Delineating the heterogeneity of senescence-induced-functional alterations in hepatocytes.

BACKGROUND AND AIM: Cellular senescence of hepatocytes involves permanent cell cycle arrest, disrupted cellular bioenergetics, resistance to cell death, and the release of pro-inflammatory cytokines. This 'zombie-like' state perpetuates harmful effects on tissues and holds potential implications for liver disease progression. Remarkably, senescence exhibits heterogeneity, stemming from two crucial factors: the inducing stressor and the cell type. As such, our present study endeavors to characterize stressor-specific changes in senescence phenotype, its related molecular patterns, and cellular bioenergetics in primary mouse hepatocytes (PMH) and hepatocyte-derived liver organoids (HepOrgs). METHODS: PMH, isolated by collagenase-perfused mouse liver (C57B6/J; 18-23 weeks), were cultured overnight in William's E-medium supplemented with 2% FBS, L-glutamine, and hepatocyte growth supplements. HepOrgs were developed by culturing cells in a 3D matrix for two weeks. The senescence was induced by DNA damage (doxorubicin, cisplatin, and etoposide), oxidative stress (H2O2, and ethanol), and telomere inhibition (BIBR-1532), p53 activation (nutlin-3a), DNA methyl transferase inhibition (5-azacitidine), and metabolism inhibitors (galactosamine and hydroxyurea). SA-ß galactosidase activity, immunofluorescence, immunoblotting, and senescence-associated secretory phenotype (SASP), and cellular bioenergetics were used to assess the senescence phenotype. RESULTS: Each senescence inducer triggers a unique combination of senescence markers in hepatocytes. All senescence inducers, except hydroxyurea and ethanol, increased SA-ß galactosidase activity, the most commonly used marker for cellular senescence. Among the SASP factors, CCL2 and IL-10 were consistently upregulated, while Plasminogen activator inhibitor-1 exhibited global downregulation across all modes of senescence. Notably, DNA damage response was activated by DNA damage inducers. Cell cycle markers were most significantly reduced by doxorubicin, cisplatin, and galactosamine. Additionally, DNA damage-induced senescence shifted cellular bioenergetics capacity from glycolysis to oxidative phosphorylation. In HepOrgs exposed to senescence inducers, there was a notable increase in γH2A.X, p53, and p21 levels. Interestingly, while showing a similar trend, SASP gene expression in HepOrgs was significantly higher compared to PMH, demonstrating a several-fold increase. CONCLUSION: In our study, we demonstrated that each senescence inducer activates a unique combination of senescence markers in PMH. Doxorubicin demonstrated the highest efficacy in inducing senescence, followed by cisplatin and H2O2, with no impact on apoptosis. Each inducer prompted DNA damage response and mitochondrial dysfunction, independent of MAPK/AKT.

Epidemiology and zoonotic potential of Livestock-associated Staphylococcus aureus isolated at Tamil Nadu, India.

BACKGROUND: Staphylococcus aureus is part of normal flora and also an opportunistic pathogen responsible for a wide range of infections in both humans and animals. Livestock-associated S. aureus (LA-SA) has gained importance in recent years due to its increased prevalence in recent years, becoming a worry in public health view. This study aimed to study the epidemiology of LA-SA strains in Madurai district, Tamil Nadu, India. METHODS: A total of 255 samples were collected from bovine and other small ruminants like goats and sheep nares (n = 129 and n = 126 respectively). Nasal swab samples were collected from study animals with sterile sample collecting cotton swabs (Hi-Media, Mumbai). Samples were transported to the lab in Cary-Blair Transport media for further analysis. The samples were tested for S. aureus using antibiotic selection and PCR-based assays. The pathogenicity of the bacteria was assessed using chicken embryo models and liver cross-sections were used for histopathology studies. RESULTS: The prevalence rate in bovine-associated samples was 42.63% but relatively low in the case of small ruminants associated samples with 28.57% only. The overall prevalence of S. aureus is found to 35.6% and MRSA 10.98% among the study samples. The antibiogram results that LA-SA isolates were susceptible to aminoglycosides and tetracyclines but resistant to ß-lactam drugs. The biofilm formation results showed that the LA-SA isolates are weak to high-capacity biofilm formers. The enterotoxigenic patterns revealed that most of the isolated strains are enterotoxigenic and possess classical enterotoxins. The survival analysis of chicken embryos suggested that the Bovine-associated strains were moderately pathogenic. CONCLUSION: The study concluded that economically important livestock animals can act as reservoirs for multi-drug resistant and pathogenic which in-turn is a concern for public health as well as livestock health.

Glass transitions in frozen systems as influenced by molecular weight of food components.

Freezing is a frequently used way to expand the storage life of foods with high water content. Under suitable cooling rates, frozen systems attain a condition of maximum freeze concentration, which is characterized by the glass transition temperature (Tg '), end point of freezing or onset of melting (Tm '), and concentration of solids (Xs ') in the maximum-freeze-concentrated matrix. The value of Tg ', Tm ', and Xs ' depends on the chemical composition of frozen system. Below Tg ', the rates of deteriorative reactions are significantly reduced. In this article, the data for Tg ', Tm ', and Xs ' of different frozen systems including sugars, starches, proteins, and food are collected and compiled. The trends in Tg ' and Tm ' data of food are investigated using molecular weight (MW) of food components. The Tg ' and Tm ' of most starches (increased by 2.46% to 87.3% and 10.8% to 85.0%) and some protein-rich foods (increased by 5.00% to 53.4% and 25.0% to 52.9%) were higher than the maximum values of sugar-rich foods. Both Tg ' and Tm ' values increased with increasing MW of solids in frozen food, reaching an asymptotic value. Moreover, there were exponential relationships between Tg ' or Tm ' values and MW for sugar and starch-rich foods taken together. Some studies found that frozen storage below Tg ' maintains the higher quality of food that was achieved by fast freezing. However, other studies found that there was no significant difference in the quality of frozen foods between storage temperature below and above Tg '. Therefore, storage below Tg ' is not the only factor for predicting the stability of frozen foods.

DNA methylation microarray uncovers a permissive methylome for cardiomyocyte differentiation in human mesenchymal stem cells.

Differentiation of Wharton's Jelly-Mesenchymal Stem cells (WJ-MSCs) into cardiomyocytes (CMs) in vitro has been reported widely although contradictions remain regarding the maturation of differentiated MSCs into fully functioning CMs. Studies suggest that use of epigenetic modifiers like 5'Azacytidine (5-AC) in MSCs de-methylates DNA and results in expression of cardiac-specific genes (CSGs). However, only partial expression of the CSG set leads to incomplete differentiation of WJ-MSCs to CMs. We used the Agilent 180 K human DNA methylation microarray on WJ-MSCs, 5-AC treated WJ-MSCs and human cardiac tissue (hCT) to analyze differential DNA methylation profiles which were then validated by bisulfite sequencing PCR (BSP). BSP confirmed that only a limited number of CSGs were de-methylated by 5-AC in WJ-MSCs. It also revealed that hCT displays a methylation profile similar to promoter regions of CSG in untreated WJ-MSCs. Thus, the presence of hypo-methylated CSGs indicates that WJ-MSCs are ideal cell types for cardiomyogenic differentiation.

Ex vivo model for studying endothelial tip cells: Revisiting the classical aortic-ring assay.

A drug undergoes several in silico, in vitro, ex vivo and in vivo assays before entering into the clinical trials. In 2014, it was reported that only 32% of drugs are likely to make it to Phase-3 trials, and overall, only one in 10 drugs makes it to the market. Therefore, enhancing the precision of pre-clinical trial models could reduce the number of failed clinical trials and eventually time and financial burden in health sciences. In order to attempt the above, in the present study, we have shown that aortic ex-plants isolated from different stages of chick embryo and different regions of the aorta (pulmonary and systemic) have differential sprouting potential and response to angiogenesis modulatory drugs. Aorta isolated from HH37 staged chick embryo showed 16% (p < 0.001) and 11% (p < 0.001) increase in the number of tip cells at 72 h of culture compared to that of HH35 and HH29 respectively. The ascending order of the number of tip cells was found as central (Gen II), proximal (Gen I) and distal (Gen III) in a virtual zonal segmentation of endothelial sprouting. The HH37 staged aortas displayed differential responses to pro- and anti-angiogenic drugs like Vascular endothelial growth factor (VEGF), nitric oxide donor (spNO), and bevacizumab (avastin), thalidomide respectively. The human placenta tissue-culture however evinced endothelial sprouting only on day 12, with a gradual decrease in the number of tip cells until 21 days. In summary, this study provides an avant-garde angiogenic model emphasized on tip cells that would enhance the precision to test next-generation angiogenic drugs.

Differential expression of CRAC channel in alloxan induced Diabetic BALB/c mice.

Objectives: CRAC (Calcium Release Activated Calcium) channel is one of the most important channels regulating calcium influx and has been involved in many autoimmune diseases. The contribution of CRAC channel in the pathogenesis of Type 1 Diabetes (T1D) has not been described much. Thus, we aimed to study the expression of CRAC channel and inflammatory cytokines like IL-1ß (Interleukin -1ß) and TNF-α (Tumor Necrosis Factor-α) in the spleen-derived cytotoxic T cells, Bone marrow monocytes (BMM) and macrophages differentiated from BMM in the alloxan induced T1D mice.Materials and methods: BALB/c mice treated with alloxan and vehicle control for 12 and 24 h. Spleen derived T cells; Bone marrow derived monocytes were isolated from the control and diabetic BALB/c mice as well as macrophages differentiated from the control and diabetic BMM.Results: We observed increased expression of CRAC channel components like STIM1 (Stromal Interaction Molecule), ORAI1 and ORAI2 and inflammatory cytokines like IL-1ß and TNF-α in the spleen derived cytotoxic T cells and Macrophages differentiated from BMM as well as the downregulated expression of the same and CRAC channel in BMM of 12 and 24 h alloxan induced BALB/c mice.Conclusions: This study suggests that differential expression of CRAC channel correlated with the expression of inflammatory cytokines, thus CRAC channel might be responsible for the increased production of inflammatory cytokines in the alloxan induced T1D mice.

Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity.

Thalidomide is an infamous teratogen and it is continuously being explored for its anticancer properties. Fibroblast growth factor receptors (FGFRs) are implicated in embryo development and cancer pathophysiology. With striking similarities observed between FGFR implicated conditions and thalidomide embryopathy, we hypothesized thalidomide targets FGFRs. We utilized three different cell lines and chicken embryo model to investigate the effects of thalidomide and analogs on FGFR expression. We performed molecular docking, KINOMEscan analysis, and kinase activity assays to study the drug-protein interactions. The expression of FGFR1 and FGFR2 was differentially regulated by all the three drugs in cells as well as in developing organs. Transcriptome analysis of thalidomide-treated chick embryo strongly suggests the modulation of FGFR signaling and key transcription factors. Corroboration with previous studies suggests that thalidomide might affect FGFR expression through the transcription factor, E2F1. At the protein level, molecular docking predicted all three analogs to interact with lysine residue at 517th and 508th positions of FGFR2 and FGFR3, respectively. This lysine coordinates the ATP binding site of FGFR, thus hinting at the possible perturbation of FGFR activity by thalidomide. Kinome analysis revealed that kinase activities of FGFR2 and FGFR3 (G697C) reduced by 31% and 65%, respectively, in the presence of 10 µM thalidomide. Further, we checked and confirmed that the analogs inhibited the FGFR2 kinase activity in a dose-dependent manner. This study suggests that FGFRs could be potential targets of thalidomide and the two analogs, and also endorses the link between the teratogenicity and antitumor activities of the drugs.

Nitric Oxide Reverses the Position of the Heart during Embryonic Development.

Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) plays crucial roles in cardiac homeostasis. Adult cardiomyocyte specific overexpression of eNOS confers protection against myocardial-reperfusion injury. However, the global effects of NO overexpression in developing cardiovascular system is still unclear. We hypothesized that nitric oxide overexpression affects the early migration of cardiac progenitor cells, vasculogenesis and function in a chick embryo. Vehicle or nitric oxide donor DEAN (500 mM) were loaded exogenously through a small window on the broad side of freshly laid egg and embryonic development tracked by live video-microscopy. At Hamburg Hamilton (HH) stage 8, the cardiac progenitor cells (CPC) were isolated and cell migration analysed by Boyden Chamber. The vascular bed structure and heart beats were compared between vehicle and DEAN treated embryos. Finally, expression of developmental markers such as BMP4, Shh, Pitx2, Noggin were measured using reverse transcriptase PCR and in-situ hybridization. The results unexpectedly showed that exogenous addition of pharmacological NO between HH stage 7⁻8 resulted in embryos with situs inversus in 28 out of 100 embryos tested. Embryos treated with NO inhibitor cPTIO did not have situs inversus, however 10 embryos treated with L-arginine showed a situs inversus phenotype. N-acetyl cysteine addition in the presence of NO failed to rescue situs inversus phenotype. The heart beat is normal (120 beats/min) although the vascular bed pattern is altered. Migration of CPCs in DEAN treated embryos is reduced by 60% compared to vehicle. BMP4 protein expression increases on the left side of the embryo compared to vehicle control. The data suggests that the NO levels in the yolk are important in turning of the heart during embryonic development. High levels of NO may lead to situs inversus condition in avian embryo by impairing cardiac progenitor cell migration through the NO-BMP4-cGMP axis.

Mechanistic insights into the differential effects of thalidomide and lenalidomide in metastatic prostate cancer.

AIM: To understand why thalidomide and lenalidomide exhibit different responses in metastatic prostate cancer (mPCa) treatment. METHODS: We analyzed the perturbation signatures of thalidomide, lenalidomide, flutamide treated mPCa cell line from Library of Integrated Network-based Cellular Signatures database and transcriptome of docetaxel-treated mPCa patients. RESULTS: Flutamide and docetaxel downregulated 'Steroid Biosynthesis', 'Cell cycle' and PCa specific transcription factor networks. Thalidomide inhibited 'Cell cycle' and 'E2F network', possibly accounting for its synergistic effects with docetaxel. Conversely, lenalidomide promoted 'Cell cycle' and 'Cholesterol biosynthesis'. CONCLUSION: Hence, we propose that lenalidomide upregulates cholesterol synthesis followed by enhanced rate of cell cycle, thereby nurturing a hyperproliferative tumor microenvironment. In summary, this study offers a possible explanation for the differential outcomes in the treatment of mPCa with thalidomide and lenalidomide.

Transcriptomic Analysis of Thalidomide Challenged Chick Embryo Suggests Possible Link between Impaired Vasculogenesis and Defective Organogenesis.

Since the conception of thalidomide as a teratogen, approximately 30 hypotheses have been put forward to explain the developmental toxicity of the molecule. However, no systems biology approach has been taken to understand the phenomena yet. The proposed work was aimed to explore the mechanism of thalidomide toxicity in developing chick embryo in the context of transcriptomics by using genome wide RNA sequencing data. In this study, we challenged the developing embryo at the stage of blood island formations (HH8), which is the most vulnerable stage for thalidomide-induced deformities. We observed that thalidomide affected the early vasculogenesis through interfering with the blood island formation extending the effect to organogenesis. The transcriptome analyses of the embryos collected on sixth day of incubation showed that liver, eye, and blood tissue associated genes were down regulated due to thalidomide treatment. The conserved gene coexpression module also indicated that the genes involved in lens development were heavily affected. Further, the Gene Ontology analysis explored that the pathways of eye development, retinol metabolism, and cartilage development were dampened, consistent with the observed deformities of various organs. The study concludes that thalidomide exerts its toxic teratogenic effects through interfering with early extra-embryonic vasculogenesis and ultimately gives an erroneous transcriptomic pattern to organogenesis.

Effect of Molecular Interactions on Electron-Transfer and Antioxidant Activity of Bis(alkanol)selenides: A Radiation Chemical Study.

Understanding electron-transfer processes is crucial for developing organoselenium compounds as antioxidants and anti-inflammatory agents. To find new redox-active selenium antioxidants, we have investigated one-electron-transfer reactions between hydroxyl ((.) OH) radical and three bis(alkanol)selenides (SeROH) of varying alkyl chain length, using nanosecond pulse radiolysis. (.) OH radical reacts with SeROH to form radical adduct, which is converted primarily into a dimer radical cation (>Se∴Se<)(+) and α-{bis(hydroxyl alkyl)}-selenomethine radical along with a minor quantity of an intramolecularly stabilized radical cation. Some of these radicals have been subsequently converted to their corresponding selenoxide, and formaldehyde. Estimated yield of these products showed alkyl chain length dependency and correlated well with their antioxidant ability. Quantum chemical calculations suggested that compounds that formed more stable (>Se∴Se<)(+) , produced higher selenoxide and lower formaldehyde. Comparing these results with those for sulfur analogues confirmed for the first time the distinctive role of selenium in making such compounds better antioxidants.

Contrasting reactions of hydrated electron and formate radical with 2-thio analogues of cytosine and uracil.

2-Thiocytosine (TC) and 2-thiouracil (TU) were subjected to hydrated electron (eaq-), formate radical (CO2˙-) and 2-hydroxypropan-2-yl radical ((CH3)2˙COH) reactions in aqueous medium. Transients were characterized by absorption spectroscopy and the experimental findings were rationalized by DFT calculations at LC-ωPBE and M06-2X levels using a 6-311+G(d,p) basis set and SMD solvation. In eaq- reactions, a ring N-atom protonated radical of TC and an exocyclic O-atom protonated radical of TU were observed via addition of eaq- and subsequent protonation by solvent molecules. However, two competing but simultaneous mechanisms are operative in CO2˙- reactions with TC and TU. The first one corresponds to formations of N(O)-atom protonated radicals (similar to eaq- reactions); the second mechanism led to 2 center-3 electron, sulfur-sulfur bonded neutral dimer radicals, TCdim˙ and TUdim˙. DFT calculations demonstrated that H-abstraction by CO2˙- from TC(TU) results in S-centered radical which upon combination with TC(TU) provide the dimer radical. In some cases, DFT energy profiles were further validated by CBS-QB3//M06-2X calculations. This is the first time report for a contradictory behavior in the mechanisms of eaq- and CO2˙- reactions with any pyrimidines or their thio analogues.

Transcriptomics-driven metabolic pathway analysis reveals similar alterations in lipid metabolism in mouse MASH model and human.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease worldwide, and can rapidly progress to metabolic dysfunction-associated steatohepatitis (MASH). Accurate preclinical models and methodologies are needed to understand underlying metabolic mechanisms and develop treatment strategies. Through meta-analysis of currently proposed mouse models, we hypothesized that a diet- and chemical-induced MASH model closely resembles the observed lipid metabolism alterations in humans. METHODS: We developed transcriptomics-driven metabolic pathway analysis (TDMPA), a method to aid in the evaluation of metabolic resemblance. TDMPA uses genome-scale metabolic models to calculate enzymatic reaction perturbations from gene expression data. We performed TDMPA to score and compare metabolic pathway alterations in MASH mouse models to human MASH signatures. We used an already-established WD+CCl4-induced MASH model and performed functional assays and lipidomics to confirm TDMPA findings. RESULTS: Both human MASH and mouse models exhibit numerous altered metabolic pathways, including triglyceride biosynthesis, fatty acid beta-oxidation, bile acid biosynthesis, cholesterol metabolism, and oxidative phosphorylation. We confirm a significant reduction in mitochondrial functions and bioenergetics, as well as in acylcarnitines for the mouse model. We identify a wide range of lipid species within the most perturbed pathways predicted by TDMPA. Triglycerides, phospholipids, and bile acids are increased significantly in mouse MASH liver, confirming our initial observations. CONCLUSIONS: We introduce TDMPA, a methodology for evaluating metabolic pathway alterations in metabolic disorders. By comparing metabolic signatures that typify human MASH, we show a good metabolic resemblance of the WD+CCl4 mouse model. Our presented approach provides a valuable tool for defining metabolic space to aid experimental design for assessing metabolism.

Steatotic liver disease, in which fat accumulates in the liver, is one of the most prevalent liver diseases worldwide and it is important to develop relevant animal models to help us understand its mechanisms. We aimed to assess the suitability of animal models for studying steatotic liver disease in humans. We developed an approach that evaluates how genes affect the metabolism or the chemical reactions and processes that occur in the body. We used it to compare a mouse model of the disease with human observations. Our results showed that there are significant changes in fat and energy metabolism in the mouse model. These observations match with changes observed in humans, suggesting it is a good model for studying human disease. Our findings could advance our understanding of the disease as well as help define strategies for its treatment.

Machine learning based-model to predict catalytic performance on removal of hazardous nitrophenols and azo dyes pollutants from wastewater.

To maintain human health and purity of drinking water, it is crucial to eliminate harmful chemicals such as nitrophenols and azo dyes, considering their natural presence in the surroundings. In this particular research study, the application of machine learning techniques was employed in order to make an estimation of the performance of reduction catalysis in the context of ecologically detrimental nitrophenols and azo dyes contaminants. The catalyst utilized in the experiment was Ag@CMC, which proved to be highly effective in eliminating various contaminants found in water, like 4-nitrophenol (4-NP). The experiments were carefully conducted at various time intervals, and the machine learning procedures used in this study were all employed to forecast catalytic performance. The evaluation of the performance of such algorithms were done by means of Mean Absolute Error. The noteworthy findings of this research indicated that the ADAM and LSTM algorithm exhibited the most favourable performance in the case of toxic compounds i.e. 4-NP. Moreover, the Ag@CMC catalyst demonstrated an impressive reduction efficiency of 98 % against nitrophenol in just 8 min. Thus, based on these compelling results, it can be concluded that Ag@CMC works as a highly effective catalyst for practical applications in real-world scenarios.

A novel framework for the evaluation of coastal protection schemes through integration of numerical modelling and artificial intelligence into the Sand Engine App.

There is growing interest in the adoption of Engineering with Nature or Nature Based Solutions for coastal protection including large mega-nourishment interventions. However, there are still many unknowns on the variables and design features influencing their functionalities. There are also challenges in the optimization of coastal modelling outputs or information usage in support of decision-making. In this study, more than five hundred numerical simulations with different sandengine designs and different locations along Morecambe Bay (UK) were conducted in Delft3D. Twelve Artificial Neural Networking ensemble models structures were trained on the simulated data to predict the influence of different sand engines on water depth, wave height and sediment transports with good performance. The ensemble models were then packed into a Sand Engine App developed in MATLAB and designed to calculate the impact of different sand engine features on the above variables based on users' inputs of sandengine designs.

Comprehensive insights into the multifaceted roles of the transient receptor potential vanilloid 1 channel in the digestive system.

The transient receptor potential vanilloid (TRPV) channel, a family of calcium transporters comprising six distinct members (TRPV1-6), takes on a paramount role in maintaining intracellular Ca2+ homeostasis in mammalian cells. Notably, TRPV1, among its counterparts, has emerged as the subject of extensive scrutiny, owing to its pervasive presence in diverse cellular, tissue, and organ settings. This ubiquitous distribution underscores its fundamental involvement in the genesis of pain, making it a central focus in pain-related research. However, recent investigations have unveiled that TRPV1's functional significance transcends the realm of pain modulation, extending its influence to encompass a wide spectrum of physiological and pathological processes. The ambit of TRPV1's influence encompasses not only pain responses but also embraces the intricate domains of nervous system disorders, cancer metastasis, as well as afflictions pertaining to the skin and heart. Moreover, compelling evidence now demonstrates that TRPV1 also wields substantial sway in the domain of digestive diseases, further highlighting its versatility and far-reaching impact on human health. Therefore, this comprehensive review endeavors to delve into the multifaceted roles played by TRPV1 in the various organs constituting the digestive system.

Formation and characterization of leaf waste into organic compost.

In solid waste management, pollution-free disposal of leaf waste in urban areas is still not standardized and adopted. According to the World Bank report, 57% of wastes generated in South East Asia are consisted of food and green waste, which can be recycled into valuable bio-compost. The present study shows a method of leaf litter waste management by composting it using essential microbe (EM) method. Different parameters, such as pH, electrical conductivity, macronutrients, micronutrients, and potentially toxic elements (PTE) were measured at zero to 50 days of composting using appropriate methods. The microbial composting was shown to mature within 20 to 40 days, and its maturity could be evaluated by the attainment of stable pH (8), electrical conductivity (0.9 mS/cm), and C:N ratio ≥ 20. The analysis was also performed on other bio-composts viz. kitchen waste compost, vermicompost, cow dung manure, municipal organic waste compost, and neem cake compost. The fertility index (FI) was evaluated based on six parameters viz. total carbon, total nitrogen, N ratio, phosphorus, potassium, and sulphur contents. The PTE values were used to calculate their clean index (CI). The results showed that leaf waste compost has a higher fertility index (FI = 4.06) than other bio-composts, except the neem cake compost (FI = 4.44). The clean index of the leaf waste compost (CI = 4.38) was also higher than other bio-composts. This indicates that leaf waste compost is a valuable bio-resource with high nutritive value and low PTE contamination, with a favourable prospective to be used in organic farming.

Hybrid mixture theory-based modeling of transport of fluids, species, and heat in food biopolymers subjected to freeze-thaw cycles.

A hybrid mixture theory (HMT)-based unsaturated transport (pores not saturated with liquid) model was applied to a food matrix subjected to freezing and freeze-thaw cycles. The model can explain the fluid, species, and heat transport, ice formation, thermomechanical changes, and the freezing point depression occurring inside food biopolymers during freezing. Volume changes during freezing were calculated using the stresses due to pore pressure and the phase-change based mechanical strain. The Eulerian-Lagrangian transformation was performed for solving the equations using a finite element mesh in Lagrangian coordinates. The predicted temperature profiles for constant and fluctuating freezing temperature conditions showed agreement with experimental data with reasonable accuracy (RMSE = 2.86°C and 2.23°C, respectively). The multiscale transport model coupled with a physical chemistry-based relation was able to predict solute concentration and the freezing point depression in potatoes with greater accuracy than an empirical equation published in the literature. Sudden temperature fluctuations representing the opening and closing of a freezer door were investigated using this solution scheme, and conditions causing less damage to the food were identified. PRACTICAL APPLICATION: Food materials are subjected to freeze-thaw cycles during storage, shipping, and distribution to the consumers. The study uses numerical modeling and experimental validation to elucidate the principles affecting ice formation, solute migration, and temperature changes. Outcomes will allow processors to improve the quality of frozen foods with improved design of freezing operation, and storage and distribution strategies.

Predicting evaporation with optimized artificial neural network using multi-objective salp swarm algorithm.

Evaporation is a crucial component to be established in agriculture management and water engineering. Evaporation prediction is thus an essential issue for modeling researchers. In this study, the multilayer perceptron (MLP) was used for predicting daily evaporation. MLP model is as one of the famous ANN models with multilayers for predicting different target variables. A new strategy was used to enhance the accuracy of the MLP model. Three multi-objective algorithms, namely, the multi-objective salp swarm algorithm (MOSSA), the multi-objective crow algorithm (MOCA), and the multi-objective particle swarm optimization (MOPSO), were respectively and separately coupled to the MLP model for determining the model parameters, the best input combination, and the best activation function. In this study, three stations in Malaysia, namely, the Muadzam Shah (MS), the Kuala Terengganu (KT), and the Kuantan (KU), were selected for the prediction of the respective daily evaporation. The spacing (SP) and maximum spread (MS) indices were used to evaluate the quality of generated Pareto front (PF) by the algorithms. The lower SP and higher MS showed better PF for the models. It was observed that the MOSSA had higher MS and lower SP than the other algorithms, at all stations. The root means square error (RMSE), mean absolute error (MAE), percent bias (PBIAS), and Nash Sutcliffe efficiency (NSE) quantifiers were used to compare the ability of the models with each other. The MLP-MOSSA had reduced RMSE compared to the MLP-MOCA, MLP-MOPSO, and MLP models by 18%, 25%, and 35%, respectively, at the MS station. The MAE of the MLP-MOSSA was 2.7%, 4.1%, and 26%, respectively lower than those of the MLP-MOCA, MLP-MOPSO, and MLP models at the KU station. The MLP-MOSSA showed lower MAE than the MLP-MOCA, MLP-MOPSO, and MLP models by 16%, 18%, and 19%, respectively, at the KT station. An uncertainty analysis was performed based on the input and parameter uncertainty. The results indicated that the MLP-MOSSA had the lowest uncertainty among the models. Also, the input uncertainty was lower than the parameter uncertainty. The general results indicated that the MLP-MOSSA had the high efficiency for predicting evaporation.

Ketogenic Diets and Hepatocellular Carcinoma.

The ketogenic diet (KD) is a low-carbohydrate, high-fat diet regarded as a potential intervention for cancers owing to its effects on tumor metabolism and behavior. Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer, and its management is worth investigating because of the high fatality rate. Additionally, as the liver is the glucose and lipid metabolism center where ketone bodies are produced, the application of KD to combat HCC is promising. Prior studies have reported that KD could reduce the energy supply and affect the proliferation and differentiation of cancer cells by lowering the blood glucose and insulin levels. Furthermore, KD can increase the expression of hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in hepatocytes and regulate lipid metabolism to inhibit the progression of HCC. In addition, ß-hydroxybutyrate can induce histone hyperacetylation and reduce the expression of inflammatory factors to alleviate damage to hepatocytes. However, there are few relevant studies at present, and the specific effects and safety of KD on HCC warrant further research. Optimizing the composition of KD and combining it with other therapies to enhance its anti-cancer effects warrant further exploration.