Slide-tags enables single-nucleus barcoding for multimodal spatial genomics.

Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed1-6. However, missing from these measurements is the ability to routinely and easily spatially localize these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are tagged with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as an input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10 µm spatial resolution and delivered whole-transcriptome data that are indistinguishable in quality from ordinary single-nucleus RNA-sequencing data. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualized receptor-ligand interactions driving B cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to almost any single-cell measurement technology. As a proof of principle, we performed multiomic measurements of open chromatin, RNA and T cell receptor (TCR) sequences in the same cells from metastatic melanoma, identifying transcription factor motifs driving cancer cell state transitions in spatially distinct microenvironments. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.

Preparation, Optimization and In vitro Evaluation of Doxorubicin-loaded into Hyaluronic Acid Coated Niosomes Against Breast Cancer.

Doxorubicin (DOX) is widely used against solid tumors. Niosomes are self-assembled nanocarriers of non-ionic surfactants. DOX loaded into cationic niosomes (DOX-Nio) was prepared via thin film hydration method. DOX-Nio was then decorated with a hyaluronic acid (DOX-HA-Nio) via electrostatic interaction. DOX-Nio and DOX-HA-Nio displayed a particle size of 120.0±1.02 and 182.9±2.3 nm, and charge of + 35.5±0.15 and -15.6±0.25 mV, respectively, with PDI < 0.3. DOX-HA-Nio showed a good stability regarding size and charge over 4 weeks at 4 °C and maintain their integrity after lyophilization. HPLC results showed a 94.1±4.2 % encapsulation efficiency of DOX with good entrapment and slow, prolonged DOX release even after 48 hrs. Cell viability assay showed an IC50 of 14.26 nM for the DOX-HA-Nio against MCF-7 cell line with micromolar IC50 results against CD-44 negative cell lines (NIH/3T3). DOX-HA-Nio was proven to be an effective, targeted nanocarrier for DOX against MCF-7 cell line.

Early Alzheimer's disease pathology in human cortex involves transient cell states.

Cellular perturbations underlying Alzheimer's disease (AD) are primarily studied in human postmortem samples and model organisms. Here, we generated a single-nucleus atlas from a rare cohort of cortical biopsies from living individuals with varying degrees of AD pathology. We next performed a systematic cross-disease and cross-species integrative analysis to identify a set of cell states that are specific to early AD pathology. These changes-which we refer to as the early cortical amyloid response-were prominent in neurons, wherein we identified a transitional hyperactive state preceding the loss of excitatory neurons, which we confirmed by acute slice physiology on independent biopsy specimens. Microglia overexpressing neuroinflammatory-related processes also expanded as AD pathology increased. Finally, both oligodendrocytes and pyramidal neurons upregulated genes associated with ß-amyloid production and processing during this early hyperactive phase. Our integrative analysis provides an organizing framework for targeting circuit dysfunction, neuroinflammation, and amyloid production early in AD pathogenesis.

Silicon dioxide nanoparticles suppress copper toxicity in Mentha arvensis L. by adjusting ROS homeostasis and antioxidant defense system and improving essential oil production.

Copper (Cu) is an essential micronutrient for plants; however, the excessive accumulation of Cu due to various anthropogenic activities generates progressive pollution of agricultural land and that causes a major constraint for crop production. Excess Cu (80 mg kg-1) in the soil diminished growth and biomass, photosynthetic efficiency and essential oil (EO) content in Mentha arvensis L., while amplifying the antioxidant enzyme's function and reactive oxygen species (ROS) production. Therefore, there is a pressing need to explore effective approaches to overcome Cu toxicity in M. arvensis plants. Thus, the present study unveils the potential of foliar supplementation of two distinct forms of silicon dioxide nanoparticles (SiO2 NPs) i.e., Aerosil 200F and Aerosil 300 to confer Cu stress tolerance attributes to M. arvensis. The experiment demonstrated that applied forms of SiO2 NPs (120 mg L-1), enhanced plants' growth and augmented the photosynthetic efficiency along with the activities of CA (carbonic anhydrase) and NR (nitrate reductase), however, the effects were more accentuated by Aerosil 200F application. Supplementation of SiO2 NPs also exhibited a beneficial effect on the antioxidant machinery of Cu-disturbed plants by raising the level of proline and total phenol as well as the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX) and glutathione reductase (GR), thereby lowering ROS and electrolytic leakage (EL). Interestingly, SiO2 NPs supplementation upscaled EO production in Cu-stressed plants with more pronounced effects received in the case of Aerosil 200F over Aerosil 300. We concluded that the nano form (Aerosil 200F) of SiO2 proved to be the best in improving the Cu-stress tolerance in plants.

Melatonin supplementation combats nickel-induced phytotoxicity in Trigonella foenum-graecum L. plants through metal accumulation reduction, upregulation of NO generation, antioxidant defence machinery and secondary metabolites.

Nickel (Ni) at a toxic level (80 mg kg-1 of soil) adversely affects the crop performance of fenugreek (Trigonella foenum-graecum L.). Melatonin (MEL), a potent plant growth regulator, is ascribed to offer promising roles in heavy metal stress alleviation. In this study, different doses viz. 0, 25, 50, 75 and 100 µM of MEL were administered to plants through foliage under normal and Ni-stress conditions. The experiment unveiled positive roles of MEL in enhancing root-shoot lengths, fresh-dry weights, seed yield and restoring photosynthetic efficiency assessed in terms of higher Fv/Fm, YII, qP, and lower NPQ values in plants exposed to Ni (80 mg kg-1). MEL supplementation (at 75 µM) effectively restricted Ni accumulation and regulated oxidative stress via modulation of MDA, O2-, H2O2 and NO generation, most prominently. Besides, MEL at 75 µM more conspicuously perked up the activities of antioxidant enzymes like SOD, POX, CAT and APX by 15.7, 20.0, 14.5 and 16.5% higher than the Ni-exposed plants for effective ROS scavenging. Likewise, MEL at 75 µM also efficiently counteracted Ni-generated osmotic stress, through an upscaled accumulation of proline (19.6%) along with the enhancement in the concentration of total phenols (13.6%), total tannins (11.2%), total flavonoids (25.5%) and total alkaloids (19.2%) in plant's leaves. Furthermore, under 80 mg kg-1 Ni stress, MEL at 75 µM improved the seed's trigonelline content by 40.1% higher compared to Ni-disturbed plants, upgrading the pharmacological actions of the plant. Thus, the present study deciphers the envisaged roles of MEL in the alleviation of Ni stress in plants to enhance overall crop productivity.

Nitric oxide induces antioxidant machinery, PSII functioning and artemisinin biosynthesis in Artemisia annua under cadmium stress.

Soil contamination by heavy metals poses a significant environmental challenge, as the practical implementation of existing remediation technologies in the field has encountered numerous obstacles. This has necessitated the requirement of finding alternate solutions to reduce the harm caused to plants. In this study, nitric oxide (NO) was investigated for its potential to reduce cadmium (Cd) toxicity in A. annua plants. Although NO plays a vital role in the growth and development of plants, information on its role in reducing abiotic stress in plants is limited. A. annua plants were exposed to 20 and 40 mg/kg Cd regardless of the addition of exogenous sodium nitroprusside (SNP), a NO donor, at 200 µM concentration. Results showed that SNP treatment improved plant growth, photosynthesis, chlorophyll fluorescence, pigment content, and artemisinin production while reducing Cd accumulation and improving membrane stability in A. annua during Cd stress. The results demonstrated that NO can effectively reverse Cd-induced damage in A. annua by modulating the antioxidant system, maintaining redox homeostasis, and improving photosynthetic performance and different fluorescence parameters such as Fv/Fm, ФPSII, and ETR. The supplementation of SNP caused a substantial improvement in chloroplast ultrastructure, stomatal behavior, and different attributes relate to glandular secretory trichomes, which in turn increased artemisinin production; 14.11 % in plants exposed to Cd stress of 20 mg/kg. Our findings highlight that NO could be useful in mediating the repair of Cd-induced damage to A. annua, and suggest that it may play a critical role in plant signaling networks, improving plant adaptability to Cd stress. The results have important implications for developing new strategies to mitigate the negative impacts of environmental contaminants on plant health, and ultimately, the ecosystem.

Slide-tags: scalable, single-nucleus barcoding for multi-modal spatial genomics.

Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed. Missing from these measurements, however, is the ability to routinely and easily spatially localise these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are 'tagged' with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10 micron spatial resolution, and delivered whole-transcriptome data that was indistinguishable in quality from ordinary snRNA-seq. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil, and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualised receptor-ligand interactions driving B-cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to virtually any single-cell measurement technology. As proof of principle, we performed multiomic measurements of open chromatin, RNA, and T-cell receptor sequences in the same cells from metastatic melanoma. We identified spatially distinct tumour subpopulations to be differentially infiltrated by an expanded T-cell clone and undergoing cell state transition driven by spatially clustered accessible transcription factor motifs. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.

Exogenous abscisic acid fine-tunes heavy metal accumulation and plant's antioxidant defence mechanism to optimize crop performance and secondary metabolite production in Trigonella foenum-graecum L. under nickel stress.

Nickel (Ni) contamination of farming soil has become currently a recurring global menace to agriculture crop productivity. The purpose of the present study was to investigate the putative contributions of abscisic acid (ABA) to extemporize Ni tolerance in Trigonella foenum-graecum L. (fenugreek) plants. The outcomes of this study exposed that exogenous supplementation of ABA at 10, 20, 40 and 80 µM considerably enhanced the growth and physiological attributes of fenugreek under 80 mg Ni kg-1 soil, however, 40 µM of ABA exhibited the best results under normal and Ni-stressed conditions. ABA-mediated Ni tolerance was marked by reductions in Ni accumulation and consequent lowering of reactive oxygen species (ROS) like hydrogen peroxide and superoxide radicals. Contrarily, NO (nitric oxide) level increased in response to ABA application under Ni stress conditions, accompanied by promoted antioxidant activities through improved levels of secondary metabolites, proline, and perked-up ROS-detoxification enzymes activities. Exogenous ABA at 40 µM concentration applied to Ni-exposed plants (80 mg Ni kg-1 soil) improved the total content of alkaloids, phenolics, flavonoids and tannins by 14.3%, 10.2%, 15.4% and 7.0%, respectively, over Ni-stressed plants alone. Additionally, seed trigonelline content imparting several pharmacological actions to the fenugreek plant exhibited a remarkable escalation upto 3.6 and 2.6 mg g-1 DW under '40 µM ABA' and '40 µM ABA + 80 mg Ni kg-1 soil' treatments, respectively. The findings of the study suggest that ABA plays a key role in enhancing the overall performance of the fenugreek crop under excessive Ni stress.

Insights into strigolactone (GR24) mediated regulation of cadmium-induced changes and ROS metabolism in Artemisia annua.

Agricultural soil contamination and subsequently crops still require alternative solutions to reduce associated environmental risks. The effects of strigolactones (SLs) in alleviating cadmium (Cd) phytotoxicity in Artemisia annua plants were investigated during this study. Strigolactones play a vital role during plant growth and development due to their complex interplay during a plethora of biochemical processes. However, information on the potential of SLs to elicit abiotic stress signaling and trigger physiological modifications in plants is limited. In order to decipher the same, A. annua plants were exposed to different concentrations of Cd (20 and 40 mg kg-1), with or without the supplementation of exogenous SL (GR24, a SL analogue) at 4 µM concentration. Under Cd stress, excess Cd accumulation resulted in reduced growth, physio-biochemical traits, and artemisinin content. However, the follow-up treatment of GR24 maintained a steady state equilibrium between reactive oxygen species and antioxidant enzymes, improved chlorophyll fluorescence parameters such as Fv/Fm, ФPSII, and ETR for improved photosynthesis, enhanced chlorophyll content, maintained chloroplast ultrastructure, improved the glandular trichome (GT) attributes and artemisinin production in A. annua. Moreover, it also resulted in improved membrane stability, reduced Cd accumulation, and regulated the behaviour of stomatal apertures for better stomatal conductance under Cd stress. The results of our study suggest that GR24 could be highly effective in alleviating Cd-induced damages in A. annua. It acts via the modulation of the antioxidant enzyme system for redox homeostasis, protection of the chloroplasts and pigments for improved photosynthetic performance, and improved GT attributes for enhanced artemisinin production in A. annua.

Isolation and characterization of bacteria residing in the oral, gut, and fecal samples of different pheasant species / Isolamento e caracterização de bactérias residentes nas amostras orais, intestinais e fecais de diferentes espécies de faisão

Abstract There is a paucity of research conducted on microbial prevalence in pheasants. The microbiota of captive birds has zoonotic significance and must be characterize. Present study is therefore planned to assess the microbiota from oral, fecal and gut content of captive avian species. It will be helpful in characterization of harmful microbes. Different samples taken from oral, gut and feces of ring-necked pheasants (Phasianus colchicus), green pheasants (Phasianus versicolor), golden pheasant (Chrysolophus pictus) and silver pheasant (Lophura nycthemera). Samples were collected, diluted, and inoculated onto different agar plates (MacConkey, SS agar, MSA and nutrient agar) for cultivation of bacterial species. Colonies of E.coli, Staphylococcus spp. Brachyspira spp. and Campylobacter spp were observed based on colony morphology. Colony forming unit showed E. coli as frequently found bacteria in fecal, oral and gut contents of all the above pheasants. The overall significance difference was found among bacterial species of golden pheasants, green pheasant, ring-necked pheasant, and silver pheasants. It was concluded that E.coli is predominant isolated from heathy pheasants followed by Campylobacter, Staphylococcus and Brachyspira.

Resumo Há uma escassez de pesquisas realizadas sobre a prevalência microbiana em faisões. A microbiota de aves em cativeiro tem significado zoonótico e deve ser caracterizada. O presente estudo está, portanto, planejado para avaliar a microbiota do conteúdo oral, fecal e intestinal de espécies aviárias em cativeiro. Será útil na caracterização de micróbios nocivos. Diferentes amostras retiradas da boca, intestino e fezes de faisões de pescoço redondo (Phasianus colchicus), faisões verdes (Phasianus versicolor), faisões dourados (Chrysolophus pictus) e faisão prateado (Lophura nycthemera). As amostras foram coletadas, diluídas e inoculadas em diferentes placas de ágar (MacConkey, ágar SS, MSA e ágar nutriente) para o cultivo de espécies bacterianas. Colônias de E. coli, Staphylococcus spp., Brachyspira spp. e Campylobacter spp foram observados com base na morfologia da colônia. A unidade formadora de colônia mostrou E. coli como bactéria frequentemente encontrada no conteúdo fecal, oral e intestinal de todos os faisões acima. A diferença de significância geral foi encontrada entre as espécies bacterianas de faisões dourados, faisões verdes, faisões de pescoço anelado e faisões prateados. Verificou-se que a E.coli é predominantemente isolada de faisões saudáveis, seguida por Campylobacter, Staphylococcus e Brachyspira.

Isolation and characterization of bacteria residing in the oral, gut, and fecal samples of different pheasant species / Isolamento e caracterização de bactérias residentes nas amostras orais, intestinais e fecais de diferentes espécies de faisão

There is a paucity of research conducted on microbial prevalence in pheasants. The microbiota of captive birds has zoonotic significance and must be characterize. Present study is therefore planned to assess the microbiota from oral, fecal and gut content of captive avian species. It will be helpful in characterization of harmful microbes. Different samples taken from oral, gut and feces of ring-necked pheasants (Phasianus colchicus), green pheasants (Phasianus versicolor), golden pheasant (Chrysolophus pictus) and silver pheasant (Lophura nycthemera). Samples were collected, diluted, and inoculated onto different agar plates (MacConkey, SS agar, MSA and nutrient agar) for cultivation of bacterial species. Colonies of E.coli, Staphylococcus spp. Brachyspira spp. and Campylobacter spp were observed based on colony morphology. Colony forming unit showed E. coli as frequently found bacteria in fecal, oral and gut contents of all the above pheasants. The overall significance difference was found among bacterial species of golden pheasants, green pheasant, ring-necked pheasant, and silver pheasants. It was concluded that E.coli is predominant isolated from heathy pheasants followed by Campylobacter, Staphylococcus and Brachyspira.

Há uma escassez de pesquisas realizadas sobre a prevalência microbiana em faisões. A microbiota de aves em cativeiro tem significado zoonótico e deve ser caracterizada. O presente estudo está, portanto, planejado para avaliar a microbiota do conteúdo oral, fecal e intestinal de espécies aviárias em cativeiro. Será útil na caracterização de micróbios nocivos. Diferentes amostras retiradas da boca, intestino e fezes de faisões de pescoço redondo (Phasianus colchicus), faisões verdes (Phasianus versicolor), faisões dourados (Chrysolophus pictus) e faisão prateado (Lophura nycthemera). As amostras foram coletadas, diluídas e inoculadas em diferentes placas de ágar (MacConkey, ágar SS, MSA e ágar nutriente) para o cultivo de espécies bacterianas. Colônias de E. coli, Staphylococcus spp., Brachyspira spp. e Campylobacter spp foram observados com base na morfologia da colônia. A unidade formadora de colônia mostrou E. coli como bactéria frequentemente encontrada no conteúdo fecal, oral e intestinal de todos os faisões acima. A diferença de significância geral foi encontrada entre as espécies bacterianas de faisões dourados, faisões verdes, faisões de pescoço anelado e faisões prateados. Verificou-se que a E.coli é predominantemente isolada de faisões saudáveis, seguida por Campylobacter, Staphylococcus e Brachyspira.

Isolation and characterization of bacteria residing in the oral, gut, and fecal samples of different pheasant species

Abstract There is a paucity of research conducted on microbial prevalence in pheasants. The microbiota of captive birds has zoonotic significance and must be characterize. Present study is therefore planned to assess the microbiota from oral, fecal and gut content of captive avian species. It will be helpful in characterization of harmful microbes. Different samples taken from oral, gut and feces of ring-necked pheasants (Phasianus colchicus), green pheasants (Phasianus versicolor), golden pheasant (Chrysolophus pictus) and silver pheasant (Lophura nycthemera). Samples were collected, diluted, and inoculated onto different agar plates (MacConkey, SS agar, MSA and nutrient agar) for cultivation of bacterial species. Colonies of E.coli, Staphylococcus spp. Brachyspira spp. and Campylobacter spp were observed based on colony morphology. Colony forming unit showed E. coli as frequently found bacteria in fecal, oral and gut contents of all the above pheasants. The overall significance difference was found among bacterial species of golden pheasants, green pheasant, ring-necked pheasant, and silver pheasants. It was concluded that E.coli is predominant isolated from heathy pheasants followed by Campylobacter, Staphylococcus and Brachyspira.

Resumo Há uma escassez de pesquisas realizadas sobre a prevalência microbiana em faisões. A microbiota de aves em cativeiro tem significado zoonótico e deve ser caracterizada. O presente estudo está, portanto, planejado para avaliar a microbiota do conteúdo oral, fecal e intestinal de espécies aviárias em cativeiro. Será útil na caracterização de micróbios nocivos. Diferentes amostras retiradas da boca, intestino e fezes de faisões de pescoço redondo (Phasianus colchicus), faisões verdes (Phasianus versicolor), faisões dourados (Chrysolophus pictus) e faisão prateado (Lophura nycthemera). As amostras foram coletadas, diluídas e inoculadas em diferentes placas de ágar (MacConkey, ágar SS, MSA e ágar nutriente) para o cultivo de espécies bacterianas. Colônias de E. coli, Staphylococcus spp., Brachyspira spp. e Campylobacter spp foram observados com base na morfologia da colônia. A unidade formadora de colônia mostrou E. coli como bactéria frequentemente encontrada no conteúdo fecal, oral e intestinal de todos os faisões acima. A diferença de significância geral foi encontrada entre as espécies bacterianas de faisões dourados, faisões verdes, faisões de pescoço anelado e faisões prateados. Verificou-se que a E.coli é predominantemente isolada de faisões saudáveis, seguida por Campylobacter, Staphylococcus e Brachyspira.

Systems biology of chromium-plant interaction: insights from omics approaches.

Plants are frequently subjected to heavy metal (HM) stress that impedes their growth and productivity. One of the most common harmful trace metals and HM discovered is chromium (Cr). Its contamination continues to increase in the environment due to industrial or anthropogenic activities. Chromium is severely toxic to plant growth and development and acts as a human carcinogen that enters the body by inhaling or taking Cr-contaminated food items. Plants uptake Cr via various transporters, such as sulfate and phosphate transporters. In nature, Cr is found in various valence states, commonly Cr (III) and Cr (VI). Cr (VI) is soil's most hazardous and pervasive form. Cr elevates reactive oxygen species (ROS) activity, impeding various physiological and metabolic pathways. Plants have evolved various complex defense mechanisms to prevent or tolerate the toxic effects of Cr. These defense mechanisms include absorbing and accumulating Cr in cell organelles such as vacuoles, immobilizing them by forming complexes with organic chelates, and extracting them by using a variety of transporters and ion channels regulated by various signaling cascades and transcription factors. Several defense-related proteins including, metallothioneins, phytochelatins, and glutathione-S-transferases aid in the sequestration of Cr. Moreover, several genes and transcriptional factors, such as WRKY and AP2/ERF TF genes, play a crucial role in defense against Cr stress. To counter HM-mediated stress stimuli, OMICS approaches, including genomics, proteomics, transcriptomics, and metallomics, have facilitated our understanding to improve Cr stress tolerance in plants. This review discusses the Cr uptake, translocation, and accumulation in plants. Furthermore, it provides a model to unravel the complexities of the Cr-plant interaction utilizing system biology and integrated OMICS approach.

Soil-applied Nickel Generates Differential Responses in Growth, Physiology and Oxidative Metabolism of Fenugreek (Trigonella foenum-graecum L.) Varieties.

This work aims to evaluate the potential of nickel (Ni), an essential micronutrient, as an oxidative stress inducer along with associated morphological and biochemical responses in different varieties of fenugreek (Trigonella foenum-graecum L.), a chief economically cultivated crop of India. Varietal differences in crop performance upon exposure to 0, 20, 40, 60 and 80 mg Ni kg- 1 soil reflects that Ni applied at 20 mg Ni kg- 1 soil offers growth-promoting effects, improved photosynthesis attributes, carbonic and nitrate reductase activities more profound in PEB followed by AFg2, AFg1 and UM185 variety. This study observed a dose-dependent reduction in all the above parameters. Maximum toxic effects were noticed at 80 mg kg- 1 Ni, manifested in the form of enhanced H2O2 and MDA contents, which were efficiently counteracted by augmentation in proline content, SOD, POX, CAT and APX activities in PEB over other varieties, suggesting that the Ni tolerance in fenugreek varieties can be organized as PEB > AFg2 > AFg1 > UM185.

Multi-Class Skin Lesions Classification Using Deep Features.

Skin cancer classification is a complex and time-consuming task. Existing approaches use segmentation to improve accuracy and efficiency, but due to different sizes and shapes of lesions, segmentation is not a suitable approach. In this research study, we proposed an improved automated system based on hybrid and optimal feature selections. Firstly, we balanced our dataset by applying three different transformation techniques, which include brightness, sharpening, and contrast enhancement. Secondly, we retrained two CNNs, Darknet53 and Inception V3, using transfer learning. Thirdly, the retrained models were used to extract deep features from the dataset. Lastly, optimal features were selected using moth flame optimization (MFO) to overcome the curse of dimensionality. This helped us in improving accuracy and efficiency of our model. We achieved 95.9%, 95.0%, and 95.8% on cubic SVM, quadratic SVM, and ensemble subspace discriminants, respectively. We compared our technique with state-of-the-art approach.

Influence of PRKCE non-synonymous variants on protein dynamics and functionality.

Novel protein kinase C (nPKC) family member, protein kinase C epsilon (PKCε) is an AGC kinase superfamily member. It is associated with neurological and metabolic diseases as well as human cancers. No study so far has been conducted to identify genetic variations and their effect on PKCε folding and functioning. The present study aimed to identify mutational hotspots in PKCε and disease-causing non-synonymous variants (nsSNPs) along with the investigation of nsSNP impact on protein dynamics. Twenty-nine in silico tools were applied to determine nsSNP deleteriousness, their impact on protein dynamics and disease association, along with the prediction of PKCε post-translational modification (PTM) sites. The present study's outcomes indicated that most nsSNPs were concentrated in the PKCε hinge region and C-terminal tail. Most pathogenic variants mapped to the kinase domain. Regulatory domain variants influenced PKCε interaction with molecular players whereas kinase domain variants were predicted to impact its phosphorylation pattern and protein-protein interactions. Most PTM sites were mapped to the hinge region. PKCε nsSNPs have an association with oncogenicity and its expression dysregulation is responsible for poor overall survival. Understanding nsSNP structural impact is a primary step necessary for delineating the relationship of genetic level differences with protein phenotype. The obtained knowledge can eventually help in disease diagnosis and therapy design.

Inhibitory effect of polyphenols (phenolic acids, lignans, and stilbenes) on cancer by regulating signal transduction pathways: a review.

Natural products, especially polyphenols (phenolic acids, lignans, and stilbenes) are suggested to be more potent anticancer drugs because of their no or less adverse effects, excess availability, high accuracy, and secure mode of action. In the present review, potential anticancer mechanisms of action of some polyphenols including phenolic acids, lignans, and stilbenes are discussed based on clinical, epidemiological, in vivo, and in vitro studies. The emerging evidence revealed that phenolic acids, lignans, and stilbenes induced apoptosis in the treatment of breast (MCF-7), colon (Caco-2), lung (SKLU-1), prostate (DU-145 and LNCaP), hepatocellular (hepG-2), and cervical (A-431) cancer cells, cell cycle arrest (S/G2/M/G1-phases) in gastric (MKN-45 and MKN-74), colorectal (HCT-116), bladder (T-24 and 5637), oral (H-400), leukemic (HL-60 and MOLT-4) and colon (Caco-2) cancer cells, and inhibit cell proliferation against the prostate (PC-3), liver (LI-90), breast (T47D and MDA-MB-231), colon (HT-29 and Caco-2), cervical (HTB-35), and MIC-1 cancer cells through caspase-3, MAPK, AMPK, Akt, NF-κB, Wnt, CD95, and SIRT1 pathways. Based on accumulated data, we suggested that polyphenols could be considered as a viable therapeutic option in the treatment of cancer cells in the near future.

Spatial genomics enables multi-modal study of clonal heterogeneity in tissues.

The state and behaviour of a cell can be influenced by both genetic and environmental factors. In particular, tumour progression is determined by underlying genetic aberrations1-4 as well as the makeup of the tumour microenvironment5,6. Quantifying the contributions of these factors requires new technologies that can accurately measure the spatial location of genomic sequence together with phenotypic readouts. Here we developed slide-DNA-seq, a method for capturing spatially resolved DNA sequences from intact tissue sections. We demonstrate that this method accurately preserves local tumour architecture and enables the de novo discovery of distinct tumour clones and their copy number alterations. We then apply slide-DNA-seq to a mouse model of metastasis and a primary human cancer, revealing that clonal populations are confined to distinct spatial regions. Moreover, through integration with spatial transcriptomics, we uncover distinct sets of genes that are associated with clone-specific genetic aberrations, the local tumour microenvironment, or both. Together, this multi-modal spatial genomics approach provides a versatile platform for quantifying how cell-intrinsic and cell-extrinsic factors contribute to gene expression, protein abundance and other cellular phenotypes.

Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches.

MAIN CONCLUSION: This review analyses the most recent scientific research conducted for the purpose of enhancing artemisinin production. It may help to devise better artemisinin enhancement strategies, so that its production becomes cost effective and becomes available to masses. Malaria is a major threat to world population, particularly in South-East Asia and Africa, due to dearth of effective anti-malarial compounds, emergence of quinine resistant malarial strains, and lack of advanced healthcare facilities. Artemisinin, a sesquiterpene lactone obtained from Artemisia annua L., is the most potent drug against malaria and used in the formulation of artemisinin combination therapies (ACTs). Artemisinin is also effective against various types of cancers, many other microbes including viruses, parasites and bacteria. However, this specialty metabolite and its derivatives generally occur in low amounts in the source plant leading to its production scarcity. Considering the importance of this drug, researchers have been working worldwide to develop novel strategies to augment its production both in vivo and in vitro. Due to complex chemical structure, its chemical synthesis is quite expensive, so researchers need to devise synthetic protocols that are economically viable and also work on increasing the in-planta production of artemisinin by using various strategies like use of phytohormones, stress signals, bioinoculants, breeding and transgenic approaches. The focus of this review is to discuss these artemisinin enhancement strategies, understand mechanisms modulating its biosynthesis, and evaluate if roots play any role in artemisinin production. Furthermore, we also have a critical analysis of various assays used for artemisinin measurement. This may help to develop better artemisinin enhancement strategies which lead to decreased price of ACTs and increased profit to farmers.

Salicylic acid-mediated alleviation of soil boron toxicity in Mentha arvensis and Cymbopogon flexuosus: Growth, antioxidant responses, essential oil contents and components.

Boron (B) toxicity is a notable abiotic hindrance that restricts crop productivity by disturbing several physiological and biochemical processes in plants. This study was aimed to elucidate the role of salicylic acid (SA) in conferring tolerance to B stress in Mentha arvensis and Cymbopogon flexuosus. Boron toxicity led to a considerable decrease in shoot height and root length, fresh and dry mass of shoot and root, and physiological and biochemical parameters. However, exogenously applied SA relieved the adverse effects caused by B toxicity and led to an increase in growth parameters under B stress and non-stress conditions. The treatment of B resulted in its increased accumulation in roots and shoots of both the plants which, in turn, caused oxidative damage as evident by increased content of malondialdehyde and catalase, peroxidase, superoxide dismutase and glutathione reductase enzyme activities. However, exogenous SA supply significantly affected antioxidant enzyme activities and protected the plants from excess B. Moreover, the essential oil content of two selected plants declined under B toxicity and significantly enhanced in SA-treated stressed plants. The contents of menthol and menthyl acetate in M. arvensis were lowered in B stressed plants which significantly improved in SA treated B-stressed and in their respective SA alone treatment. Similarly, citral-A and citral-B content of C. flexuosus declined under B toxicity, however, SA reversed the negative effects of B toxicity on essential oil components. This assessment stipulated the promising role of exogenously applied SA in alleviating B toxicity in M. arvensis and C. flexuosus by improving antioxidant machinery and limiting B uptake which protects the structural integrity of leaves and also helps in increasing essential oil content.