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Overcoming resistance to therapy is a major challenge in castration-resistant prostate cancer (CRPC). Lineage plasticity towards a neuroendocrine phenotype enables CRPC to adapt and survive targeted therapies. However, the molecular mechanisms of epigenetic reprogramming during this process are still poorly understood. Here we show that the protein kinase PKCλ/ι-mediated phosphorylation of enhancer of zeste homolog 2 (EZH2) regulates its proteasomal degradation and maintains EZH2 as part of the canonical polycomb repressive complex (PRC2). Loss of PKCλ/ι promotes a switch during enzalutamide treatment to a non-canonical EZH2 cistrome that triggers the transcriptional activation of the translational machinery to induce a transforming growth factor β (TGFβ) resistance program. The increased reliance on protein synthesis creates a synthetic vulnerability in PKCλ/ι-deficient CRPC. The transition of androgen receptor-dependent prostate cancer to a therapy resistant cancer with neuroendocrine phenotype is an important process that remains poorly understood. Here, the authors show that PKCλ/ι-loss promotes epigenetic reprogramming resulting in a TGFβ resistance programme via transcriptional upregulation of translational machinery.

Presently, one of the most important aspects for the development of enzymatic biofuel cells (EBFCs) is to synthesize the novel electrode materials that possess high current density, low open-circuit voltage (OCV) and long-term stability. To achieve the above attributes, lots of new strategies are being used by the researchers for the development of advanced materials. Nowadays, nanomaterials and nanocomposites are the promising material that has been utilized as effective electrode material in solar cells, supercapacitors and biofuel cells application. Herein, we account for a novel electrocatalyst as electrode material that comprised ZnO nanoparticles decorated on the surface of polyindole (PIn)-multi-walled carbon nanotube (MWCNT), for the immobilization of glucose oxidase (GOx) enzyme and mediator (Ferritin). The PIn-MWCNT scaffold is prepared via in situ chemical oxidative polymerization of indole on the surface of MWCNT and assessed by myriad techniques. The micrograph of scanning electron microscopy (SEM) designated the interconnected morphology of MWCNTs in the polymer matrix. X-ray diffraction spectroscopy (XRD) and Fourier transform infrared spectroscopy (FTIR), confirm the crystallinity and different functional groups available in the synthesized material, respectively. The electrochemical assessment demonstrates that the ZnO/PIn-MWCNT/Frt/GOx nanobiocatalyst exhibits much higher electrocatalytic activity towards the oxidation of glucose with a maximum current density of 4.9 mA cm −2 by consuming 50 mM glucose concentration in phosphate buffer saline (PBS) (pH 7.4) as the testing solution by applying 100 mVs −1 scan rates. The outcomes reflect that the as-prepared ZnO/PIn-MWCNTs/Frt/GOx biocomposite is a promising bioanode for the development of EBFCs.

In emerging economies, it has been observed that corporate operations have always been a major force behind environmental degradation and associated human rights crises. This study demonstrates a quantitative environmental, social, and governance framework using data from India’s Business Responsibility and Sustainability Reporting to evaluate the environmental performance of corporations using novel intensity measures. Key findings show that cement industry exhibits some of the highest purchasing power parity (PPP)-adjusted emissions at nearly 0.89 tCO₂e/₹ crore (tonnes of CO₂ equivalent per rupee crore or per 10 million Indian Rupees) or nearly 7.5 tCO₂e/ million US$ revenue. Mining operations in water-stressed regions show a 19%–37% excess over basin recharge capacity. Additionally, 88% of the companies do not report Scope 3 emissions, leaving behind critical lacunae in value chain accountability. Data validation shows the existence of a 72% accuracy in the emission reporting and 68% accuracy in water metrics. The equations in the framework that factor in regional PPP factors and aquifer stress percentages give the model a replicable methodology for quantifying corporate environmental impacts in data-scarce regions with potential for adaptation across developing nations with similar industrialisation-environment trade-offs.

Literature review demonstrated a surprising lack of publications on digital e-learning pathology resources for senior medical undergraduates and interns. An interactive Digital Pathology Repository (iDPR) integrating two- and three-dimensional (2D, 3D) high-resolution anatomical pathology images with correlated digital histopathology was developed. The novel iDPR was rigorously evaluated using mixed methods to assess pathology knowledge gains (pre- and post-tests), quality impact analysis (questionnaire), user feedback (focus group discussions) and user visual behaviour (eye gaze tracking analysis of 2D/ 3D images). Exposure to iDPR appeared to improve user pathology knowledge, as observed by significantly increased test scores on topic-related quizzes ( n  = 69, p  < 0.001). In addition, most users were highly satisfied with the key design elements of the iDPR tool. Focus group discussion revealed the iDPR was regarded as a relevant online learning resource, although some minor technical issues were also noted. Interestingly, visual behaviour trends indicated that specific diagnostic pathological lesions could be correctly identified faster in 3D images, when compared to 2D images. The iDPR offers promise and potential in pathology education for senior clinical students and interns, gauging from both qualitative and quantitative positive user feedback. With incorporation of image annotations and interactive functionality, and with further technology development, this would prove a useful tool for diagnostic pathology and telepathology. As images with added visual-spatial dimension can provide enhanced detail and aid more rapid diagnosis, future applications of the iDPR could include virtual reality or holographic images of anatomical pathology specimens.

Pyridazinone derivatives are a great template for developing cyclooxygenase-2 (COX-2) inhibitors. The 2-butyl-6-phenyl-4,5-dihydropyridazin-3(2H)-one was prepared by reacting 6-phenyl-4,5-dihydropyridazin-3(2H)-one with n-butyl bromide in the presence of potassium carbonate. The structure of the compound was confirmed based on its FTIR, 1H-NMR, 13C-NMR, and Mass data. The molecular docking studies assessed the COX-2 binding capability of the synthesized compound. The in silico physicochemical and pharmacokinetic parameters of this compound concerning selected drugs were also calculated. The COX-2/COX-1 analysis revealed the synthesized compound as a novel potent COX-2 inhibitor, in comparison to indomethacin, with a promising physicochemical and pharmacokinetic profile.

Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five-membered heterocyclic moiety with an extensive therapeutic profile, viz., anti-inflammatory, anti-microbial, anti-anxiety, anticancer, analgesic, antipyretic, etc. Due to the expansion of pyrazolecent red pharmacological molecules at a quicker pace, there is an urgent need to put emphasis on recent literature with hitherto available information to recognize the status of this scaffold for pharmaceutical research. The reported potential pyrazole-containing compounds are highlighted in the manuscript for the treatment of cancer and inflammation, and the results are mentioned in % inhibition of inflammation, % growth inhibition, IC50, etc. Pyrazole is an important heterocyclic moiety with a strong pharmacological profile, which may act as an important pharmacophore for the drug discovery process. In the struggle to cultivate suitable anti-inflammatory and anticancer agents, chemists have now focused on pyrazole biomolecules. This review conceals the recent expansion of pyrazole biomolecules as anti-inflammatory and anticancer agents with an aim to provide better correlation among different research going around the world.

We propose a design of 1 × 4 planar antenna array for wideband millimeter-wave (mm-wave) applications, integrated with a metasurface reflector. The single radiating element of the array is composed of a modified ring resonator, designed by combining two rings of different radii. This leads to a compact antenna with dimensions reducing the overall size of the array. For the excitation of array elements, a broadband feeding network is designed, while the wideband characteristics are achieved using a partial ground plane loaded with a square notch. For high gain and improved radiation characteristics, an array of 3 × 10 metasurface unit cells are built and placed at the back side of the antenna array at a specific distance. A prototype of the proposed antenna system is fabricated, and measurements are made to verify the simulated performance. From the results obtained, it is noted that the 1 × 4 planar antenna array with a metasurface reflector offers 12.86 GHz of impedance bandwidth in the range 27.14–40 GHz, and a maximum gain of 12.3 dBi is achieved in the operating frequency range. Furthermore, the directional radiation characteristics are obtained, especially for the low- and mid-band frequencies.

For many decades, the thiazole moiety has been an important heterocycle in the world of chemistry. The thiazole ring consists of sulfur and nitrogen in such a fashion that the pi (π) electrons are free to move from one bond to other bonds rendering aromatic ring properties. On account of its aromaticity, the ring has many reactive positions where donor–acceptor, nucleophilic, oxidation reactions, etc., may take place. Molecules containing a thiazole ring, when entering physiological systems, behave unpredictably and reset the system differently. These molecules may activate/stop the biochemical pathways and enzymes or stimulate/block the receptors in the biological systems. Therefore, medicinal chemists have been focusing their efforts on thiazole-bearing compounds in order to develop novel therapeutic agents for a variety of pathological conditions. This review attempts to inform the readers on three major classes of thiazole-bearing molecules: Thiazoles as treatment drugs, thiazoles in clinical trials, and thiazoles in preclinical and developmental stages. A compilation of preclinical and developmental thiazole-bearing molecules is presented, focusing on their brief synthetic description and preclinical studies relating to structure-based activity analysis. The authors expect that the current review may succeed in drawing the attention of medicinal chemists to finding new leads, which may later be translated into new drugs.

Acacia seyal is an important source of gum Arabic. The availability, traditional, medicinal, pharmaceutical, nutritional, and cosmetic applications of gum acacia have pronounced its high economic value and attracted global attention. In addition to summarizing the inventions/patents applications related to gum A. seyal, the present review highlights recent updates regarding its phytoconstituents. Traditional, cosmetic, pharmaceutical, and medicinal uses with the possible mechanism of actions have been also reviewed. The patent search revealed the identification of 30 patents/patent applications of A. seyal. The first patent related to A. seyal was published in 1892, which was related to its use in the prophylaxis/treatment of kidney and bladder affections. The use of A. seyal to treat cancer and osteoporosis has also been patented. Some inventions provided compositions and formulations containing A. seyal or its ingredients for pharmaceutical and medical applications. The inventions related to agricultural applications, food industry, cosmetics, quality control of gum Arabic, and isolation of some chemical constituents (L-rhamnose and arabinose) from A. seyal have also been summarized. The identification of only 30 patents/patent applications from 1892 to 15 November 2021 indicates a steadily growing interest and encourages developing more inventions related to A. seyal. The authors recommend exploring these opportunities for the benefit of society.

A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. In this study, we have made an attempt to investigate the SARS-CoV-2 genome reported from 13 different countries, identification of mutations in major coronavirus proteins of these different SARS-CoV-2 genomes and compared with SARS-CoV. These thirteen complete genome sequences of SARS-CoV-2 showed high identity (>99%) to each other, while they shared 82% identity with SARS-CoV. Here, we performed a very systematic mutational analysis of SARS-CoV-2 genomes from different geographical locations, which enabled us to identify numerous unique features of this viral genome. This includes several important country-specific unique mutations in the major proteins of SARS-CoV-2 namely, replicase polyprotein, spike glycoprotein, envelope protein and nucleocapsid protein. Indian strain showed mutation in spike glycoprotein at R408I and in replicase polyprotein at I671T, P2144S and A2798V,. While the spike protein of Spain & South Korea carried F797C and S221W mutation, respectively. Likewise, several important country specific mutations were analyzed. The effect of mutations of these major proteins were also investigated using various in silico approaches. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. It was found that the R60C mutation in Mpro affects the protein dynamics, thereby, affecting the binding of inhibitor within its active site. The implications of mutation on structural characteristics were determined. The information provided in this manuscript holds great potential in further scientific research towards the design of potential vaccine candidates/small molecular inhibitor against COVID19.