Physiologically Based Pharmacokinetic Models (PBPK) are mechanistical tools generally employed in the pharmaceutical industry and environmental health risk assessment. These models are recognised by regulatory authorities for predicting organ concentration-time profile, pharmacokinetic and daily intake dose of xenobiotics. Extension of PBPK models to capture sensitive populations like pediatric, geriatric, pregnant females, fetus etc. and diseased population like renal impairment, liver cirrhosis etc. is a must. However, the current modelling practice and existing models are not mature enough to confidently predict the risk in these populations. A multidisciplinary collaboration between clinicians, experimental and modeler scientist is vital to improve the physiology, and calculation of biochemical parameters for integrating the knowledge and refining existing PBPK models. Specific PBPK covering compartments like cerebrospinal fluid, and hippocampus are required to gain mechanistic understanding about xenobiotic disposition in these sub-parts. The PBPK model assists in building quantitative adverse outcome pathways (qAOPs) for several endpoints like developmental neurotoxicity (DNT), hepatotoxicity and cardiotoxicity. Machine learning algorithms can predict physicochemical parameters required to develop in-silico models where experimental data is unavailable. Integrating machine learning with PBPK carries the potential to revolutionize the field of drug discovery and development and environmental risk. Overall, this review tried to summarize the recent developments in the in-silico models, building qAOPs, use of machine learning for improving existing models along with a regulatory perspective. This review can act as a guide for toxicologists who wish to build their careers in kinetic modeling.

Polyethylene terephthalate (PET) pollution poses significant environmental consequences, and thus new degradation methods must be explored to mitigate this problem. We previously demonstrated that a consortium of three Pseudomonas and two Bacillus species can synergistically degrade PET in culture. The consortium more readily consumes Bis(2-Hydroxyethyl) terephthalate (BHET), a byproduct made in PET depolymerization, compared to PET, and can fully convert BHET into metabolically usable monomers terephthalic acid (TPA) and ethylene glycol (EG). Because of its crystalline structure, the main limitation of the biodegradation of post-consumer PET is the initial transesterification from PET to BHET, depicting the need for the transesterification step in the degradation process. Additionally, there have been numerous studies done on the depolymerization reaction of PET to BHET, yet few have tested the biocompatibility of that product with a bacterial consortium. In this report, a two-step process was implemented for sustainable PET biodegradation, where PET is first depolymerized to form BHET using an Orange Peel Ash (OPA) catalyzed glycolysis reaction, followed by complete degradation of the BHET glycolysis product by the bacterial consortium. Results show that OPA-catalyzed glycolysis reactions can fully depolymerize PET, with an average BHET yield of 92% (w/w) and that the reaction product is biocompatible with the bacterial consortium. After inoculation with the consortium, 19% degradation of the glycolysis product was observed in 2 weeks, for a total degradation percentage of 17% when taking both steps into account. Furthermore, the 10-week total BHET degradation rate was 35%, demonstrating that the glycolysis products are biocompatible with the consortium for longer periods of time, for a total two-step degradation rate of 33% over 10 weeks. While we predict complete degradation is achievable using this method, further experimentation with the consortium can allow for a circular recycling process, where TPA can be recovered from culture media and reused to create new materials.

Salmon aquaculture generates 80% of the total revenue of finfish aquaculture across Canada. Salmon farming is carried out in a multilevel process, and at least 60% of the total production is considered as by-products, including skin, head, viscera, trimming, frames, bones, and roes. These by-products are an excellent source of protein, which can be converted to protein hydrolysates through enzymatic hydrolysis and non-enzymatic processes such as chemical hydrolysis (acid and alkaline) and salt extraction. Several studies have reported that peptides from salmon protein hydrolysates possess bioactivities, including antihypertensive, antioxidant, anticancer, antimicrobial, antidiabetic, anti-allergic, and cholesterol-lowering effects. Incorporating in-silico computational methods is gaining more attention to identify potential peptides from source protein. The in-silico methods can be used to predict the properties of the peptides and thereby predetermine the processing, isolation, and purification steps that can be used for the peptides of interest. Therefore, it is essential to implement robust, standardized, and cost-effective processing techniques that can easily be transferrable and scale up for industrial applications. This contribution summarizes the latest research information on Atlantic salmon, production statistics, growth lifecycle, processing, protein production techniques, nutritional and functional properties, peptide production and purification processes, as well as potential health benefits as a nutraceutical product.

Geijera Schott is a plant genus of the Rutaceae Juss. (rue and citrus) family, comprising six species which are all native to Oceania. Of the plants belonging to this genus, the most significant species that has a customary use is Geijera parviflora, which was used by Indigenous Australians, primarily as a pain reliever. Herein, a comprehensive review of the literature published on the genus Geijera from 1930-2023 was conducted. This is the first review for this plant genus and it highlights the chemical constituents reported to date, together with the range of pharmacological properties described from the various species and different parts of the plant. These properties include anti-inflammatory, anti-microbial, anti-parasitic, insect repellent, analgesic, neuroactive, and anti-cancer activities. Finally, a reflection on some of the important areas for future focused studies of this plant genus is provided.

Solid tumors are typically associated with unbridled proliferation of malignant cells, accompanied by an immature and dysfunctional tumor-associated vascular network. Consequent impairment in transport of nutrients and oxygen eventually leads to a hypoxic environment wherein cells must adapt to survive and overcome these stresses. Hypoxia inducible factors (HIFs) are central transcription factors in the hypoxia response and drive the expression of a vast number of survival genes in cancer cells and in cells in the tumor microenvironment. HIFs are tightly controlled by a class of oxygen sensors, the HIF-prolyl hydroxylase domain proteins (PHDs), which hydroxylate HIFs, thereby marking them for proteasomal degradation. Remarkable and intense research during the past decade has revealed that, contrary to expectations, PHDs are often overexpressed in many tumor types and that inhibition of PHDs can lead to decreased tumor growth, impaired metastasis and diminished tumor-associated immune-tolerance. Therefore, PHDs represent an attractive therapeutic target in cancer research. Multiple PHD inhibitors have been developed that have either been recently accepted in China as erythropoiesis stimulating agents (ESA) or are currently in phase III trials. We review here the function of HIFs and PHDs in cancer and related therapeutic opportunities.

Erythropoiesis is a complex process driving the production of red blood cells. During homeostasis, adult erythropoiesis takes place in the bone marrow and is tightly controlled by erythropoietin (EPO), a central hormone mainly produced in renal EPO-producing cells. The expression of EPO is strictly regulated by local changes in oxygen partial pressure (pO₂) as under deprived oxygen (hypoxia) the transcription factor Hypoxia Inducible Factor-2 induces EPO. However, erythropoiesis regulation extends beyond the well-established HIF-EPO axis, and involves processes modulated by other hypoxia pathway proteins (HPPs), including proteins involved in iron metabolism. The importance of a number of these factors is evident as their altered expression has been associated with various anemia-related disorders, including chronic kidney disease. Eventually, our emerging understanding of HPPs and their regulatory feedback will be instrumental in developing specific therapies for anemic patients and beyond.

The changing dynamics in climate is the primary and important determinant of agriculture productivity. The effects of this changing climate on overall productivity in agriculture can be understood when we study the effects of individual components contributing to the changing climate on plants and crops. Elevated CO₂ (eCO₂) and drought due to high variability in rainfall is one of the important manifestations of the changing climate. There is a considerable amount of literature that addresses climate effects on plant systems from molecules to ecosystems. Of particular interest is the effect of increased CO₂ on plants in relation to drought and water stress. As it is known that one of the consistent effects of increased CO₂ in the atmosphere is increased photosynthesis, especially in C₃ plants, it will be interesting to know the effect of drought in relation to elevated CO₂. The potential of elevated CO₂ ameliorating the effects of water deficit stress is evident from literature suggesting that these two are agents are brothers in arms protecting the plant from stress rather than partnering in crime, specifically water deficit when in isolation. The possible mechanisms by which this occurs will be discussed in this minireview. Interpreting the effects of short-term and long-term exposure of plants to elevated CO₂ in the context of ameliorating the negative impacts of drought will show us the possible ways by which there can be effective adaption to crops in the changing climate scenario.

The purpose of this article is to draw attention to the challenges faced by business organizations implementing sustainable solutions in the United Arab Emirates (UAE) and the wider Gulf Coast Countries (GCC) region. To this end, our study examines an academic theory supporting the implementation of responsible solutions to the market. Ultimately, the authors hope to inspire the reader to consider what he or she can do to ameliorate the existing challenges encountered by sustainable businesses. The analysis presented in this article implies that in recent markets, the implementation of the sustainability theory is essential for further development. The research project contributes to the increase of knowledge about corporate and organizational challenges related to running a responsible business, as well as challenges related to the application of environmental, social and economic aspects of sustainable business practices. The research is currently limited to conceptual analysis, literature review and a survey conducted during the Sustainability Week 2019 in Abu Dhabi, United Arab Emirates. Nevertheless, this is the first stage of the research project conducted by the research team in cooperation with enterprises that implement responsible solutions in many global markets, and in UAE market. The scope of the first stage of the study was limited to the analysis of data clarifying the concept of the model specified in the research. To prove the validity of the model it will be implemented and tested in cooperation with organizations participating in the research.

Development of high nutritious bakery products with optimum utilization of food waste is a major challenge for food industries. Food waste is major challenge in an each country. The optimum utilization of food waste for sustainable development goal of country is important ant for growth of the nation. The aim of the present work is to prepare value-added composite flour mixed bread from wastes of fruit and vegetables. The composite flour was prepared in four formulations of Peel and Pomace Wheat Flour (PPWF), as PPWF1, PPWF2, PPWF3 and PPWF4. Compositing flour was blended by a mix of vegetable and fruits pomace powders and whole wheat flour. Indian gooseberry pomace powder, apple pomace powder, bottle gourd peel powder, and potato peel powder were used with whole wheat flour to make pomace and whole wheat flour compositions as PPWF1, PPWF2, PPWF3 and PPWF4. Broadly this work was divided into three phases, first phase has conducted nutritional and functional analysis on peel and pomace powders individually, which shows the significance of using them for our research work. The second phase works in the creation of composite flours with different composition ratios as discussed above as PPWF. This phase shows the nutritional and functional analysis of four composite flours. Out of these four flours, PPWF3 contained a good amount of fiber 8.16%, crude protein 3.18%, total phenolic content 14.48%, moisture 9.5%, vitamin C 13.64mg/100g, and total phenolic compound 14.48(mg/GAE/g) which are maximum and acceptable range values as compared to other three composite flours and the wheat flour-control group flour. Then in the third phase, the PPWF3 is used as a partial replacement ratio of wheat flour in wheat flour due to its high phenolic content, Vitamin C, and the richness of fibers. This composite flour is used to make bread dough, two samples G1 and G2 are made; out of which G2 offers better nutritional, functional, and sensory evaluations in comparison with refined wheat four bread is taken as a control group. Thus, such utilization of food wastes in bread making can generate a value of wastes and can improve nutritional attributes of bread, which may improve an individual’s health.

The connection between marital status and suicidal behavior has been poorly assessed in South Asia. We aimed to see the proportion of marital status in individuals in suicidal behavior in South Asian countries. We followed PRISMA guidelines and registered the protocol in advance (PROSPERO 2023 CRD42023399906). A systematic search was conducted in Medline, Embase, and PsycINFO. Meta-analyses were performed to pool the proportion of married individuals with suicidal behavior (total, suicide, and suicide attempt) in South Asian countries. Our search identified 47 studies for this review from six countries published from 1999 to 2022 with a sample size ranging from 27 to 89178. The proportion of married individuals was 55.4% (95% CI 50.1-60.5) for suicidal behavior, 52.7% (95% CI 44.5 – 60.7) for suicides, and 43.1 (95% CI 32.9 – 53.9) for suicide attempts. The proportion of married persons among suicide attempts varied significantly across countries (p=0.016) which was highest (61.8%; 95% CI: 57.2 – 66.2) in India, followed by Bangladesh (52.5%; 95% CI 41.8% - 62.9%) and Pakistan (45.1%; 95% CI 30.9 – 59.9). As the current study did not assess any cause-and-effect association, a cautious interpretation is warranted while considering married marital status as a risk factor.

In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4 positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers was noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gallbladder) in comparison to primary tumors. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.

Objectives: COVID-19, a respiratory disease caused by SARS-COV2 and transmitted from person-to-person through viral droplets remains a global pandemic. There is a need to understand the transmission modes, populations at risk, and how to mitigate the spread and case fatality in the United States (US) and globally. The current study aimed to assess the global COVID-19 transmission and case fatality, examine similar parameters by countries and determine evidence-based practice in extreme epidemiology response in epidemic curve flattening and case fatality reduction. Methods: A cross-sectional ecologic design was used to assess the preexisting data on confirmed COVID-19 cases and mortality in March 2020 from the CDC, WHO, Worldodomter, and STATISTA. A rapid assessment between March 23^rd and 31^st, 2020, was utilized for the extreme epidemiology response. The case fatality, termed fatality proportion, was examined using mortality in relation to confirmed cases involving the world, United States of America (USA), United Kingdom (UK), Italy, France, Spain, China, Germany, India and South Korea. Results: The COVID-19 is a global pandemic, with the US as the epicenter for transmission, representing 20.9% of all confirmed cases worldwide, while Italy is the epicenter for case fatality, 30.6% of mortality as at 03/31/ 2020. The fatality proportion (FP) in Italy was 11.4%, Spain (8.8%), France (6.8%) and UK (6.4%). Despite the increased number of confirmed cases, the lowest FP was observed in Germany (0.96%) and South Korea (1.66%). There is increasing linear tends in transmission in the US, R²=0.97 as well as positive daily percentage change, ranging from 1.27% to 20.5%. Conclusions: The USA remains the epicenter for COVID-19 transmission, while Italy is the epicenter for case fatality. The observed relatively low case fatality in Germany and South Korea is due to an “extreme epidemiology” response through the application of Wuhan, China’s early data on COVID-19 transmission control measures and optimized patient care. These data are suggestive of relaxing the clinical guidelines in the United States in COVID-19 testing, application of contact tracing and testing, case isolation and most importantly enhancing resources for case management and social and physical distancing globally, hence epidemic curve flattening and case fatality reduction.