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Post-processing contamination of Listeria monocytogenes has remained a major concern for the safety of ready-to-eat (RTE) meat products that are not reheated before consumption. Mathematical models are rapid and cost-effective tools to predict pathogen behavior, product shelf life, and safety. The objective of this study was to develop and validate a comprehensive model to predict the Listeria growth rate in RTE meat products as a function of temperature, pH, water activity, nitrite, acetic, lactic, and propionic acids. The Listeria growth data in RTE food matrices, including RTE beef, pork, and poultry products (731 data sets), were collected from the literature and databases like ComBase. The growth parameters were estimated using the logistic-with-delay primary model. The good-quality growth rate data (n = 596, R2 > 0.9) were randomly divided into 80% training (n = 480) and 20% testing (n = 116) datasets. The training growth rates were used to develop a secondary gamma model, followed by validation in testing data. The growth model’s performance was evaluated by comparing the predicted and observed growth rates. The goodness-of-fit parameter of the secondary model includes R2 of 0.86 and RMSE of 0.06 (μmax) during the development stage. During validation, the gamma model with interaction included an RMSE of 0.074 (μmax), bias, and accuracy factor of 0.95 and 1.50, respectively. Overall, about 81.03% of the relative errors (RE) of the model’s predictions were within the acceptable simulation zone (RE ± 0.5 log CFU/h). In lag time model validation, predictions were 7% fail-dangerously biased, and the accuracy factor of 2.23 indicated that the lag time prediction is challenging. The model may be used to quantify the Listeria growth in naturally contaminated RTE meats. This model may be helpful in formulations, shelf-life assessment, and decision-making for the safety of RTE meat products.

This study proposes a conceptual framework emphasising ambidextrous HRM's ability to foster organisational capabilities to survive and succeed in a challenging business environment. We include ambidextrous HRM systems in our discussion on the effectiveness of HRM fit and flexibility. To achieve this, we draw linkages between HRM systems facilitating organisational capabilities in a suitable organisational design, operating within a particular market and corresponding environmental conditions. We further discuss the relevance and operationalisation of ambidextrous HRM systems in the context of the platform-based gig economy.

India's growing population and extensive unscientific structures put the country at risk of suffering major casualties during earthquakes. To make buildings more earthquake-resistant, and develop safe and durable structures for future, we need seismic sustainability. For this purpose, Cities should adopt ‘seismic microzonation’, which includes Site response analysis (SRA). In this paper, SRA for eight places in Varanasi (India) was performed using the equivalent linear technique subjected to four significantly different strong motions (Bhuj, Uttarkashi, Chamba, and Kobe motion). Geotechnical data from various government and private entities have been gathered for this purpose. Analysis has been conducted using equivalent linear approach in DEEPSOIL software. The results of the study have been formulated in terms of surface time histories, response spectra, Fourier spectra and PGA along the depth. These findings may be applied to dynamic analysis and structural design, as well as the preparation of advanced dynamic lab tests. Furthermore, sites in Varanasi have been found to considerably enhance ground motion, thus a site-specific design approach must be implemented for important constructions.

Hypoxia is caused by a cancer-promoting milieu characterized by persistent inflammation. NF-κB and HIF-1α are critical participants in this transition. Tumor development and maintenance are aided by NF-κB, while cellular proliferation and adaptability to angiogenic signals are aided by HIF-1α. Prolyl hydroxylase-2 (PHD-2) has been hypothesized to be the key oxygen-dependent regulator of HIF-1α and NF-transcriptional B’s activity. Without low oxygen levels, HIF-1α is degraded by the proteasome in a process dependent on oxygen and 2-oxoglutarate. As opposed to the normal NF-κB activation route, where NF-κB is deactivated by PHD-2-mediated hydroxylation of IKK, this method actually activates NF-κB. HIF-1α is protected from degradation by proteasomes in hypoxic cells, where it then activates transcription factors involved in cellular metastasis and angiogenesis. The Pasteur phenomenon causes lactate to build up inside the hypoxic cells. As part of a process known as lactate shuttle, MCT-1 and MCT-4 cells help deliver lactate from the blood to neighboring, non-hypoxic tumour cells. Non-hypoxic tumour cells use lactate, which is converted to pyruvate, as fuel for oxidative phosphorylation. OXOPHOS cancer cells are characterized by a metabolic switch from glucose-facilitated oxidative phosphorylation to lactate-facilitated oxidative phosphorylation. Although PHD-2 was found in OXOPHOS cells. There is no clear explanation for the presence of NF-kappa B activity. The accumulation of the competitive inhibitor of 2-oxo-glutarate, pyruvate, in non-hypoxic tumour cells is well established. So, we conclude that PHD-2 is inactive in non-hypoxic tumour cells due to pyruvate-mediated competitive suppression of 2-oxo-glutarate. This results in canonical activation of NF-κB. In non-hypoxic tumour cells, 2-oxoglutarate serves as a limiting factor, rendering PHD-2 inactive. However, FIH prevents HIF-1α from engaging in its transcriptional actions. Using the existing scientific literature, we conclude in this study that NF-κB is the major regulator of tumour cell growth and proliferation via pyruvate-mediated competitive inhibition of PHD-2.

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.

Abstract Background In the present study, fatty acid synthesis is targeted to combat mammary gland carcinoma by activating prolyl hydroxylase-2 with Voacamine alone and in combination with Tamoxifen. It was hypothesized that the activation of prolyl hydroxylase-2 would inhibit the hypoxia-induced fatty acid synthesis and mammary gland carcinoma. Mammary gland carcinoma was induced with a single dose administration of N-methyl-N-nitrosourea (50 mg/kg,i.p.) and treatment with Voacamine and Tamoxifen 15 days after carcinogen administration. Results At the end of the study, hemodynamic profiling of animals was recorded to assess the cardiotoxic potential of the drug. Blood serum was separated and subjected to nuclear magnetic resonance spectroscopy. Carmine staining and histopathology of mammary gland tissue were performed to evaluate the anti-angiogenic potential of the drug. The antioxidant potential of the drug was measured with antioxidant markers. Western blotting was performed to study the effect of the drug at the molecular level. Conclusion Results of the study have shown that Voacamine treatment stopped further decrease in body weight of experimental animals. The hemodynamic study evidenced that Voacamine at a low dose is safe in cardiac patients. Microscopic evaluation of mammary gland tissue documented the anti-angiogenic potential of Voacamine and Tamoxifen therapy. Perturbed serum metabolites were also restored to normal along with antioxidant markers. Immunoblotting of mammary gland tissue also depicted restoration of proteins of the hypoxic and fatty acid pathway. Conclusively, Voacamine and its combination with Tamoxifen activated prolyl hydroxylase-2 to combat mammary gland carcinoma.

The current study investigated the role of combination therapy with voacamine and vincristine in preventing mammary gland carcinoma through prolyl hydroxylase-2 activation. Prolyl hydroxylase-2 activation leads to the downregulation of hypoxia-inducible factor-1α and fatty acid synthase. Overexpression of hypoxia-inducible factor-1α and fatty acid synthase has been previously reported in solid tumors of the mammary gland. After screening a battery of natural compounds similar to vincristine, voacamine was selected as a possible prolyl hydroxylase-2 activator, and its activity was evaluated using a 7,12-dimethylbenz[a]anthracene-induced rat model. The combination therapy was evaluated for cardiac toxicity using a hemodynamic profile. Angiogenic markers were evaluated by carmine staining. Monotherapy and combination therapy were also evaluated for liver and kidney toxicity using hematoxylin and eosin staining. The antioxidant potential was delineated using oxidative stress markers. The serum metabolomic profile was studied using NMR spectroscopy, and the disruption of fatty acids was evaluated using gas chromatography. Western blotting of proteins involved in hypoxic pathways was performed to decipher the action of therapy at the molecular level. Immunoblotting analysis validated that combination therapy has potential toss with prolyl hydroxylase-2 activity and thus initiates proteolytic degradation of hypoxia-inducible factor-1α and its consequent effects. Combination therapy also stimulated programmed cell death (apoptosis) in rapidly dividing cancer cells. The present study explored the role of voacamine inactivation of prolyl hydroxylase-2, which can decrease the overexpression of hypoxia-inducible factor-1α and fatty acid synthase in mammary gland carcinoma cells.

Alarmed by the frequent recurrence of industrial unrest, scholars in the field of employment relations have started to revisit the factors influencing employees’ perception of industrial relations climate. This paper proposes ethical leadership as a key ingredient in developing positive employment relations in organisations. Looking at the leader as a crucial link between employee and management, the effect of ethical leadership on employee voice behaviour through the perceived industrial relations climate is studied from the lens of social support theory. Further, the model looks at the negative association between ethical leadership and union commitment. Interestingly, ethical leadership shapes the ethical climate which, in turn, influences employees’ perception of the industrial relations climate. The proposed conceptual model integrates three key participants of employment relations viz., unions, employees, and leaders. Implications of the model for future research and practice have been discussed in detail. Keywords: Ethical leadership, Industrial relations climate, Ethical climate, Employee voice behaviour, Union commitment

Abstract Background This study evaluates the anti-cancer effects of Tadalafil (potent PDE-5 inhibitor) in female albino wistar rats against n-methyl n-nitrosourea induced mammary gland carcinogenesis. Methods The animals were selected and randomly divided among four groups and each group contains six animals per group. The animal tissue and serum samples were evaluated for the presence of antioxidant parameters and the cellular morphology was studied using carminic staining, haematoxylin staining and scanning electron microscopy followed by immunoblotting analysis. Results On the grounds of hemodynamic recordings and morphology, n-methyl n-nitrosourea treated group showed distorted changes along with distorted morphological parameters. For morphological analysis, the mammary gland tissues were evaluated using scanning electron microscopy, whole mount carmine staining, haematoxylin and eosin staining. The serum samples were evaluated for the evaluation of oxidative stress markers and inflammatory markers. The level of caspase 3 and 8 were also evaluated for the estimation of apoptosis. The fatty acid profiling of mammary gland tissue was evaluated using fatty acid methyl esters formation. The mitochondrial mediated apoptosis and inflammatory markers were evaluated using immunoblotting assay. Conclusion The results confirm that Tadalafil treatment restored all the biological markers to the normal and its involvement in mitochondrial mediated death apoptosis pathway along with inhibition of inflammatory markers.

The novel SARS-CoV-2virus that caused the disease COVID-19 is currently a pandemic worldwide. The virus requires an alveolar type-2 pneumocyte in the host to initiate its life cycle. The viral S1 spike protein helps in the attachment of the virus on toACE-2 receptors present on type-2 pneumocytes, and the S2 spike protein helps in the fusion of the viral membrane with the host membrane. Fusion of the SARS-CoV-2virus and host membrane is followed by entry of viral RNA into the host cells which is directly translated into the replicase-transcriptase complex (RTC) following viral RNA and structural protein syntheses. As the virus replicates within type-2 pneumocytes, the host immune system is activated and alveolar macrophages start secreting cytokines and chemokines, acting as an inflammatory mediator, and chemotactic neutrophils, monocytes, natural NK cells, and CD8+ T cells initiate the local phagocytosis of infected cells. It is not the virus that kills COVID-19 patients; instead, the aberrant host immune response kills them. Modifying the response from the host immune system could reduce the high mortality due to SARS-CoV-2 infection. The present study examines the viral life cycle intype-2 pneumocytes and resultant host immune response along with possible therapeutic targets.

Studies establish that job crafting, i.e. the proactive changes made in one's work through balancing available job demands and resources, results in various positive outcomes at the individual, job, and organisational levels. This study examines how employees proactively craft their jobs to avoid stress and burnout, and become better performers. We ground our study in the occupational health context of knowledge workers. Structural equation models on data from 268 Information Technology (IT) management professionals demonstrate the coping effect of job crafting in decreasing role stress and burnout, and increasing one's psychological availability, along with multiple mediation effects in improving job performance. Keywords: Job crafting, Psychological availability, Burnout, Stress, Performance, Knowledge workers

The present research was ventured to examine the effect of l-cysteine on neuro-inflammation persuaded by peripheral lipopolysaccharides (LPS, 125 μg/kg, i.p.) administration. No behavioral, biochemical, and inflammatory abnormality was perceived in the brain tissues of experimental animals after LPS administration. l-cysteine precipitated marginal symptoms of toxicity in the brain tissue. Similar pattern of wholesome effect of LPS were perceived when evaluated through the brain tissue fatty acid profile, histopathologically and NF-ĸBP65 protein expression. LPS was unsuccessful to alter the levels of hydrogen sulphide (H2S), cyclooxygenase (COX) and lipoxygenase (LOX) enzyme in brain tissue. LPS afforded significant peripheral toxicity, when figured out through inflammatory markers (COX, LOX), gaseous signaling molecules nitric oxide (NO), H2S, liver toxicity (SGOT, SGPT), and inflammatory transcription factor (NF-ĸBP65) and l-cysteine also provided a momentous protection against the same as well. The study inculcated two major finding, firstly LPS (i.p.) cannot impart inflammatory changes to brain and secondly, l-cysteine can afford peripheral protection against deleterious effect of LPS (i.p.) Keywords: Hydrogen sulphide, l-cysteine, Inflammation, Lipopolysaccharide, Neuroinflammation

Computer Aided Drug Design (CADD) molecular docking program used in this study and as a result Rifabutin was retrieved as structurally similar drug molecule to Lixisenatide (A widely used GLP-1 agonist). To afford beneficial reason in vitro study conducted which too provides a favourable mark for prospective inhibition of α-glucosidase and α-amylase enzyme and thereby evaluated for its antidiabetic potential against Streptozotocin (STZ) and Nicotinamide (NA) induced diabetes in albino wistar rats. Rifabutin demonstrated significant efficacy towards restoring the blood glucose, insulin and distorted lipid profile in the animals treated with STZ-NA. Rifabutin also regulated the inflammatory (Nitric Oxide) and oxidative stress (TBARs, SOD, Catalase, GSH and protein carbonyl) markers in the pancreatic tissue of the STZ-NA treated animals. When scrutinized on the grounds electrocardiographic and heart rate variability (HRV) changes, Rifabutin decreased the heart rate, without much affecting the QRS, QT and QTc interval. Rifabutin was also evident to be less hepatotoxic in comparison to the standard metformin, providing an added advantage as an anti-diabetic agent. The study concluded that the low dose of rifabutin can favourably regulate of the blood glucose and other biochemical paradigms in comparison to high dose of rifabutin.

The present work was undertaken to study the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on 1, 2-dimethyhydrazine (DMH) induced colon cancer and role of the cholinergic anti-inflammatory pathways (CAP) in the same. Groups of rats were randomly divided into ten groups (n = 8). DMH administration was very well apparent for autonomic dysfunction as observed through distorted hemodynamic (electrocardiogram and heart rate variability), increased aberrant crypt foci and flat neoplastic lesions (methylene blue staining, scanning electron microscopy and Hematoxylin and eosin staining). DMH administration was also recorded for per-oxidative damage. taVNS application restored the autonomic function, cellular morphology and curtailed the oxidative damage. DMH application conspicuously inhibited the mitochondrial apoptosis which was restored back after taVNS application, when scrutinized through immunoblotting and quantitative real time polymerase chain reaction studies. taVNS application up-regulated the CAP as perceived through increased expression for α7 nicotinic acetylcholine receptor(α7nAchR) and decreased expression for nuclear factor kappa-ligand-chain-enhancer of activated B cells (NFκBp65), tissue necrosis factor-α and high mobility group box-1 at protein and mRNA levels. All in all, taVNS up-surged the CAP to counteract DMH induced colon carcinogenesis. Among all the stimulation parameters used, taVNS 3 (pulse width-1 ms, frequency-6 Hz, voltage-6 v, duration-240 min) was observed to be the most effective. Since only chemotherapy and surgery are available options for management of CRC, which are troublesome and painful, there is currently no non-invasive method available for management of CRC. Results of the current study affirmed the effectiveness of taVNS against DMH induced colon cancer. The present study established taVNS as a novel and non-invasive approach toward the management of CRC.

Particular dramatic macromolecule proteins are responsible for various cellular events in our body system. Lipids have recently recognized a lot more attention of scientists for understanding the relationship between lipid and cellular function and human health However, a biological membrane is formed with a lipid bilayer, which is called a P–L–P design. Our body system is balanced through various communicative signaling pathways derived from biological membrane proteins and lipids. In the case of any fatal disease such as cancer, the biological membrane compositions are altered. To repair the biological membrane composition and prevent cancer, dietary fatty acids, such as omega-3 polyunsaturated fatty acids, are essential in human health but are not directly synthesized in our body system. In this review, we will discuss the alteration of the biological membrane composition in breast cancer. We will highlight the role of dietary fatty acids in altering cellular composition in the P–L–P bilayer. We will also address the importance of omega-3 polyunsaturated fatty acids to regulate the membrane fluidity of cancer cells.

The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibitor) were validated for their effect against methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase). The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through 1H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments.

Autism spectrum disorders (ASDs) are often considered to be genetic. They are characterized by unificational behavioral abnormalities which are classified in two basic domains: social relations and social communication, and restricted and repetitive pattern of behaviors and activity. Clinical research has evidenced that genetic and environmental factors play a major role in the development of ASD, and it is contemplated to be a multifactorial as well. Augmentation in the field of molecular genetics and neuroscience allows the pharmacologist to explore more features of ASDs using genetic, humanoid, and nonhumanoid models. Hence, the present review was undertaken to elucidate the major concepts associated with the models of ASD, such as gene or chromosome incrimination; face, predict, and construct validities; behavioral assays; and advantages and disadvantages of preclinical models along with constrains in developing genetic models for ASD.