies greatly across the world, often with systems that do not maximize potential benefits. With a global focus, the pertinent practical, theoretical and social aspects of RWH are reviewed in order to ascertain the state of the art. Avenues for future research are also identified. A major finding is that the degree of RWH systems implementation and the technology selection are strongly influenced by economic constraints and local regulations. Moreover, despite design protocols having been set up in many countries, recommendations are still often organized only with the objective of conserving water without considering other potential benefits associated with the multiple-purpose nature of RWH. It is suggested that future work on RWH addresses three priority challenges. Firstly, more empirical data on system operation is needed to allow improved modelling by taking into account multiple objectives of RWH systems. Secondly, maintenance aspects and how they may impact the quality of collected rainwater should be explored in the future as a way to increase confidence on rainwater use. Finally, research should be devoted to the understanding of how institutional and socio-political support can be best targeted to improve system efficacy and community acceptance.

Development of hydrocolloid Bi-layer dressing with bio-adhesive and non-adhesive properties.

Bio-active bi-layer thin film having both bio-adhesive and non-adhesive end composed of polyvinyl alcohol (PVA) and gelatin/chitosan/polyethylene glycol (PEG) blend was developed for biomedical applications especially as an alternative of advanced tissue scaffold. The developed composite film was subjected to mechanical, thermal and physico-chemical characterization such as tensile strength (TS) and elongation at break (Eb), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), fluid drainage capacity and biocompatibility. Suitable packaging was also selected and stability study and aging test of the composite film were performed after packing. The incorporation of chitosan and PEG into gelatin showed improved mechanical properties of both TS and Eb, which suggested the occurrence of interaction among gelatin, chitosan and PEG molecules in the composite film. The presence of crosslinking as an interaction of above three polymers was also confirmed by FTIR study. Results from the DSC study suggested increased thermal stability after crosslinking. On the other hand, water uptake studies suggested excellent fluid drainage capability and hydro-stability of the composite film. The proposed dressing also showed excellent biocompatibility. Based on the studies related to the performance with confirmed identity, we concluded that our developed bi-layer film is very potential as an ideal wound dressing material.

Morus alba Accumulates Reactive Oxygen Species to Initiate Apoptosis via FOXO-Caspase 3-Dependent Pathway in Neuroblastoma Cells.

Morus alba root extract (MARE) has been used to treat hyperglycaemic conditions in oriental medicine. Here, we studied whether MARE possesses a cytotoxic effect on neuroblastoma. To check the cytotoxicity generated by MARE was whether relatively higher against the cancer cells rather than normal cells, we chose a neuroblastoma cell line (B103) and a normal cell line (Rat-2). A CCK assay revealed that MARE (10 µg/ml) reduced cell viability to approximately 60% compared to an untreated control in B103 cells. But in Rat-2 cells, MARE induced relatively lower cytotoxicity. To investigate the mechanisms underlying the cytotoxic effect of MARE, we used flow cytometry combined with immunoblot analyses. We found that MARE-treatment could accumulate ROS and depolarize mitochondria membrane potential of B103 cells. Further treatment with MARE in B103 cells also could damage DNA and induce apoptosis. An expression study of p-Akt also suggested that there was a reduction in cellular proliferation and transcription along with the process of apoptosis, which was further evidenced by an increase in Bax and cleaved-caspase 3 activity. Together, our findings suggest that MARE produces more cytotoxicity in cancer cells while having a relatively attenuated effect on normal cells. As such, MARE may be a safer option in cancer therapeutics, and it also shows potential for the patients with symptoms of hyperglycemia and cancer.

A Bayesian regression approach to assess uncertainty in pollutant wash-off modelling.

Due to knowledge gaps in relation to urban stormwater quality processes, an in-depth understanding of model uncertainty can enhance decision making. Uncertainty in stormwater quality models can originate from a range of sources such as the complexity of urban rainfall-runoff-stormwater pollutant processes and the paucity of observed data. Unfortunately, studies relating to epistemic uncertainty, which arises from the simplification of reality are limited and often deemed mostly unquantifiable. This paper presents a statistical modelling framework for ascertaining epistemic uncertainty associated with pollutant wash-off under a regression modelling paradigm using Ordinary Least Squares Regression (OLSR) and Weighted Least Squares Regression (WLSR) methods with a Bayesian/Gibbs sampling statistical approach. The study results confirmed that WLSR assuming probability distributed data provides more realistic uncertainty estimates of the observed and predicted wash-off values compared to OLSR modelling. It was also noted that the Bayesian/Gibbs sampling approach is superior compared to the most commonly adopted classical statistical and deterministic approaches commonly used in water quality modelling. The study outcomes confirmed that the predication error associated with wash-off replication is relatively higher due to limited data availability. The uncertainty analysis also highlighted the variability of the wash-off modelling coefficient k as a function of complex physical processes, which is primarily influenced by surface characteristics and rainfall intensity.