Exploring the robustness of DNA nanotubes framework for anticancer theranostics toward the 2D/3D clusters of hypopharyngeal respiratory tumor cells.

This study aimed to develop a robust approach for the early diagnosis and treatment of tumors. Short circular DNA nanotechnology synthesized a stiff and compact DNA nanotubes (DNA-NTs) framework. TW-37, a small molecular drug, was loaded into DNA-NTs for BH3-mimetic therapy to elevate the intracellular cytochrome-c levels in 2D/3D hypopharyngeal tumor (FaDu) cell clusters. After anti-EGFR functionalization, the DNA-NTs were tethered with a cytochrome-c binding aptamer, which can be applied to evaluate the elevated intracellular cytochrome-c levels via in situ hybridization (FISH) analysis and fluorescence resonance energy transfer (FRET). The results showed that DNA-NTs were enriched within the tumor cells via anti-EGFR targeting with a pH-responsive controlled release of TW-37. In this way, it initiated the triple inhibition of "BH3, Bcl-2, Bcl-xL, and Mcl-1". The triple inhibition of these proteins caused Bax/Bak oligomerization, leading to the perforation of the mitochondrial membrane. This led to the elevation of intracellular cytochrome-c levels, which reacted with the cytochrome-c binding aptamer to produce FRET signals. In this way, we successfully targeted 2D/3D clusters of FaDu tumor cells and achieved the tumor-specific and pH-triggered release of TW-37, causing tumor cell apoptosis. This pilot study suggests that anti-EGFR functionalized, TW-37 loaded, and cytochrome-c binding aptamer tethered DNA-NTs might be the hallmark for early tumor diagnosis and therapy.

Functional Gastrointestinal Diseases and Dietary Practices among Pakistani Children-A Schools Based Cross-Sectional Study.

BACKGROUND: Functional gastrointestinal diseases (FGIDs) are an important yet highly under explored area among public health issues. FGIDs' complex etiology makes them of interest along with their prevalence in children steadily increasing, especially in the developing world. We aimed to determine the burden FGIDs pose on school-going children, and to determine its association with the dietary intake patterns in Pakistani children. METHODOLOGY: The study included 385 school-children from public and private schools in Pakistan through multistage random sampling, from March to August 2022. We used the Food Frequency Questionnaire (FFQ) and Rome IV Criteria for a comprehensive exploration of the issue. Associations between the FGIDs and dietary factors were analyzed using chi-square and Fischer's exact tests in SPSS version 26.0. RESULTS: Females constituted 77.4% (n = 298) of all respondents, while 44.9% (n = 173) of the total reported a family history of gastrointestinal diseases. FFQ analysis showed varying consumption frequencies for different food groups. Functional abdominal pain and irritable bowel syndrome (IBS) were the highest reported FGIDs with a prevalence of 38.7% (n = 149) and 24.9% (n = 96), respectively. Statistical associations were found between different FGIDs and gender, age, household income, family members, and dietary variables such as fruit, vegetable, beverage and pulse consumption. CONCLUSION: FGIDs were found to be associated with a number of socio-demographic and dietary factors which calls for small scale and large scale attention to the issue. Results from the current study and further studies may help develop guidelines to manage these disorders in Pakistan.

Nanoscale packing of DNA tiles into DNA macromolecular lattices.

Nanoscale double-crossovers (DX), antiparallel (A), and even half-turns-perimeter (E) DNA tiles (DAE-tiles) with rectangular shapes can be packed into large arrays of micrometer-scale lattices. But the features and mechanical strength of DNA assembly made from differently shaped large-sized DAE DNA tiles and the effects of various geometries on the final DNA assembly are yet to be explored. Herein, we focused on examining DNA lattices synthesized from DX bi-triangular, DNA tiles (T) with concave and convex regions along the perimeter of the tiles. The bi-triangular DNA tiles "T(A) and T(B)" were synthesized by self-assembling the freshly prepared short circular scaffold (S) strands "S(A) and S(B)", each of 106 nucleotides (NT) lengths. The tiles "T(A) and T(B)" were then coupled together to get assembled via sticky ends. It resulted in the polymerization of DNA tiles into large-sized DNA lattices with giant micrometer-scale dimensions to form the "T(A) + T(B)" assembly. These DNA macro-frameworks were visualized "in the air" under atomic force microscopy (AFM) employing tapping mode. We have characterized how curvature in DNA tiles may undergo transitions and transformations to adjust the overall torque, strain, twists, and the topology of the final self-assembly array of DNA tiles. According to our results, our large-span DX tiles assembly "T(A) + T(B)" despite the complicated curvatures and mechanics, was successfully packed into giant DNA lattices of the width of 30-500 nm and lengths of 500 nm to over 10 µm. Conclusively, the micrometer-scale "T(A) + T(B)" framework assembly was rigid, stable, stiff, and exhibited enough tensile strength to form monocrystalline lattices.

Disrupting biofilm and eradicating bacteria by Ag-Fe3O4@MoS2 MNPs nanocomposite carrying enzyme and antibiotics.

In this study, novel multilayered magnetic nanoparticles (ML-MNPs) loaded with DNase and/or vancomycin (Vanc) were fabricated for eliminating multispecies biofilms. Iron-oxide MNPs (IO-core) (500-800 nm) were synthesized via co-precipitation; further, the IO-core was coated with heavy-metal-based layers (Ag and MoS2 NPs) using solvent evaporation. DNase and Vanc were loaded onto the outermost layer of the ML-MNP formed by nanoporous MoS2 NPs through physical deposition and adsorption. The biofilms of S. mutans or E. faecalis (or both) were formed in a brain-heart-infusion broth (BHI) for 3 days, followed by treatment with ML-MNPs for 24 h. The results revealed that coatings of Ag (200 nm) and ultrasmall MoS2 (20 nm) were assembled as outer layers of ML-MNPs successfully, and they formed Ag-Fe3O4@MoS2 MNPs (3-5 µm). The DNase-Vanc-loaded MNPs caused nanochannels digging and resulted in the enhanced penetration of MNPs towards the bottom layers of biofilm, which resulted in a decrease in the thickness of the 72-h biofilm from 48 to 58 µm to 0-4 µm. The sustained release of Vanc caused a synergistic bacterial killing up to 96%-100%. The heavy-metal-based layers of MNPs act as nanozymes to interfere with bacterial metabolism and proliferation, which adversely affects biofilm integrity. Further, loading DNase/Vanc onto the nanoporous-MoS2-layer of ML-MNPs promoted nanochannel creation through the biofilm. Therefore, DNase-and Vanc-loaded ML-MNPs exhibited potent effects on biofilm disruption and bacterial killing.

Recent Advances in Genomics-Based Approaches for the Development of Intracellular Bacterial Pathogen Vaccines.

Infectious diseases continue to be a leading cause of morbidity and mortality worldwide. The majority of infectious diseases are caused by intracellular pathogenic bacteria (IPB). Historically, conventional vaccination drives have helped control the pathogenesis of intracellular bacteria and the emergence of antimicrobial resistance, saving millions of lives. However, in light of various limitations, many diseases that involve IPB still do not have adequate vaccines. In response to increasing demand for novel vaccine development strategies, a new area of vaccine research emerged following the advent of genomics technology, which changed the paradigm of vaccine development by utilizing the complete genomic data of microorganisms against them. It became possible to identify genes related to disease virulence, genetic patterns linked to disease virulence, as well as the genetic components that supported immunity and favorable vaccine responses. Complete genomic databases, and advancements in transcriptomics, metabolomics, structural genomics, proteomics, immunomics, pan-genomics, synthetic genomics, and population biology have allowed researchers to identify potential vaccine candidates and predict their effects in patients. New vaccines have been created against diseases for which previously there were no vaccines available, and existing vaccines have been improved. This review highlights the key issues and explores the evolution of vaccines. The increasing volume of IPB genomic data, and their application in novel genome-based techniques for vaccine development, were also examined, along with their characteristics, and the opportunities and obstacles involved. Critically, the application of genomics technology has helped researchers rapidly select and evaluate candidate antigens. Novel vaccines capable of addressing the limitations associated with conventional vaccines have been developed and pressing healthcare issues are being addressed.

Effect of Biosynthesized Silver Nanoparticles on Bacterial Biofilm Changes in S. aureus and E. coli.

One approach for solving the problem of antibiotic resistance and bacterial persistence in biofilms is treatment with metals, including silver in the form of silver nanoparticles (AgNPs). Green synthesis is an environmentally friendly method to synthesize nanoparticles with a broad spectrum of unique properties that depend on the plant extracts used. AgNPs with antibacterial and antibiofilm effects were obtained using green synthesis from plant extracts of Lagerstroemia indica (AgNPs_LI), Alstonia scholaris (AgNPs_AS), and Aglaonema multifolium (AgNPs_AM). Nanoparticles were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDX) analysis. The ability to quench free radicals and total phenolic content in solution were also evaluated. The antibacterial activity of AgNPs was studied by growth curves as well as using a diffusion test on agar medium plates to determine minimal inhibitory concentrations (MICs). The effect of AgNPs on bacterial biofilms was evaluated by crystal violet (CV) staining. Average minimum inhibitory concentrations of AgNPs_LI, AgNPs_AS, AgNPs_AM were 15 ± 5, 20 + 5, 20 + 5 µg/mL and 20 ± 5, 15 + 5, 15 + 5 µg/mL against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, respectively. The E. coli strain formed biofilms in the presence of AgNPs, a less dense biofilm than the S. aureus strain. The highest inhibitory and destructive effect on biofilms was exhibited by AgNPs prepared using an extract from L. indica.

Gauging the air quality of New York: a non-linear Nexus between COVID-19 and nitrogen dioxide emission.

The primary objective of the study is to analyse the relationship between COVID-19 and nitrogen dioxide in New York City during the global pandemic. Notably, the study has investigated the direct influence of lockdown circumstances (due to COVID-19) and plunge in the population of New York on its environmental contamination. The study utilized the Non-Linear Autoregressive Distributed Lag (NARDL) model to ascertain the asymmetric impact of COVID-19 on the environmental quality of the USA. The results reveal that lockdown has played a significant role in the environmental quality of the USA. Notably, an escalation in the registered cases of COVID-19 has a meaningful and indirect relationship with environmental pollution in the UAS. Besides, as the lockdown state goes normal, it results in an explosion in the environmental pollution in the USA. Also, deaths due to COVID-19 substantively improve the environmental quality in the short-term period as well as in the long-term period.

Silver Nanomaterials for Wound Dressing Applications.

Silver nanoparticles (AgNPs) have recently become very attractive for the scientific community due to their broad spectrum of applications in the biomedical field. The main advantages of AgNPs include a simple method of synthesis, a simple way to change their morphology and high surface area to volume ratio. Much research has been carried out over the years to evaluate their possible effectivity against microbial organisms. The most important factors which influence the effectivity of AgNPs against microorganisms are the method of their preparation and the type of application. When incorporated into fabric wound dressings and other textiles, AgNPs have shown significant antibacterial activity against both Gram-positive and Gram-negative bacteria and inhibited biofilm formation. In this review, the different routes of synthesizing AgNPs with controlled size and geometry including chemical, green, irradiation and thermal synthesis, as well as the different types of application of AgNPs for wound dressings such as membrane immobilization, topical application, preparation of nanofibers and hydrogels, and the mechanism behind their antimicrobial activity, have been discussed elaborately.