A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes.

Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes. Moreover, in vivo physiological analysis revealed that each subtype has a distinct threshold and range of responses to mechanical and/or thermal stimuli. These findings support a model in which morphologically and physiologically distinct cutaneous DRG sensory neuron subtypes tile mechanical and thermal stimulus space to collectively encode a wide range of natural stimuli.

DRG afferents that mediate physiologic and pathologic mechanosensation from the distal colon.

The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology and gastrointestinal (GI) disease. Here, we report genetically defined subsets of colon-innervating DRG neurons with diverse morphologic and physiologic properties. Four colon-innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This Aδ-HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous DRG mechanoreceptor populations, colon-innervating mechanoreceptors exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon-innervating HTMRs mediate pathophysiological responses to colon distension, revealing a target population for therapeutic intervention.

A Shortcut to Activity-Dependent Transcription.

Neuronal activity results in the rapid induction of gene transcription through a series of defined molecular events. Madabhushi et al. describe an unexpected role for the cutting of promoter DNA by topoisomerase IIB to facilitate transcription of activity-induced genes.

Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network.

Behavioural experiences activate the FOS transcription factor in sparse populations of neurons that are critical for encoding and recalling specific events1-3. However, there is limited understanding of the mechanisms by which experience drives circuit reorganization to establish a network of Fos-activated cells. It is also not known whether FOS is required in this process beyond serving as a marker of recent neural activity and, if so, which of its many gene targets underlie circuit reorganization. Here we demonstrate that when mice engage in spatial exploration of novel environments, perisomatic inhibition of Fos-activated hippocampal CA1 pyramidal neurons by parvalbumin-expressing interneurons is enhanced, whereas perisomatic inhibition by cholecystokinin-expressing interneurons is weakened. This bidirectional modulation of inhibition is abolished when the function of the FOS transcription factor complex is disrupted. Single-cell RNA-sequencing, ribosome-associated mRNA profiling and chromatin analyses, combined with electrophysiology, reveal that FOS activates the transcription of Scg2, a gene that encodes multiple distinct neuropeptides, to coordinate these changes in inhibition. As parvalbumin- and cholecystokinin-expressing interneurons mediate distinct features of pyramidal cell activity4-6, the SCG2-dependent reorganization of inhibitory synaptic input might be predicted to affect network function in vivo. Consistent with this prediction, hippocampal gamma rhythms and pyramidal cell coupling to theta phase are significantly altered in the absence of Scg2. These findings reveal an instructive role for FOS and SCG2 in establishing a network of Fos-activated neurons via the rewiring of local inhibition to form a selectively modulated state. The opposing plasticity mechanisms acting on distinct inhibitory pathways may support the consolidation of memories over time.

The emergence of transcriptional identity in somatosensory neurons.

More than twelve morphologically and physiologically distinct subtypes of primary somatosensory neuron report salient features of our internal and external environments1-4. It is unclear how specialized gene expression programs emerge during development to endow these subtypes with their unique properties. To assess the developmental progression of transcriptional maturation of each subtype of principal somatosensory neuron, we generated a transcriptomic atlas of cells traversing the primary somatosensory neuron lineage in mice. Here we show that somatosensory neurogenesis gives rise to neurons in a transcriptionally unspecialized state, characterized by co-expression of transcription factors that become restricted to select subtypes as development proceeds. Single-cell transcriptomic analyses of sensory neurons from mutant mice lacking transcription factors suggest that these broad-to-restricted transcription factors coordinate subtype-specific gene expression programs in subtypes in which their expression is maintained. We also show that neuronal targets are involved in this process; disruption of the prototypic target-derived neurotrophic factor NGF leads to aberrant subtype-restricted patterns of transcription factor expression. Our findings support a model in which cues that emanate from intermediate and final target fields promote neuronal diversification in part by transitioning cells from a transcriptionally unspecialized state to transcriptionally distinct subtypes by modulating the selection of subtype-restricted transcription factors.

Interferon induction by STING requires its translocation to the late endosomes.

To combat microbial infections, mammalian cells use a variety of innate immune response pathways to induce synthesis of anti-microbial proteins. The cGAS/STING pathway recognizes cytoplasmic viral or cellular DNA to elicit signals that lead to type I interferon and other cytokine synthesis. cGAMP, synthesized by DNA-activated cGAS, activates the ER-associated protein, STING, which oligomerizes and translocates to other intracellular membrane compartments to trigger different branches of signaling. We have reported that, in the ER, EGFR-mediated phosphorylation of Tyr245 of STING is required for its transit to the late endosomes, where it recruits and activates the transcription factor IRF3 required for IFN induction. In the current study, we inquired whether STING Tyr245 phosphorylation per se or STING's location in the late endosomes was critical for its ability to recruit IRF3 and induce IFN. Using pharmacological inhibitors or genetic ablation of proteins that are essential for specific steps of STING trafficking, we demonstrated that the presence of STING in the late endosomal membranes, even without Tyr245 phosphorylation, was sufficient for IRF3-mediated IFN induction.

Suppressors of fixation can increase average fitness beyond amplifiers of selection.

Evolutionary dynamics on graphs has remarkable features: For example, it has been shown that amplifiers of selection exist that-compared to an unstructured population-increase the fixation probability of advantageous mutations, while they decrease the fixation probability of disadvantageous mutations. So far, the theoretical literature has focused on the case of a single mutant entering a graph-structured population, asking how the graph affects the probability that a mutant takes over a population and the time until this typically happens. For continuously evolving systems, the more relevant case is that mutants constantly arise in an evolving population. Typically, such mutations occur with a small probability during reproduction events. We thus focus on the low mutation rate limit. The probability distribution for the fitness in this process converges to a steady state at long times. Intuitively, amplifiers of selection are expected to increase the population's mean fitness in the steady state. Similarly, suppressors of selection are expected to decrease the population's mean fitness in the steady state. However, we show that another set of graphs, called suppressors of fixation, can attain the highest population mean fitness. The key reason behind this is their ability to efficiently reject deleterious mutants. This illustrates the importance of the deleterious mutant regime for the long-term evolutionary dynamics, something that seems to have been overlooked in the literature so far.

Cell-type-specific need of Ddx3 and PACT for interferon induction by RNA viruses.

IMPORTANCE: Interferon-stimulated genes (ISGs) are induced in response to interferon expression due to viral infections. Role of these ISGs can be variable in different cells or organs. Our study highlights such cell-specific role of an ISG, Ddx3, which regulates the translation of mRNAs essential for interferon induction (PACT) and interferon signaling (STAT1) in a cell-specific manner. Our study also highlights the role of PACT in RNA virus-induced RLR signaling. Our study depicts how Ddx3 regulates innate immune signaling pathways in an indirect manner. Such cell-specific behavior of ISGs helps us to better understand viral pathogenesis and highlights the complexities of viral tropism and innate immune responses.

Ifit2 restricts murine coronavirus spread to the spinal cord white matter and its associated myelin pathology.

Interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is critical in restricting neurotropic murine-ß-coronavirus, RSA59 infection. RSA59 intracranial injection of Ifit2-deficient (-/-) compared to wild-type (WT) mice results in impaired acute microglial activation, reduced CX3CR1 expression, limited migration of peripheral lymphocytes into the brain, and impaired virus control followed by severe morbidity and mortality. While the protective role of Ifit2 is established for acute viral encephalitis, less is known about its influence during the chronic demyelinating phase of RSA59 infection. To understand this, RSA59 infected Ifit2-/- and Ifit2+/+ (WT) were observed for neuropathological outcomes at day 5 (acute phase) and 30 post-infection (chronic phase). Our study demonstrates that Ifit2 deficiency causes extensive RSA59 spread throughout the spinal cord gray and white matter, associated with impaired CD4+ T and CD8+ T cell infiltration. Further, the cervical lymph nodes of RSA59 infected Ifit2-/- mice showed reduced activation of CD4+ T cells and impaired IFNγ expression during acute encephalomyelitis. Interestingly, BBB integrity was better preserved in Ifit2-/- mice, as evidenced by tight junction protein Claudin-5 and adapter protein ZO-1 expression surrounding the meninges and blood vessels and decreased Texas red dye uptake, which may be responsible for reduced leukocyte infiltration. In contrast to sparse myelin loss in WT mice, the chronic disease phase in Ifit2-/- mice was associated with severe demyelination and persistent viral load, even at low inoculation doses. Overall, our study highlights that Ifit2 provides antiviral functions by promoting acute neuroinflammation and thereby aiding virus control and limiting severe chronic demyelination. IMPORTANCE Interferons execute their function by inducing specific genes collectively termed as interferon-stimulated genes (ISGs), among which interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is known for restricting neurotropic viral replication and spread. However, little is known about its role in viral spread to the spinal cord and its associated myelin pathology. Toward this, our study using a neurotropic murine ß-coronavirus and Ifit2-deficient mice demonstrates that Ifit2 deficiency causes extensive viral spread throughout the gray and white matter of the spinal cord accompanied by impaired microglial activation and T cell infiltration. Furthermore, infected Ifit2-deficient mice showed impaired activation of T cells in the cervical lymph node and relatively intact blood-brain barrier integrity. Overall, Ifit2 plays a crucial role in mounting host immunity against neurotropic murine coronavirus in the acute phase while preventing mice from developing viral-induced severe chronic neuroinflammatory demyelination, the characteristic feature of human neurological disease multiple sclerosis (MS).

Self-loops in evolutionary graph theory: Friends or foes?

Evolutionary dynamics in spatially structured populations has been studied for a long time. More recently, the focus has been to construct structures that amplify selection by fixing beneficial mutations with higher probability than the well-mixed population and lower probability of fixation for deleterious mutations. It has been shown that for a structure to substantially amplify selection, self-loops are necessary when mutants appear predominately in nodes that change often. As a result, for low mutation rates, self-looped amplifiers attain higher steady-state average fitness in the mutation-selection balance than well-mixed populations. But what happens when the mutation rate increases such that fixation probabilities alone no longer describe the dynamics? We show that self-loops effects are detrimental outside the low mutation rate regime. In the intermediate and high mutation rate regime, amplifiers of selection attain lower steady-state average fitness than the complete graph and suppressors of selection. We also provide an estimate of the mutation rate beyond which the mutation-selection dynamics on a graph deviates from the weak mutation rate approximation. It involves computing average fixation time scaling with respect to the population sizes for several graphs.

Chemomechanics of Rechargeable Batteries: Status, Theories, and Perspectives.

Chemomechanics is an old subject, yet its importance has been revived in rechargeable batteries where the mechanical energy and damage associated with redox reactions can significantly affect both the thermodynamics and rates of key electrochemical processes. Thanks to the push for clean energy and advances in characterization capabilities, significant research efforts in the last two decades have brought about a leap forward in understanding the intricate chemomechanical interactions regulating battery performance. Going forward, it is necessary to consolidate scattered ideas in the literature into a structured framework for future efforts across multidisciplinary fields. This review sets out to distill and structure what the authors consider to be significant recent developments on the study of chemomechanics of rechargeable batteries in a concise and accessible format to the audiences of different backgrounds in electrochemistry, materials, and mechanics. Importantly, we review the significance of chemomechanics in the context of battery performance, as well as its mechanistic understanding by combining electrochemical, materials, and mechanical perspectives. We discuss the coupling between the elements of electrochemistry and mechanics, key experimental and modeling tools from the small to large scales, and design considerations. Lastly, we provide our perspective on ongoing challenges and opportunities ranging from quantifying mechanical degradation in batteries to manufacturing battery materials and developing cyclic protocols to improve the mechanical resilience.

Whole genome analysis of more than 10 000 SARS-CoV-2 virus unveils global genetic diversity and target region of NSP6.

Whole genome analysis of SARS-CoV-2 is important to identify its genetic diversity. Moreover, accurate detection of SARS-CoV-2 is required for its correct diagnosis. To address these, first we have analysed publicly available 10 664 complete or near-complete SARS-CoV-2 genomes of 73 countries globally to find mutation points in the coding regions as substitution, deletion, insertion and single nucleotide polymorphism (SNP) globally and country wise. In this regard, multiple sequence alignment is performed in the presence of reference sequence from NCBI. Once the alignment is done, a consensus sequence is build to analyse each genomic sequence to identify the unique mutation points as substitutions, deletions, insertions and SNPs globally, thereby resulting in 7209, 11700, 119 and 53 such mutation points respectively. Second, in such categories, unique mutations for individual countries are determined with respect to other 72 countries. In case of India, unique 385, 867, 1 and 11 substitutions, deletions, insertions and SNPs are present in 566 SARS-CoV-2 genomes while 458, 1343, 8 and 52 mutation points in such categories are common with other countries. In majority (above 10%) of virus population, the most frequent and common mutation points between global excluding India and India are L37F, P323L, F506L, S507G, D614G and Q57H in NSP6, RdRp, Exon, Spike and ORF3a respectively. While for India, the other most frequent mutation points are T1198K, A97V, T315N and P13L in NSP3, RdRp, Spike and ORF8 respectively. These mutations are further visualised in protein structures and phylogenetic analysis has been done to show the diversity in virus genomes. Third, a web application is provided for searching mutation points globally and country wise. Finally, we have identified the potential conserved region as target that belongs to the coding region of ORF1ab, specifically to the NSP6 gene. Subsequently, we have provided the primers and probes using that conserved region so that it can be used for detecting SARS-CoV-2. Contact:indrajit@nitttrkol.ac.inSupplementary information: Supplementary data are available at http://www.nitttrkol.ac.in/indrajit/projects/COVID-Mutation-10K.

Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis.

STING is a nodal point for cellular innate immune response to microbial infections, autoimmunity and cancer; it triggers the synthesis of the antiviral proteins, type I interferons. Many DNA viruses, including Herpes Simplex Virus 1 (HSV1), trigger STING signaling causing inhibition of virus replication. Here, we report that HSV1 evades this antiviral immune response by inducing a cellular microRNA, miR-24, which binds to the 3' untranslated region of STING mRNA and inhibits its translation. Expression of the gene encoding miR-24 is induced by the transcription factor AP1 and activated by MAP kinases in HSV1-infected cells. Introduction of exogenous miR-24 or prior activation of MAPKs, causes further enhancement of HSV1 replication in STING-expressing cells. Conversely, transfection of antimiR-24 inhibits virus replication in those cells. HSV1 infection of mice causes neuropathy and death; using two routes of infection, we demonstrated that intracranial injection of antimiR-24 alleviates both morbidity and mortality of the infected mice. Our studies reveal a new immune evasion strategy adopted by HSV1 through the regulation of STING and demonstrates that it can be exploited to enhance STING's antiviral action.

Characterisation of SARS-CoV-2 clades based on signature SNPs unveils continuous evolution.

Since the emergence of SARS-CoV-2 in Wuhan, China more than a year ago, it has spread across the world in a very short span of time. Although, different forms of vaccines are being rolled out for vaccination programs around the globe, the mutation of the virus is still a cause of concern among the research communities. Hence, it is important to study the constantly evolving virus and its strains in order to provide a much more stable form of cure. This fact motivated us to conduct this research where we have initially carried out multiple sequence alignment of 15359 and 3033 global dataset without Indian and the dataset of exclusive Indian SARS-CoV-2 genomes respectively, using MAFFT. Subsequently, phylogenetic analyses are performed using Nextstrain to identify virus clades. Consequently, the virus strains are found to be distributed among 5 major clades or clusters viz. 19A, 19B, 20A, 20B and 20C. Thereafter, mutation points as SNPs are identified in each clade. Henceforth, from each clade top 10 signature SNPs are identified based on their frequency i.e. number of occurrences in the virus genome. As a result, 50 such signature SNPs are individually identified for global dataset without Indian and dataset of exclusive Indian SARS-CoV-2 genomes respectively. Out of each 50 signature SNPs, 39 and 41 unique SNPs are identified among which 25 non-synonymous signature SNPs (out of 39) resulted in 30 amino acid changes in protein while 27 changes in amino acid are identified from 22 non-synonymous signature SNPs (out of 41). These 30 and 27 amino acid changes for the non-synonymous signature SNPs are visualised in their respective protein structure as well. Finally, in order to judge the characteristics of the identified clades, the non-synonymous signature SNPs are considered to evaluate the changes in proteins as biological functions with the sequences using PROVEAN and PolyPhen-2 while I-Mutant 2.0 is used to evaluate their structural stability. As a consequence, for global dataset without Indian sequences, G251V in ORF3a in clade 19A, F308Y and G196V in NSP4 and ORF3a in 19B are the unique amino acid changes which are responsible for defining each clade as they are all deleterious and unstable. Such changes which are common for both global dataset without Indian and dataset of exclusive Indian sequences are R203M in Nucleocapsid for 20B, T85I and Q57H in NSP2 and ORF3a respectively for 20C while for exclusive Indian sequences such unique changes are A97V in RdRp, G339S and G339C in NSP2 in 19A and Q57H in ORF3a in 20A.

Quorum sensing inhibitors as Therapeutics: Bacterial biofilm inhibition.

The overuse and inappropriate use of antibiotics to treat bacterial infections has led to the development of multiple drug resistant strains. Biofilm is a complex microorganism aggregation defined by the presence of a dynamic, sticky, and protective extracellular matrix made of polysaccharides, proteins, and nucleic acids. The infectious diseases are caused by bacteria that flourish within quorum sensing (QS) mediated biofilms. Efforts to disrupt biofilms have enabled the identification of bioactive molecules produced by prokaryotes and eukaryotes. The QS system is quenched predominantly by these molecules. The phenomenon is also termed as quorum sensing (QS). Both synthetic and natural substances have been discovered to be useful in QS. This review describes natural and synthetic quorum sensing inhibitors (QSIs) with the potential to treat bacterial infections. It includes the discussion on quorum sensing, mechanism of quorum sensing, effect of substituents on the activity. These discoveries could result in effective therapies using far lower dosages of medications, particularly antibiotics, are currently needed.

Analysis and forecasting of air quality index based on satellite data.

OBJECTIVE: The air quality index (AQI) forecasts are one of the most important aspects of improving urban public health and enabling society to remain sustainable despite the effects of air pollution. Pollution control organizations deploy ground stations to collect information about air pollutants. Establishing a ground station all-around is not feasible due to the cost involved. As an alternative, satellite-captured data can be utilized for AQI assessment. This study explores the changes in AQI during various COVID-19 lockdowns in India utilizing satellite data. Furthermore, it addresses the effectiveness of state-of-the-art deep learning and statistical approaches for forecasting short-term AQI. MATERIALS AND METHODS: Google Earth Engine (GEE) has been utilized to capture the data for the study. The satellite data has been authenticated against ground station data utilizing the beta distribution test before being incorporated into the study. The AQI forecasting has been explored using state-of-the-art statistical and deep learning approaches like VAR, Holt-Winter, and LSTM variants (stacked, bi-directional, and vanilla). RESULTS: AQI ranged from 100 to 300, from moderately polluted to very poor during the study period. The maximum reduction was recorded during the complete lockdown period in the year 2020. Short-term AQI forecasting with Holt-Winter was more accurate than other models with the lowest MAPE scores. CONCLUSIONS: Based on our findings, air pollution is clearly a threat in the studied locations, and it is important for all stakeholders to work together to reduce it. The level of air pollutants dropped substantially during the different lockdowns.

Investigation of the effectiveness of vagus nerve stimulation for pediatric drug-resistant epilepsies secondary to nonaccidental trauma.

PURPOSE: Epilepsy following non-accidental trauma (NAT) occurs in 18% of pediatric patients. About 33% of patients with epilepsy develop drug-resistant epilepsy. For these patients, vagus nerve stimulation (VNS) is a palliative treatment option. We aimed to investigate the effectiveness of VNS among pediatric NAT-related epilepsy patients compared to those with non-NAT-related epilepsy. METHODS: We performed an 11-year retrospective analysis of VNS implantations for drug-resistant epilepsy at UPMC Children's Hospital of Pittsburgh. Patients were split into two groups: NAT vs. non-NAT. The primary outcome was the attainment of ≥ 50% seizure frequency reduction at 1-year post-VNS implantation. Fisher's exact tests and Wilcoxon rank-sum tests were used to compare groups. Significance was assessed at the alpha = 0.05 level. RESULTS: This analysis included data from 370 pediatric VNS patients, of whom 9 had NAT-related epilepsy. NAT patients had a significantly younger age of epilepsy onset than non-NAT patients (0.3 years vs. 3.3 years). Otherwise, there were no statistically significant baseline differences between groups, including patient sex and quantity of antiseizure medications pre-VNS. Overall, 71% of NAT patients experienced ≥ 50% seizure frequency reduction compared to 48% of non-NAT patients (p = 0.269). CONCLUSION: VNS may allow a higher proportion of pediatric patients with NAT-related epilepsy to achieve ≥ 50% seizure frequency reduction compared to other epilepsy etiologies. While the results of this study were not statistically significant, the effect size was large. Our results underscore the need for larger, multi-center studies to validate the effectiveness of VNS for this patient population.

Twelve tips for optimising learning for postgraduate doctors in the operating theatre.

Learning in the operating theatre forms a critical part of postgraduate medical education. Postgraduate doctors present a diverse cohort of learners with a wide range of learning needs that will vary by their level of experience and curriculum requirements. With evidence of both trainee dissatisfaction with the theatre learning experience and reduced time spent in the operating theatre, which has been exacerbated by the effects of the Covid-19 pandemic, it is vital that every visit to the operating theatre is used as a learning opportunity. We have devised 12 tips aimed at both learners and surgeons to optimise learning in the operating theatre, set out into four domains: educational context, preparation, learning in theatre, feedback and reflection. These tips have been created by a process of literature review and acknowledgment of established learning theory, with further discussion amongst surgical trainees, senior surgical faculty, surgical educators and medical education faculty.

Synthesis, Biological Evaluation and in Silico Study of N-(2- and 3-Pyridinyl)benzamide Derivatives as Quorum Sensing Inhibitors against Pseudomonas aeruginosa.

The effectiveness of treating bacterial infections is seriously threatened by the emergence of bacterial resistance to chemical treatment. Growth of microbes in biofilm is one of the main causes of resistance to antimicrobial drugs. Quorum sensing (QS) inhibition, which targets the QS signalling system by obstructing cell-cell communication, was developed as an alternative treatment by creating innovative anti-biofilm drugs. Therefore, the goal of this study is to develop novel antimicrobial drugs that are effective against Pseudomonas aeruginosa by inhibiting QS and acting as anti-biofilm agents. In this study, N-(2- and 3-pyridinyl)benzamide derivatives were selected to design and syntheses. Antibiofilm activity was revealed by all the synthesized compounds and the biofilm was visibly impaired, and the OD595nm readings of solubilized biofilm cells presented a momentous difference between the treated and untreated biofilms. The best anti-QS zone was observed for compound 5d and found to be 4.96 mm. Through in silico research, the physicochemical characteristics and binding manner of these produced compounds were examined. For the purpose of understanding the stability of the protein and ligand complex, molecular dynamic simulation was also carried out. The overall findings showed that N-(2- and 3-pyridinyl)benzamide derivatives could be the key to creating effective newer anti-quorum sensing drugs that are effective against different bacteria.

Synthesis, in Silico Study and Biological Evaluation of N-(Benzothiazol/Thiazol-2-yl)benzamide Derivatives as Quorum Sensing Inhibitors against Pseudomonas aeruginosa.

The development of bacterial resistance to chemical therapy poses a severe danger to efficacy of treating bacterial infections. One of the key factors for resistance to antimicrobial medications is growth of bacteria in biofilm. Quorum sensing (QS) inhibition was created as an alternative treatment by developing novel anti-biofilm medicines. Cell-cell communication is impeded by QS inhibition, which targets QS signaling pathway. The goal of this work is to develop newer drugs that are effective against Pseudomonas aeruginosa by decreasing QS and acting as anti-biofilm agents. In this investigation, N-(benzo[d]thiazol-2-yl)benzamide/N-(thiazol-2-yl)benzamide derivatives 3a-h were designed and synthesized in good yields. Further, molecular docking analyses revealed that binding affinity values were founded -11.2 to -7.6 kcal/mol that were moderate to good. The physicochemical properties of these prepared compounds were investigated through in-silico method. Molecular dynamic simulation was also used to know better understanding of stability of the protein and ligand complex. Comparing N-(benzo[d]thiazol-2-yl)benzamide 3a to salicylic acid (4.40±0.10) that was utilised as standard for quorum sensing inhibitor, the anti-QS action was found greater for N-(benzo[d]thiazol-2-yl)benzamide 3a (4.67±0.45) than salicylic acid (4.40±0.10). Overall, research results suggested that N-(benzo[d]thiazol-2-yl)benzamide/N-(thiazol-2-yl)benzamide derivatives 3a-h may hold to develop new quorum sensing inhibitors.