Nose-to-Brain Drug Delivery and Physico-Chemical Properties of Nanosystems: Analysis and Correlation Studies of Data from Scientific Literature.

Background: In the last few decades, nose-to-brain delivery has been investigated as an alternative route to deliver molecules to the Central Nervous System (CNS), bypassing the Blood-Brain Barrier. The use of nanotechnological carriers to promote drug transfer via this route has been widely explored. The exact mechanisms of transport remain unclear because different pathways (systemic or axonal) may be involved. Despite the large number of studies in this field, various aspects still need to be addressed. For example, what physicochemical properties should a suitable carrier possess in order to achieve this goal? To determine the correlation between carrier features (eg, particle size and surface charge) and drug targeting efficiency percentage (DTE%) and direct transport percentage (DTP%), correlation studies were performed using machine learning. Methods: Detailed analysis of the literature from 2010 to 2021 was performed on Pubmed in order to build "NANOSE" database. Regression analyses have been applied to exploit machine-learning technology. Results: A total of 64 research articles were considered for building the NANOSE database (102 formulations). Particle-based formulations were characterized by an average size between 150-200 nm and presented a negative zeta potential (ZP) from -10 to -25 mV. The most general-purpose model for the regression of DTP/DTE values is represented by Decision Tree regression, followed by K-Nearest Neighbors Regressor (KNeighbor regression). Conclusion: A literature review revealed that nose-to-brain delivery has been widely investigated in neurodegenerative diseases. Correlation studies between the physicochemical properties of nanosystems (mean size and ZP) and DTE/DTP parameters suggest that ZP may be more significant than particle size for DTP/DTE predictability.

Comparison of Soft Tissue Chin Thickness in Adult Patients With Various Mandibular Divergence Patterns.

Objective This study aimed to compare the soft tissue chin (STC) thickness at different levels in patients presenting for orthodontic treatment with different vertical facial types. Materials and methods This comparative cross-sectional study was conducted at Sharif Medical & Dental College, Lahore, Pakistan, on 195 subjects. Patients presenting for orthodontic treatment, both genders, aged from 18 to 32 years, and Pakistani nationals were included. Patients with any craniofacial deformity, syndrome, cleft lip and palate, previous orthodontic or orthognathic treatment, and multiple missing teeth and prostheses in edentulous areas were excluded. Vertical facial patterns and STC thickness were recorded from pre-treatment lateral cephalograms. One-way analysis of variance (ANOVA) was applied to compare STC among various vertical facial patterns. Post-hoc analysis was done using the Tukey test. Results There were 126 females (64.62%) and 69 males (35.38%). The mean age was 21.66 ± 3.44 years. All three soft tissue chin thickness distances significantly differed among vertical facial patterns (p<0.001). Multiple comparisons show that the distance between soft and hard tissue pogonion was insignificant between low and normal angle facial heights (p=0.5). Similarly, no significant difference was observed for the distance between soft and hard tissue menton in low and normal angle subjects (p=0.4). The rest of the multiple comparisons were statistically significant (p<0.05). Conclusion The STC thickness is significantly associated with vertical facial divergence. While planning orthognathic surgery or genioplasty of the mandible, due consideration should be given to vertical divergence of the face to avoid unwanted facial changes.

Pervasive influence of heavy metals on metabolic pathways is potentially relieved by hesperidin to enhance the phytoremediation efficiency of Bassia scoparia.

Hesperidin (HSP), a flavonoid, is a potent antioxidant, metal chelator, mediator of signaling pathways, and regulator of metal uptake in plants. The study examined the ameliorative effects of HSP (100 µM) on Bassia scoparia grown under excessive levels of heavy metals (zinc (500 mg kg-1), copper (400 mg kg-1), cadmium (100 mg kg-1), and chromium (100 mg kg-1)). The study clarifies the underlying mechanisms by which HSP lessens metabolic mayhem to enhance metal stress tolerance and phytoremediation efficiency of Bassia scoparia. Plants manifested diminished growth because of a drop in chlorophyll content and nutrient acquisition, along with exacerbated deterioration of cellular membranes reflected in elevated reactive oxygen species (ROS) production, lipid peroxidation, and relative membrane permeability. Besides the colossal production of cytotoxic methylglyoxal, the activity of lipoxygenase was also higher in plants under metal toxicity. Conversely, hesperidin suppressed the production of cytotoxic ROS and methylglyoxal. Hesperidin improved oxidative defense that protected membrane integrity. Hesperidin caused a more significant accumulation of osmolytes, non-protein thiols, and phytochelatins, thereby rendering metal ions non-toxic. Hydrogen sulfide and nitric oxide endogenous levels were intricately maintained higher in plants treated with HSP. Hesperidin increased metal accumulation in Bassia scoparia and thereby had the potential to promote the reclamation of metal-contaminated soils.

Correction: Abbas et al. Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies. Antioxidants 2022, 11, 1160.

In the original publication [...].

On topological analysis of two-dimensional covalent organic frameworks via M-polynomial.

Covalent organic frameworks (ZnP-COFs) made of zinc-porphyrin have become effective materials with a variety of uses, including gas storage and catalysis. To simulate the structural and electrical features of ZnP-COFs, this study goes into the computation of polynomials utilizing degree-based indices. We gave a methodical study of these polynomial computations using Excel, illustrating the complex interrelationships between the various indices. Degree-based indices provide valuable insights into the connectivity of vertices within a network. M-polynomials, on the other hand, offer a mathematical framework for representing and studying the properties of 2D COFs. By encoding structural information into a polynomial form, M-polynomials facilitate the calculation of various topological indices, including the Wiener index, Zagreb indices, and more. The different behavior of ZnP-COFs based on degree-based indices was illustrated graphically, and this comparison provided insightful information for prospective applications and the construction of innovative ZnP-COF structures. Moreover, we discuss the relevance of these techniques in the broader context of materials science and the design of functional covalent organic frameworks.

On characterization of entropy measure using logarithmic regression model for Copper(II) Fluoride.

The versatile uses of Copper(II) Fluoride (CuF2) are well known; these include its usage as a precursor in chemical synthesis as well as its contribution to the creation of sophisticated materials and electronics. There are interesting opportunities to study the interactions between these elements because of their unique crystal structure, which contains copper ions and fluoride anions. Its potential in optoelectronic devices and conductive qualities also make it a viable material for next-generation technologies. To better understand the structural properties of CuF2 and how they affect its entropy, we present new Zagreb indices in this study and use them to calculate entropy measures. We also build a regression model to clarify the relationship between the calculated indices and entropy levels. The findings of our investigation offer significant understanding regarding the ability of the suggested Zagreb indices to extract meaningful content and their correlation with entropy in the context of CuF2. This information is important for understanding CuF2 alloys and for exploring related complex materials.

On topological indices and entropy measures of beryllonitrene network via logarithmic regression model.

Chemical graph theory, a subfield of graph theory, is used to investigate chemical substances and their characteristics. Chemical graph analysis sheds light on the connection, symmetry, and reactivity of molecules. It supports chemical property prediction, research of molecular reactions, drug development, and understanding of molecular networks. A crucial part of computational chemistry is chemical graph theory, which helps researchers analyze and manipulate chemical structures using graph algorithms and mathematical models. Beryllonitrene , a compound of interest due to its potential applications in various fields, is examined through the lens of graph theory and mathematical modeling. The study involves the calculation and interpretation of topological indices and graph entropy measures, which provide valuable insights into the structural and energetic properties of Beryllonitrene's molecular graph. Logarithmic regression models are employed to establish correlations between these indices, entropy, and other relevant molecular attributes. The results contribute to a deeper understanding of Beryllonitrene's complex characteristics, facilitating its potential applications in diverse scientific and technological domains. In this study, degree-based topological indices TI are determined, as well as the entropy of graphs based on these TI .

Effect of hesperidin on growth, photosynthesis, antioxidant systems and uptake of cadmium, copper, chromium and zinc by Celosia argentea plants.

Rapid industrialization and extensive agricultural practices are the major causes of soil heavy metal contamination, which needs urgent attention to safeguard the soils from contamination. However, the phytotoxic effects of excessive metals in plants are the primary obstacle to efficient phytoextraction. The present study evaluated the effects of hesperidin (HSP) on metals (Cu, Cd, Cr, Zn) phytoextraction by hyperaccumulator (Celosia argentea L.) plants. For this purpose, HSP, a flavonoid compound with strong antioxidant potential to assist metal phytoextraction was used under metal stress in plants. Celosia argentea plants suffered significant (P ≤ 0.001) oxidative damage due to the colossal accumulation of metals (Cu, Cd, Cr, Zn). However, HSP supplementation notably (P ≤ 0.001) abated ROS generation (O2•‒, •OH, H2O2), lipoxygenase activity, methylglyoxal production, and relative membrane permeability that clearly indicated HSP-mediated decline in oxidative injury in plants. Exogenous HSP improved (P ≤ 0.001) the production of non-protein thiol, phytochelatins, osmolytes, and antioxidant compounds. Further, HSP enhanced (P ≤ 0.001) H2S and NO endogenous production, which might have improved the GSH: GSSG ratio. Consequently, HSP-treated C. argentea plants had higher biomass alongside elevated metal accumulation mirrored as profound modifications in translocation factor (TF), bioaccumulation coefficient (BAC), and bioconcentration factor (BCF). In this context, HSP significantly enhanced TF of Cr (P ≤ 0.001), Cd (P ≤ 0.001), and Zn (P ≤ 0.01), while BAC of Cr (P ≤ 0.001), Cd (P ≤ 0.001), and Zn (P ≤ 0.001). Further, BCF was significant (P ≤ 0.05) only in plants grown under Cr-spiked soil. Overall, HSP has the potential for phytoremediation of metals by C. argentea, which might be a suitable strategy for metal-polluted soils.

On analysis of iron (II) chloride via graph entropy measures and statistical models.

The crystalline material that is greenish-white and dissolves in water is iron chloride. It is utilized in sewage treatment, dyeing, and medicine. Graph entropy plays a significant role in measuring the complexity of atoms, molecules, and structures in nature. It has specific chemical applications in biology, neuroscience, and chemistry. A compound's molecular structure consists of many atoms. Particularly, hydrocarbons are a chemical combination of hydrogen and carbon atoms. In this article, we discuss the entropy of the chemical structure Iron (II) Chloride. Additionally, we discuss the idea of degree-based indices and compute the Shannon entropy(ENT) using these indices. The linear regression(LR) of various indices and entropies for iron chloride, FeCl2, is also discussed. Also, we link the degree-based indices and entropies via line fit.

On K-Banhatti indices and entropy measure for rhodium (III) chloride via linear regression models.

Rhodium (III) chloride is a metallic compound characterized by its shiny and silvery-white appearance. It possesses high reflectivity and exhibits excellent resistance to corrosion. This makes it a popular choice for applications such as plating materials in jewelry and other decorative items, imparting a lustrous and reflective surface to the coated objects. Topological indices are numerical parameters employed to characterize the topology of a molecular structure. These indices are derived from the connectivity of atoms within the molecule and serve as predictors for various molecular properties, including reactivity, stability, and solubility. On the other hand, the Shannon entropy of a graph finds extensive applications in network science. It is utilized in the analysis of diverse networks, such as social networks, biological networks, and transportation networks. The Shannon entropy allows for the characterization of a network's topology and structure, aiding in the identification of crucial nodes or structures that play significant roles in network functionality and stability. In this paper, our primary objective is to compute different K-Banhatti indices and employ them to evaluate the entropy measure of Rhodium (III) chloride RhCl3. Additionally, we conducted an examination through linear regression analysis involving various indices and entropies associated with Rhodium chloride. Moreover, we established a correlation between degree-based Banhatti indices and entropies via the line fit method.

Investigating the role of aae-miR-34-5p in the regulation of juvenile hormone biosynthesis genes in the mosquito Aedes aegypti.

Juvenile hormone (JH) controls the development and reproduction of insects. Therefore, a tight regulation of the expression of JH biosynthetic enzymes is critical. microRNAs (miRNAs) play significant roles in the post-transcriptional regulation of gene expression by interacting with complementary sequences in target genes. Previously, we reported that several miRNAs were differentially expressed during three developmental stages of Aedes aegypti mosquitoes with different JH levels (no JH, high JH, and low JH). One of these miRNAs was aae-miR-34-5p. In this study, we identified the presence of potential target sequences of aae-miR-34-5p in the transcripts of some genes encoding JH biosynthetic enzymes. We analysed the developmental expression patterns of aae-miR-34-5p and the predicted target genes involved in JH biogenesis. Increases in miRNA abundance were followed, with a delay, by decreases in transcript levels of target genes. Application of an inhibitor and a mimic of aae-miR-34-5p led respectively to increased and decreased levels of thiolase transcripts, which is one of the early genes of JH biosynthesis. Female adult mosquitoes injected with an aae-miR-34-5p inhibitor exhibited significantly increased transcript levels of three genes encoding JH biosynthetic enzymes, acetoacetyl-CoA thiolase (thiolase), farnesyl diphosphate phosphatase, and farnesal dehydrogenase. Overall, our results suggest a potential role of miRNAs in JH production by directly targeting genes involved in its biosynthesis.

Copper radionuclides for theranostic applications: towards standardisation of their nuclear data. A mini-review.

Copper has several clinically relevant radioisotopes and versatile coordination chemistry, allowing attachment of its radionuclides to biological molecules. This characteristic makes it suitable for applications in molecular imaging or radionuclide targeted therapy. Of particular interest in nuclear medicine today is the theranostic approach. This brief review considers five radionuclides of copper. These are Cu-60, Cu-61, Cu-62, Cu-64, and Cu-67. The first four are positron emitters for imaging, and the last one Cu-67 is a ß--emitting radionuclide suitable for targeted therapy. The emphasis here is on theory-aided evaluation of available experimental data with a view to establishing standardised cross-section database for production of the relevant radionuclide in high purity. Evaluated cross section data of the positron emitters have been already extensively reported; so here they are only briefly reviewed. More attention is given to the data of the 68Zn(p,2p)67Cu intermediate energy reaction which is rather commonly used for production of 67Cu.

Analysing inhibition of dengue virus in Wolbachia-infected mosquito cells following the removal of Wolbachia.

Wolbachia pipientis is known to block replication of positive sense RNA viruses. Previously, we created an Aedes aegypti Aag2 cell line (Aag2.wAlbB) transinfected with the wAlbB strain of Wolbachia and a matching tetracycline-cured Aag2.tet cell line. While dengue virus (DENV) was blocked in Aag2.wAlbB cells, we found significant inhibition of DENV in Aag2.tet cells. RNA-Seq analysis of the cells confirmed removal of Wolbachia and lack of expression of Wolbachia genes that could have been due to lateral gene transfer in Aag2.tet cells. However, we noticed a substantial increase in the abundance of phasi charoen-like virus (PCLV) in Aag2.tet cells. When RNAi was used to reduce the PCLV levels, DENV replication was significantly increased. Further, we found significant changes in the expression of antiviral and proviral genes in Aag2.tet cells. Overall, the results reveal an antagonistic interaction between DENV and PCLV and how PCLV-induced changes could contribute to DENV inhibition.

Wolbachia RNase HI contributes to virus blocking in the mosquito Aedes aegypti.

The endosymbiotic bacterium Wolbachia pipientis blocks replication of several arboviruses in transinfected Aedes aegypti mosquitoes. However, the mechanism of virus blocking remains poorly understood. Here, we characterized an RNase HI gene from Wolbachia, which is rapidly induced in response to dengue virus (DENV) infection. Knocking down w RNase HI using antisense RNA in Wolbachia-transinfected mosquito cell lines and A. aegypti mosquitoes led to increased DENV replication. Furthermore, overexpression of wRNase HI, in the absence of Wolbachia, led to reduced replication of a positive sense RNA virus, but had no effect on a negative sense RNA virus, a familiar scenario in Wolbachia-infected cells. Altogether, our results provide compelling evidence for the missing link between early Wolbachia-mediated virus blocking and degradation of viral RNA. These findings and the successful pioneered knockdown of Wolbachia genes using antisense RNA in cell line and mosquitoes enable new ways to manipulate and study the complex endosymbiont-host interactions.

Anti-microbial host factor HDAC6 is antagonised by the influenza A virus through host caspases and viral PA.

Histone deacetylase 6 (HDAC6), through the repertoire of its substrate proteins, plays a critical role in human physiology, and an aberrant function of HDAC6 contributes to various pathophysiological conditions. HDAC6 is also known to be an anti-microbial host factor and has been implicated in restricting or clearing the infection of various human viral and bacterial pathogens. However, the state and the mechanisms of its antagonism in infected cells are not understood. Here, we demonstrate that influenza A virus (IAV) antagonises HDAC6 by recruiting both viral and host components. We found that HDAC6 mRNA expression, and consequently, the HDAC6 polypeptide expression is downregulated in human lung epithelial cells during early stage of IAV infection but can be rescued by depleting the expression of viral polymerase acidic (PA) protein, a subunit of IAV RNA polymerase. In addition, during later stage of the infection, the HDAC6 polypeptide undergoes caspase-mediated cleavage at two sites, generating two cleaved fragments. Both these fragments disappeared when the expression of caspase 3 was depleted in infected cells, whereas only second fragment disappeared when the expression of caspase 6 was depleted. But both fragments disappeared and the level of full-length HDAC6 polypeptide was rescued when the expression of PA was depleted in infected cells. Collectively, these data indicated that IAV antagonises the HDAC6 by decreasing its expression level in infected cells, both at mRNA and polypeptide level via PA gene, which has been implicated in auxiliary functions like degradation of host mRNA and induction of apoptosis.

On network construction and module detection for molecular graph of titanium dioxide.

Titanium dioxide is the most common and valuable oxide among four types of oxides of titanium. Its physicochemical properties make it a very valuable compound. The main objective of this article is to initially detect the modules based on highly connected links of the network of the degree-based topological indices. This information is lately integrated with different physical properties of the chemical compound of titanium dioxide to develop different mathematical frameworks based on master regulatory indices of the modules. This connection can be helpful in studying the physical measures at a deeper level in the form of different degree based topological indices.Communicated by Ramaswamy H. Sarma.

Analysis of Aedes aegypti microRNAs in response to Wolbachia wAlbB infection and their potential role in mosquito longevity.

The mosquito Aedes aegypti is the primary vector of a range of medically important viruses including dengue, Zika, West Nile, yellow fever, and chikungunya viruses. The endosymbiotic bacterium Wolbachia pipientis wAlbB strain is a promising biocontrol agent for blocking viral transmission by Ae. aegypti. To predict the long-term efficacy of field applications, a thorough understanding of the interactions between symbiont, host, and pathogen is required. Wolbachia influences host physiology in a variety of ways including reproduction, immunity, metabolism, and longevity. MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that regulate gene expression in eukaryotes and viruses. Several miRNAs are known to regulate biological processes in Drosophila and mosquitoes, including facilitating Wolbachia maintenance. We generated the first chromosomal map of Ae. aegypti miRNAs, and compared miRNA expression profiles between a wAlbB-transinfected Ae. aegypti mosquito line and a tetracycline cleared derivative, using deep small RNA-sequencing. We found limited modulation of miRNAs in response to wAlbB infection. Several miRNAs were modulated in response to age, some of which showed greater upregulation in wAlbB-infected mosquitoes than in tetracycline cleared ones. By selectively inhibiting some differentially expressed miRNAs, we identified miR-2946-3p and miR-317-3p as effecting mosquito longevity in Wolbachia-infected mosquitoes.

The Involvement of Atlastin in Dengue Virus and Wolbachia Infection in Aedes aegypti and Its Regulation by aae-miR-989.

Endoplasmic reticulum (ER)-shaping atlastin proteins (ATLs) have been demonstrated to play a functional role during flavivirus replication in mammalian cells. For dengue virus (DENV), atlastin is required in the formation of the replication organelles and RNA replication, virion assembly, production of the infectious virus particles, and trafficking or directing the association of vesicle packets with furin. Here, we investigated the involvement of atlastin in DENV replication in the mosquito Aedes aegypti and explored the possibility of its manipulation by the endosymbiotic bacterium Wolbachia to interfere with DENV replication. Results showed the expression of Ae. aegypti atlastin gene (AaATL) was upregulated in DENV-infected Aag2 cells, and its silencing led to reduced DENV replication. Contrary to our assumption that AaATL could be downregulated by Wolbachia, we did not find evidence for that in Wolbachia-infected cell lines, but this was the case in mosquitoes. Further, silencing AaATL did not have any effect on Wolbachia density. Our results also suggest that aae-miR-989 miRNA negatively regulates AaATL. The oversupply of the miRNA mimic led to reduced DENV replication consistent with the positive role of AaATL in DENV replication. Overall, the results favor AaATL's involvement in DENV replication; however, there is no support that the protein is involved in Wolbachia-mediated DENV inhibition. In addition, the results contribute to discerning further possible overlapping functions of ATLs in mosquitoes and mammalian cells. IMPORTANCE Atlastin is a protein associated with the endoplasmic reticulum and has been shown to play a role in replication of flaviviruses in mammalian cells. This study aimed to investigate the role of mosquito Aedes aegypti atlastin (AaATL) in dengue virus replication and maintenance of Wolbachia, an endosymbiotic bacterium, in the mosquito. Our results suggest that AaATL facilitates dengue virus replication in mosquito cells, considering silencing the gene led to reductions in virus replication and virion production. Further, AaATL was found to be regulated by a mosquito microRNA, aae-miR-989. Despite an effect on dengue virus, AaATL silencing did not affect Wolbachia replication and maintenance in mosquito cells. The results shed light on the role of atlastins in mosquito-pathogen interactions and their overlapping roles in mosquito and mammalian cells.

An empirical investigation of firm performance through corporate governance and information technology investment with mediating role of corporate social responsibility: Evidence from Saudi Arabia telecommunication sector.

This study intended to examine the effect of information technology (IT) investment and corporate governance mechanism on the performance of the Saudi telecommunication sector with mediating role of corporate social responsibility (CSR). A survey method was used to collect data from the targeted Saudi telecom firm. Results show that corporate governance practices, i.e., internal audit, internal audit committee, and internal board size, have a significant and positive relationship with firm performance. Furthermore, IT investment positively affects the performance of Saudi telecommunication firms. Moreover, CSR mediates the relationship among internal audit, internal audit committee, internal board size, IT investment, and firm performance. This study contributes to the body of knowledge regarding IT investment, corporate governance mechanism, corporate social responsibilities, and firm performance of telecommunication firms in emerging markets. Furthermore, this study will help the top management of the telecom firms to improve corporate governance and IT investment, which will be beneficial to enhance firm performance.

Knockout of Dicer-2 in the Sf9 cell line enhances the replication of Spodoptera frugiperda rhabdovirus and conditionally increases baculovirus replication.

The Sf9 cell line, originally isolated from the ovarian tissue of Spodoptera frugiperda larvae, is widely used in academia and industry for the baculovirus-mediated production of recombinant proteins and virus-like particles. RNA interference (RNAi) is a conserved antiviral pathway present in eukaryotic organisms and is the primary antiviral defence mechanism in insects. Recent evidence has implicated RNAi as an antiviral response to baculovirus infection in Sf9 cells. To test this hypothesis, CRISPR/Cas9 technology was used to disable the RNAi pathway in Sf9 cells by knocking out Dicer-2, the protein responsible for cleaving viral double-stranded RNA precursors into short interfering RNAs. Infection of Dicer-2 knockout Sf9 cells with either the wild-type baculovirus Autographa californica nucleopolyhedrovirus (AcMNPV), recombinant AcMNPV (rAcMNPV) expressing ß-galactosidase (ß-gal), or rAcMNPV expressing a wasp venom protein (Vn50) at a multiplicity of infection (m.o.i.) of 1 resulted in a modest increase in virus replication compared to control Sf9 cells under adherent culture conditions. In contrast, Dicer-2 knockout Sf9 monolayer or suspension cultures infected by the rAcMNPV expressing ß-gal at higher m.o.i.s (3.5 and 20) did not exhibit increases in either viral DNA replication or ß-gal production. Intriguingly, during long-term passaging in suspension, Dicer-2 knockout Sf9 cultures underwent transient crashes in cell proliferation and viability. It was discovered that these periods of low growth and viability coincided with a dramatic increase in the RNA levels of S. frugiperda rhabdovirus, a recently identified adventitious virus that persistently infects the Sf9 cell line, suggesting a role for Dicer-2 in managing chronic viral infections in this industrially relevant insect cell line.