Design of a Controlled-Release Delivery Composite of Antibacterial Agent Gatifloxacin by Spherical Silica Nanocarrier

In this study, a spherical silica nanoparticle was explored as a gatifloxacin carrier synthesized by the chemical precipitation method. It was found that there was no new chemical bond formation during the loading process between gatifloxacin and silica, which implies that the binding was driven by physical interaction. In addition, the drug loading and encapsulation efficiency could be improved by appropriately increasing nano-silica content in the loading process. Meanwhile, the release rate of gatifloxacin after loading nano-silica was also improved, suggesting the successful design of a controlled-release delivery composite. The silica nanocarrier could significantly improve the antibacterial performance of Escherichia coli by 2.1 times, which was higher than the pure gatifloxacin. The 24 h bacteriostatic rate was higher than that of a simple mixture of silica nanoparticles and gatifloxacin. Strong reactive oxygen species (ROS) in GAT-SiO2 NPs suggests that ROS might be associated with bactericidal activity. The synergy between the physicochemical effect and ROS production of this material is proposed as the mechanism of its antibacterial activity, which can also be confirmed by the cell membrane damage observed under electron microscopy and DNA damage experiments. Collectively, our finding indicates that nano-silica microspheres could serve as a promising carrier for the sustained release of gatifloxacin, thereby providing a new carrier design scheme for the improvement of the antibacterial effect.

HDAC6 Interacts With Poly (GA) and Modulates its Accumulation in c9FTD/ALS

The aberrant translation of a repeat expansion in chromosome 9 open reading frame 72 (C9orf72), the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), results in the accumulation of toxic dipeptide repeat (DPR) proteins in the central nervous system We have found that, among the sense DPR proteins, HDAC6 specifically interacts with the poly (GA) and co-localizes with inclusions in both patient tissue and a mouse model of this disease (c9FTD/ALS). Overexpression of HDAC6 increased poly (GA) levels in cultured cells independently of HDAC6 deacetylase activity, suggesting that HDAC6 can modulate poly (GA) pathology through a mechanism that depends upon their physical interaction. Moreover, decreasing HDAC6 expression by stereotaxic injection of antisense oligonucleotides significantly reduced the number of poly (GA) inclusions in c9FTD/ALS mice. These findings suggest that pharmacologically reducing HDAC6 levels could be of therapeutic value in c9FTD/ALS.

General Relativity and Causality, Reasoning from Metaphysics, and E. J. Lowe’s Ontology

The paper aims to show the importance of reasoning “from metaphysics” in the course of a consistent interpretation of the “against neoscholasticism” thesis (J. Ladyman). The idea that “the subject of metaphysics is metaphysical possibilities, and science determines which of them are actually achieved” (E. J. Lowe, J. Katz, etc.) reinforces the role of reasoning “from metaphysics” within the field of metaphysics of science. The general theory of relativity violates the common prevailing intuition that “causality is the subject of local physical interaction” (J. Bigelow). Interpretation of causality in terms of “forces” and “coming into” within the framework of E. J. Lowe's ontology makes it possible to talk about causality in terms of “finding” and “going out” of existence of the corresponding modes of objects connected by a formal “causal relationship”. The transition to E. J. Lowe's ontology helps not only to overcome the intuition of the locality of causality, but also reveals in its own way, for example, such seemingly simple common intuitions as the dependence of the truth of propositions on time or the understanding of time as a dimension. All this once again brings us back to the understanding of the importance of the fact that a scientist, constructing or interpreting a scientific theory, as a rule, uses non-trivial philosophical assumptions that should be the subject of its own philosophical analysis.

Disruption of c-MYC Binding and Chromosomal Looping Involving Genetic Variants Associated With Ankylosing Spondylitis Upstream of the RUNX3 Promoter

Background: Ankylosing Spondylitis (AS) is a common form of inflammatory spinal arthritis with a complex aetiology and high heritability, involving more than 100 genetic associations. These include several AS-associated single nucleotide polymorphisms (SNPs) upstream of RUNX3, which encodes the multifunctional RUNT-related transcription factor (TF) 3. The lead associated SNP rs6600247 (p = 2.6 × 10−15) lies ∼13kb upstream of the RUNX3 promoter adjacent to a c-MYC TF binding-site. The effect of rs6600247 genotype on DNA binding and chromosome looping were investigated by electrophoretic mobility gel shift assays (EMSA), Western blotting-EMSA (WEMSA) and Chromosome Conformation Capture (3C).Results: Interrogation of ENCODE published data showed open chromatin in the region overlapping rs6600247 in primary human CD14+ monocytes, in contrast to the Jurkat T cell line or primary human T-cells. The rs6600247 AS-risk allele is predicted to specifically disrupt a c-MYC binding-site. Using a 50bp DNA probe spanning rs6600247 we consistently observed reduced binding to the AS-risk “C” allele of both purified c-MYC protein and nuclear extracts (NE) from monocyte-like U937 cells. WEMSA on U937 NE and purified c-MYC protein confirmed these differences (n = 3; p < 0.05). 3C experiments demonstrated negligible interaction between the region encompassing rs6600247 and the RUNX3 promoter. A stronger interaction frequency was demonstrated between the RUNX3 promoter and the previously characterised AS-associated SNP rs4648889.Conclusion: The lead SNP rs6600247, located in an enhancer-like region upstream of the RUNX3 promoter, modulates c-MYC binding. However, the region encompassing rs6600247 has rather limited physical interaction with the promoter of RUNX3. In contrast a clear chromatin looping event between the region encompassing rs4648889 and the RUNX3 promoter was observed. These data provide further evidence for complexity in the regulatory elements upstream of the RUNX3 promoter and the involvement of RUNX3 transcriptional regulation in AS.

The Struggle to Balance Work and Family Life During the COVID-19 Pandemic: Insights Based on the Situations of Working Women in Delhi

The COVID-19 pandemic generated economic contraction across the world. In India, the stringent lockdown led to extreme distress. The unprecedented situation adversely affected the women’s efforts to balance professional life with family life because of a disproportionate increase in their domestic work burden and a shift in their workstation to home. Since every job cannot be performed remotely, women employed in healthcare services, banks and media witnessed additional risks of commuting and physical interaction at the workplace. Based on personal interviews of women in the Delhi-NCR region, the study aims to explore the commonalities and variances in the challenges experienced by the women engaged in diverse occupations. Using the qualitative methodology of flexible coding, the study finds that a relatively larger section of women travelling to their office during the pandemic, rather than those working from home, had an effective familial support system that helped them navigate this tough time.

Analisis Termodinamika dan Kinetika Nanopartikel Karbon (C-Dot) dari Buah Durian Sebagai Inhibitor Korosi Tembaga

Corrosion is a physical interaction between the metal and its environment, which results in changes in the metal's properties due to chemical or electrochemical reactions. The corrosion rate can be reduced by adding a corrosion inhibitor. Uses of nanotechnology for corrosion prevention is one of the first technical because almost made structures rely on the stability of a 1–2 nm thick passive film which provides stability to the underlying material. Herein we report the thermodynamic and kinetic analysis of carbon-dots from Durian as inhibitor copper corrosion. To test the anticorrosive performance and analyze thermodynamic properties in its role as a corrosion inhibitor on copper using potentiodynamic polarization. The thermodynamic-kinetic parameters of corrosion obtained values of H‡ = 60.44 kJmol-1, ΔS‡ = -73.9 kJmol-1, and ΔG‡ = 82.83 kJmol-1, show that the attendance of C-dot as a corrosion inhibitor causes a non-spontaneous reaction rate to be proven by increasing spontaneity (ΔG‡). The value of activation energy samples was higher than the blank, indicates the presence of C-dot effective to reduce the rate of corrosion of the metal.

Mechanical Property, Thermal Stability and BioDegradability Studies on PLA based Bio-Nanocomposites derived from Agricultural Residues

Looking at the environmental hazards being posed by indiscriminate use of synthetic plastics, abundant research is being done to explore various bio-degradable polymers. In the present study, Cellulose Nano Fibers (CNFs) were extracted from Pineapple Crown using mechano chemical treatment, PLA was synthesized by Simultaneous Saccharification and Fermentation using cellulase enzyme on Acacia Arabica as substrate. Further, ZnO nanoparticles were synthesized by using different precursors. The biocomposite sheets of PLA, PLA+ 5%-20% CNFs, PLA+5% ZnO+5-20 % CNFs and PLA+10% ZnO+5-20 % CNFs were solvent casted. Microbial efficacy test was done using E.coli and with inclusion of ZnO nanoparticles the microbial resistance has increased. Noteworthy vibration band of the sheets were observed in the wavelength range of 3700 to 2800 cm-1 from the FTIR analysis, which shows that there is only a physical interaction rather than chemical. The crystallinity increased for initial concentration, but was similar to the neat PLA. Significant increase in tensile strength and maximum elongation at break was observed in PLA + 5% ZnO + 10% CNFs sheet. Sheets were allowed to degrade naturally and significant weight loss was observed after 120 days with maximum reduction of 38.4 %. Morphological analysis through SEM revealed the uniform distribution of fillers in the polymer matrix. TGA studies have shown that the degradation temperatures were in the range of 320-405oC. The thermal stability decreased with the increase in ZnO concentration. The results have shown a promising and sustainable use in various applications in view of microbial resistance and bio-degradability.

Interleukin 4 controls the role of macrophages in pulmonary metastatic tumor cell seeding and growth

Metastasis is the systemic manifestation of cancer and the main cause of death from breast cancer. In mouse models of lung metastases, recruitment of classical monocytes from blood to the lung and their differentiation to metastasis-associated macrophages (MAMs) facilitate cancer cell extravasation, survival, and growth. Ablation of MAMs or their monocytic progenitors inhibits metastasis. We hypothesized that factors controlling macrophage polarization modulate tumor cell extravasation in the lung. We evaluated whether signaling by Th1 or Th2 cytokines in macrophages affected trans-endothelial migration of tumor cells in vitro. Interferon γ and LPS inhibited macrophage-dependent tumor cell extravasation while the Th2 cytokine interleukin-4 (IL4) enhanced this process. We demonstrated that IL4 receptor (IL4rα) null mice develop fewer and smaller lung metastasis. Adoptive transfer of wild type monocytes to IL4rα deficient mice rescued this phenotype. IL4 signaling in macrophages controls the expression of the chemokine receptor CXCR2, necessary for IL4-mediated tumor cell extravasation in vitro. Furthermore, IL4 signaling in macrophages transcriptionally regulates several other genes already causally associated with lung metastasis including CCL2, CSF1, CCR1, HGF and FLT1. The central role for IL4 signaling in MAMs was confirmed by high-resolution intravital imaging of the lung in mice at the time of metastatic seeding, which showed reduced physical interaction between tumor cells and IL4rα-deficient macrophages. This interaction enhances tumor cell survival. These data indicate that IL4 signaling in monocytes and macrophages is key during seeding and growth of breast metastasis in the lung as it regulates pro-tumoral paracrine signaling between cancer cells and macrophages.

Economic and Social Impacts of Social Entrepreneurship Implementation Service to Community

The government's policy to prevent the spread of COVID-19 has limited physical interaction between communities, creating problems for various everyday economic activities. One of which is the existence of a grant given by the Ministry of Research and Technology / National Innovation Research Agency of the Republic of Indonesia for the implementation of community service by guiding the development of micro?businesses in society. This type of research is a descriptive method with a qualitative approach. Data collection was conducted by interviewing eight informants consisting of recipients of the Family Hope Program assistance. Documentation and observation were also carried out to strengthen the data. Data analysis used an interactive model following Milles and Huberman's opinion, namely: data reduction, data presentation, and conclusion drawing.

Impact of COVID-19 on perceived wellbeing, self-management and views of novel modalities of care among medically vulnerable patients in Singapore

Objectives This study aims to examine the impact of COVID-19 measures on wellbeing and self-management in medically vulnerable non-COVID patients and their views of novel modalities of care in Singapore. Methods Patients with cardiovascular disease (CVD), respiratory disease, chronic kidney disease, diabetes and cancer were recruited from the SingHealth cluster and national cohort of older adults. Data on demographics, chronic conditions and perceived wellbeing were collected using questionnaire. We performed multivariable regression to examine factors associated with perceived wellbeing. Qualitative interviews were conducted to elicit patient's experience and thematically analyzed. Results A total of 91 patients participated. Male patients compared with female patients perceived a lower impact of the pandemic on subjective wellbeing. Patients with CVD compared to those having conditions other than CVD perceived a lower impact. Impacts of the pandemic were primarily described in relation to emotional distress and interference in maintaining self-care. Hampering of physical activity featured prominently, but most did not seek alternative ways to maintain activity. Despite general willingness to try novel care modalities, lack of physical interaction and communication difficulties were perceived as main barriers. Discussion Findings underline the need to alleviate emotional distress and develop adaptive strategies to empower patients to maintain wellbeing and self-care.