Cancer is the second leading cause of death globally. Chemotherapy and radiation therapy and other medications are employed to treat various types of cancer. However, each treatment has its own set ...of side effects, owing to its low specificity. As a result, there is an urgent need for newer therapeutics that do not disrupt healthy cells’ normal functioning. Depriving nutrient or non/semi-essential amino acids to which cancerous cells are auxotrophic remains one such promising anticancer strategy.
l
-Arginine (Arg) is a semi-essential vital amino acid involved in versatile metabolic processes, signaling pathways, and cancer cell proliferation. Hence, the administration of Arg depriving enzymes (ADE) such as arginase, arginine decarboxylase (ADC), and arginine deiminase (ADI) could be effective in cancer therapy. The Arg auxotrophic cancerous cells like hepatocellular carcinoma, human colon cancer, leukemia, and breast cancer cells are sensitive to ADE treatment due to low expression of crucial enzymes argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), and ornithine transcarbamylase (OCT). These therapeutic enzyme treatments induce cell death through inducing autophagy, apoptosis, generation of oxidative species, i.e., oxidative stress, and arresting the progression and expansion of cancerous cells at certain cell cycle checkpoints. The enzymes are undergoing clinical trials and could be successfully exploited as potential anticancer agents in the future.
G20 countries are responsible for more than 80% of global energy consumption and the largest CO
2
emissions in the world. Literature related to the energy consumption-environmental quality-subjective ...wellbeing nexus is limited and lacks consensus. This paper analyses the impact of energy consumption and environmental quality on subjective wellbeing in G20 countries from 2006 to 2019 using a panel-corrected standard error (PCSE) model. Cantril life ladder data is used as a proxy of subjective wellbeing. For robustness, the Newey-West standard error model is used. The findings reveal that renewable energy consumption and environmental quality, i.e. lesser carbon emissions, enhance subjective wellbeing in G20 countries. In contrast, non-renewable energy consumption degrades subjective wellbeing. Moreover, the study also finds bidirectional causality between renewable energy consumption, non-renewable energy consumption, and economic growth. The policymakers of these countries should encourage renewable energy production and its consumption to reduce carbon emissions for conserving the environment and enhancing their people’s subjective wellbeing.
Objective
The application of phytases helps in releasing bound phosphorus and other nutrients in cattle feed eventually reducing the need for supplementations. However, high production cost owing to ...the unavailability of cheaper sources of phytases has limited their usage in developing countries. Herein, firstly isolation, identification of a phytase from fungal isolate,
Aspergillus niger
NT7 was carried out followed by optimizing of all production parameters, through solid-state fermentation (SSF). Secondly, crude phytase was characterized and potential applicability of crude phytase was evaluated for dephytinization of wheat bran.
Results
The highest phytase production (208.30 ± 0.22 U/gds) was achieved using wheat bran as cheap agro-industrial substrate for SSF. The various physiological parameters were optimized including inoculum age and level (3-day old inoculum and 15 × 10
7
spores/ml), temperature (35 °C), a moistening agent (distilled water), medium pH (5), and supplementation of various biochemicals like sugar (Mannitol), nitrogen (ammonium sulphate) and detergent (Tween 80). Process optimization through one variable at a time (OVAT) approach increased the difference in productivity to more than 200%. The crude phytase of
A. niger
NT7 was thermostable, with optimal activity at 60 °C and also displayed optimal activity over a broad range of acidic pH. Further, enhancement in phytase activity was found specifically in the presence of Ca
2+
, Zn
2+
, and Co
2+
ions, while other metal ions including Fe
2+
, Fe
3+
, Mn
2+
, Mg
2+
and Cu
2+
inhibited its activity. Finally, the phytase showed efficient and sustained release of inorganic phosphate, proteins, and reducing sugars (> 60 h) from livestock feed.
Conclusion
Overall, our report highlights the production of an efficient and thermotolerant phytase with potential as a low-cost animal feed supplement.
Graphic abstract
Postmenopausal women are at high risk of developing breast cancer due to estrogen production in peripheral tissues of the body other than ovaries. Aromatase is present in breast tissue, leading to ...local estrogen production which can be inhibited by a variety of steroidal and nonsteroidal aromatase inhibitors. There are many aromatase inhibitors available in clinical practice like exemestane, formestane, anastrozole, letrozole, fadrozole, vorozole, and so forth, but the major challenge in anti‐breast cancer therapy is the toxicity associated with aromatase inhibitors, especially the steroidal class of drugs. It is, therefore, urgently required to develop novel anticancer drugs having better safety and efficacy for the treatment of breast cancer. This study highlights the aromatase inhibitors reported in the current literature as well as the recent advances in the management of breast cancer.
There are many aromatase inhibitors available in clinical practice, but the major challenge in anti‐breast cancer therapy is the toxicity associated with them, especially the steroidal class of drugs. This study highlights the aromatase inhibitors reported in the current literature as well as recent advances in the management of breast cancer.
Metal cations such as Zn
2+
, Al
3+
, Hg
2+
, Cd
2+
, Sn
2+
, Fe
2+
, Fe
3+
and Cu
2+
play important roles in biology, medicine, and the environment. However, when these are not maintained in proper ...concentration, they can be lethal to life. Therefore, selective sensing of metal cations is of great importance in understanding various metabolic processes, disease diagnosis, checking the purity of environmental samples, and detecting toxic analytes. Schiff base probes have been largely used in designing fluorescent sensors for sensing metal ions because of their easy processing, availability, fast response time, and low detection limit. Herein, an in-depth report on metal ions recognition by some Schiff base fluorescent sensors, their sensing mechanism, their practical applicability in cell imaging, building logic gates, and analysis of real-life samples has been presented. The metal ions having biological, industrial, and environmental significance are targeted. The compiled information is expected to prove beneficial in designing and synthesis of the related Schiff base fluorescent sensors.
The current study aimed to achieve the enhanced phytase production from
Aspergillus niger
NT7 using the statistical method in solid-state fermentation to diminish their cost significantly for ...commercial purposes. The six different variables — the substrate’s amount, temperature, incubation time, pH, the concentration of mannitol, and ammonium sulfate — identified as critical parameters from the one variable at a time (OVAT) approach, were further modeled and optimized in solid-state fermentation using response surface methodology (RSM). Increased phytase production (521 ± 28.16 Ugds
−1
) by RSM was attained with 5-g wheat bran supplemented with 2% mannitol, 0.5% ammonium sulfate, and pH 4.3 at 35 °C after five days of fermentation. The phytase production was enhanced by 6.8- and 2.5-fold after statistical optimization compared to unoptimized culture conditions and OVAT methodology, respectively. Further, dephytinization of maize bran using crude phytase preparation resulted in ameliorated nutritional status with the release of phosphorous, reducing sugars, proteins, and minerals (Mn, Fe, Mg, Zn, and Ca). To the best of our knowledge, this is the first report showing the nutritional enhancement of maize bran and the analysis of released minerals by ICP-MS using crude enzyme preparation. The current study successfully demonstrates the potential application of
A
.
niger
NT7 phytase for mitigating the antinutrient nature of phytate molecules in feed supplementation.
Graphical abstract
Pralsetinib (PRL) is a selective Rearranged during Transfection (RET) inhibitor, developed by Blueprint Medicines Corporation for the treatment of RET fusion non-small-cell lung cancer (NSCLC), ...papillary thyroid cancer (PTC), and medullary thyroid carcinoma (MTC). RET is a known proto-oncogene found in NSCLC, PTC, and MTC. PRL was recently granted accelerated USFDA approval with the brand name GAVRETO™ on 4 September 2020 to treat metastatic RET fusion-positive NSCLC and was updated on 1 December 2020 with the addition of advanced and metastatic RET-altered MTC and PTC in the USA. On 19 November 2021, the European Commission granted conditional marketing authorization to PRL for use as a single agent in adult patients with RET fusion-positive advanced NSCLC. They were not previously treated with an RET inhibitor. This review article summarizes the milestones in the development of PRL, chemistry, chemical (synthesis) research and development, characterization and identification of PRL-resistant RET mutants, the structural basis of resistance to PRL, mechanism of action, pharmacokinetics, pharmacodynamic, adverse effects, and regulatory status, including ongoing clinical trial of PRL and other potential drug candidates, leading to this first approval of PRL for the treatment of various solid tumors (RET fusion NSCLC, MTC, and PTC).
Two new lanthanide complexes with the general formula Ln(hqtsc)
2
Cl, where Ln = Eu
3+
/Tb
3+
and hqtsc is (E)-2-((8-hydroxyquinolin-2-yl)methylene)hydrazine-1-carbothioamide have been synthesized. ...The structures of the complexes have been elucidated through IR,
1
H NMR,
13
C NMR and HR-mass spectroscopy. The coordination behavior of the ligand was investigated with proton and two trivalent lanthanides, Eu(III) and Tb(III), by potentiometric and spectrophotometric methods in a highly aqueous medium. The studies reveal that the two lanthanides form complexes of the type ML
2
H
2
, ML
2
H
1
, ML
2
, ML
2
H
−1,
and ML
2
H
−2
. The high formation constants of ML with log β = 26.55 and 27.13 indicate that these complexes will become promising candidates for chelation therapy, radioimmunotherapy, and other biomedical applications. Further, the change in colour and electronic spectra of the complexes in the presence of anions showed the selective colorimetric sensing ability towards H
2
PO
4
−
(orange/yellow→, colorless) and CN
−
(orange/yellow → red). The DFT studies were also carried out to establish the structure, bonding, and sensing mechanism of the complexes.
•Mathematical model of cooling tower based on analogy to distillation column.•Aspen Plus model was developed for cooling tower.•Both models were validated with real plant operating data.•Controller ...was designed to control performance of cooling tower with climate.•Resulted in 30% reduction in overall power consumption of cooling tower.
Cooling towers are unit operations that are used in almost every industry to cool down process water either by natural draft or forced draft. The energy intensive components of cooling towers are draft fans and circulating pumps which in traditional practise run at full rated capacities throughout the year ignoring the underlying opportunities for energy savings. The efficiency of a cooling tower is a function of ambient air temperature, relative humidity and wet bulb temperature. This work brings out a novel model of cooling tower along with an energy harnessing control system based on prevailing climatic conditions thus improving the overall efficiency of the system. Based on analogy to a distillation column with hypothetical stages a model for cooling tower is developed. Then a model predictive control is designed to control the draft fan speed and pump flow rate of cooling tower based on climatic conditions. Both the model and control strategy was developed using Aspen Plus (V12.1), MATLAB (R2018b) and Simulink softwares and has been validated and trained based on plant operating data. The developed model was then tested at a pilot cooling tower facility of capacity 1 Ton of Refrigeration and was observed to attain approximately 30% reduction in energy consumption compared to the traditional operation.
Well-differentiated renal neuroendocrine tumors are rare tumors. As their biologic behavior is not fully known, there is a need to know more about these cases. We performed a retrospective chart ...review of all the cases diagnosed with renal neuroendocrine tumors from January 2016 to December 2020 (five years) in order to understand their clinical features, morphological characteristics and outcome. We included six cases with mean age of 46.2 years (4 males) in our study. All patients underwent radical nephrectomy. Histologically all showed tumor disposed in nests and trabeculae and majority of the tumors belonged to well-differentiated neuroendocrine tumor Grade 1 (WHO criteria of gastoroenteropancreatic neuroendocrine neoplasms). Lymph node metastasis was seen in two cases at the time of clinical presentation. All the tumors were diffusely positive for neuroendocrine tumor markers (synaptophysin, chromogranin, NSE, CD56). Follow-up data was available in all cases with an average follow-up of two years and neither has shown evidence of metastasis or relapse till last follow-up. Role of morphological patterns and immunohistochemical markers is highlighted with the importance of including Ki-67 index in grading them to better understand their outcome.
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