Harnessing the power of hybrid deep learning algorithm for the estimation of global horizontal irradiance.

Accurately and precisely estimating global horizontal irradiance (GHI) poses significant challenges due to the unpredictable nature of climate parameters and geographical limitations. To address this challenge, this study proposes a forecasting framework using an integrated model of the convolutional neural network (CNN), long short-term memory (LSTM), and gated recurrent unit (GRU). The proposed model uses a dataset of four different districts in Rajasthan, each with unique solar irradiance patterns. Firstly, the data was preprocessed and then trained with the optimized parameters of the standalone and hybrid models and compared. It can be observed that the proposed hybrid model (CNN-LSTM-GRU) consistently outperformed all other models regarding Mean absolute error (MAE) and Root mean squared error (RMSE). The experimental results demonstrate that the proposed method forecasts accurate GHI with a RMSE of 0.00731, 0.00730, 0.00775, 0.00810 and MAE of 0.00516, 0.00524, 0.00552, 0.00592 for Barmer, Jaisalmer, Jodhpur and Bikaner respectively. This indicates that the model is better at minimizing prediction errors and providing more accurate GHI estimates. Additionally, the proposed model achieved a higher coefficient of determination (R (Ghimire et al., 2019)), suggesting that it best fits the dataset. A higher R2 value signifies that the proposed model could explain a significant portion of the variance in the GHI dataset, further emphasizing its predictive capabilities. In conclusion, this work demonstrates the effectiveness of the hybrid algorithm in improving adaptability and enhancing prediction accuracy for GHI estimation.

Unraveling the anti-breast cancer activity of Cimicifugae rhizoma using biological network pathways and molecular dynamics simulation.

Cimicifugae is a commonly used treatment for breast cancer, but the specific molecular mechanisms underlying its effectiveness remain unclear. In this research, we employ a combination of network pharmacology, molecular docking, and molecular dynamics simulations to uncover the most potent phytochemical within Cimicifugae rhizoma in order to delve into its interaction with the target protein in breast cancer treatment. We identified 18 active compounds and 89 associated targets, primarily associated to various biological processes such as lipid metabolism, the signaling pathway in diabetes, viral infections, and cancer-related pathways. Molecular docking analysis revealed that the two most active compounds, Formononetin and Cimigenol, exhibit strong binding to the target protein AKT1. Through molecular dynamics simulations, we found that the Cimigenol-AKT1 complex exhibits greater structural stability and lower interaction energy compared to the stigmasterol-AKT1 complex. Our study demonstrates that Cimicifugae rhizoma exerts its effects in breast cancer treatment through a multi-component, multi-target synergistic approach. Furthermore, we propose that Cimigenol, targeting AKT-1, represents the most effective compound, offering valuable insights into the molecular mechanisms underpinning its role in breast cancer therapy.

PHA-665752's Antigrowth and Proapoptotic Effects on HSC-3 Human Oral Cancer Cells.

c-Met is a tyrosine-kinase receptor, and its aberrant activation plays critical roles in tumorigenesis, invasion, and metastatic spread in many human tumors. PHA-665752 (PHA) is an inhibitor of c-Met and has antitumor effects on many hematological malignancies and solid cancers. However, the activation and expression of c-Met and its role and the antitumor effect of PHA on human oral squamous cell carcinoma (OSCC) cells remain unclear. Here, we investigated the activation and expression of c-Met and the effects of PHA on the growth of a highly tumorigenic HSC-3 human OSCC cell line with high c-Met phosphorylation and expression. Of note, c-Met was highly expressed and phosphorylated on Y1234/1235 in HSC-3 cells, and PHA treatment significantly suppressed the growth and induced apoptosis of these cells. Moreover, PHA that inhibited the phosphorylation (activation) of c-Met further caused the reduced phosphorylation and expression levels of Src, protein kinase B (PKB), mammalian target of rapamycin (mTtor), and myeloid cell leukemia-1 (Mcl-1) in HSC-3 cells. In addition, the antiangiogenic property of PHA in HSC-3 cells was shown, as evidenced by the drug's suppressive effect on the expression of hypoxia-inducible factor-1α (HIF-1α), a critical tumor angiogenic transcription factor. Importantly, genetic ablation of c-Met caused the reduced growth of HSC-3 cells and decreased Src phosphorylation and HIF-1α expression. Together, these results demonstrate that c-Met is highly activated in HSC-3 human oral cancer cells, and PHA exhibits strong antigrowth, proapoptotic, and antiangiogenic effects on these cells, which are mediated through regulation of the phosphorylation and expression of multiple targets, including c-Met, Src, PKB, mTOR, Mcl-1, and HIF-1α.

Ecosystem-based fishery enhancement through pen culture of Indian major carp Labeo catla in a tropical floodplain wetland of North Eastern Region, India, during COVID pandemic.

The present study was conducted with the objective of developing ecologically and economically feasible pen culture protocols for Labeo catla as an alternate income source for wetland fishers in the context of the COVID-19 pandemic. Yearlings of L. catla (12.33 ± 1.99 cm mean total length and 26.05 ± 6.57 g mean weight) were reared in HDPE pens (500 m2 area each) at three different stocking densities of 3 (SD3), 6 (SD6) and 9 (SD9) no. m-2 in triplicates. Fishes were fed with floating pelleted feed containing 28% crude protein and 5% crude lipid two times daily at 1.5-3% of body weight. During the culture period, fish grew from 26.05 ± 6.57 to 434.61 ± 30.63 g, 306.13 ± 10.68 g and 221.13 ± 14.92 g, respectively, at stocking densities of 3, 6 and 9 no. m-2 respectively. Weight gain percentage and specific growth rate declined with increase in stocking density. Gross fish yield increased with increase in stocking density and was highest at SD9 (657.92 ± 53.55 kg pen-1), while net fish yield increased initially from SD3 to SD6 (594.31 ± 29.72 kg pen-1) and then declined with further increase in stocking density. Important water quality parameters influencing fish growth were measured, and significant difference (p > 0.05) was not observed between treatments (inside pens) and reference site (outside pen at 10-m distance). Weight gain was positively correlated (p < 0.05) to water temperature (r = 0.989) and total phosphorus (r = 0.81). Benefit cost ratio and net return was highest at SD3 (1.61; US $518.88, respectively). Stocking density of 3 no. m-2 can be considered economically feasible for table fish production of L. catla in pens. Post pen culture, monthly income of fishers increased by 10.76-179.11%, with a mean increase of 90.57%, compared to the period of first COVID-19 wave in India. The present findings can provide an impetus for effective utilization of pen enclosures for income generation and livelihood enhancement of small-scale wetland fishers during pandemic.

Repurposing integrase inhibitors against human T-lymphotropic virus type-1: a computational approach.

Adult T-cell Lymphoma (ATL) is caused by the delta retrovirus family member known as Human T-cell Leukaemia Type I (HTLV-1). Due to the unavailability of any cure, the study gained motivation to identify some repurposed drugs against the virus. A quick and accurate method of screening licensed medications for finding a treatment for HTLV-1 is by cheminformatics drug repurposing in order to analyze a dataset of FDA approved integrase antivirals against HTLV-1 infection. To determine how the antiviral medications interacted with the important residues in the HTLV-1 integrase active regions, molecular docking modeling was used. The steady behavior of the ligands inside the active region was then confirmed by molecular dynamics for the probable receptor-drug complexes. Cabotegravir, Raltegravir and Elvitegravir had the best docking scores with the target, indicating that they can tightly bind to the HTLV-1 integrase. Moreover, MD simulation revealed that the Cabotegravir-HTLV-1, Raltegravir-HTLV-1 and Elvitegravir-HTLV-1 interactions were stable. It is obvious that more testing of these medicines in both clinical trials and experimental tests is necessary to demonstrate their efficacy against HTLV-1 infection.Communicated by Ramaswamy H. Sarma.

Molecular docking, molecular dynamics and binding free energy based identification of novel potential multitarget inhibitors of Nipah virus.

Nipah virus (NiV) is one of the most common viral diseases affecting the brain and nervous system of the body. To date, there is no significant antiviral drug specifically designed to inhibit NiV. In the last ten years, there has been a significant increase in interest in multitarget drug development. Therefore, the reported work focuses on designing a multitarget inhibitor for NiV. Among the twelve designed compounds, five exhibited better drug-likeness and ADMET properties, hence being selected for further analysis. In a molecular docking study, these compounds possessed better binding affinity as compared to Favipiravir. The RMSD of these compounds was ≤2Å and the number of H-bonds signified the better stability of the complexes formed. The ΔGbind of C4, C6 and C7 was found to be comparatively higher than the other screened compounds, revealing their greater ability to bind efficiently with NiV-G, NiV-F and NiV-N receptors, respectively. Therefore, based on molecular docking, molecular dynamics, and MM/PBSA analysis, these compounds can act as potential inhibitors of multitargets of NiV.Communicated by Ramaswamy H. Sarma.

Identification of 3, 4-dihydroxy complexes as potential antiviral via DFT, molecular docking, molecular dynamics and MM/PBSA against rabies and dengue receptors.

The quest to identify antiviral drug candidates for dengue and rabies viral diseases is a great challenge for the researchers. While different research is being conducted on the repurposed drugs against these two viruses, no drug compound has gained success in treating them. Therefore, in this study, 3, 4-dihydroxy complexes have been virtually designed to investigate their antiviral properties and analyze their efficiency in interaction with the concerned viral diseases. DFT calculations are carried out to study the electronic and thermodynamic properties to understand the stability and reactivity of the reported compounds. These compounds were subjected to molecular docking studies to understand the binding interactions with NS5 Dengue virus mRNA 2'-O-methyltransferase and phosphoprotein C-terminal domain of Rabies virus. MD simulation, hydrogen bond analysis, and MM/PBSA were performed at 100 ns to support the obtained docking results.Communicated by Ramaswamy H. Sarma.

In silico identification of cyclosporin derivatives as potential inhibitors for RdRp of rotavirus by molecular docking and molecular dynamic studies.

Rotavirus is one of the most common gastrointestinal viral diseases. Till date, there are only two vaccines available in the markets, which are specifically to be administered to young babies. In this study, VP1 RdRp is selected as potential target to carry out inhibitory activities. Cyclosporin A (Cys A) derivatives were designed via FBDD, pharmacokinetics, molecular docking, molecular dynamics (MD) simulation and molecular mechanics generalized born surface area was applied on these compounds. The results from these investigations were analyzed and it was found that the considered derivatives in this study were nontoxic and docking results revealed that the derivatives made some important bonds inside the active site of the receptors within a catalytic triad (Serine-Histidine-Aspartate). After analyzing the mean values of root mean square density (RMSD), root mean square fluctuation (RMSF), radius of gyration (RoG) and solvent accessible surface area (SASA) at 100 ns MD simulation of the selected compounds, it was found that compound 1 exhibits RMSD of 0.74 ± 0.10 Å, RMSF of 0.85 ± 0.15 Å, RoG of 16.45 ± 0.40 Å, SASA of 66.55 ± 0.35 nm2 and ΔGbind of -32.76 ± 0.02 kcal/mol. Therefore, the study revealed that amongst the designed and reported compounds, compound 1 was more stable within the active region of the RdRp and also this compound possesses lower binding free energy as compared to other selected compounds and Cys A as well.Communicated by Ramaswamy H. Sarma.

In silico identification and molecular dynamic simulations of derivatives of 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide against main protease 3CLpro of SARS-CoV-2 viral infection.

CONTEXT: The unavailability of target-specific antiviral drugs for SARS-CoV-2 viral infection kindled the motivation to virtually design derivatives of 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide as potential antiviral inhibitors against the concerned virus. The molecular docking and molecular dynamic results revealed that the reported derivatives have a potential to act as antiviral drug against SARS-CoV-2. The reported hit compounds can be considered for in vitro and in vivo analyses. METHODS: Fragment-based drug designing was used to model the derivatives. Furthermore, DFT simulations were carried out using B3LYP/6-311G** basis set. Docking simulations were performed by using a combination of empirical free energy force field with a Lamarckian genetic algorithm under AutoDock 4.2. By the application of AMBER14 force field and SPCE water model, molecular dynamic simulations and MM-PBSA were calculated for 100 ns.

AMPK-like proteins and their function in female reproduction and gynecologic cancer.

Serine-threonine kinase (STK11), also known as liver kinase B1 (LKB1), is a regulator of cellular homeostasis through regulating the cellular ATP-to-ADP ratio. LKB1 is classified as a tumor suppressor and functions as the key activator of AMP-activated protein kinase (AMPK) and a family of serine-threonine kinases called AMPK-like proteins. These proteins include novel (nua) kinase family 1 (NUAK1 and 2), salt inducible kinase (SIK1), QIK (known as SIK2), QSK (known as SIK3 kinase), and maternal embryonic leuzine zipper kinase (MELK) on tightly controlled and specific residual sites. LKB1 also regulates brain selective kinases 1 and 2 (BRSK1 and 2), additional members of AMPK-like protein family, which functions are probably less studied. AMPK-like proteins play a role in variety of reproductive physiology functions such as follicular maturation, menopause, embryogenesis, oocyte maturation, and preimplantation development. In addition, dysfunctional activity of AMPK-like proteins contributes to apoptosis blockade in cancer cells and induction of the epithelial-mesenchymal transition required for metastasis. Dysregulation of these proteins occurs in ovarian, endometrial, and cervical cancers. AMPK-like proteins are still undergoing further classification and may represent novel targets for targeted gynecologic cancer therapies. In this chapter, we describe the AMPK-like family of proteins and their roles in reproductive physiology and gynecologic cancers.

The complex nature of heterogeneity and its roles in breast cancer biology and therapeutic responsiveness.

Heterogeneity is a complex feature of cells and tissues with many interacting components. Depending on the nature of the research context, interacting features of cellular, drug response, genetic, molecular, spatial, temporal, and vascular heterogeneity may be present. We describe the various forms of heterogeneity with examples of their interactions and how they play a role in affecting cellular phenotype and drug responses in breast cancer. While cellular heterogeneity may be the most widely described and invoked, many forms of heterogeneity are evident within the tumor microenvironment and affect responses to the endocrine and cytotoxic drugs widely used in standard clinical care. Drug response heterogeneity is a critical determinant of clinical response and curative potential and also is multifaceted when encountered. The interactive nature of some forms of heterogeneity is readily apparent. For example, the process of metastasis has the properties of both temporal and spatial heterogeneity within the host, whereas each individual metastatic deposit may exhibit cellular, genetic, molecular, and vascular heterogeneity. This review describes the many forms of heterogeneity, their integrated activities, and offers some insights into how heterogeneity may be understood and studied in the future.

Identification of novel potential inhibitor of thymidylate kinase from Variola virus.

A hit compound was designed using Fragment Based Drug Designing (FBDD) approach, density functional theory (DFT) calculations were performed to find the structural and electronic properties. Additionally, pharmacokinetic properties were studied to understand the biological response of the compound. Docking studies were carried out with the protein structure of VrTMPK and HssTMPK with the reported hit compound. The favored docked complex was further carried to perform MD simulations; the RMSD plot and H-bond analysis was done for 200 ns. Also, MM-PBSA was done to understand the binding energy constituents and stability of the complex. A comparative study of the designed hit compound was done with FDA approved Tecovirimat. As a result, it was found that the reported compound (POX-A)is a potential selective inhibitor for Variola virus. Hence, it can be used to study further in vivo and in vitro behavior of the compound.Communicated by Ramaswamy H. Sarma.

Suppression of Lipid Accumulation in the Differentiation of 3T3-L1 Preadipocytes and Human Adipose Stem Cells into Adipocytes by TAK-715, a Specific Inhibitor of p38 MAPK.

Excessive preadipocyte differentiation is linked with obesity. Although previous studies have shown that p38 MAPK is associated with adipogenesis, the regulation of preadipocyte differentiation by TAK-715, an inhibitor of p38 mitogen-activated protein kinase (MAPK), remains unclear. Interestingly, TAK-715 at 10 µM vastly suppressed the accumulation of lipid and intracellular triglyceride (TG) content with no cytotoxicity during 3T3-L1 preadipocyte differentiation. On mechanistic levels, TAK-715 significantly decreased the expressions of the CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), fatty acid synthase (FAS), and perilipin A. Similarly, the phosphorylation of the signal transducer and activator of transcription-3 (STAT-3) in differentiating 3T3-L1 cells was also reduced with TAK-715 treatment. Moreover, TAK-715 significantly blocked the phosphorylation of activating transcription factor-2 (ATF-2), a p38 MAPK downstream molecule, during 3T3-L1 preadipocyte differentiation. Of importance, TAK-715 also markedly impeded the phosphorylation of p38 MAPK and suppressed lipid accumulation during the adipocyte differentiation of human adipose stem cells (hASCs). Concisely, this is the first report that TAK-715 (10 µM) has potent anti-adipogenic effects on the adipogenesis process of 3T3-L1 cells and hASCs through the regulation of the expression and phosphorylation of p38 MAPK, C/EBP-α, PPAR-γ, STAT-3, FAS, and perilipin A.

Design of optimal cascade control approach for LFM of interconnected power system.

In the present era, due to increasing power demand and complex power system structures having various load disturbances, a load frequency management (LFM) scheme is indispensable to provide uninterrupted power to consumers. This research deals with a fractional-order proportional derivative - (one + fractional order integrator) (FOPD-(1+FOI)) cascade controller as a novel control structure to ameliorate the execution of automatic generation control (AGC) for the LFM of interconnected power system (PS). The implementation of this controller is uncomplicated, and it joins the output of the FOPD controller to (1+FOI) controller, where area control error and power error are considered in the outer and inner feedback control loops, respectively. A maiden attempt of a wild horse optimizer-assisted FOPD-(1+FOI) cascade controller for AGC of considered interconnected PS has been performed in this work. To benchmark the proposed control scheme, two areas reheat thermal PS with GDB and GRC nonlinearities is chosen as the test bench. A vivid comparative analysis of six state-of-the-art control techniques is performed, and the results reveal the potency of the presented control approach. Eigenvalues-based stability assessment of interconnected PS in conjunction with the proposed controller is also performed. Finally, for the real PS implementation of the presented control architecture a new england IEEE 39 test bus is considered and analyzed.

BWOA assisted PIDF-(1+I) controller for intelligent load frequency management of standalone micro-grid.

The study made in this paper has been directed towards a novel load frequency management (LFM) scheme for solar-wind-based standalone micro-grid (SMG). For LFM, this brief deals with the introduction of proportional-integral-derivative with filter - (one plus integral), i.e., PIDF-(1+I) cascade controller. A maiden endeavor has been performed to employ a recently developed black widow optimization algorithm (BWOA) to obtain the supplementary controller parameters. The considered SMG consists of the wind turbine generator, diesel engine generator, solar photovoltaic as distributed generation unit, and flywheel and ultra-capacitor are considered as energy storage systems. Generation rate constraints and governor dead-band type power system's nonlinearities are also included in this study. This work aims to mitigate the effect of mismatch in demand and generation and minimize the change in frequency deviation (CFD). The maximum obtained CFD with the proposed controller is 0.048 Hz, which is entirely satisfactory and under the permissible limit of IEEE standard. A vivid comparative analysis of artificial bee colony and BWOA tuned controllers like conventional PID, PIDF, and PIDF-(1+I) is also performed. Finally, the detailed robustness assessment of the proposed controller with its real-time implementation through the standard New England IEEE 39 test bus system presents the controller's superiority.

Co-Prevalence of Virulence and Pathogenic Potential in Multiple Antibiotic Resistant Aeromonas spp. from Diseased Fishes with In Silico Insight on the Virulent Protein Network.

Aeromonas species exhibit widespread presence in food, poultry, and aquaculture. They are major multi-drug-resistant fish pathogens. This study aims to identify Aeromonas species harbouring virulence genes aerolysin, flagellin, and lipase from diseased fishes of Assam wetlands with association with antibiotic resistance and in vivo pathogenicity. One hundred and thirty-four Aeromonas strains were isolated and thirty representative species identified using genus-specific 16S rRNA gene amplification. A. veronii was most prevalent (53.7%) followed by A. hydrophila (40.2%), A. caviae (4.47%), and A. dhakensis (1.49%). Ninety percent (90%) of strains harboured at least one of the studied virulence genes: aerA (73.3%), lip (46.6%), and flaA (26.6%). The highest multiple antibiotic resistance (MAR) index 0.8 corresponded to A. hydrophila DBTNE1 (MZ723069), containing all the studied genes. The lowest LD50 values (1.6 × 106 CFU/fish) corresponded to isolates having both aerA and lip. ß-lactams showed utmost resistance and lowest for aminoglycosides. There was a significant (p < 0.05) Pearson chi-square test of association between the occurrence of virulence and antibiotic resistance. The in silico protein−protein interaction revealed important drug targets, such as σ28 transcription factor, aminoacyl-tRNA synthetase, and diacylglycerol kinase, with significant (p < 0.05) enrichment. This study suggests that fish-isolate Aeromonas strains represent potential threat to aquaculture with subsequent risk of transferring antibiotic resistance to human pathogens.

Anti-adipogenic and Pro-lipolytic Effects on 3T3-L1 Preadipocytes by CX-4945, an Inhibitor of Casein Kinase 2.

Casein kinase 2 (CK2) is a ubiquitously expressed serine/threonine kinase and is upregulated in human obesity. CX-4945 (Silmitasertib) is a CK2 inhibitor with anti-cancerous and anti-adipogenic activities. However, the anti-adipogenic and pro-lipolytic effects and the mode of action of CX-4945 in (pre)adipocytes remain elusive. Here, we explored the effects of CX-4945 on adipogenesis and lipolysis in differentiating and differentiated 3T3-L1 cells, a murine preadipocyte cell line. CX-4945 at 15 µM strongly reduced lipid droplet (LD) accumulation and triglyceride (TG) content in differentiating 3T3-L1 cells, indicating the drug's anti-adipogenic effect. Mechanistically, CX-4945 reduced the expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and perilipin A in differentiating 3T3-L1 cells. Strikingly, CX-4945 further increased the phosphorylation levels of cAMP-activated protein kinase (AMPK) and liver kinase B-1 (LKB-1) while decreasing the intracellular ATP content in differentiating 3T3-L1 cells. In differentiated 3T3-L1 cells, CX-4945 had abilities to stimulate glycerol release and elevate the phosphorylation levels of hormone-sensitive lipase (HSL), pointing to the drug's pro-lipolytic effect. In addition, CX-4945 induced the activation of extracellular signal-regulated kinase-1/2 (ERK-1/2), and PD98059, an inhibitor of ERK-1/2, attenuated the CX4945-induced glycerol release and HSL phosphorylation in differentiated 3T3-L1 cells, indicating the drug's ERK-1/2-dependent lipolysis. In summary, this investigation shows that CX-4945 has strong anti-adipogenic and pro-lipolytic effects on differentiating and differentiated 3T3-L1 cells, mediated by control of the expression and phosphorylation levels of CK2, C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, AMPK, LKB-1, ERK-1/2, and HSL.

Anti-Growth, Anti-Angiogenic, and Pro-Apoptotic Effects by CX-4945, an Inhibitor of Casein Kinase 2, on HuCCT-1 Human Cholangiocarcinoma Cells via Control of Caspase-9/3, DR-4, STAT-3/STAT-5, Mcl-1, eIF-2α, and HIF-1α.

Overexpression of casein kinase 2 (CK2) has an oncogenic and pro-survival role in many cancers. CX-4945 (Silmitasertib) is a CK2 inhibitor with anti-cancerous and anti-angiogenic effects. Up to date, the anti-cancer effect and mechanism of CX-4945 on human cholangiocarcinoma (CCA) remain unclear. This study investigated whether CX-4945 inhibits growth and induces apoptosis of HuCCT-1 cells, a human CCA cell line. Of note, treatment with CX-4945 at 20 µM markedly reduced survival and induced apoptosis of HuCCT-1 cells, as evidenced by nuclear DNA fragmentation, PARP cleavage, activation of caspase-9/3, and up-regulation of DR-4. Although CX-4945 did not affect the phosphorylation and expression of CK2, it vastly inhibited the phosphorylation of CK2 substrates, supporting the drug's efficacy in inhibiting CK2 and its downstream pathway. Importantly, knockdown of CK2 that partially suppressed the phosphorylation of CK2 substrates resulted in a significant reduction of HuCCT-1 cell survival. In addition, CX-4945 reduced the phosphorylation and expression of STAT-3 and STAT-5 in HuCCT-1 cells, and pharmacological inhibition or respective knockdown of these proteins resulted in significant growth suppression of HuCCT-1 cells. CX-4945 also had abilities to decrease Mcl-1 expression while increasing eIF-2α phosphorylation in HuCCT-1 cells. Furthermore, there was a time-differential negative regulation of HIF-1α expression by CX-4945 in HuCCT-1 cells, and knockdown of HIF-1α caused a significant reduction of the cell survival. In summary, these results demonstrated that CX-4945 has anti-growth, anti-angiogenic, and pro-apoptotic effects on HuCCT-1 cells, which are mediated through control of CK2, caspase-9/3, DR-4, STAT-3/5, Mcl-1, eIF-2α, and HIF-1α.

Expression and Role of ß3-Adrenergic Receptor during the Differentiation of 3T3-L1 Preadipocytes into Adipocytes.

ß3-adrenergic receptor (ß3-AR) is expressed predominantly in mature white and brown/beige adipocytes. Although the lipolytic and thermogenic role of ß3-AR in brown/beige adipocytes is well defined, the adipogenic role of ß3-AR in white adipocytes remains unclear at present. In this study, we investigated the expression and function of ß3-AR in differentiating 3T3-L1 cells, murine white preadipocytes. Of note, the expression of ß3-AR at the protein and mRNA levels was highly induced in a time-dependent manner during 3T3-L1 preadipocyte differentiation. Interestingly, the results of the pharmacological inhibition study demonstrated the roles of p38 MAPK and PKC in the induction of ß3-AR expression in differentiating 3T3-L1 cells. Knockdown of ß3-AR led to less lipid accumulation and triglyceride (TG) content during 3T3-L1 preadipocyte differentiation with no cytotoxicity. Furthermore, knockdown of ß3-AR resulted in a decrease in not only expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FASN), perilipin A, and leptin but also phosphorylation levels of signal transducer and activator of transcription-5 (STAT-5) during 3T3-L1 preadipocyte differentiation. In summary, these results demonstrate firstly that ß3-AR expression is highly up-regulated in p38 MAPK and PKC-dependent manners, and the up-regulated ß3-AR plays a crucial role in lipid accumulation in differentiating 3T3-L1 cells, which is mediated through control of expression and phosphorylation levels of C/EBP-α, PPAR-γ, STAT-5, FASN, and perilipin A.

Role of Workplace Spirituality, Empathic Concern and Organizational Politics in Employee Wellbeing: A Study on Police Personnel.

Employee wellbeing as a central aspect of organizational growth has been widely regarded and accepted. Therefore, a considerable growth in the number of researches focusing on employee wellbeing has been comprehended in recent years. Employee wellbeing characterizes the individual's own cognitive interpretation of his/her life at work. The present study made an attempt to examine how workplace spirituality, empathic concern and organizational politics influences employee wellbeing. It was hypothesized that empathic concern mediates the relationship between workplace spirituality and employee wellbeing while organizational politics act as a moderator in this relationship. A survey was conducted on 253 employees working in Uttar Pradesh Police department (Uttar Pradesh, India). The results obtained revealed that workplace spirituality, empathic concern and employee wellbeing carries a positive association among them whereas these variables were found to be negatively correlated with organizational politics. Results also depicted that empathic concern significantly mediates between workplace spirituality and employee wellbeing. Further, moderated mediation analysis confirmed employee wellbeing as a function of workplace spirituality, empathic concern and organizational politics. The present study has put forward several practical implications for business practitioners and research directions for academicians, emphasizing upon the need to investigate the comprehensive impact of employee wellbeing in organization and the society as a whole.