TLR-4: a promising target for chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) affects a significant majority of cancer patients, with up to 80% experiencing this severe and dose-limiting side effect while undergoing anti-cancer treatment. CIPN can be induced by a variety of drugs commonly employed in the management of both solid tumors and hematologic cancers. The inadequacies in comprehending the pharmacological interventions associated with CIPN and the subsequent signaling pathways have significantly contributed to the disappointing outcomes of several drugs in clinical trials. Recent investigations in pain research have demonstrated a growing inclination toward addressing neuro-inflammation as a strategy for managing chronic pain conditions. Notably, toll-like receptor-4 (TLR-4) has emerged as a key player in immune system activation and is undergoing extensive research. In this review, we emphasize the potential role of TLR-4 in neuropathic pain, highlighting its promise as a target for CIPN treatment. Furthermore, we explore and analyse the intricate interplay between TLR-4, diverse immune cells, downstream pathways, and receptors within the context of CIPN. A comprehensive exploration of these interactions provides valuable insights into the central role of TLR-4 in CIPN development, paving the way for potential ground-breaking therapeutic approaches to alleviate this debilitating condition.

Microplastics-biofilm in aquatic ecosystem: Formation, pollutants complexation, greenhouse gas emission and ecotoxicology.

The omnipresent microplastics (MPs) have gradually become a significant environmental problem due to its adverse consequences for ecological systems. MPs serve as substrates for biofilms colonization, which enhances adsorption of harmful contaminants on MPs surface in the aquatic ecosystem. The present study provides a critical discussion on the mechanism involved in MPs-biofilm formation, microbial colonization and the robust factors influencing the process in the aquatic ecosystem. Subsequently, the impact of MPs-biofilm on adsorption of inorganic and organic contaminants is explored. The ecological significance of MPs-biofilm associated pollutant complex for promoting greenhouse gases (GHGs) emissions from aquatic ecosystem is extensively discussed for understanding the climatic risk. Furthermore, the discussion is extended over ecotoxicological impact of MPs-biofilm on aquatic biodiversity and humans. The protective extracellular polymeric substances secreted by colonised bacteria over MPs during biofilm formation creates sticky MPs surface for heteroaggregates formation with swift adsorption of chemical compounds and microorganisms. MPs with functional aromatic groups facilitate the bacterial adhesion on the surface, but affect formation of biofilm. Alternatively, MPs-biofilm promotes the Mn and Fe hydrous oxides formation that can co-precipitate with heavy metal ions and facilitate in remediation measures. However, MPs biodegradation generates GHGs emission per unit mass, comparably more from freshwater than marine ecosystem. Considering the toxicity, MPs-biofilm induces the oxidative response in fishes, causing painful death and thus, destroys aquatic biodiversity. This study will be useful to address MPs-biofilm associated pollution scenario via trace, test and treat strategy involving future engineering research framework for ecological restoration.

A comparative cross-sectional study on the quality of life in Grave's disease patients: urban vs. rural perspectives.

Grave's disease affects numerous patients globally, but its impact on health-related quality of life (HR-QoL) in relation to geographical disparities remains under-explored. This cross-sectional study aimed to assess the influence of urban versus rural residence on HR-QoL among patients diagnosed with Graves' Disease in Rajasthan, India. One hundred seven Graves' disease patients from rural and urban endocrine centers were analyzed. The rural group included 52 patients (24 males, 28 females), averaging 38.9 ± 10.9 years of age, while the urban group had 55 (13 males, 42 females) with an average age of 39.1 ± 14.2 years. We found differences between rural and urban patients in terms of gender ratio, BMI, smoking habits, and obesity. Multivariable linear regression was used in both groups to determine the association between the baseline characteristics of Graves' patients from both areas and HR-QOL. Health-related quality of life, assessed via the SF-36 questionnaire, indicated higher general health and role emotional scores among urban patients. Our study found that the duration of Graves' disease in rural centers negatively impacted physical health scores. In urban patients, age and BMI influenced physical health, while gender and disease duration affected mental health scores in rural patients. Age impacted mental health in urban patients. Rural patients had a poorer quality of life compared to urban patients. Differences in gender distribution, BMI, smoking habits, and obesity rates revealed disparities in Graves' disease between rural and urban patients in India, highlighting the need for better healthcare infrastructure and awareness in rural areas.

Development of Epigallocatechin and Ascorbic Acid Dual Delivery Transferosomes for Managing Alzheimer's Disease: In Vitro and in Vivo Studies.

Epigallocatechin-3-gallate (EGCG) and ascorbic acid (AA)-loaded transferosomes (TRANS) were developed for brain delivery. The investigation covered EGCG-TRANS, AA-TRANS, and EGCG-AA-TRANS formulations using the film hydration technique. We analyzed the formed transferosomes to confirm the presence of vesicles loaded with the respective drugs and their performance within a living organism. The sizes of the particles for EGCG-TRANS, AA-TRANS, and EGCG-AA-TRANS were measured correspondingly at 174.2 ± 1.80, 132.7 ± 12.22, and 184.31 ± 9.5 nm. The appearance of diffused rings in the scanning electron microscopic image suggests that the payload has a crystalline structure. The atomic force microscope image displayed minimal surface irregularities, potentially indicating the presence of a lipid layer on the surface. Hemolysis results indicated the safety of the vesicles. The results showed 10.23, 7.21, and 8.20% of hemolysis for EGCG-TRANS, AA-TRANS, and EGCG-AA-TRANS, respectively. In the case of EGCG-AA-TRANS, the release of EGCG was determined to be 61.65% ± 4.61 after 72 h when exposed to phosphate buffer saline (pH 7.4). In vivo studies show a good response against Alzheimer's disease (AD). EGCG-AA-TRANS (82.166%) exhibited a higher percentage of AChE inhibition in comparison to EGCG-TRANS (66.550%) and AA-TRANS (53.466%). Intranasal delivery of EGCG-AA-TRANS resulted in approximately a 5-fold enhancement in memory. Formulation allowed EGCG and AA to accumulate in various organs, including the brain. The results suggest that EGCG-AA-TRANS could be safe and effective for treating AD.

Microplastics pollution in the Asian water tower: Source, environmental distribution and proposed mitigation strategy.

Microplastics generated from fragmentation of leftover plastics and industrial waste has reached in the remotely located Asian water tower (AWT) region, the 3rd pole of earth and origin site of several freshwater rivers. The accumulation of microplastics in AWT ecosystem has potential to alter the climatic condition contributing in global warming and disturbing the biodiversity structural dynamics. The present paper provides a comprehensive critical discussion over quantitative assessment of microplastics in different ecosystems (i.e. river, lakes, sediment and snow or glacier) of AWT. The hydrodynamic fate and transport of microplastics and their ecological impact on hydromorphology and biodiversity of AWT has been exemplified. Furthermore, key challenges, perspectives and research directions are identified to mitigate microplastics associated problems. During survey, the coloured polyethylene and polyurethane fibers are the predominant microplastics found in most areas of AWT. These bio-accumulated MPs alter the rhizospheric community structure and deteriorate nitrogen fixation process in plants. Significance in climate change, MPs pollution is enhancing the emissions of greenhouse gases (NH3 by ∼34% and CH4 by ∼9%), contributing in global warming. Considering the seriousness of MPs pollution, this review study can enlighten the pathways to investigate the effect of MPs and to develop monitoring tools and sustainable remediation technologies with feasible regulatory strategies maintaining the natural significance of AWT region.

In vitro profiling and molecular dynamics simulation studies of berberine loaded MCM-41 mesoporous silica nanoparticles to prevent neuronal apoptosis.

Neuronal loss in Alzheimer's disease has been reported to display features of apoptosis, pyroptosis (programmed necrosis), or necroptosis. This study thoroughly examines the production and characterization of MCM-41 based berberine (BBR)-loaded porous silica nanoparticles (MSNs) by a modified Stöber method, focusing on their possible role in inhibiting the apoptotic process. Particle size, polydispersity index, morphology, drug loading, zeta potential, entrapment efficiency, and drug release were examined. The formulation was analyzed using various spectroscopic techniques. The surface area was computed by the Brunauer-Emmett-Teller plot. Computational models were developed for molecular dynamics simulation studies. A small PDI value indicated an even distribution of particles at nanoscale sizes (80-100 nm). Results from XRD and SEAD experiments confirmed the amorphous nature of BBR in nanoparticles. Nanoparticles had high entrapment (75.21 ± 1.55%) and drug loading (28.16 ± 2.5%) efficiencies. A negative zeta potential value (-36.861.1 mV) indicates the presence of silanol groups on the surface of silica. AFM findings reveal bumps due to the surface drug that contributed to the improved roughness of the MSNs-BBR surface. Thermal gravimetric analysis confirmed the presence of BBR in MSNs. Drug release was controlled by simple diffusion or quasi-diffusion. Molecular dynamics simulations confirmed the existence of diffused drug molecules. Cellular studies using SH-SY-5Y cells revealed dose-dependent growth inhibition. Fragmented cell nuclei and nuclear apoptotic bodies in DAPI-stained cells exposed to nanoparticles showed an increase in apoptotic cells. Flow cytometry analysis demonstrated a lower red-to-green ratio in SH-SY-5Y cells treated with nanoparticles. This suggests improved mitochondrial health, cellular viability restoration, and prevention of the apoptotic process. This study provides essential data on the synthesis and potential of MSNs loaded with BBR, which may serve as a viable therapeutic intervention for conditions associated with apoptosis.

Burden of COVID-19 pandemic on tuberculosis hospitalisation patterns at a tertiary care hospital in Rajasthan, India: a retrospective analysis.

OBJECTIVE: This study aimed to investigate the burden of the COVID-19 pandemic on tuberculosis (TB) trends, patient demographics, disease types and hospitalisation duration within the Respiratory Medicine Department over three distinct phases: pre-COVID-19, COVID-19 and post-COVID-19. DESIGN: Retrospective analysis using electronic medical records of patients with TB admitted between June 2018 and June 2023 was done to explore the impact of COVID-19 on patients with TB. The study employed a meticulous segmentation into pre-COVID-19, COVID-19 and post-COVID-19 eras. SETTING: National Institute of Medical Science Hospital in Jaipur, Rajasthan, India. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome includes patients admitted to the Respiratory Medicine Department of the hospital and secondary outcome involves the duration of hospital stay. RESULTS: The study encompassed 1845 subjects across the three eras, revealing a reduction in TB incidence during the post-COVID-19 era compared with the pre-COVID-19 period (p<0.01). Substantial demographic shifts were observed, with 5.2% decline in TB incidence among males in the post-COVID-19 era (n=529) compared with the pre-COVID-19 era (n=606). Despite the decrease, overall TB incidence remained significantly higher in males (n=1460) than females (n=385), with consistently elevated rates in rural (65.8%) as compared with the urban areas (34.2%). Extended hospital stays were noted in the post-COVID-19 era compared with the pre-COVID-19 era (p<0.01). CONCLUSION: The study underscores the influence of the COVID-19 pandemic on the TB landscape and hospitalisation dynamics. Notably, patient burden of TB declined during the COVID-19 era, with a decline in the post-COVID-19 era compared with the pre-COVID-19 era. Prolonged hospitalisation in the post-COVID-19 period indicates the need for adaptive healthcare strategies and the formulation of public health policies in a post-pandemic context. These findings contribute to a comprehensive understanding of the evolving TB scenario, emphasising the necessity for tailored healthcare approaches in the aftermath of a global health crisis.

Prevalence of breast cancer in rural population of Jaipur: a survey-based observational study.

Breast cancer, a global health concern predominantly affecting women, recorded 2.3 million new cases and 685,000 deaths in 2020. Alarmingly, projections suggest that by 2040, there could be over 3 million new cases and 1 million deaths. To assess breast cancer prevalence in 24 rural villages within a 60 km radius of NIMS Hospital, Tala Mod, Jaipur, Rajasthan, North India 303,121. A study involving 2023 participants conducted initial screenings, and positive cases underwent further tests, including ultrasound, mammography, and biopsy. SPSSv28 analysed collected data. Among 2023 subjects, 3 screened positive for breast lumps. Subsequent clinical examination and biopsy identified 1 normal case and 2 with breast cancer, resulting in a prevalence proportion of 0.0009 or 98 per 100,000. This study helps fill gap in breast cancer prevalence data for rural Rajasthan. The results highlight a concerning prevalence of breast cancer in the rural area near NIMS hospital, emphasizing the urgent need for increased awareness, early detection, and better healthcare access. Challenges like limited resources, awareness programs, and delayed diagnosis contribute to this high incidence. To address this, comprehensive approach is necessary, including improved screening programs and healthcare facilities in rural areas. Prioritizing rural healthcare and evidence-based strategies can reduce the burden of breast cancer and improve health outcomes.

Folate-Mediated Targeting and Controlled Release: PLGA-Encapsulated Mesoporous Silica Nanoparticles Delivering Capecitabine to Pancreatic Tumor.

The discovery of specifically tailored therapeutic delivery systems has sparked the interest of pharmaceutical researchers considering improved therapeutic effectiveness and fewer adverse effects. The current study concentrates on the design and characterization of PLGA (polylactic-co-glycolic acid) capped mesoporous silica nanoparticles (MSN)-based systems for drug delivery for pH-sensitive controlled drug release in order to achieve a targeted drug release inside the acidic tumor microenvironment. The physicochemical properties of the nanoformulations were analyzed using TEM, zeta potential, AFM, TGA, FTIR, and BET analyses in addition to DLS size. The final formed PLGA-FoA-MSN-CAP and pure MSN had sizes within the therapeutic ranges of 164.5 ± 1.8 and 110.7 ± 2.2, respectively. Morphological characterization (TEM and AFM) and elemental analysis (FTIR and XPS) confirmed the proper capping and tagging of PLGA and folic acid (FoA). The PLGA-coated FoA-MSN exhibited a pH-dependent controlled release of the CAP (capecitabine) drug, showing efficient release at pH 6.8. Furthermore, the in vitro MTT test on PANC1 and MIAPaCa-2 resulted in an IC50 value of 146.37 µg/ml and 105.90 µg/ml, respectively. Mitochondrial-mediated apoptosis was confirmed from the caspase-3 and annexin V/PI flow cytometry assay, which displayed a cell cycle arrest at the G1 phase. Overall, the results predicted that the designed nanoformulation is a potential therapeutic agent in treating pancreatic cancer.

Post-COVID-19 cardio-pulmonary manifestations after 1-year of SARS-CoV-2 infection among Indian population: A single centre, case-control study (OneCoV2 study).

BACKGROUND: The evolving challenge of persistent symptoms post-Coronavirus disease-2019 (COVID-19), particularly debilitating cardio-pulmonary manifestations, necessitates further exploration. Our study aimed to assess the cardio-pulmonary complications in patients a year after hospital discharge from severe COVID-19, contrasting these with findings from a non-COVID group. METHODS: The OneCoV2 study, a prospective, case-control study, was conducted at a tertiary care teaching hospital in northern India. We enrolled 43 subjects, with a mean age of 25.57 ± 7.94 years (COVID group) and 27.30 ± 8.17 years (non-COVID group). Comprehensive tests included pulmonary function tests, cardiac function tests, 6-min walk tests, and laboratory investigations. RESULTS: Significant differences were found in the pulmonary function [forced vital capacity (FVC) (p = 0.037), forced expiratory flow (FEF) 25-75 % (p = 0.013)], and cardiac function [left ventricular ejection fraction (LVEF) (p = 0.032), heart rate (HR) (p = 0.047)], along with the six-minute walk test results between the two groups. In the COVID group, Pearson's correlation showed a negative correlation between FVC and C-reactive protein (CRP) [r = -0.488, p = 0.007] and a positive correlation between the six-minute walk test [r = 0.431, p = 0.003] and HR [r = 0.503, p = 0.013]. CONCLUSIONS: Our data suggest that pulmonary abnormalities are prevalent in COVID patients even after 1-year of hospital discharge. Cardiac biomarkers also show an inclination towards the COVID group. While we found significant correlations involving some parameters like FVC, CRP, HR, and results from the six-minute walk test, we did not find any significant correlations with the other tested parameters in our study.

Cis-regulatory effect of HPV integration is constrained by host chromatin architecture in cervical cancers.

Human papillomavirus (HPV) infections are the primary drivers of cervical cancers, and often HPV DNA gets integrated into the host genome. Although the oncogenic impact of HPV encoded genes is relatively well known, the cis-regulatory effect of integrated HPV DNA on host chromatin structure and gene regulation remains less understood. We investigated genome-wide patterns of HPV integrations and associated host gene expression changes in the context of host chromatin states and topologically associating domains (TADs). HPV integrations were significantly enriched in active chromatin regions and depleted in inactive ones. Interestingly, regardless of chromatin state, genomic regions flanking HPV integrations showed transcriptional upregulation. Nevertheless, upregulation (both local and long-range) was mostly confined to TADs with integration, but not affecting adjacent TADs. Few TADs showed recurrent integrations associated with overexpression of oncogenes within them (e.g. MYC, PVT1, TP63 and ERBB2) regardless of proximity. Hi-C and 4C-seq analyses in cervical cancer cell line (HeLa) demonstrated chromatin looping interactions between integrated HPV and MYC/PVT1 regions (~ 500 kb apart), leading to allele-specific overexpression. Based on these, we propose HPV integrations can trigger multimodal oncogenic activation to promote cancer progression.

Exploring the risk of glycemic variability in non-diabetic depressive individuals: a cross-sectional GlyDep pilot study.

Background: Data on the correlation between glycemic variability and depression in nondiabetic patients remain limited. Considering the link between increased glycemic variability and cardiovascular risks, this relationship could be significant in depressed patients. Methods: In this single-center pilot study, we utilized Flash Glucose Monitoring (Abbott Libre Pro) to study glycemic variability. The CES-D (Center for Epidemiological Studies- Depression) scale was employed to measure depression levels. Based on CES-D scores, patients were classified into two groups: those with scores ≥ 33 and those with scores < 33. We analyzed various glycemic variability indices, including HBGI, CONGA, ADDR, MAGE, MAG, LI, and J-Index, employing the EasyGV version 9.0 software. SPSS (version 28) facilitated the data analysis. Results: We screened patients with depression visiting the department of psychiatry, FGM was inserted in eligible patients of both the groups which yielded a data of 196 patient-days (98 patient-days for CES-D ≥ 33 and 98 patient-days for CES-D < 33). The glycemic variability indices CONGA (mg/dl), (76.48 ± 11.9 vs. 65.08 ± 7.12) (p = 0.048), MAGE (mg/dl) (262.50 ± 25.65 vs. 227.54 ± 17.72) (p = 0.012), MODD (mg/dl) (18.59 ± 2.77 vs. 13.14 ± 2.39) (p = 0.002), MAG(mg/dl) (92.07 ± 6.24vs. 63.86 ± 9.38) (p = <0.001) were found to be significantly higher in the CES-D ≥ 33 group. Conclusion: Patients with more severe depressive symptoms, as suggested by CES-D ≥ 33, had higher glycemic variability.

MRTF-A gain-of-function in mice impairs homeostatic renewal of the intestinal epithelium.

The actin-regulated transcription factor MRTF-A represents a central relay in mechanotransduction and controls a subset of SRF-dependent target genes. However, gain-of-function studies in vivo are lacking. Here we characterize a conditional MRTF-A transgenic mouse model. While MRTF-A gain-of-function impaired embryonic development, induced expression of constitutively active MRTF-A provoked rapid hepatocyte ballooning and liver failure in adult mice. Specific expression in the intestinal epithelium caused an erosive architectural distortion, villus blunting, cryptal hyperplasia and colonic inflammation, resulting in transient weight loss. Organoids from transgenic mice repeatedly induced in vitro showed impaired self-renewal and defective cryptal compartments. Mechanistically, MRTF-A gain-of-function decreased proliferation and increased apoptosis, but did not induce fibrosis. MRTF-A targets including Acta2 and Pai-1 were induced, whereas markers of stem cells and differentiated cells were reduced. Our results suggest that activated MRTF-A in the intestinal epithelium shifts the balance between proliferation, differentiation and apoptosis.

DeePMD-kit v2: A software package for deep potential models.

DeePMD-kit is a powerful open-source software package that facilitates molecular dynamics simulations using machine learning potentials known as Deep Potential (DP) models. This package, which was released in 2017, has been widely used in the fields of physics, chemistry, biology, and material science for studying atomistic systems. The current version of DeePMD-kit offers numerous advanced features, such as DeepPot-SE, attention-based and hybrid descriptors, the ability to fit tensile properties, type embedding, model deviation, DP-range correction, DP long range, graphics processing unit support for customized operators, model compression, non-von Neumann molecular dynamics, and improved usability, including documentation, compiled binary packages, graphical user interfaces, and application programming interfaces. This article presents an overview of the current major version of the DeePMD-kit package, highlighting its features and technical details. Additionally, this article presents a comprehensive procedure for conducting molecular dynamics as a representative application, benchmarks the accuracy and efficiency of different models, and discusses ongoing developments.

Disentangling the enigmatic role of ephrin signaling in chronic pain: Moving towards future anti-pain therapeutics.

Chronic pain is a common and debilitating condition with a huge social and economic burden worldwide. Currently, available drugs in clinics are not adequately effective and possess a variety of severe side effects leading to treatment withdrawal and poor quality of life. The ongoing search for new therapeutics with minimal side effects for chronic pain management remains a high research priority. Erythropoietin-producing human hepatocellular carcinoma cell receptor (Eph) is a tyrosine kinase receptor that is involved in neurodegenerative disorders, including pain. The Eph receptor interacts with several molecular switches, such as N methyl d-aspartate receptor (NMDAR), mitogen-activated protein kinase (MAPK), calpain 1, caspase 3, protein kinase a (PKA), and protein kinase Cy (PKCy), which in turn regulates pathophysiology of chronic pain. Here we highlight the emerging evidence of the Ephs/ephrin system as a possible near-future therapeutic target for the treatment of chronic pain and discuss the various mechanism of its involvement. We critically analyse the present status of Eph receptor system and conclude that extrapolating the pharmacological and genetic approaches using a strong therapeutic development framework could serve as next-generation analgesics for the management of chronic pain.

Occurrence of antibiotics in wastewater: Potential ecological risk and removal through anaerobic-aerobic systems.

Antibiotics are intensively used to improve public health, prevent diseases and enhance productivity in animal farms. Contrarily, when released, the antibiotics laden wastewater produced from pharmaceutical industries and their application sources poses a potential ecological risk to the environment. This study provides a discussion on the occurrence of various antibiotics in wastewater and their potential ecological risk in the environment. Further, a critical review of anaerobic-aerobic processes based on three major systems (such as constructed wetland, high-rate bioreactor, and integrated treatment technologies) applied for antibiotics removal from wastewater is performed. The review also explores microbial dynamics responsible for antibiotic biodegradation in anaerobic-aerobic systems and its economic feasibility at wider-scale applications. The operational problems and prospective modifications are discussed to define key future research directions. The appropriate selection of treatment processes, sources control, understanding of antibiotic fate, and adopting precise monitoring strategies could eliminate the potential ecological risks of antibiotics. Integrated bio-electrochemical systems exhibit antibiotics removal ≥95% by dominant Geobacter sp. at short HRT ∼4-10 h. Major process factors like organic loading rate, hydraulic loading rate (HRT), and solid retention time significantly affect the system performance. This review will be beneficial to the researchers by providing in-depth understanding of antibiotic pollution and its abatement via anaerobic-aerobic processes to develop sustainable wastewater treatment technology in the future.

Heavy Metal Contamination in the Aquatic Ecosystem: Toxicity and Its Remediation Using Eco-Friendly Approaches.

Urbanization and industrialization are responsible for environmental contamination in the air, water, and soil. These activities also generate large amounts of heavy metal ions in the environment, and these contaminants cause various types of health issues in humans and other animals. Hexavalent chromium, lead, and cadmium are toxic heavy metal ions that come into the environment through several industrial processes, such as tanning, electroplating, coal mining, agricultural activities, the steel industry, and chrome plating. Several physical and chemical methods are generally used for the heavy metal decontamination of wastewater. These methods have some disadvantages, including the generation of secondary toxic sludge and high operational costs. Hence, there is a need to develop a cost-effective and eco-friendly method for the removal of heavy metal ions from polluted areas. Biological methods are generally considered eco-friendly and cost-effective. This review focuses on heavy metal contamination, its toxicity, and eco-friendly approaches for the removal of heavy metals from contaminated sites.

Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries.

Vertebrate genomes are partitioned into chromatin domains or topologically associating domains (TADs), which are typically bound by head-to-head pairs of CTCF binding sites. Transcription at domain boundaries correlates with better insulation; however, it is not known whether the boundary transcripts themselves contribute to boundary function. Here we characterize boundary-associated RNAs genome-wide, focusing on the disease-relevant INK4a/ARF and MYC TAD. Using CTCF site deletions and boundary-associated RNA knockdowns, we observe that boundary-associated RNAs facilitate recruitment and clustering of CTCF at TAD borders. The resulting CTCF enrichment enhances TAD insulation, enhancer-promoter interactions, and TAD gene expression. Importantly, knockdown of boundary-associated RNAs results in loss of boundary insulation function. Using enhancer deletions and CRISPRi of promoters, we show that active TAD enhancers, but not promoters, induce boundary-associated RNA transcription, thus defining a novel class of regulatory enhancer RNAs.

Nanovaccine: A Hope to Triumph the Battle Against Novel Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel coronavirus 2019 (COVID-19) infection has caused the global emergence of coronavirus in humans during the last 12 months. Till May 11, 2021, the confirmed global COVID-19 cases and deaths reached 158551526 and 3296855, respectively. METHODS: Goblet cells and ciliated cells in the nose act as the initial infection site of SARS-CoV-2. Thus, mucus immunity is important to protect from infection. The outburst of SARS-CoV-2 infection can be halted only when an effective vaccine will be developed. RESULTS: Globally, over 100 different vaccines are under investigation, including DNA vaccines, RNA vaccines, inactivated virus vaccines, adenovirus-based vaccines, recombinant/subunit protein vaccines, peptide vaccines, virus-like particles, etc. Inactivated virus vaccines and mRNA, and adenovirus-based vaccines have moved fast into patent clinical trials. CONCLUSION: Vaccines containing spike protein of SARS-CoV as subunit could effectively prevent binding of coronavirus to the host cell and membrane fusion. Thus, spike protein can be used as a major target for subunit vaccine preparation.