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In chickpea breeding, drought is a major concern and a complex trait controlled by several genes. To develop drought-tolerant varieties, it is essential to use the available germplasm and genomic resources. Over the years, the landraces have proven to be a good source for the dissection of genes for different yield and yield-related traits. The present investigation for marker-trait associations (MTAs) and candidate gene identification was conducted by studying 125 chickpea landraces collected from the West Asia and North Africa (WANA) region, along with 4 varieties suitable for irrigated and rainfed environments. This study analyzed 13 physio-morphological traits in 2 consecutive years at two isolated locations (IARI, New Delhi, and Dharwad). A strong correlation coefficient was observed between the trait seed yield (SY) and biological yield (BY) under both conditions. The Drought Susceptibility Index (DSI) ranged from 0.02 to 1.84 and 0.10 to 2.04 at the IARI, New Delhi and Dharwad locations, respectively. The genotypic data of 6,367 single nucleotide polymorphisms (SNPs) distributed across the genome were used for genetic diversity study, population structure, and genome-wide association study (GWAS). The average polymorphic information content (PIC) value observed was 0.25, and the average linkage disequilibrium (LD) decay distance was 152,269 bp across the genome. A total of four subgroups were observed within the population for genotypic data. Fixed and random model Circulating Probability Unification (FarmCPU) was used for the GWAS analysis, which considered both fixed- and random-effect models. A total of 52 significant SNPs were reported in both irrigated and rainfed conditions at low locations; 7 SNPs were associated with more than one trait, which may have pleiotropic effects. Significant SNPs were annotated in the pulse database. The identified genomic region found in or near MTA under rainfed conditions encodes for guard cell hydrogen peroxideresistant1 (GHR1), late embryogenesis-abundant, E3 ubiquitin-protein ligase, walls are thin1 (WAT1), and beta-galactosidase that are known to be associated with drought tolerance. [ABSTRACT FROM AUTHOR]

One of the main causes of death worldwide is lung cancer, which is largely caused by cigarette smoking. The crucial transcription factor NF-κB, which controls inflammatory responses and various cellular processes, is a constitutively present cytoplasmic protein strictly regulated by inhibitors like IκB proteins. Upon activation by external stimuli, it undergoes phosphorylation, translocates into the nucleus, and modulates the expression of specific genes. The incontrovertible association between pulmonary malignancy and tobacco consumption underscores and highlights a public health concern. Polycyclic aromatic hydrocarbons and nitrosamines, potent carcinogenic compounds present in the aerosol emitted from combusted tobacco, elicit profound deleterious effects upon inhalation, resulting in severe perturbation of pulmonary tissue integrity. The pathogenesis of smoking-induced lung cancer encompasses an intricate process wherein NF-κB activation plays a pivotal role, triggered by exposure to cigarette smoke through diverse signaling pathways, including those associated with oxidative stress and pro-inflammatory cytokines. Unraveling the participation of NF-κB in smoking-induced lung cancer provides pivotal insights into molecular processes, wherein intricate crosstalk between NF-κB and pathways such as MAPK and PI3K-Akt amplifies the inflammatory response, fostering an environment conducive to the formation of lung cancer. This study reviews the critical function of NF-κB in the complex molecular pathways linked to the initiation and advancement of lung carcinogenesis as well as potential treatment targets.

Abstract Erlotinib is a reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that acts by inhibiting signaling pathways, resulting in the disruption of cancerous cell proliferation. Erlotinib is a promising anticancer agent mainly utilized in the mitigation of non-small cell lung cancer cells (NSCLC) and pancreatic tumor. Apart from NSCLC and pancreatic tumor, erlotinib has also been employed in different malignancies, including metastatic colorectal cancer, malignant glioma, breast cancer, gastrointestinal cancers, etc. Despite erlotinib’s distinctive qualities as a targeted drug, its applications are still limited by poor solubility, variable oral bioavailability, a high daily dose requirement, large protein binding, and primitive or acquired therapeutic resistance. Nanotechnology is a favorable approach to increase therapeutic effectiveness of erlotinib. It is one of the newest scientific field directed toward the diagnosis and targeted treatment of cancer. This technology aids in the distinction between normal and malignant cells, which overlays the strategy for targeted delivery. This manuscript discussed the advances of erlotinib nanoformulations in the management of different cancers. Moreover, the manuscript also comprises various research outcomes of erlotinib nanoformulations with other therapeutic agents as combinational therapy. Erlotinib can be delivered to a precise target in the body utilizing different polymers, lipids, and metals.

The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation of biological functions. The study investigates the elusive link between circRNAs and the Transforming Growth Factor-β (TGF-β) signalling pathway, exploring their collective influence on cancer progression and metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns in diverse cancer types, revealing a repertoire of circRNAs intricately linked to the TGF-β pathway. Through integrated bioinformatics analyses and functional experiments, we elucidate the specific circRNA-mRNA interactions that modulate TGF-β signalling, unveiling the regulatory controls governing this crucial pathway. Furthermore, we provide compelling evidence of the impact of circRNA-mediated TGF-β modulation on key cellular processes, including epithelial-mesenchymal transition (EMT), migration, and cell proliferation. In addition to their mechanistic roles, circRNAs have shown promise as diagnostic and prognostic biomarkers, as well as potential molecular targets for cancer therapy. Their ability to modulate critical pathways, such as the TGF-β signalling axis, underscores their significance in cancer biology and clinical applications. The intricate interplay between circRNAs and TGF-β is dissected, uncovering novel regulatory circuits that contribute to the complexity of cancer biology. This review unravels a previously unexplored dimension of carcinogenesis, emphasizing the crucial role of circRNAs in shaping the TGF-β signalling landscape.

Orthotropic steel bridge decks (OSDs) are very popular all over the world because of the low dead load, high stiffness in the longitudinal direction, high strength ratio to weight, and can be used in various types of bridges. The life of these bridges is affected by fatigue cracks in different portions. One of major areas where the fatigue cracks appear in these bridges is rib-to-deck connection. In this research finite element analysis is carried out by using ABAQUS/CAE 2022 software to determine the ways to increase the fatigue life at rib to deck connection in OSDs. In the first part, smaller models are simulated; stress concentration is analyzed and hot spot stress (HSS) is calculated according to International Institute of Welding (IIW) and Det Norske Veritas (DNV) recommendations. In the second part, a parametric analysis is carried out to analyze the effect of weld penetration, thickness of deck, thickness of rib and rib to deck connection type. In the third part, simulation of models similar to the real field is carried out to determine whether the double welded connections are better than single welded connections. Different models are analyzed for different load cases like single wheel load, double wheel load and also the position of the wheels is changed. The boundary conditions are changed to analyze whether the boundary condition has any significant effect on the result obtained. It is found that thicker decks, thinner ribs, and low penetrated welded connections reduce the stress concentrations at rib to deck connections which ultimately increase fatigue life. Among the parameters examined, deck thickness is the most important parameter. It is found that the percentage of stress increase with percentage decrease in deck thickness follows a power relation. The overall fatigue life of double welded connection is excepted to be lower since the stress concentration is maximum at the weld toe at deck on the outer side of the closed stiffener; however, if the cracks initiate on the inner side of closed stiffener, the cracks at the weld root of single welded connection can propagate much rapidly than the cracks initiating on the inner side of the closed stiffener at the weld toe, thereby reducing the fatigue life of the single-welded specimen significantly.

This study aimed to improve the stability and prolonged gefitinib release from the nanoliposomes. Nanoliposomes were prepared by reverse-phase evaporation and optimized using Box-Behnken design to investigate the influence of sonication time (X1), tween 80 / soya phosphatidylcholine ratio (X2), and cholesterol / soya phosphatidylcholine ratio (X3) on nanoliposomes. Optimized nanoliposomes were quasi-spherical shaped, with a mean dimension of 93.2 nm and an encapsulation efficiency of 87.56±0.17 %. Surface decoration of the optimized batch was done using different concentrations of chitosan. The optimal chitosan concentration required to adorn the surface of nanoliposomes was 0.01 %. In comparison to unadorned nanoliposomes (82.16±0.65 %), adorned nanoliposomes (78.04±0.35 %) released the drug consistently over 24 h via Fickian diffusion. The IC50 values for surface-adorned nanoliposomes in A549 and H1299 cells were 6.53±0.75 and 4.73±0.46 µM, respectively. Cytotoxicity of the surface-decorated nanoliposomes may be due to their higher zeta potential and prolonged drug release. At 4°C, adorned and unadorned nanoliposomes are most stable. In conclusion, the developed nanoliposomes may offer a new path for melanoma clinics.

Hazardous debris flows are common in the tectonically active young Himalayas. The present study is focused on the recurrent, almost seasonal, landslides and debris flows initiated from Kalli village in Achham District of Nepal, located in the Lesser Himalayas. Such geological hazards pose a significant threat to the neighboring communities. The field survey reveals vulnerable engineering geological conditions and adverse environmental factors in the study area. It is found that a typical complete debris transport process may consist of two stages depending on the rainfall intensity. In the first stage, debris flows mobilized from a landslide have low mobility and their runout distance is quite modest; in the second stage, with an increase in water content they are able to travel a longer distance. Numerical simulations based on a multi-phase flow model are conducted to analyze the characteristics of the debris flows in motion, including the debris deposition profiles and runout distances in both stages. Overall, the numerical results are reasonably consistent with relevant field observations. Future debris flows may likely occur again in this area due to the presence of large soil blocks separated by tension cracks, rampant in the field; numerical simulations predict that these potential debris flows may exhibit similar characteristics to past events.