Prevalence and factors associated with digital addiction among students taking university entrance tests: a GIS-based study.

BACKGROUND: The surge in digital media consumption, coupled with the ensuing consequences of digital addiction, has witnessed a rapid increase, particularly after the initiation of the COVID-19 pandemic. Despite some studies exploring specific technological addictions, such as internet or social media addiction, in Bangladesh, there is a noticeable gap in research focusing on digital addiction in a broader context. Thus, this study aims to investigate digital addiction among students taking the university entrance test, examining its prevalence, contributing factors, and geographical distribution using GIS techniques. METHODS: Data from a cross-sectional survey were collected from a total of 2,157 students who were taking the university entrance test at Jahangirnagar University, Bangladesh. A convenience sampling method was applied for data collection using a structured questionnaire. Statistical analyses were performed with SPSS 25 Version and AMOS 23 Version, whereas ArcGIS 10.8 Version was used for the geographical distribution of digital addiction. RESULTS: The prevalence of digital addiction was 33.1% (mean score: 16.05 ± 5.58). Those students who are attempting the test for a second time were more likely to be addicted (42.7% vs. 39.1%), but the difference was not statistically significant. Besides, the potential factors predicted for digital addiction were student status, satisfaction with previous mock tests, average monthly expenditure during the admission test preparation, and depression. No significant difference was found between digital addiction and districts. However, digital addiction was higher in the districts of Manikganj, Rajbari, Shariatpur, and Chittagong Hill Tract areas, including Rangamati, and Bandarban. CONCLUSIONS: The study emphasizes the pressing need for collaborative efforts involving educational policymakers, institutions, and parents to address the growing digital addiction among university-bound students. The recommendations focus on promoting alternative activities, enhancing digital literacy, and imposing restrictions on digital device use, which are crucial steps toward fostering a healthier digital environment and balanced relationship with technology for students.

Multi-armed bandit algorithm for sequential experiments of molecular properties with dynamic feature selection.

Sequential optimization is one of the promising approaches in identifying the optimal candidate(s) (molecules, reactants, drugs, etc.) with desired properties (reaction yield, selectivity, efficacy, etc.) from a large set of potential candidates, while minimizing the number of experiments required. However, the high dimensionality of the feature space (e.g., molecular descriptors) makes it often difficult to utilize the relevant features during the process of updating the set of candidates to be examined. In this article, we developed a new sequential optimization algorithm for molecular problems based on reinforcement learning, multi-armed linear bandit framework, and online, dynamic feature selections in which relevant molecular descriptors are updated along with the experiments. We also designed a stopping condition aimed to guarantee the reliability of the chosen candidate from the dataset pool. The developed algorithm was examined by comparing with Bayesian optimization (BO), using two synthetic datasets and two real datasets in which one dataset includes hydration free energy of molecules and another one includes a free energy difference between enantiomer products in chemical reaction. We found that the dynamic feature selection in representing the desired properties along the experiments provides a better performance (e.g., time required to find the best candidate and stop the experiment) as the overall trend and that our multi-armed linear bandit approach with a dynamic feature selection scheme outperforms the standard BO with fixed feature variables. The comparison of our algorithm to BO with dynamic feature selection is also addressed.

Pollution area identification, receptor model-oriented sources and probabilistic health hazards to prioritize control measures for heavy metal management in soil.

Identifying the primary source of heavy metals (HMs) pollution and the key pollutants is crucial for safeguarding eco-health and managing risks in industrial vicinity. For this purpose, this investigation was carried out to investigate the pollution area identification with soil static environmental capacity (QI), receptor model-oriented critical sources, and Monte Carlo simulation (MCS) based probabilistic environmental and human health hazards associated with HMs in agricultural soils of Narayanganj, Bangladesh. The average concentration of Cr, Ni, Cu, Cd, Pb, Co, Zn, and Mn were 98.67, 63.41, 37.39, 1.28, 23.93, 14.48, 125.08, and 467.45 mg/kg, respectively. The geoaccumulation index identified Cd as the dominant metal, indicating heavy to extreme contamination in soils. The QI revealed that over 99% of the areas were polluted for Ni and Cd with less uncertain regions whereas Cr showed a significant portion of areas with uncertain pollution status. The positive matrix factorization (PMF) model identified three major sources: agricultural (29%), vehicular emissions (25%), and industrial (46%). The probabilistic assessment of health hazards indicated that both carcinogenic and non-carcinogenic risks for adult male, adult female, and children were deemed unacceptable. Moreover, children faced a higher health hazard compared to adults. For adult male, adult female, and children, industrial operations contributed 48.4%, 42.7%, and 71.2% of the carcinogenic risks, respectively and these risks were associated with Ni and Cr as the main pollutants of concern. The study emphasizes valuable scientific insights for environmental managers to tackle soil pollution from HMs by effectively managing anthropogenic sources. It could aid in devising strategies for environmental remediation engineering and refining industry standards.

Customized Production of Holey Graphene Oxides via a Continuous Flow Process.

Continuous flow manufacturing is an innovative technology mainly applied in the chemical and pharmaceutical industries that is progressively being adapted to the manufacturing of nanomaterials to overcome the challenge of reproducing a product with consistent characteristics at a large scale. Here, a flow photochemical system is designed and prototyped for the synthesis of holey graphene oxides (hGOs). Compared to existing methods for the synthesis of hGO, the process is fast, highly scalable, and controllable. Through a combination of rigorous data analysis using machine learning algorithms on transmission electron microscope images and systematic studies of process parameters, it is demonstrated that characteristics of the produced hGO (i.e., porosity and pore size) are remarkably reproducible to the extent that it can be predicted by empirical models of processing-property correlations. Depending on the tailored nanopore structures, the synthesized hGOs out-performed GO in a range of applications that can benefit from the nanoporous two-dimensional (2D) sheets such as in supercapacitors, gas adsorption, and nanofiltration membranes. These results are significant in offering new perspectives on the low-cost industrialization of 2D nanomaterials.

Nematic to Cholesteric Transformation in the Cellulose Nanocrystal Droplet Phase.

Nucleation, growth, and transformation of chirality in nanomaterial systems is a growing research topic with broad interest in tunable and configurable chiroptical materials. Similar to other one-dimensional nanomaterials, cellulose nanocrystals (CNCs), which are nanorods of naturally abundant biopolymer cellulose, display chiral or cholesteric liquid crystal (LC) phases in the form of tactoids. However, the nucleation and growth of the cholesteric CNC tactoids to equilibrium chiral structures and their morphological transformations are yet to be critically assessed. We noticed that the onset of liquid crystal formation in CNC suspensions is characterized by the nucleation of a nematic tactoid that grows in volume and spontaneously transforms into a cholesteric tactoid. The cholesteric tactoids merge with the neighboring tactoids to form bulk cholesteric mesophases with various configurational palettes. We applied scaling laws from the energy functional theory and found suitable agreement with the morphological transformation of the tactoid droplets monitored for their fine structure and orientation by quantitative polarized light imaging.

Fli1 Promotes Vascular Morphogenesis by Regulating Endothelial Potential of Multipotent Myogenic Progenitors.

[Figure: see text].

Lactic acid bacteria in the functional food industry: biotechnological properties and potential applications.

With the growing demand for functional foods having better nutraceutical properties, lactic acid bacteria (LAB) has become an important industrial microorganism. LAB play a significant role in the functional food industry by exhibiting probiotic properties and has the ability to produce various biologically active metabolites such as γ-aminobutyric acid (GABA), exopolysaccharides (EPSs), conjugated linoleic acid (CLA), bacteriocins, reuterin and reutericyclin, which provides enhanced nutraceutical properties to the final food products. LAB are also known to produce several specific enzymes essential for producing substrate-derived bioactive compounds, such as polyphenols, bioactive peptides, inulin-type fructans and ß-glucans, fatty acids, and polyols. These compounds exhibit many health benefits, including better mineral absorption, oxidative stress protection, blood glucose and cholesterol-lowering properties, prevention of gastrointestinal tract infections and improved cardiovascular function. Further, metabolically engineered LAB have been widely used for the nutritive enhancement of different food products and the application of CRISPR-Cas9 holds tremendous potential for the engineering of food cultures. This review provides an overview of the use of LAB as probiotics, its application in producing fermented foods and nutraceutical products, and its health benefits on the host.

Cold-adaptive traits identified by comparative genomic analysis of a lipase-producing Pseudomonas sp. HS6 isolated from snow-covered soil of Sikkim Himalaya and molecular simulation of lipase for wide substrate specificity.

The genomic analysis of industrially important bacteria can help in understanding their capability to withstand extreme environments and shed light on their metabolic capabilities. The whole genome of a previously reported broad temperature active lipase-producing Pseudomonas sp. HS6, isolated from snow-covered soil of the Sikkim Himalayan Region, was analyzed to understand the capability of the bacterium to withstand cold temperatures and study its lipolytic nature. Pseudomonas sp. HS6 was found to be psychrotolerant with an optimal growth temperature ranging between 25 and 30 °C, with the ability to grow at 5 °C. The genome harbours various cold-adaptation genes, such as cold-shock proteins, fatty acid alteration, and cold stress-tolerance genes, supporting the psychrotolerant nature of the organism. The comparative analysis of Pseudomonas sp. HS6 genome showed the presence of amino acid substitutions in genes that favor efficient functioning and flexibility at cold temperatures. Genome mining revealed the presence of four triacylglycerol lipases, among which the putative lipase 3 was highly similar to the broad temperature-active lipase purified and characterized in our previous study. In silico studies of putative lipase 3 revealed broad substrate specificity with partial and no inhibition of the enzyme activity in the presence of PMSF and orlistat. The presence of genes associated with cold adaptations and true lipases with activity at broad temperature and substrate specificity in the genome of Pseudomonas sp. HS6 makes this bacterium a suitable candidate for industrial applications.

Parabiosis reveals the correlation between the recruitment of circulating antigen presenting cells to the retina and the induction of spontaneous autoimmune uveoretinitis.

BACKGROUND: Characterizing immune cells and conditions that govern their recruitment and function in autoimmune diseases of the nervous system or in neurodegenerative processes is an area of active investigation. We sought to analyze the origin of antigen presenting cells associated with the induction of retinal autoimmunity using a system that relies on spontaneous autoimmunity, thus avoiding uncertainties associated with immunization with adjuvants at remotes sites or adoptive transfer of in vitro activated T cells. METHODS: R161H mice (B10.RIII background), which spontaneously and rapidly develop severe spontaneous autoimmune uveoretinitis (SAU), were crossed to CD11cDTR/GFP mice (B6/J) allowing us to track the recruitment to and/or expansion within the retina of activated, antigen presenting cells (GFPhi cells) in R161H+/- × CD11cDTR/GFP F1 mice relative to the course of SAU. Parabiosis between R161H+/- × CD11cDTR/GFP F1 mice and B10.RIII × B6/J F1 (wild-type recipient) mice was done to explore the origin and phenotype of antigen presenting cells crucial for the induction of autoimmunity. Analysis was done by retinal imaging, flow cytometry, and histology. RESULTS: Onset of SAU in R161H+/- × CD11cDTR/GFP F1 mice was delayed relative to B10.RIII-R161H+/- mice revealing a disease prophase prior to frank autoimmunity that was characterized by expansion of GFPhi cells within the retina prior to any clinical or histological evidence of autoimmunity. Parabiosis between mice carrying the R161H and CD11cDTR/GFP transgenes and transgene negative recipients showed that recruitment of circulating GFPhi cells into retinas was highly correlative with the occurrence of SAU. CONCLUSIONS: Our results here contrast with our previous findings showing that retinal antigen presenting cells expanding in response to either sterile mechanical injury or neurodegeneration were derived from myeloid cells within the retina or optic nerve, thus highlighting a unique facet of retinal autoimmunity.

Suicide in Bangla Movie and Drama: A Content Analysis.

We aimed to assess how suicidality has been depicted in Bangla movies and dramas. We conducted a search on YouTube by using search terms to identify movies and dramas with suicidal scripts. The search was performed between February and May 2022 resulting in 71 items consisting of 35 Bangla movies and 36 Bangla dramas. We scrutinized the contents of movies and dramas against our pre-designed instrument and we assessed their quality against World Health Organization guidelines. Among the 71 suicidal behaviors, 46.5% were suicides, 72% of the suicidal behavior was noted in young adults, 63.9% were unmarried, and 69% attempts were found in prominent characters. Hanging was found as the most prominent method (25.4%) and premarital and extramarital affairs and sexual harassment were the most prominent risk factors (60.6%). The potentially harmful characteristics were present in almost all events whereas potentially helpful contents were mentioned very minimally.

Biotechnological approaches for the production of designer cheese with improved functionality.

Cheese is a product of ancient biotechnological practices, which has been revolutionized as a functional food product in many parts of the world. Bioactive compounds, such as peptides, polysaccharides, and fatty acids, have been identified in traditional cheese products, which demonstrate functional properties such as antihypertensive, antioxidant, immunomodulation, antidiabetic, and anticancer activities. Besides, cheese-making probiotic lactic acid bacteria (LAB) exert a positive impact on gut health, aiding in digestion, and improved nutrient absorption. Advancement in biotechnological research revealed the potential of metabolite production with prebiotics and bioactive functions in several strains of LAB, yeast, and filamentous fungi. The application of specific biocatalyst producing microbial strains enhances nutraceutical value, resulting in designer cheese products with multifarious health beneficial effects. This review summarizes the biotechnological approaches applied in designing cheese products with improved functional properties.

Response and resilience of Asian agrifood systems to COVID-19: An assessment across twenty-five countries and four regional farming and food systems.

Context: The COVID-19 pandemic has been affecting health and economies across the world, although the nature of direct and indirect effects on Asian agrifood systems and food security has not yet been well understood. Objectives: This paper assesses the initial responses of major farming and food systems to COVID-19 in 25 Asian countries, and considers the implications for resilience, food and nutrition security and recovery policies by the governments. Methods: A conceptual systems model was specified including key pathways linking the direct and indirect effects of COVID-19 to the resilience and performance of the four principal Asian farming and food systems, viz, lowland rice based; irrigated wheat based; hill mixed; and dryland mixed systems. Based on this framework, a systematic survey of 2504 key informants (4% policy makers, 6% researchers or University staff, 6% extension workers, 65% farmers, and 19% others) in 20 Asian countries was conducted and the results assessed and analysed. Results and conclusion: The principal Asian farming and food systems were moderately resilient to COVID-19, reinforced by government policies in many countries that prioritized food availability and affordability. Rural livelihoods and food security were affected primarily because of disruptions to local labour markets (especially for off-farm work), farm produce markets (notably for perishable foods) and input supply chains (i.e., seeds and fertilisers). The overall effects on system performance were most severe in the irrigated wheat based system and least severe in the hill mixed system, associated in the latter case with greater resilience and diversification and less dependence on external inputs and long market chains. Farming and food systems' resilience and sustainability are critical considerations for recovery policies and programmes, especially in relation to economic performance that initially recovered more slowly than productivity, natural resources status and social capital. Overall, the resilience of Asian farming and food systems was strong because of inherent systems characteristics reinforced by public policies that prioritized staple food production and distribution as well as complementary welfare programmes. With the substantial risks to plant- and animal-sourced food supplies from future zoonoses and the institutional vulnerabilities revealed by COVID-19, efforts to improve resilience should be central to recovery programmes. Significance: This study was the first Asia-wide systems assessment of the effects of COVID-19 on agriculture and food systems, differentiating the effects of the pandemic across the four principal regional farming and food systems in the region.

Metagenomics revealing molecular profiling of community structure and metabolic pathways in natural hot springs of the Sikkim Himalaya.

BACKGROUND: Himalaya is an ecologically pristine environment. The geo-tectonic activities have shaped various environmental niches with diverse microbial populations throughout the Himalayan biosphere region. Albeit, limited information is available in terms of molecular insights into the microbiome, including the uncultured microbes, of the Himalayan habitat. Hence, a vast majority of genomic resources are still under-explored from this region. Metagenome analysis has simplified the extensive in-depth exploration of diverse habitats. In the present study, the culture-independent whole metagenome sequencing methodology was employed for microbial diversity exploration and identification of genes involved in various metabolic pathways in two geothermal springs located at different altitudes in the Sikkim Himalaya. RESULTS: The two hot springs, Polok and Reshi, have distinct abiotic conditions. The average temperature of Polok and Reshi was recorded to be 62 °C and 43 °C, respectively. Both the aquatic habitats have alkaline geochemistry with pH in the range of 7-8. Community profile analysis revealed genomic evidence of plentiful bacteria, with a minute fraction of the archaeal population in hot water reservoirs of Polok and Reshi hot spring. Mesophilic microbes belonging to Proteobacteria and Firmicutes phyla were predominant at both the sites. Polok exhibited an extravagant representation of Chloroflexi, Deinococcus-Thermus, Aquificae, and Thermotogae. Metabolic potential analysis depicted orthologous genes associated with sulfur, nitrogen, and methane metabolism, contributed by the microflora in the hydrothermal system. The genomic information of many novel carbohydrate-transforming enzymes was deciphered in the metagenomic description. Further, the genomic capacity of antimicrobial biomolecules and antibiotic resistance were discerned. CONCLUSION: The study provided comprehensive molecular information about the microbial treasury as well as the metabolic features of the two geothermal sites. The thermal aquatic niches were found a potential bioresource of biocatalyst systems for biomass-processing. Overall, this study provides the whole metagenome based insights into the taxonomic and functional profiles of Polok and Reshi hot springs of the Sikkim Himalaya. The study generated a wealth of genomic data that can be explored for the discovery and characterization of novel genes encoding proteins of industrial importance.

Determinants of tobacco cultivation in Bangladesh.

BACKGROUND: Tobacco production continues to increase in low-income and middle-income countries including in Bangladesh. It has spreads to different parts of Bangladesh and is now threatening food cultivation, the environment and health. The aim of this study is to determine the factors those are influenced farmers' decisions to grow tobacco. METHODS: We surveyed 371 tobacco farmers using a simple random sampling in the Meherpur district of Bangladesh. Binary logistic regression was used to examine the variables affecting farmers' decision to cultivate tobacco. RESULTS: Approximately 87.0% of the respondents were contract farmers with different tobacco companies. Almost 83.3% of the farmers had intentions to continue tobacco farming. Binary logistic regression results suggest that company's incentives to farmers, farmers' profitability, a guaranteed market for the tobacco crop and economic viability were the variables most affecting the decision to cultivate tobacco. CONCLUSIONS: Governments seeking to shift farmers away from tobacco will need to consider how to address the dynamics revealed in this research.

The retinal environment induces microglia-like properties in recruited myeloid cells.

BACKGROUND: Microglia are essential to the development of the CNS and its homeostasis. Our prior findings suggested a niche model to describe the behaviors of retinal microglia. Here, we ask whether new myeloid cells recruited to the retina are constrained to resemble endogenous microglia morphologically and functionally. METHODS: Use of CD11cDTR/GFP transgenic mouse allowed identification of two niches of retinal microglia distinguished by being GFPlo or GFPhi. We also used transgenic mice in which CX3CR1+ cells expressed YFP and were depletable following tamoxifen-induced expression of diphtheria toxin subunit A. We employed several ablation and injury stimulation protocols to examine the origin and fate of myeloid cells repopulating the retina. Analysis of retinal myeloid cells was done by microscopy, flow cytometry, and qRT-PCR. RESULTS: We found that the origin of new GFPhi and GFPlo myeloid cells in the retina of CD11cDTR/GFP mice, whether recruited or local, depended on the ablation and stimulation protocols. Regardless of origin, new GFPlo and GFPhi retinal myeloid cells were CD45medCD11b+Ly6G-Ly6CloIba1+F4/80+, similar to endogenous microglia. Following tamoxifen-induced diphtheria toxin ablation, myeloid cell repopulation differed in the retina compared to the brain and optic nerve. Stimulation of replacement GFPhi cells was substantially attenuated in repopulating retinas after tamoxifen-induced diphtheria toxin ablation compared to control or radiation-ablated mice. In radiation bone marrow chimeric mice, replacement GFPhi myeloid cells from the circulation were slow to repopulate the retina unless stimulated by an optic nerve crush injury. However, once stimulated, recruited GFPhi cells were found to concentrate on injured retinal ganglion cells and were morphologically similar to GFPhi cells in non-ablated control CD11cDTR/GFP mice. CONCLUSIONS: The results support the idea that GFPhi cells in the CD11cDTR/GFP mouse, whether recruited or from resident microglia, mark a unique niche of activated retinal myeloid cells. We conclude that the retinal environment has a potent influence on the function, morphology, and proliferative capacity of new myeloid cells regardless of their origin, compelling them to be equivalent to the endogenous microglia.

Accurate Diabetes Risk Stratification Using Machine Learning: Role of Missing Value and Outliers.

Diabetes mellitus is a group of metabolic diseases in which blood sugar levels are too high. About 8.8% of the world was diabetic in 2017. It is projected that this will reach nearly 10% by 2045. The major challenge is that when machine learning-based classifiers are applied to such data sets for risk stratification, leads to lower performance. Thus, our objective is to develop an optimized and robust machine learning (ML) system under the assumption that missing values or outliers if replaced by a median configuration will yield higher risk stratification accuracy. This ML-based risk stratification is designed, optimized and evaluated, where: (i) the features are extracted and optimized from the six feature selection techniques (random forest, logistic regression, mutual information, principal component analysis, analysis of variance, and Fisher discriminant ratio) and combined with ten different types of classifiers (linear discriminant analysis, quadratic discriminant analysis, naïve Bayes, Gaussian process classification, support vector machine, artificial neural network, Adaboost, logistic regression, decision tree, and random forest) under the hypothesis that both missing values and outliers when replaced by computed medians will improve the risk stratification accuracy. Pima Indian diabetic dataset (768 patients: 268 diabetic and 500 controls) was used. Our results demonstrate that on replacing the missing values and outliers by group median and median values, respectively and further using the combination of random forest feature selection and random forest classification technique yields an accuracy, sensitivity, specificity, positive predictive value, negative predictive value and area under the curve as: 92.26%, 95.96%, 79.72%, 91.14%, 91.20%, and 0.93, respectively. This is an improvement of 10% over previously developed techniques published in literature. The system was validated for its stability and reliability. RF-based model showed the best performance when outliers are replaced by median values.

Fli1 acts downstream of Etv2 to govern cell survival and vascular homeostasis via positive autoregulation.

RATIONALE: Cardiovascular health depends on proper development and integrity of blood vessels. Ets variant 2 (Etv2), a member of the E26 transforming-specific family of transcription factors, is essential to initiate a transcriptional program leading to vascular morphogenesis in early mouse embryos. However, endothelial expression of the Etv2 gene ceases at midgestation; therefore, vascular development past this stage must continue independent of Etv2. OBJECTIVE: To identify molecular mechanisms underlying transcriptional regulation of vascular morphogenesis and homeostasis in the absence of Etv2. METHODS AND RESULTS: Using loss- and gain-of-function strategies and a series of molecular techniques, we identify Friend leukemia integration 1 (Fli1), another E26 transforming-specific family transcription factor, as a downstream target of Etv2. We demonstrate that Etv2 binds to conserved Ets-binding sites within the promoter region of the Fli1 gene and governs Fli1 expression. Importantly, in the absence of Etv2 at midgestation, binding of Etv2 at Ets-binding sites in the Fli1 promoter is replaced by Fli1 protein itself, sustaining expression of Fli1 as well as selective Etv2-regulated endothelial genes to promote endothelial cell survival and vascular integrity. Consistent with this, we report that Fli1 binds to the conserved Ets-binding sites within promoter and enhancer regions of other Etv2-regulated endothelial genes, including Tie2, to control their expression at and beyond midgestation. CONCLUSIONS: We have identified a novel positive feed-forward regulatory loop in which Etv2 activates expression of genes involved in vasculogenesis, including Fli1. Once the program is activated in early embryos, Fli1 then takes over to sustain the process in the absence of Etv2.

Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets for triple negative breast cancer therapy.

INTRODUCTION: Targeted therapies for aggressive breast cancers like triple negative breast cancer (TNBC) are needed. The use of small interfering RNAs (siRNAs) to disable expression of survival genes provides a tool for killing these cancer cells. Cyclin dependent kinase 11 (CDK11) is a survival protein kinase that regulates RNA transcription, splicing and mitosis. Casein kinase 2 (CK2) is a survival protein kinase that suppresses cancer cell death. Eliminating the expression of these genes has potential therapeutic utility for breast cancer. METHODS: Expression levels of CDK11 and CK2 mRNAs and associated proteins were examined in breast cancer cell lines and tissue arrays. RNA expression levels of CDC2L1, CDC2L2, CCNL1, CCNL2, CSNK2A1, CSNK2A2, and CSNK2B genes in breast cancer subtypes were analyzed. Effects following transfection of siRNAs against CDK11 and CK2 in cultured cells were examined by viability and clonal survival assays and by RNA and protein measures. Uptake of tenfibgen (TBG) nanocapsules by TNBC cells was analyzed by fluorescence-activated cell sorting. TBG nanocapsules delivered siRNAs targeting CDK11 or CK2 in mice carrying TNBC xenograft tumors. Transcript cleavage and response parameters were evaluated. RESULTS: We found strong CDK11 and CK2 mRNA and protein expression in most human breast cancer cells. Immunohistochemical analysis of TNBC patient tissues showed 100% of tumors stained positive for CDK11 with high nuclear intensity compared to normal tissue. The Cancer Genome Atlas analysis comparing basal to other breast cancer subtypes and to normal breast revealed statistically significant differences. Down-regulation of CDK11 and/or CK2 in breast cancer cells caused significant loss of cell viability and clonal survival, reduced relevant mRNA and protein expression, and induced cell death changes. TBG nanocapsules were taken up by TNBC cells both in culture and in xenograft tumors. Treatment with TBG- siRNA to CDK11 or TBG- siRNA to CK2αα' nanocapsules induced appropriate cleavage of CDK11 and CK2α transcripts in TNBC tumors, and caused MDA-MB-231 tumor reduction, loss of proliferation, and decreased expression of targeted genes. CONCLUSIONS: CDK11 and CK2 expression are individually essential for breast cancer cell survival, including TNBC. These genes serve as promising new targets for therapeutic development in breast cancer.

ACE Inhibitory and Antioxidant Activities of Collagen Hydrolysates from the Ribbon Jellyfish (Chrysaora sp.).

Collagen isolated from the ribbon jellyfish (Chrysaora sp.) was hydrolysed using three different proteases (i.e. trypsin, alcalase and Protamex) to obtain bioactive peptides. Angiotensin-I-converting enzyme (ACE) inhibitory activity and antioxidant activities (i.e. ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity) of the peptides were measured and compared, and the effect of the duration of hydrolysis on the bioactivity (ACE inhibitory and antioxidant activities) of peptides was also evaluated. FRAP activity was the highest in Protamex-induced (25-27 mM) and trypsin-induced hydrolysates (24-26 mM) at 7 and 9 h, respectively. Conversely, hydrolysates produced by trypsin for 1 and 3 h showed the highest DPPH radical scavenging activities (94 and 92%, respectively). Trypsin-induced hydrolysates (at 3 h) also showed the highest ACE inhibitory activity (89%). The peptide sequences with the highest activities were identified using tandem mass spectrometry, and the results show that the hydrolysates had a high content of hydrophobic amino acids as well as unique amino acid sequences, which likely contribute to their biological activities.

Investigation on synthesized sulfonamide Schiff base with DFT approaches and in silico pharmacokinetic studies: Topological, NBO, and NLO analyses.

The sulfonamide Schiff base (C16H14N4O3S) was successfully synthesized and experimentally ascertained. The main purpose of this research is to investigate the geometry of the aforesaid molecule using both experimental and density functional theory (DFT) techniques and determine its drug likeness characteristics, docking ability as an insulysin inhibitor, and its NLO property. For the computational investigations the DFT approaches were utilized at the B3LYP level with the 6-311G+(d,p) basic set. The experimental results of the compound (such as FT-IR, UV-Vis, and 1H NMR) were compared with simulated data. The both results were well and consistent with previously related published data. The obtained spectral results confirm the formation of the Schiff base compound. Both π-π* and n-π* interactions were found in experimental and computational UV-Vis spectra, as well as in the natural bond orbital (NBO) study. The molecular, electronic, covalent, and non-covalent interactions were analyzed using DFT studies. Both experimental and simulation results revealed that the compound is successfully formed and relatively stable. The compound with a lower band gap showed high chemical reactivity. The medicinal characteristics of the compound were evaluated using in silico medicinal methods. The investigated compound was also followed Pfizer, Golden Triangle, GSK as well as Lipinski's rules. Therefore, the compound has more favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile and it can be used as non-toxic oral drug candidate. The compound was exhibited good insulysin inhibitory activity and it has almost eighteen times higher non-linear optical properties than urea and three times higher than potassium dihydrogen phosphate (KDP).