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Cancer, the main cause of human deaths in the modern world is a group of diseases. Anticancer drug discovery is a challenge for scientists because of involvement of multiple survival pathways of cancer cells. An extensive study on the regulation of each step of these pathways may help find a potential cancer target. Up-regulated HIF-1 expression and altered metabolic pathways are two classical characteristics of cancer. Oxygen-dependent (through pVHL, PHDs, calcium-mediated) and independent (through growth factor signaling pathway, mdm2 pathway, HSP90) regulation of HIF-1α leads to angiogenesis, metastasis, and cell survival. The two subunits of HIF-1 regulates in the same fashion through different mechanisms. HIF-1α translation upregulates via mammalian target of rapamycin and mitogen-activated protein kinase signaling pathways, whereas HIF-1β through calmodulin kinase. Further, the stabilized interactions of these two subunits are important for proper functioning. Also, metabolic pathways crucial for the formation of building blocks (pentose phosphate pathway) and energy generation (glycolysis, TCA cycle and catabolism of glutamine) are altered in cancer cells to protect them from oxidative stress and to meet the reduced oxygen and nutrient supply. Up-regulated anaerobic metabolism occurs through enhanced expression of hexokinase, phosphofructokinase, triosephosphate isomerase, glucose 6-phosphate dehydrogenase and down-regulation of aerobic metabolism via pyruvate dehydrogenase kinase and lactate dehydrogenase which compensate energy requirements along with high glucose intake. Controlled expression of these two pathways through their common intermediate may serve as potent cancer target in future.

Since carotenoids are important as natural colorants, antioxidants, neutraceutics and pharmaceutics, the aim of the present study was to find a new good source of these pigments. We hereby report a green microalga Asterarcys quadricellulare PUMCC 5.1.1 as a new and good producer of carotenoids. The organism produced 35±1.75 μg carotenoids mg-1 dry biomass during stationary phase in control cultures. The growth and carotenoids production by the test microalga were optimized by varying nutrient growth media, pH, nitrogen and phosphate source, salinity, light quality, intensity and duration. The optimized conditions for carotenoid production were: Bold basal (BB) medium with pH 8.5, containing with10 mM nitrate, 3.5 mM phosphate and 0.17 mM salinity and illuminated with blue light with 60 μmol m-2 s-1 photon flux light intensity. Cultivation of cultures in the above mentioned optimized conditions resulted in nearly 3.0 fold increase in carotenoid production compared to the control cultures grown in unmodified BB medium. Using HPTLC, four carotenoids have been identified as β-carotene, lutein, astaxanthin and canthaxanthin. Further, carotenoids were also separated and purified by flash chromatography and the amounts of purified carotenoids were determined by HPLC. The organism produced 47.0, 28.7, 15.5 and 14.0 μg β-carotene, lutein, astaxanthin and canthaxanthin mg-1 dry biomass, respectively, under optimized conditions. The amount of total carotenoids (118 μg mg-1 dry biomass) produced by Asterarcys quadricellulare PUMCC 5.1.1 under optimized culture conditions was significantly higher than control cultures. Thus, this microalgal strain is a promising candidate for carotenoid production at commercial level.

This study investigates the behavior of stabilized Incinerated Bottom Ash (BA) reinforced with fiber when tested under Triaxial conditions. A number of lab-based Unconsolidated Undrained (UU) tests were performed on BA specimens with changing cement content (0–10%) and fiber length (6–18 mm). Cement stabilization enhances shear strength, while fiber inclusion shifts behavior from brittle to ductile. Initially, unconsolidated-undrained strength increases with fiber addition, then decreases. Optimal results were achieved with 0.5% 12 mm fibers and 7% cement, showing a 71.43% strength improvement after 28 days. Prediction of shear strength using a Back Propagation neural network and Adaptive Neuro-fuzzy system yields stronger correlations than regression analysis. The properties of stabilizer and reinforcement on compaction, shear strength, and secant modulus of elasticity (E 50 ) were investigated. PP fiber inclusion enhances shear strength and ductility, with cement content and curing period as dominant factors. Scanning electron microscopy shows stabilizer addition leads to cementitious compounds binding bottom particles, increasing interaction between ash and fiber, thus affecting overall shear strength.

This article presents a power-efficient DC-DC converter based on a switched-capacitor (SC) cell in power management systems supplied for fully integrated photovoltaic (PV) modules. These modules shall provide high-performance point-of-load voltage regulation. The primary objective of this study is to better utilize capacitance and switches by selecting a proper SC topology in order to improve the power efficiency of SC converters. A general steady-state performance model is investigated to optimize and compare a variety of SC DC-DC topologies. The investigation method relies on a charge-multiplier approach and considers the impact of area constraint on capacitors. To identify the most suitable topology for a given conversion ratio, the performance-limit metrics of SC converters are calculated. The analysis provides framework to determine optimum switch size and switching frequency for a two-phase 3:1 series–parallel converter for a target load current of 10 mA implemented on a 22 nm process technology. The results shows that a minimum of 250 MHz switching frequency is desirable for achieving a target efficiency greater than 85% while maintaining the minimum output voltage of 0.34 V. The analysis results are verified through MATLAB and PSpice-based simulations.

Individual plants encounter a vast number of microbes including bacteria, viruses, fungi and oomycetes through their growth cycle, yet few of these pathogens are able to infect them. Plant species have diverged over millions of years, co-evolving with few specific pathogens. The host boundaries of most pathogen species can be clearly defined. In general, the greater the genetic divergence from the preferred host, the less likely that pathogen would be able to infect that plant species. Co-evolution and divergence also occur within pathogen species, leading to highly specialized subspecies with narrow host ranges. For example, cereal rust and mildew pathogens (Puccinia and Blumeria spp.) display high host specificity as a result of ongoing co-evolution with a narrow range of grass species. In rare cases, however, some plant species are in a transition from host to nonhost or are intermediate hosts (near nonhost). Barley was reported as a useful model for genetic and molecular studies of nonhost resistance due to rare susceptibility to numerous heterologous rust and mildew fungi. This review evaluates host specificity in numerous Puccinia/Blumeria–cereal pathosystems and discusses various approaches for transferring nonhost resistance (NHR) genes between crop species to reduce the impact of important diseases in food production.

An effective diagnosis system and suitable treatment planning require the precise segmentation of thyroid nodules in ultrasound imaging. The advancement of imaging technologies has not resolved traditional imaging challenges, which include noise issues, limited contrast, and dependency on operator choices, thus highlighting the need for automated, reliable solutions. The researchers developed TATHA, an innovative deep learning architecture dedicated to improving thyroid ultrasound image segmentation accuracy. The model is evaluated using the digital database of thyroid ultrasound images, which includes 99 cases across three subsets containing 134 labelled images for training, validation, and testing. It incorporates data pre-treatment procedures that reduce speckle noise and enhance contrast, while edge detection provides high-quality input for segmentation. TATHA outperforms U-Net, PSPNet, and Vision Transformers across various datasets and cross-validation folds, achieving superior Dice scores, accuracy, and AUC results. The distributed thyroid segmentation framework generates reliable predictions by combining results from multiple feature extraction units. The findings confirm that these advancements make TATHA an essential tool for clinicians and researchers in thyroid imaging and clinical applications.

Mitochondrial impairment, energetic crisis and elevated oxidative stress have been demonstrated to play a pivotal role in the pathological processes of Huntington’s disease (HD). 3-Nitropropionic acid (3-NPA) is a natural neurotoxin that mimics the neurological dysfunctions, mitochondrial impairments and oxidative imbalance of HD. The current investigation was undertaken to demonstrate the neuroprotective effect of 4-(methylthio)butyl isothiocyanate (4-MTBITC) against the 3-NPA induced neurotoxicity in human dopaminergic SH-SY5Y cells. The experimental evidence of oxidative DNA damage by 3-NPA was elucidated by pBR322 DNA nicking assay. In contrast, the 4-MTBITC considerably attenuated the DNA damage, suggesting its free radical scavenging action against 3-NPA and Fenton's reagent. The dose and time-dependent increase of 3-NPA revealed its neurotoxic dose as 0.5 mM after 24 h of treatment of SH-SY5Y cells in MTT assay. In order to determine the optimal dose at which 4-MTBITC protects cell death, the 3-NPA (IC 50 ) induced cells were pretreated with different concentrations of 4-MTBITC for 1 h. The neuroprotective dose of 4-MTBITC against 3-NPA was found to be 0.25 μM. Additionally, the elevated GSH levels in cells treated with 4-MTBITC indicate its propensity to eliminate reactive species generated as a result of 3-NPA-induced mitochondrial dysfunction. Likewise, it was determined through microscopic and flow cytometric experiments that 3-NPA's induced overproduction of reactive species and a decline in mitochondrial membrane potential (MMP) could be efficiently prevented by pre-treating cells with 4-MTBITC. To elucidate the underlying molecular mechanism, the RT-qPCR analysis revealed that the pre-treatment of 4-MTBITC effectively protected neuronal cells against 3-NPA-induced cell death by preventing Caspase-3 activation, Brain-derived neurotrophic factor (BDNF) upregulation, activation of cAMP response element-binding protein (CREB) and Nrf2 induction. Together, our findings lend credence to the idea that pre-treatment with 4-MTBITC reduced 3-NPA-induced neurotoxicity by lowering redox impairment, apoptotic state, and mitochondrial dysfunction. The present work, in conclusion, presented the first proof that the phytoconstituent 4-MTBITC supports the antioxidant system, BDNF/TrkB/CREB signaling, and neuronal survival in dopaminergic SH-SY5Y cells against 3-NPA-induced oxidative deficits.

Cytokinesis requires precise coordination of contractile-ring constriction, vesicle trafficking and fusion to the plasma membrane, and extracellular matrix assembly/remodeling at the cleavage furrow to ensure faithful cell division and maintain cell integrity. These processes and proteins involved are broadly conserved across eukaryotes, yet molecular mechanisms controlling the spatiotemporal pathways of membrane trafficking remain poorly understood. Here, using fission yeast genetics, microscopy, and in vitro binding assays, we identify a conserved module including the Munc13 protein Ync13, F-BAR protein Rga7, and coiled-coil protein Rng10 to be critical for precise and selective vesicle targeting to the plasma membrane during cytokinesis. The module specifically recruits the TRAPP-II but not the exocyst complex to tether vesicles containing the glucan synthases Bgs4 and Ags1 along the cleavage furrow. Ync13 subsequently interacts with the SM protein Sec1 for vesicle fusion. Mutations in this pathway disrupt septum integrity and lead to cell lysis. Our work provides key insights into how membrane trafficking is tightly controlled to maintain cell integrity during cytokinesis.