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Proximal tubule (PT) transports most of the renal Ca2+, which was usually described as paracellular (passive). We found a regulated Ca2+ entry pathway in PT cells via the apical transient receptor potential canonical 3 (TRPC3) channel, which initiates transcellular Ca2+ transport. Although TRPC3 knockout (−/−) mice were mildly hypercalciuric and displayed luminal calcium phosphate (CaP) crystals at Loop of Henle (LOH), no CaP + calcium oxalate (CaOx) mixed urine crystals were spotted, which are mostly found in calcium nephrolithiasis (CaNL). Thus, we used oral calcium gluconate (CaG; 2%) to raise the PT luminal [Ca2+]o further in TRPC3−/− mice for developing such mixed stones to understand the mechanistic role of PT-Ca2+ signaling in CaNL. Expectedly, CaG-treated mice urine samples presented with numerous mixed crystals with remains of PT cells, which were pronounced in TRPC3−/− mice, indicating PT cell damage. Notably, PT cells from CaG-treated groups switched their mode of Ca2+ entry from receptor-operated to store-operated pathway with a sustained rise in intracellular [Ca2+] ([Ca2+]i), indicating the stagnation in PT Ca2+ transport. Moreover, those PT cells from CaG-treated groups demonstrated an upregulation of calcification, inflammation, fibrotic, oxidative stress, and apoptotic genes; effects of which were more robust in TRPC3 ablated condition. Furthermore, kidneys from CaG-treated groups exhibited fibrosis, tubular injury and calcifications with significant reactive oxygen species generation in the urine, thus, indicating in vivo CaNL. Taken together, excess PT luminal Ca2+ due to escalation of hypercalciuria in TRPC3 ablated mice induced surplus CaP crystal formation and caused stagnation of PT [Ca2+]i, invoking PT cell injury, hence mixed stone formation.

Copyright © 2022 The Authors. Brexit has caused a seismic shift in the British socio-economic and political landscapes, creating widespread uncertainties, while simultaneously giving hope and national pride to millions. The decision by a number of organizations to reshore their production has opened a new era for business management that challenges the axiomatic assumption of the benefits of offshored production. Although reshoring predates Brexit, the link between the two in the British context is not just serendipitous and they are argued to have reasonable interlinkages. However, there is inadequate empirical evidence to suggest that British consumers’ attitude towards Brexit has any effect on their intention to purchase reshored brands. Through a mixed-methods study comprising a survey of 415 respondents and 20 in-depth interviews, this paper addresses this research gap. Findings suggest that corporate social responsibility (CSR) and consumer reshoring sentiment (CRS) have positive effects on consumers’ attitude towards reshored brands. Despite CRS's positive influence on attitude towards Brexit, the latter does not have any significant effects on the intention to purchase a reshored brand, which is positively influenced by the attitude towards the same brand. As such, companies should enhance the image of their brands and CSR in order to harness the benefits of reshoring. University of Western Australia, as part of the Wiley – The University of Western Australia agreement via the Council of Australian University Librarians.

Despite improved screening and surveillance guidelines, significant race/ethnicity‐specific disparities in hepatocellular carcinoma (HCC) continue to exist and disproportionately affect minority and disadvantaged populations. This trend indicates that social determinants, genetic, and environmental factors are driving the epidemic at the population level. Race and geography had independent associations with risk of mortality among patients with HCC. The present review discusses the risk factors and issues related to disparities in HCC. The underlying etiologies for these disparities are complex and multifactorial. Some of the risk factors for developing HCC include hepatitis B (HBV) and hepatitis C (HCV) viral infection, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, smoking and alcohol consumption. In addition, population genetics; socioeconomic and health care access; treatment and prevention differences; and genetic, behavioral, and biological influences can contribute to HCC. Acculturation of ethnic minorities, insurance status, and access to health care may further contribute to the observed disparities in HCC. By increasing awareness, better modalities for screening and surveillance, improving access to health care, and adapting targeted preventive and therapeutic interventions, disparities in HCC outcomes can be reduced or eliminated., Population genetics, socioeconomic and health care access, treatment and prevention differences, dietary composition, and genetic, behavioral and biological influences can contribute to hepatocellular carcinoma (HCC). Acculturation of ethnic minorities, insurance status and access to healthcare may further contribute to the observed disparities in HCC. By increasing awareness and better modalities for screening and surveillance, targeted preventive and therapeutic interventions for reducing disparities can be successfully improved.

Smart retail technologies are transforming the way companies engage with customers in retailing context. However, the real onset is unknown of which smart retail technology (SRT) characteristics and customer responses pave the way for customer engagement behaviour. This research investigates customer engagement behaviour in smart retailing by integrating meta-UTAUT and SRT characteristics. By analysing quantitative survey data using PLS path modelling, customer engagement manifestations are measured. Results show complex relationships between SRT characteristics (novelty, effectiveness, and interaction quality) and meta-UTAUT variables (performance expectancy, effort expectancy, social influence, and facilitating conditions) in influencing customers’ attitude, behavioural intention, and engagement behaviour towards smart retailing. Retailers can use the findings to influence customers’ attitudes towards smart retail technologies, encouraging them to display customer engagement behaviour.

Background: Combustion of traditional biomass fuels and coal has been found to be associated with exposure to particulates and volatile organic compounds (VOCs) and cause a series of adverse health effects. Characterization-quantification of such exposure achieved so far is not optimum, and establishment of a protective mechanism with proven efficacy is the urgent need. Methods: The present study was planned to characterize exposure from fuel during cooking in a village of India and understand the effect of using intervention measure. In this study, exposure to different pollutants was examined by personal monitoring in different cooking arrangements with traditional and modified oven. Results: It is observed that level of the pollutants has lessened by several folds while cooking with modified oven in comparison to unmodified oven. Such change of pollutants levels with the use of modified oven was found to be statistically significant in cases of benzene (P < 0.001), toluene (P < 0.01), and particulates (P < 0.0001). Conclusions: This study highlights the exposure from indoor air pollution during cooking and promotes use of low-cost protective mechanisms to curb resulting human health adversities. This study also calls for concerted awareness generation activity among the rural population (especially women) regarding adverse health effect of cooking fuels and protective effect of installed mechanisms.

Regional Occupational Health Centre (Eastern), (Indian Council of Medical Research), Block DP, Sector V, Salt Lake, Kolkata-700 091, India E-mail : ashit_mukherjee@yahoo.com Department of Chemistry, Inorganic Chemistry Section, Jadavpur University, Kolkata-700 032, India Manuscript received 27 June 2017, revised 06 November 2017, accepted 07 November 2017 Chronic arsenic toxicity through drinking water is still one of the major problems across the world. Bangladesh and India (particularly the state of West Bengal) are the worst affected countries with such problem. Millions of people all over the world are affected by arsenic related diseases. In our study, concentration of ground water arsenic, urine arsenic, hair arsenic and nail arsenic from adult individuals were measured from exposed areas of West Bengal, India respectively by flow injection atomic spectroscopy and transverselyheated graphite atomiser techniques. Porphyrins, uroporphyrin III, heptacarboxyporphyrin I, hexacarboxyporphyrin I, pentacarboxyporphyrin I, coproporphyrin III in urine were analysed separately by HPLC using fluorescence detector as well as level of vitamin B6 , vitamin B9 and vitamin B12 were carried out in serum samples among the population in the selected area in North 24-Parganas, West Bengal, India. Concentration of uro III, hepta I, copro III and copro III/uro III were observed to increase irrespective of gender and also in total; whereas level of B vitamins were found to decrease with increase in exposure to arsenic contaminated drinking water from underground sources. The difference of vitamin B6 (p < 0.01) between the population exposed to 50 µg/L arsenic in drinking water was found to be significant. Significant difference was also noticed in case of uro III (p < 0.05), copro III (p < 0.01) and copro III/uro III (p < 0.05) between two exposure categories. This study demonstrated increasing tendency in urinary porphyrins as well as inverse relationships of serum B vitamins with increased water arsenic concentration.

Regional Occupational Health Centre (Eastern) (Indian Council of Medical Research), Block DP, Sector V, Salt Lake, Kolkata-700 091, India E-mail : ashit_mukherjee@yahoo.com Department of Chemistry, Inorganic Chemistry Section, Jadavpur University, Kolkata-700 032, India Manuscript received 27 June 2017, revised 07 September 2017, accepted 17 November 2017 Arsenic contamination in ground water has been received much attention in recent times because of its carcinogenicity. Chronic exposure to arsenic through drinking water causes several multi-organ diseases including cancer. This study reports urinary porphyrins profile as a mark of disturbances in heme biosynthetic pathway due to chronic exposure to arsenic contaminated drinking water in endemic area of North 24- Parganas district of West Bengal. Arsenic in drinking water and urine were measured respectively by flow injection analysis system – Atomic Absorption Spectrometry (FIAS-AAS) and Transversely heated graphite atomizer (THGA-AAS) techniques. Urinary porphyrins were estimated simultaneously by reverse phase HPLC. Arsenic level in water was >50 µg/L in 57.7% tube wells, of which 13.3% were, >500 µg/L. Urinary arsenic (µg/g creatinine) was found to increase with increasing exposure. Study showed altered urinary porphyrins with changes in water arsenic (W-As) content as well as with duration of exposure. Higher porphyrin levels were observed in group, exposed to water arsenic, >250 µg/L, having exposure, ≥15 years, irrespective of gender. Significant differences between urinary porphyrins and duration of exposure of the subjects was noticed in the cases, uro III (p < 0.001), penta I (p < 0.05), copro III (p < 0.001) and the ratio of copro III/ uro III (p < 0.05). An increasing trend of urinary porphyrins noticed with exposure to arsenic, though the difference between urinary porphyrins and exposure to water arsenic was insignificant. The study suggests that urinary porphyrins may serve as biomarker of chronic exposure to arsenic among population in the endemic area.

Transcription factor CCAAT/enhancer-binding protein (C/EBP)-beta is crucial for regulating transcription of genes involved in a number of diverse cellular processes, including those involved in some cytokine-induced responses. However, the mechanisms that contribute to its diverse transcriptional activity are not yet fully understood. To gain an understanding into its mechanisms of action, we took a proteomic approach and identified cellular proteins that associate with C/EBP-beta in an interferon (IFN)-gamma-dependent manner. Transcriptional mediator (Mediator) is a multisubunit protein complex that regulates signal-induced cellular gene transcription from enhancer-bound transcription factor(s). Here, we report that the Med1 subunit of the Mediator as a C/EBP-beta-interacting protein. Using gene knock-out cells and mutational and RNA interference approaches, we show that Med1 is critical for IFN-induced expression of certain genes. Med1 associates with C/EBP-beta through a domain located between amino acids 125 and 155 of its N terminus. We also show that the MAPK, ERK1/2, and an ERK phosphorylation site within regulatory domain 2, more specifically the Thr(189) residue, of C/EBP-beta are essential for it to bind to Med1. Last, an ERK-regulated site in Med1 protein is also essential for up-regulating IFN-induced transcription although not critical for binding to C/EBP-beta.

Background: Mammalian forkhead members of the class O (FOXO) transcription factors, including FOXO1, FOXO3a, and FOXO4, are implicated in the regulation of several biological processes, including the stress resistance, metabolism, cell cycle, apoptosis and DNA repair. The objectives of this study were to examine the molecular mechanisms by which FOXO transcription factors induced cell cycle arrest and apoptosis and enhanced antiproliferative effects of sulforaphane (SFN, an active compound in cruciferous vegetables) in pancreatic cancer cells.Results: Our data demonstrated that SFN inhibited cell proliferation and colony formation, and induced apoptosis through caspase-3 activation in pancreatic cancer cells. The inhibition of PI3K/AKT and MEK/ERK pathways activated FOXO transcription factors. SFN inhibited phosphorylation of AKT and ERK, and activated FOXO transcription factors, leading to cell cycle arrest and apoptosis. Phosphorylation deficient mutants of FOXO proteins enhanced FOXO transcriptional activity, and further enhanced SFN-induced FOXO activity and apoptosis. SFN induced the expression of p21/CIP1 and p27/KIP1, and inhibited the expression of cyclin D1.Conclusion: These data suggest that inhibition of PI3K/AKT and ERK pathways acts together to activate FOXO transcription factor and enhances SFN-induced FOXO transcriptional activity, leading to cell cycle arrest and apoptosis.