PScL-2LSAESM: bioimage-based prediction of protein subcellular localization by integrating heterogeneous features with the two-level SAE-SM and mean ensemble method.

MOTIVATION: Over the past decades, a variety of in silico methods have been developed to predict protein subcellular localization within cells. However, a common and major challenge in the design and development of such methods is how to effectively utilize the heterogeneous feature sets extracted from bioimages. In this regards, limited efforts have been undertaken. RESULTS: We propose a new two-level stacked autoencoder network (termed 2L-SAE-SM) to improve its performance by integrating the heterogeneous feature sets. In particular, in the first level of 2L-SAE-SM, each optimal heterogeneous feature set is fed to train our designed stacked autoencoder network (SAE-SM). All the trained SAE-SMs in the first level can output the decision sets based on their respective optimal heterogeneous feature sets, known as 'intermediate decision' sets. Such intermediate decision sets are then ensembled using the mean ensemble method to generate the 'intermediate feature' set for the second-level SAE-SM. Using the proposed framework, we further develop a novel predictor, referred to as PScL-2LSAESM, to characterize image-based protein subcellular localization. Extensive benchmarking experiments on the latest benchmark training and independent test datasets collected from the human protein atlas databank demonstrate the effectiveness of the proposed 2L-SAE-SM framework for the integration of heterogeneous feature sets. Moreover, performance comparison of the proposed PScL-2LSAESM with current state-of-the-art methods further illustrates that PScL-2LSAESM clearly outperforms the existing state-of-the-art methods for the task of protein subcellular localization. AVAILABILITY AND IMPLEMENTATION: https://github.com/csbio-njust-edu/PScL-2LSAESM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PScL-HDeep: image-based prediction of protein subcellular location in human tissue using ensemble learning of handcrafted and deep learned features with two-layer feature selection.

Protein subcellular localization plays a crucial role in characterizing the function of proteins and understanding various cellular processes. Therefore, accurate identification of protein subcellular location is an important yet challenging task. Numerous computational methods have been proposed to predict the subcellular location of proteins. However, most existing methods have limited capability in terms of the overall accuracy, time consumption and generalization power. To address these problems, in this study, we developed a novel computational approach based on human protein atlas (HPA) data, referred to as PScL-HDeep, for accurate and efficient image-based prediction of protein subcellular location in human tissues. We extracted different handcrafted and deep learned (by employing pretrained deep learning model) features from different viewpoints of the image. The step-wise discriminant analysis (SDA) algorithm was applied to generate the optimal feature set from each original raw feature set. To further obtain a more informative feature subset, support vector machine-based recursive feature elimination with correlation bias reduction (SVM-RFE + CBR) feature selection algorithm was applied to the integrated feature set. Finally, the classification models, namely support vector machine with radial basis function (SVM-RBF) and support vector machine with linear kernel (SVM-LNR), were learned on the final selected feature set. To evaluate the performance of the proposed method, a new gold standard benchmark training dataset was constructed from the HPA databank. PScL-HDeep achieved the maximum performance on 10-fold cross validation test on this dataset and showed a better efficacy over existing predictors. Furthermore, we also illustrated the generalization ability of the proposed method by conducting a stringent independent validation test.

PScL-DDCFPred: an ensemble deep learning-based approach for characterizing multiclass subcellular localization of human proteins from bioimage data.

MOTIVATION: Characterization of protein subcellular localization has become an important and long-standing task in bioinformatics and computational biology, which provides valuable information for elucidating various cellular functions of proteins and guiding drug design. RESULTS: Here, we develop a novel bioimage-based computational approach, termed PScL-DDCFPred, to accurately predict protein subcellular localizations in human tissues. PScL-DDCFPred first extracts multiview image features, including global and local features, as base or pure features; next, it applies a new integrative feature selection method based on stepwise discriminant analysis and generalized discriminant analysis to identify the optimal feature sets from the extracted pure features; Finally, a classifier based on deep neural network (DNN) and deep-cascade forest (DCF) is established. Stringent 10-fold cross-validation tests on the new protein subcellular localization training dataset, constructed from the human protein atlas databank, illustrates that PScL-DDCFPred achieves a better performance than several existing state-of-the-art methods. Moreover, the independent test set further illustrates the generalization capability and superiority of PScL-DDCFPred over existing predictors. In-depth analysis shows that the excellent performance of PScL-DDCFPred can be attributed to three critical factors, namely the effective combination of the DNN and DCF models, complementarity of global and local features, and use of the optimal feature sets selected by the integrative feature selection algorithm. AVAILABILITY AND IMPLEMENTATION: https://github.com/csbio-njust-edu/PScL-DDCFPred. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Assessment of Pb and Ni and potential health risks associated with the consumption of vegetables grown on the roadside soils in District Swat, Khyber Pakhtunkhwa, Pakistan.

Vegetables cultivated near roads absorb toxic metals from polluted soil, which enter the human body through the food chain and cause serious health problems to humans. The present study investigated the concentration of lead (Pb) and nickel (Ni) in soils and vegetables grown along the roadside of District Swat, Pakistan, and the health risks associated with the consumption of the tested vegetables. In results, Pb concentration was higher in plants located at the distance between 0-10 m away from the roadside than the WHO permissible limit. In such plants, Pb concentration was higher than Ni. Rumex dentatus contained the highest concentration of Pb (75.63 mg kg-1 DW) among the tested vegetables while Ni concentration (27.57 mg kg-1 DW) was highest in Trachyspermum ammi as compared to other plants. Concentration and accumulation of both the metals decreased in soil and plants with increasing distance from the road. Similarly, target hazard quotient values noted for Pb (up to 3.37) were greater than unity, which shows that there is a potential risk associated with the consumption of tested vegetables near the road. Moreover, the values of target cancer risk (up to 0.8413) were greater than 0.0001, which shows that there is a risk of cancer with the consumption of tested vegetables. In conclusion, the consumption of tested vegetables was very dangerous as it may lead to higher risks of cancer. Strict regulatory control is recommended on the cultivation of these vegetables along the roadside to avoid any contamination due to roadside exhaust.

Naked Mole-Rats: Resistant to Developing Cancer or Good at Avoiding It?

It is widely accepted that cancer is driven by genetic mutations that confer uncontrolled cell proliferation and tumor formation. For tumors to take hold and grow, cancer cells evolve mechanisms to favorably shape their microenvironment and avoid being cleared by the immune system. Cancer is not unique to human, but rather affects nearly all multicellular organisms albeit to different degrees. The different degrees of cancer susceptibility across the animal kingdom could be attributed to several factors, which have been the subject of several studies in recent years. The naked mole-rat (NMR, Heterocephalus glaber), an exceptionally long-lived rodent, which, as discussed in detail in the next section, displays significant cancer resistance with only a small number of animals being reported to exhibit spontaneous neoplasms. The reason why studying cancer resistance in NMRs is of particular interest is that not only are they now an established laboratory species, but that NMRs are mammals and thus there is great potential for translating knowledge about their cancer resistance into preventing and/or treating cancer in humans and companion animals.

A genetic-demographic approach reveals a gender-specific association of SLC6A3/DAT1 40 bp-VNTR with life-expectancy.

Several recent lines of evidence are proving an important role for dopamine in the aging process and in the determination of life span. Components of the dopaminergic system may represent good candidates for longevity studies. Herein, we tested the possible association of the functional SLC6A3/DAT1 40-bp VNTR with life-expectancy in a healthy population of Central Italy (N = 993) by applying a genetic-demographic approach that takes into account the demographic information and different survival rates between sexes for modeling the survival of specific allele carriers in the population. Male carriers of S*/S* genotype showed a lower survival chance across most of the lifespan respect to the survival of DAT1*L-carriers (P = 0.021). The same analyses gave non-significant results in females. Several studies already reported significant sex differences in dopamine metabolism and its related biological pathways. Thus, we can hypothesize that the SLC6A3/DAT1 40 bp-VNTR may affect life expectancy in a sex-specific way. Moreover, it is conceivable that DAT1 S*/S* carriers, who are prone to assume "risk" type behaviors, may be dropped out of the "healthy" population by a sort of "demographic selection".

Risk assessment and soil heavy metal contamination near marble processing plants (MPPs) in district Malakand, Pakistan.

Soil heavy metals (HMs) pollution is a growing global concern, mainly in regions with rapid industrial growth. This study assessed the concentrations, potential sources, and health risks of HMs in agricultural soils near marble processing plants in Malakand, Pakistan. A total of 21 soil samples were analyzed for essential and toxic HMs via inductively coupled plasma‒optical emission spectrometry (ICP‒OES), and probabilistic health risks were evaluated via Monte Carlo simulation. The concentrations (mg/kg) of Ca (29,250), P (805.5) and Cd (4.5) exceeded the average shale limits of 22,100, 700, and 3.0 mg/kg, respectively, and indices such as Nemerow's synthetic contamination index (NSCI) and the geoaccumulation index (Igeo) categorized the soil sites as moderately polluted. The potential ecological risk index (PERI) indicated considerable to high ecological risk for As and Cd. The deterministic analysis indicated non-carcinogenic risks for children (HI > 1), whereas the probabilistic analysis suggested no significant risk (HI < 1) for both adults and children. Both methods indicated that the total cancer risk for Cr, Ni, Cd, and As exceeded the USEPA safety limits of 1.0E-06 and 1.0E-04. Sensitivity analysis identified heavy metal concentration, exposure duration, and frequency as key risk factors. The study suggested that HM contamination is mainly anthropogenic, poses a threat to soil and human health, and highlights the need for management strategies and surveillance programs to mitigate these risks.

Unveiling the therapeutic and nutritious potential of Vigna unguiculata in line with its phytochemistry.

Background: Vigna unguiculata, belonging to the Fabaceae family, commonly known as cowpea is an important edible legume, distributed mainly across the African and Asian countries. Traditionally, the plant has an outstanding background for the management of multiple diseases, animal feeding and human consumption. Objective: This review aims to mainly focus on the traditional applications, pharmacological activities, phytochemistry as well as nutritious composition of the V. unguiculata. Methods: Data present in the literature on the V. unguiculata, were collected from major scientific databases including Science Direct, SpringerLink, Google Scholar, Medline Plus, Web of Science, PubMed and Elsevier. Results: Number of compounds have been isolated including flavonoids, steroids, alkaloids, phenolic compounds, saponins, fatty acids, tannins, carbohydrates, vitamins, amino acids, carotenoids and fibers from various parts of plant. These compounds exhibit widespread pharmacological potentials both in-vitro and in-vivo including anthelmintic, antibacterial, antinociceptive, thrombolytic, antidiabetic, hypocholestrolemic and antiatherogenic effect, antimicrobial, anti-sickling, antioxidant, anti-covid activity, anticancer and neurobehavioral activities. These compounds have strong pharmacological background and might be responsible for the traditional uses of this plant that are not investigated. Conclusion: It is concluded that V. unguiculata possessed strong pharmacological, nutritious and phytochemical potential, therefore, it is strongly recommended for additional comprehensive investigations in order to determine its clinical utility.

EstroGene2.0: A multi-omic database of response to estrogens, ER-modulators, and resistance to endocrine therapies in breast cancer.

Endocrine therapies targeting the estrogen receptor (ER/ESR1) are the cornerstone to treat ER-positive breast cancers patients, but resistance often limits their effectiveness. Understanding the molecular mechanisms is thus key to optimize the existing drugs and to develop new ER-modulators. Notable progress has been made although the fragmented way data is reported has reduced their potential impact. Here, we introduce EstroGene2.0, an expanded database of its precursor 1.0 version. EstroGene2.0 focusses on response and resistance to endocrine therapies in breast cancer models. Incorporating multi-omic profiling of 361 experiments from 212 studies across 28 cell lines, a user-friendly browser offers comprehensive data visualization and metadata mining capabilities (https://estrogeneii.web.app/). Taking advantage of the harmonized data collection, our follow-up meta-analysis revealed substantial diversity in response to different classes of ER-modulators including SERMs, SERDs, SERCA and LDD/PROTAC. Notably, endocrine resistant models exhibit a spectrum of transcriptomic alterations including a contra-directional shift in ER and interferon signaling, which is recapitulated clinically. Furthermore, dissecting multiple ESR1-mutant cell models revealed the different clinical relevance of genome-edited versus ectopic overexpression model engineering and identified high-confidence mutant-ER targets, such as NPY1R. These examples demonstrate how EstroGene2.0 helps investigate breast cancer's response to endocrine therapies and explore resistance mechanisms.

Effects of zinc oxide nanoparticles on antioxidants, chlorophyll contents, and proline in Persicaria hydropiper L. and its potential for Pb phytoremediation.

Applications of nanoparticles and plants for efficient restoration of heavy metal-polluted water and soil are an emerging approach and need to be explored. Hydroponic study was performed to find the role of zinc oxide nanoparticles (ZnO NPs) in plant growth, antioxidative response, and lead (Pb) accumulation in Persicaria hydropiper. Seedlings were grown in Pb-polluted media amended with 5, 10, 15, and 20 mg L-1 ZnO NPs. Inductively coupled plasma spectroscopy (ICP) was used for Pb analysis in plant tissues. Pb significantly inhibited seedling growth, and ZnO NPs alleviated Pb-induced stress by promoting plant growth, and improved chlorophyll and carotenoid contents. Oxidative stress ameliorated in ZnO NPs exposed seedlings through enhanced production of free proline, phenolics, flavonoids, and activation of antioxidative enzymes. Pb accumulation boosted in ZnO NP treatments, and highly significant increase in Pb accumulation in roots (255.60±4.80 mg kg-1), stem (124.07±2.84 mg kg-1), and leaves (92.00±3.22 mg kg-1) was observed in T3 (15 mg L-1 ZnO NPs) for P. hydropiper. Contrarily, ZnO NPs at 20 mg L-1 dose suppressed plant growth, Pb accumulation, secondary metabolites, and antioxidative enzyme activities. Moreover, positive correlation was found in Pb accumulation with free proline and secondary metabolite contents in plant tissues. These results suggest that ZnO NPs at optimum concentration may augment efficacy of plants to remove heavy metal from polluted water through nanophytoremediation.

Plant growth regulators and EDTA improve phytoremediation potential and antioxidant response of Dysphania ambrosioides (L.) Mosyakin & Clemants in a Cd-spiked soil.

Soil pollution due to potentially toxic elements is a worldwide challenge for health and food security. Chelate-assisted phytoextraction along with the application of plant growth regulators (PGRs) could increase the phytoremediation efficiency of metal-contaminated soils. The present study was conducted to investigate the effect of different PGRs [Gibberellic acid (GA3) and indole acetic acid (IAA)] and synthetic chelator (EDTA) on growth parameters and Cd phytoextraction potential of Dysphania ambrosioides (L.) Mosyakin & Clemants grown under Cd-spiked soil. GA3 (10-7 M) and IAA (10-5 M) were applied four times with an interval of 10 days through a foliar spray, while EDTA (40 mg kg-1 soil) was once added to the soil. The results showed that Cd stress significantly decreased fresh biomass, dry biomass, total water contents, and photosynthetic pigments as compared to control. Application of PGRs significantly enhanced plant growth and Cd phytoextraction. The combined application of GA3 and IAA with EDTA significantly increased Cd accumulation (6.72 mg pot-1 dry biomass) and bioconcentration factor (15.21) as compared to C1 (Cd only). The same treatment significantly increased chlorophyll, proline, phenolic contents, and antioxidant activities (CAT, SOD, and POD) while MDA contents were reduced. In roots, Cd accumulation showed a statistically significant and positive correlation with proline, phenolics, fresh biomass, and dry biomass. Similarly, Cd accumulation showed a positive correlation with antioxidant enzyme activities in leaves. D. ambrosioides showed hyperaccumulation potential for Cd, based on bioconcentration factor (BCF) > 1. In conclusion, exogenous application of GA3 and IAA reduces Cd stress while EDTA application enhances Cd phytoextraction and ultimately the phytoremediation potential of D. ambrosioides.

Application of spore morphology to solve identification problems in certain species of family Dryopteridaceae from Malakand Division, Pakistan.

Here we investigate the morphology of the spores of 12 native taxa of Dryopteridaceae that grow in Malakand division, Pakistan; most of these species not fully described before. This study intends to survey the taxonomic significance of spore morphological features and their variation useful for species identification in 7 species of Polystichum and 5 taxa of Dryopteris. The spores examinations were accomplished utilizing a light microscope (LM), and scanning electron microscope (SEM). The spores are monolete, medium-sized, with variable shapes in both equatorial and polar views. The mean estimation of equatorial diameter ranging from 28.3 to 58.3 µm and the polar diameter varied from 27.6 to 45.8 µm. The exospore thickness ranges between 1.6 to 3.8 µm, and the thickness of perispore is 0.8-6.7 µm. The perispore is perforated, ornamentation elements occur in different ways in the studied taxa of Polystichum. In investigated Dryopteris taxa, rugate perispore type is found. Results of multivariate statistical analysis (UPGMA, and PCA) established on quantitative and qualitative morphological traits of spores demonstrate that the species form distinct groups, not reflecting any phylogenetic relationships. A key to the spores types is provided for species identification, which dependent on the diagnostic characters of spores. The results of this study indicate that variation of spore morphological traits; in particular, the ornamentation and perispore characteristics, which is surface texture, have diagnostic value at the species level. Our data will help in the identification of spores of the family Dryopteridaceae in palynological and taxonomic studies.

Spore morphology and leaf epidermal anatomy as a taxonomic source in the identification of Asplenium species from Malakand division Pakistan.

Several studies have demonstrated the usefulness of leaf epidermal, and spore morphological characters in the taxonomy of genus Asplenium. However, works on the Pakistani species of Asplenium are not existent. With the objective to verify the efficacy of leaf epidermal and spore morphological traits, the leaf epidermis and spore morphology in nine Asplenium species occurring in Malakand division was studied. The spores were studied under light microscope (LM) and scanning electron microscope (SEM), whereas for leaf epidermal anatomy, the LM was used. The spores are monolete, ellipsoidal in shape, the equatorial and polar diameter ranges between 28.3 and 50.2 × 27.6 and 45.8 µm. The exospore thickness varied from 0.5 to 3.8 µm. The perispore is 0.8-3.5 µm thick, ornamented, and morphologically variable. The spores characters specifically the perispore ornamentation are useful in distinguishing species within the genus. The irregular spore shape and unusual development of perispore wall surface characterize aborted spores in the species of Asplenium × alternifolium. The most informative quantitative characters appeared to be length and width of epidermal cells, and length and width of stomata were useful to distinguish species. The most significant qualitative characters to distinguish species were the anticlinal wall pattern. Our study has shown that considerable variations exist in the leaf epidermis of Asplenium species, at least some of which has taxonomic significance. We confirmed the prevalent taxonomic value of stomatal and epidermal cells traits. The leaf epidermal anatomy and spore morphological features showed to be a good source of information for taxonomy of the genus Asplenium.

Magnesium oxide nanoparticles and thidiazuron enhance lead phytoaccumulation and antioxidative response in Raphanus sativus L.

An in vitro study was conducted to evaluate the effects of thidiazuron (TDZ) growth regulator and magnesium oxide (MgO) nanoparticles on radish (Raphanus sativus L.) under lead (Pb) stress. Effects of TDZ and MgO on seed germination, growth, biomass, total phenolics and flavonoids, antioxidant potential, and Pb phytoaccumulation in different plant parts were assessed. Nanoparticles of MgO were synthesized with leaf extract of Sageretia thea (Osbeck) plant. Thidiazuron and MgO nanoparticles were added to growth media in individual and in combinations. Lead (50 mg L-1) was added to growth media. Thidiazuron and MgO nanoparticles increased plant growth, phenolic and flavonoid contents, free radical scavenging activity, and lead phytoaccumulation. The increase was highly significant in TDZ and MgO nanoparticle combination treatments (T5, T6). Treatment (T6) showed a sixfold increase in Pb accumulation (1721.73 ± 17.4 µg g-1 dry biomass) as compared to control (274.29 ± 4.23 µg-1g-1). Total phenolic and dry biomass showed significantly positive correlation in leaves (R2 = 0.73), stem (R2 = 0.58), and roots (R2 = 0.72). The correlation of Pb accumulation and phenolic contents was significantly positive in root (R2 = 0.80), stem (R2 = 0.92), and leaves (R2 = 0.69). Flavonoid showed a positive correlation with dry biomass and Pb accumulation. Antioxidant activity was highly increased in leaves followed by stem and root. Findings show that TDZ in combination with MgO nanoparticles can play a significant role in secondary metabolite production and Pb phytoaccumulation.

Growth stage and molybdenum treatment affect cadmium accumulation, antioxidant defence and chlorophyll contents in Cannabis sativa plant.

Cadmium (Cd) uptake and accumulation in plant tissues is affected by physiological stage of a plant and presence of mineral nutrients in soil. We investigate the effect of micronutrient Mo (0.5, 1.0 and 2.0 ppm) on biomass, Cd accumulation, photosynthetic pigments and endogenous phenolics and soluble proline in Cannabis sativa plant grown in 25 and 50 ppm Cd polluted soil. Molybdenum was applied as seed soaking and soil addition treatments. The plants were harvested in two stages i.e. vegetative (6 weeks) and reproductive stages (12 weeks). It was found that seed soaking treatment of 1.0 ppm Mo most significantly increased biomass, Cd accumulation (1.76 ±â€¯0.19 mg Cd/DBM) and phenolics (104.5 ±â€¯4.46 ppm) concentration in the plant tissues. Molybdenum treatments highly increased Cd bio-concentration at reproductive stage as compared to vegetative stage in plants grown in 50 ppm Cd polluted soil. Translocation of Cd from roots into leaves was significantly increased by Mo treatments at reproductive stage as compared to vegetative stage. Strong inter-correlations existed between total phenolics, Cd accumulation, dry biomass and chlorophyll contents of the plant.

The material properties of naked mole-rat hyaluronan.

Hyaluronan (HA) is a key component of the extracellular matrix. Given the fundamental role of HA in the cancer resistance of the naked mole-rat (NMR), we undertook to explore the structural and soft matter properties of this species-specific variant, a necessary step for its development as a biomaterial. We examined HA extracted from NMR brain, lung, and skin, as well as that isolated from the medium of immortalised cells. In common with mouse HA, NMR HA forms a range of assemblies corresponding to a wide distribution of molecular weights. However, unique to the NMR, are highly folded structures, whose characteristic morphology is dependent on the tissue type. Skin HA forms tightly packed assemblies that have spring-like mechanical properties in addition to a strong affinity for water. Brain HA forms three dimensional folded structures similar to the macroscopic appearance of the gyri and sulci of the human brain. Lung HA forms an impenetrable mesh of interwoven folds in a morphology that can only be described as resembling a snowman. Unlike HA that is commercially available, NMR HA readily forms robust gels without the need for chemical cross-linking. NMR HA gels sharply transition from viscoelastic to elastic like properties upon dehydration or repeated loading. In addition, NMR HA can form ordered thin films with an underlying semi-crystalline structure. Given the role of HA in maintaining hydration in the skin it is plausible that the folded structures contribute to both the elasticity and youthfulness of NMR skin. It is also possible that such densely folded materials could present a considerable barrier to cell invasion throughout the tissues, a useful characteristic for a biomaterial.

CBF/DREB transcription factor genes play role in cadmium tolerance and phytoaccumulation in Ricinus communis under molybdenum treatments.

The C-repeat binding factor/dehydration responsive element binding proteins (CBF/DREB) constitute a large group of transcriptional factors. Their role in abiotic stresses such as drought, salinity and low temperature tolerance in plants have been well established, while little information about their role in metals stress tolerance is available. Transcriptomic analyses of four genes (DREB-1A, DREB-1B, DREB-1F and CBF) were carried out in industrially important plant Ricinus communis under cadmium (Cd) and molybdenum (Mo) treatments. Cadmium (in soil) and Mo (as foliar spray) were used separate as well as in combinations. All the genes (except DREB 1A) expressed under Cd stress, while Mo further enhanced their expression. The proline (55.68 ±â€¯5.51 ppm) and phenolic (120.00 ±â€¯14.40 ppm) contents were significant increase in combination treatments of Cd and Mo. Positive and significant correlations of DREB 1B, DREB 1F and CBF genes expressions with free proline (0.92, 0.93 and 0.88 respectively), phenolic (075, 0.77 and 0.62 respectively) contents and Cd accumulation were demonstrated. Nucleotide sequence of R. comunis DREB1F and CBF genes showed more than 80% homology with related genes of other flowering plants. Predicted amino acids sequence of R. communis DREB 1F and CBF protein fragment demonstrated more than 75% homology with related proteins from other flowering plants.

BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma.

Patients diagnosed with lung squamous cell carcinoma (LUSC) have limited targeted therapies. We report here the identification and characterisation of BCL11A, as a LUSC oncogene. Analysis of cancer genomics datasets revealed BCL11A to be upregulated in LUSC but not in lung adenocarcinoma (LUAD). Experimentally we demonstrate that non-physiological levels of BCL11A in vitro and in vivo promote squamous-like phenotypes, while its knockdown abolishes xenograft tumour formation. At the molecular level we found that BCL11A is transcriptionally regulated by SOX2 and is required for its oncogenic functions. Furthermore, we show that BCL11A and SOX2 regulate the expression of several transcription factors, including SETD8. We demonstrate that shRNA-mediated or pharmacological inhibition of SETD8 selectively inhibits LUSC growth. Collectively, our study indicates that BCL11A is integral to LUSC pathology and highlights the disruption of the BCL11A-SOX2 transcriptional programme as a novel candidate for drug development.

Potassium and zinc increase tolerance to salt stress in wheat (Triticum aestivum L.).

Potassium and zinc are essential elements in plant growth and metabolism and plays a vital role in salt stress tolerance. To investigate the physiological mechanism of salt stress tolerance, a pot experiment was conducted. Potassium and zinc significantly minimize the oxidative stress and increase root, shoot and spike length in wheat varieties. Fresh and dry biomass were significantly increased by potassium followed by zinc as compared to control C. The photosynthetic pigment and osmolyte regulator (proline, total phenolic, and total carbohydrate) were significantly enhanced by potassium and zinc. Salt stress increases MDA content in wheat varieties while potassium and zinc counteract the adverse effect of salinity and significantly increased membrane stability index. Salt stress decreases the activities of antioxidant enzymes (superoxide dismutase, catalase and ascorbate peroxidase) while the exogenous application of potassium and zinc significantly enhanced the activities of these enzymes. A significant positive correlation was found of spike length with proline (R2 = 0.966 ∗∗∗), phenolic (R2 = 0.741∗) and chlorophyll (R2 = 0.853∗∗). The MDA content showed significant negative correlation (R2 = 0.983∗∗∗) with MSI. It is concluded that potassium and zinc reduced toxic effect of salinity while its combine application showed synergetic effect and significantly enhanced salt tolerance.