Experts have suggested that the next few decades will herald the fourth industrial revolution. The fourth industrial revolution will be powered by digitization, information and communications ...technology, machine learning, robotics and artificial intelligence; and will shift more decision-making from humans to machines. The ensuing societal changes will have a profound impact on both personal selling and sales management research and practices. In this article, we focus on machine learning and artificial intelligence (AI) and their impact on personal selling and sales management. We examine that impact on a small area of sales practice and research based on the seven steps of the selling process. Implications for theory and practice are derived.
Plant hormones have been extensively studied for their roles in the regulation of various aspects of plant development. However, in the last decade important new insights have been made into their ...action during development and ripening, in both dry and fleshy fruits. Emerging evidence suggests that relative functions of plant hormones are not restricted to a particular stage, and a complex network of more than one plant hormone is involved in controlling various aspects of fruit development. Though some areas are extensively covered, considerable gaps in our knowledge and understanding still exist in the control of hormonal networks and crosstalk between different hormones during fruit expansion, maturation, and various other aspects of ripening. Here, we evaluate the new knowledge on their relative roles during tomato fruit development with a view to understand their mechanism of action in fleshy fruits. For a better understanding, pertinent evidences available on hormonal crosstalk during fruit development in other species are also discussed. We envisage that such detailed knowledge will help design new strategies for effective manipulation of fruit ripening.
Named as the guardian of the genome, p53 is a tumor suppressor that regulates cell function, often through many different mechanisms such as DNA repair, apoptosis, cell cycle arrest, senescence, ...metabolism, and autophagy. One of the genes that p53 activates is MDM2, which forms a negative feedback loop since MDM2 induces the degradation of p53. When p53 activity is inhibited, damaged cells do not undergo cell cycle arrest or apoptosis. As 50% of human cancers inactivate p53 by mutation, current research focuses on reactivating p53 by developing drugs that target the p53-MDM2 interaction, which includes the binding of MDM2 and phosphorylation of p53. The objective of this article is to provide a short list and description of p53-MDM2 antagonists that may be excellent candidates for inducing cancer cell death. Relevant articles were searched for and identified using online databases such as PubMed and ScienceDirect. Increasing p53 levels, by targeting the p53-MDM2 interaction, can help p53 play its role as a tumor suppressor and induce cancer cell death. Researchers have identified different compounds that can act as inhibitors, either by directly binding to MDM2 or by modifying p53 with phosphorylation. The results associated with the drugs demonstrate the importance of targeting such interactions to inhibit cancer cell growth, which indicates that the use of the compounds may improve cancer therapeutics.
Severe alcoholic hepatitis has high short-term mortality. The aim of this study was to test the hypothesis that treatment of patients with alcoholic hepatitis with granulocyte colony-stimulating ...factor (G-CSF) might mobilize bone marrow-derived stem cells and promote hepatic regeneration and thus improve survival.
Forty-six patients with severe alcoholic hepatitis were prospectively randomized in an open study to standard medical therapy (SMT) plus G-CSF (group A; n=23) at a dose of 5 μg/kg subcutaneously every 12 h for 5 consecutive days or to SMT alone (group B; n=23) at a tertiary care center. We assessed the mobilization of CD34(+) cells on day 6, Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), and modified Maddrey's discriminant function (mDF) scores, and survival until day 90.
There was a statistically significant increase in the number of CD34(+) cells in peripheral blood in group A as compared with group B (P=0.019) after 5 days of G-GSF therapy. There was a significant reduction in median Δ change% in CTP, MELD, and mDF at 1, 2, and 3 months in group A as compared with group B (P<0.05). There was marked improvement in survival in group A as compared with group B (78.3% vs. 30.4%; P=0.001) at 90 days.
G-CSF is safe and effective in the mobilization of hematopoietic stem cells and improves liver function as well as survival in patients with severe alcoholic hepatitis.
Incorporation of selenium (Se) atom into small molecules can substantially enhance their antioxidant, anti-inflammatory, antimutagenic, antitumoral or chemopreventive, antiviral, antibacterial, ...antifungal, antiparasitic, and neuroprotective effects. Specifically, selenazo compounds have received great attention owing to their chemical properties, pharmaceutical applications, and low toxicity. In this Perspective, we compile extensive literature evidence with the description and discussion of the most recent advances in different selenazo and selenadiazo motifs as potential pharmacological candidates. We also provide some perspectives on the challenges and future directions in the advancement of these selenazo compounds, each of which could generate drug candidates for various diseases.
Colorectal cancer (CRC) has one of the highest mortality rates despite the advancement of treatment options. Aggressive CRC remains difficult to treat owing to the activation of oncogenic signaling ...pathways such as the Notch signaling pathway. The role of Notch receptors varies according to the difference in their structures; in particular, aberrant activation of Notch1 has been attributed to the severity of CRC. Notch1 activation in CRC is inhibited by small molecule inhibitors that target γ-secretase, an enzyme responsible for the third and last cleavage step of Notch receptors. γ-Secretase also produces the intracellular domain that finally carries out cellular functions by activating downstream effectors. However, most inhibitors block γ-secretase non-selectively and cause severe toxicity. Plant-source-derived small molecules, monoclonal antibodies, biological molecules (such as SiRNAs), and compounds targeting the Notch1 receptor itself or the downstream molecules such as
are some of the options that are in advanced stages of clinical trials. The Negative Regulatory Region (NRR), which plays a central role in the transduction of Notch1 signaling in the event of ligand-dependent and ligand-independent Notch1 processing is also being targeted specifically by monoclonal antibodies (mAbs) to prevent aberrant Notch1 activation. In this review, we discuss the role of Notch1 in CRC, particularly its metastatic phenotype, and how mutations in Notch1, specifically in its NRR region, contribute to the aberrant activation of Notch1 signaling, which, in turn, contributes to CRC pathogenesis. We also discuss prevailing and emerging therapies that target the Notch1 receptor and the NRR region, and we highlight the potential of these therapies in abrogating Notch signaling and, thus, CRC development and progression.
Plants, being sessile organisms, constantly withstand environmental fluctuations, including
low- temperature, also referred as cold stress. Whereas cold poses serious challenges at both physiological
...and developmental levels to plants growing in tropical or sub-tropical regions, plants from
temperate climatic regions can withstand chilling or freezing temperatures . Several cold inducible
genes have already been isolated and used in transgenic approach to generate cold tolerant plants. The
conventional breeding methods and marker assisted selection have helped in developing plant with
improved cold tolerance, however, the development of freezing tolerant plants through cold acclimation
remains an unaccomplished task. Therefore, it is essential to have a clear understanding of how
low temperature sensing strategies and corresponding signal transduction act during cold acclimation
process. Herein, we synthesize the available information on the molecular mechanisms underlying
cold sensing and signaling with an aim that the summarized literature will help develop efficient
strategies to obtain cold tolerant plants.
Since the beginning of history, natural products have been an abundant source of bioactive molecules for the treatment of different diseases, including cancer. Many allyl derivatives, which have ...shown anticancer activity both in vitro and in vivo in a large number of cancers, are bioactive molecules found in garlic, cinnamon, nutmeg, or mustard. In addition, synthetic products containing allyl fragments have been developed showing potent anticancer properties. Of particular note is the allyl derivative 17-AAG, which has been evaluated in Phase I and Phase II/III clinical trials for the treatment of multiple myeloma, metastatic melanoma, renal cancer, and breast cancer. In this Perspective, we compile extensive literature evidence with descriptions and discussions of the most recent advances in different natural and synthetic allyl derivatives that could generate cancer drug candidates in the near future.
Sphingosine kinase (SphK) is an oncogenic lipid kinase that regulates the sphingolipid metabolic pathway that has been shown to play a role in numerous hyperproliferative/inflammatory diseases. The ...SphK isoforms (SphK1 and SphK2) catalyze the conversion of the proapoptotic substrate d-erythrosphingosine to the promitogenic/migratory product sphingosine 1-phosphate (S1P). Accumulation of S1P has been linked to the development/progression of cancer and various other diseases including, but not limited to, asthma, inflammatory bowel disease, rheumatoid arthritis, and diabetic nephropathy. SphK therefore represents a potential new target for developing novel therapeutics for cancer and other diseases. This finding has stimulated the development and evaluation of numerous SphK inhibitors over the past decade or so. In this review, we highlight the recent advancement in the field of SphK inhibitors including SphK1 and SphK2 specific inhibitors. Both sphingolipid based and nolipidic small molecule inhibitors and their importance in treatment of cancer and other diseases are discussed.
Primary route of transmission of SARS-CoV-2 among humans is droplets and direct contact. Airborne transmission of this virus is not established conclusively and so is the role of airborne particulate ...matter. This commentary examines the existing evidence about the role of particulate matter pollutants in SARS-CoV-2 transmission. PM2.5and other small particulate matter have been shown to carry viable virus particles in the air and incriminated in spread of measles and SARS coronavirus. Empirical evidence has been provided regarding role of air pollution in accelerated transmission of SARS-CoV-2 in Italy as well as Wuhan. Lockdown-related reduction in PM2.5levels in ambient air may have contributed to reduce transmission of SARS-CoV-2. High PM2.5levels in the past might have added to SARS-CoV-2 related mortality due to air pollution relate comorbidities. Post-lockdown increase in PM2.5levels may accelerate covid-19 transmission and can add to the burden of COVID-19 morbidity and mortality.
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