Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer

A hallmark of prostate cancer progression is dysregulation of lipid metabolism via overexpression of fatty acid synthase (FASN), a key enzyme in de novo fatty acid synthesis. Metastatic castration-resistant prostate cancer (mCRPC) develops resistance to inhibitors of androgen receptor (AR) signaling through a variety of mechanisms, including the emergence of the constitutively active AR variant V7 (AR-V7). Here, we developed an FASN inhibitor (IPI-9119) and demonstrated that selective FASN inhibition antagonizes CRPC growth through metabolic reprogramming and results in reduced protein expression and transcriptional activity of both full-length AR (AR-FL) and AR-V7. Activation of the reticulum endoplasmic stress response resulting in reduced protein synthesis was involved in IPI-9119-mediated inhibition of the AR pathway. In vivo, IPI-9119 reduced growth of AR-V7-driven CRPC xenografts and human mCRPC-derived organoids and enhanced the efficacy of enzalutamide in CRPC cells. In human mCRPC, both FASN and AR-FL were detected in 87% of metastases. AR-V7 was found in 39% of bone metastases and consistently coexpressed with FASN. In patients treated with enzalutamide and/or abiraterone FASN/AR-V7 double-positive metastases were found in 77% of cases. These findings provide a compelling rationale for the use of FASN inhibitors in mCRPCs, including those overexpressing AR-V7.Giorgia Zadra, Caroline F. Ribeiro, Paolo Chetta, Yeung Ho, Stefano Cacciatore ... Lisa M. Butler ... et al

A QTL study on late leaf spot and rust revealed one major QTL for molecular breeding for rust resistance in groundnut (Arachis hypogaea L.)

Late leaf spot (LLS) and rust are two major foliar diseases of groundnut (Arachis hypogaea L.) that often occur together leading to 50–70% yield loss in the crop. A total of 268 recombinant inbred lines of a mapping population TAG 24 × GPBD 4 segregating for LLS and rust were used to undertake quantitative trait locus (QTL) analysis. Phenotyping of the population was carried out under artificial disease epiphytotics. Positive correlations between different stages, high to very high heritability and independent nature of inheritance between both the diseases were observed. Parental genotypes were screened with 1,089 simple sequence repeat (SSR) markers, of which 67 (6.15%) were found polymorphic. Segregation data obtained for these markers facilitated development of partial linkage map (14 linkage groups) with 56 SSR loci. Composite interval mapping (CIM) undertaken on genotyping and phenotyping data yielded 11 QTLs for LLS (explaining 1.70–6.50% phenotypic variation) in three environments and 12 QTLs for rust (explaining 1.70–55.20% phenotypic variation). Interestingly a major QTL associated with rust (QTLrust01), contributing 6.90–55.20% variation, was identified by both CIM and single marker analysis (SMA). A candidate SSR marker (IPAHM 103) linked with this QTL was validated using a wide range of resistant/susceptible breeding lines as well as progeny lines of another mapping population (TG 26 × GPBD 4). Therefore, this marker should be useful for introgressing the major QTL for rust in desired lines/varieties of groundnut through marker-assisted backcrossing

Extrinsic Pseudocapacitive NiSe/rGO/g-C3N4 Nanocomposite for High-Performance Hybrid Supercapacitors

Battery-type materials with ultrahigh energy density show great potential for hybrid supercapacitors (HSCs). In this work, we have developed a nickel selenide (NiSe)/reduced graphene oxide (rGO)/graphitic carbon nitride (g-C3N4) ternary composite as a promising positive electrode for hybrid supercapacitors (HSCs). The extended π-conjugated planar layers of g-C3N4 promote strong interconnectivity with rGO, which further enhances surface area, surface free energy, and efficient electron/ionic path. Additionally, it establishes clear ion diffusion pathways, serving as ion reservoirs during charge and discharge and facilitating efficient redox reactions. As a result, the NiSe/g-C3N4/rGO nanocomposite electrode displayed a specific capacity of 412.6 mA h g-1 at 1 A g-1. Later, the HSC device was assembled using the nanocomposite as the positive electrode and activated carbon as the negative electrode, which delivered an energy density of 65.2 Wh kg-1 at a power density of 750 W kg-1. Notably, the HSC device maintained excellent cyclic stability, preserving 93.3% of its initial performance and Coulombic efficiency of 86.6% for 10,000 charge-discharge cycles at 5 A g-1. These findings underscore the potential utility of NiSe/g-C3N4/rGO as a versatile and effective electrode material for the strategic development of HSC devices.</p

Emergence of Ni-Based Chalcogenides (S and Se) for Clean Energy Conversion and Storage

Nickel chalcogenide (S and Se) based nanostructures intrigued scientists for some time as materials for energy conversion and storage systems. Interest in these materials is due to their good electrochemical stability, eco-friendly nature, and low cost. The present review compiles recent progress in the area of nickel-(S and Se)-based materials by providing a comprehensive summary of their structural and chemical features and performance. Improving properties of the materials, such as electrical conductivity and surface characteristics (surface area and morphology), through strategies like nano-structuring and hybridization, are systematically discussed. The interaction of the materials with electrolytes, other electro-active materials, and inactive components are analyzed to understand their effects on the performance of energy conversion and storage devices. Finally, outstanding challenges and possible solutions are briefly presented with some perspectives toward the future development of these materials for energy-oriented devices with high performance.</p

Emergence of Ni-Based Chalcogenides (S and Se) for Clean Energy Conversion and Storage

Nickel chalcogenide (S and Se) based nanostructures intrigued scientists for some time as materials for energy conversion and storage systems. Interest in these materials is due to their good electrochemical stability, eco-friendly nature, and low cost. The present review compiles recent progress in the area of nickel-(S and Se)-based materials by providing a comprehensive summary of their structural and chemical features and performance. Improving properties of the materials, such as electrical conductivity and surface characteristics (surface area and morphology), through strategies like nano-structuring and hybridization, are systematically discussed. The interaction of the materials with electrolytes, other electro-active materials, and inactive components are analyzed to understand their effects on the performance of energy conversion and storage devices. Finally, outstanding challenges and possible solutions are briefly presented with some perspectives toward the future development of these materials for energy-oriented devices with high performance.</p

A simple biota removal algorithm for 35 GHz cloud radar measurements

Cloud radar reflectivity profiles can be an important measurement for the investigation of cloud vertical structure (CVS). However, extracting intended meteorological cloud content from the measurement often demands an effective technique or algorithm that can reduce error and observational uncertainties in the recorded data. In this work, a technique is proposed to identify and separate cloud and non-hydrometeor echoes using the radar Doppler spectral moments profile measurements. The point and volume target-based theoretical radar sensitivity curves are used for removing the receiver noise floor and identified radar echoes are scrutinized according to the signal decorrelation period. Here, it is hypothesized that cloud echoes are observed to be temporally more coherent and homogenous and have a longer correlation period than biota. That can be checked statistically using  ∼ 4 s sliding mean and standard deviation value of reflectivity profiles. The above step helps in screen out clouds critically by filtering out the biota. The final important step strives for the retrieval of cloud height. The proposed algorithm potentially identifies cloud height solely through the systematic characterization of Z variability using the local atmospheric vertical structure knowledge besides to the theoretical, statistical and echo tracing tools. Thus, characterization of high-resolution cloud radar reflectivity profile measurements has been done with the theoretical echo sensitivity curves and observed echo statistics for the true cloud height tracking (TEST). TEST showed superior performance in screening out clouds and filtering out isolated insects. TEST constrained with polarimetric measurements was found to be more promising under high-density biota whereas TEST combined with linear depolarization ratio and spectral width perform potentially to filter out biota within the highly turbulent shallow cumulus clouds in the convective boundary layer (CBL). This TEST technique is promisingly simple in realization but powerful in performance due to the flexibility in constraining, identifying and filtering out the biota and screening out the true cloud content, especially the CBL clouds. Therefore, the TEST algorithm is superior for screening out the low-level clouds that are strongly linked to the rainmaking mechanism associated with the Indian Summer Monsoon region's CVS

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