Gunshot Injury to Distal Tibial Physis and Talus: A Case Report.

Introduction: Gunshot injuries, while relatively uncommon in pediatric patients, can have lasting consequences, both physically and psychologically. Physeal injuries to the distal tibia are very common just second distal radius physis. Disruption of physis often leads to growth disturbances and deformities if not managed appropriately. This case report discusses the experience of a 9-year-old girl who sustained a gunshot injury to her left ankle injuring her distal tibial epiphysis. The report highlights the importance of long-term follow-up and rehabilitation in pediatric gunshot injury cases. Case Report: The patient is a 9-year-old girl who suffered a gunshot wound to her left ankle. The bullet's trajectory traversed her tibia and talus, miraculously avoiding any significant neurovascular injury. Immediate medical attention was sought, and she underwent surgical intervention to address the damage caused by the gunshot wound. The surgical procedure aimed to stabilize the fractured bone, remove any foreign bodies, and repair soft tissue damage. Patient has been followed up for 2 years, with remarkable recovery considering the severity of her injury. The patient has returned to her daily routine activities with slight chronic pain and some degree of the limitation of movement owing to injury and subsequent surgery. This case underscores the importance of long-term rehabilitation and follow-up care in pediatric gunshot injuries, as the effects can be far-reaching and persistent. Conclusion: Injury to physis of weight bearing bones can be challenging to the patient as well as the surgeon. Long-term follow-up with continued medical and psychological support for the patients is necessary to ensure the better prognosis and quality of life after such traumatic events.

Locally Advanced oral Squamous cell Carcinomas: Auditing and Outcome Appraisal.

Introduction: Patients with OSCC in India (oral squamous cell carcinoma) presents at a later stage with approximately 28% presenting at stage III and 64% at stage IV disease. In this retrospective study we have reviewed the treatment modalities rendered and outcomes associated for the management of locally advanced oral squamous cell carcinoma in our Institute. We evaluated the survival data and the factors effecting survival. Methods: Kaplan Meir method was used to evaluate OS and DFS rate and log rank test was used to compare the survival amongst groups. Cox regression analysis (univariate and multivariate) was used to evaluate the hazard ratio to find out the possible factors influencing risk of death and disease. Results: The median OS and DFS in our study were 32 and 24 months respectively. On a subset analysis of only T4b patients who underwent either upfront surgery or induction chemotherapy followed by surgery there was no significant difference in OS and DFS. All patients with TURD had partial response after induction chemotherapy and were subjected to surgical resection followed by adjuvant therapy. Conclusion: Extracapsular spread, bone involvement, skin infiltration, treatments, surgical margins and Lymph node size are the prime predictors of survival.Upfront surgery remains the standard of care for resectable LAOSCC. Induction chemotherapy might improve the resectability in technically unresectable OSCC. There is no difference in survival between concurrent chemoradiation, sequential chemoradiation and radical radiotherapy in the management of unresectable disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04168-4.

Rare Case of Bizarre Parosteal Osteochondromatous Proliferation of Foot.

Introduction: Nora's lesion or bizarre parosteal osteochondromatous proliferation (BPOP) is a rare, benign lesion of small bones of hands and feet in adults. It composed of differing amounts of cartilage, bone, and spindle cells and an unusual form of calcified cartilage so-called "blue bone". Case Report: A 23-year-old male presented with swelling at the lateral side of the fifth toe of his right foot, which was separated from the adjacent toe. Radiographs showed a mass arising from the proximal phalanx of the little toe, with no medullary and cortical continuity. Excisional biopsy of the mass was performed, and a histologic diagnosis of BPOP of bone (Nora's lesion) was made. Conclusion: This case presented with a cartilaginous cap around tumor which is suggestive for benign nature of this tumor with some histological variation from bizarre variant along with no recurrence which is unlikely seen in BPOP.

Modulation of quorum sensing and biofilm of Gram-negative bacterial pathogens by Cinnamomum zeylanicum L.

The development of antibiotic resistant microbial pathogens has become a global health threat and a major concern in modern medicine. The problem of antimicrobial resistance (AMR) has majorly arisen due to sub-judicious use of antibiotics in health care and livestock industry. A slow progress has been made in last two decades in discovery of new antibiotics. A new strategy in combatting AMR is to modulate or disarm the microbes for their virulence and pathogenicity. Plants are considered as promising source for new drugs against AMR pathogens. In this study, fraction-based screening of the Cinnamomum zeylanicum extract was performed followed by detailed investigation of antiquorum sensing and antibiofilm activities of the most active fraction that is, C. zeylanicum hexane fraction (CZHF). More than 75% reduction in violacein pigment of C. violaceum 12472 was overserved. CZHF successfully modulated the virulence of Pseudomonas aeruginosa PAO1 by 60.46%-78.35%. A similar effect was recorded against Serratia marcescens MTCC 97. A broad-spectrum inhibition of biofilm development was found in presence of sub-MICs of CZHF. The colonization of bacteria onto the glass coverslips was remarkably reduced apart from the reduction in exopolymeric substances. Alkaloids and terpenoids were found in CZHF. GC/MS analysis revealed the presence of cinnamaldehyde dimethyl acetal, 2-propenal, coumarin, and α-copaene as major phytocompounds. This study provides enough evidence to support potency of C. zeylanicum extract in targeting the virulence of Gram -ve pathogenic bacteria. The plant extract or active compounds can be developed as successful drugs after careful in vivo examination to target microbial infections. RESEARCH HIGHLIGHTS: Hexane fraction of Cinnamomum zeylanicum is active against QS and biofilms. The broad-spectrum antibiofilm activity was further confirmed by microscopic analysis. Dimethyl acetal, 2-propenal, coumarin, α-copaene, and so forth are major phytocompounds.

Attenuation of quorum sensing regulated virulence functions and biofilm of pathogenic bacteria by medicinal plant Artemisia annua and its phytoconstituent 1, 8-cineole.

The emergence of multidrug resistance (MDR) in bacterial pathogens is a serious public health concern. A significant therapeutic target for MDR infections is the quorum sensing-regulated bacterial pathogenicity. Determining the anti-quorum sensing abilities of certain medicinal plants against bacterial pathogens as well as the in-silico interactions of particular bioactive phytocompounds with QS and biofilm-associated proteins were the objectives of the present study. In this study, 6 medicinal plants were selected based on their ethnopharmacological usage, screened for Anti-QS activity and Artemisia annua leaf extract (AALE) demonstrated pigment inhibitory activity against Chromobacterium violaceum CV12472. Further, the methanol active fraction significantly inhibited the virulence factors (pyocyanin, pyoverdine, rhamnolipid and swarming motility) of Pseudomonas aeruginosa PAO1 and Serratia marcescens MTCC 97 at respective sub-MICs. The inhibition of biofilm was determined using a microtiter plate test and scanning electron microscopy. Biofilm formation was impaired by 70%, 72% and 74% in P. aeruginosa, C. violaceum and S. marcescens, respectively at 0.5xMIC of the extract. The phytochemical content of the extract was studied using GC-MS and 1, 8-cineole was identified as major bioactive compound. Furthermore, 1, 8-cineole was docked with quorum sensing (QS) proteins (LasI, LasR, CviR, and rhlR) and biofilm proteins (PilY1 and PilT). In silico docking and dynamics simulations studies suggested interactions with QS-receptors CviR', LasI, LasR, and biofilm proteins PilY1, PilT for anti-QS activity. Further, 1, 8-cineole demonstrated 66% and 51% reduction in violacein production and biofilm formation, respectively to validate the findings of computational analysis. Findings of the present investigation suggests that 1, 8-cineole plays a crucial role in the QS and biofilm inhibitory activity demonstrated by Artemisia annua extract. RESEARCH HIGHLIGHTS: Artemisia annua leaf extract (AALE) methanol fraction demonstrated broad-spectrum QS and biofilm inhibition Scanning electron microscopy (SEM) confirmed biofilm inhibition Molecular docking and simulation studies suggested positive interactions of 1,8-cineol with QS-receptors and biofilm proteins.

Transcriptomic characterization of Trichoderma harzianum T34 primed tomato plants: assessment of biocontrol agent induced host specific gene expression and plant growth promotion.

In this study, we investigated the intricate interplay between Trichoderma and the tomato genome, focusing on the transcriptional and metabolic changes triggered during the late colonization event. Microarray probe set (GSE76332) was utilized to analyze the gene expression profiles changes of the un-inoculated control (tomato) and Trichoderma-tomato interactions for identification of the differentially expressed significant genes. Based on principal component analysis and R-based correlation, we observed a positive correlation between the two cross-comaparable groups, corroborating the existence of transcriptional responses in the host triggered by Trichoderma priming. The statistically significant genes based on different p-value cut-off scores [(padj-values or q-value); padj-value < 0.05], [(pcal-values); pcal-value < 0.05; pcal < 0.01; pcal < 0.001)] were cross compared. Through cross-comparison, we identified 156 common genes that were consistently significant across all probability thresholds, and showing a strong positive corelation between p-value and q-value in the selected probe sets. We reported TD2, CPT1, pectin synthase, EXT-3 (extensin-3), Lox C, and pyruvate kinase (PK), which exhibited upregulated expression, and Glb1 and nitrate reductase (nii), which demonstrated downregulated expression during Trichoderma-tomato interaction. In addition, microbial priming with Trichoderma resulted into differential expression of transcription factors related to systemic defense and flowering including MYB13, MYB78, ERF2, ERF3, ERF5, ERF-1B, NAC, MADS box, ZF3, ZAT10, A20/AN1, polyol sugar transporter like zinc finger proteins, and a novel plant defensin protein. The potential bottleneck and hub genes involved in this dynamic response were also identified. The protein-protein interaction (PPI) network analysis based on 25 topmost DEGS (pcal-value < 0.05) and the Weighted Correlation Gene Network Analysis (WGCNA) of the 1786 significant DEGs (pcal-value < 0.05) we reported the hits associated with carbohydrate metabolism, secondary metabolite biosynthesis, and the nitrogen metabolism. We conclude that the Trichoderma-induced microbial priming re-programmed the host genome for transcriptional response during the late colonization event and were characterized by metabolic shifting and biochemical changes specific to plant growth and development. The work also highlights the relevance of statistical parameters in understanding the gene regulatory dynamics and complex regulatory networks based on differential expression, co-expression, and protein interaction networks orchestrating the host responses to beneficial microbial interactions.

Electrochemical synthesis and antimicrobial evaluation of some N-phenyl α-amino acids.

In the present report, the authors describe a synthetic route for the generation of N-phenyl amino acid derivatives using CO2via a C-C coupling reaction in an undivided cell containing a combination of Mg-Pt electrodes. The reactions were completed in a short time without the formation of any other side product. The final products were purified via a simple recrystallization procedure. The structures of the newly prepared compounds were established using advanced spectroscopic techniques including 1H, 13C NMR, IR, and ESI-MS. All the prepared derivatives show good-to-excellent activity when tested against bacterial and fungal strains. Interestingly, it was observed that the presence of polar groups (capable of forming H-bonds) such as -OH (4d) and -NO2 (4e) at the para position of the phenyl ring show activity equivalent to the standard drugs.

Multi-targeting of virulence factors of P. aeruginosa by ß-lactam antibiotics to combat antimicrobial resistance.

Antimicrobial resistance poses a significant challenge to public health, especially in developing countries, due to a substantial rise in bacterial resistance. This situation has become so concerning that we are now at risk of losing the effectiveness of antibiotics altogether. Recent research has firmly established that bacteria engage in a process called quorum sensing (QS). QS regulates various functions, including nutrient scavenging, immune response suppression, increased virulence, biofilm formation and mobility. Pseudomonas aeruginosa, an opportunistic bacterial pathogen, plays a significant role in various medical conditions such as chronic wounds, corneal infections, burn wounds and cystic fibrosis. While antibiotics are effective in killing bacteria, only a few antibiotics, particularly those from the ß-lactam group, have been studied for their impact on the quorum sensing of P. aeruginosa. Given the lack of concentrated efforts in this area, we have investigated the role of ß-lactam antibiotics on various potential targets of P. aeruginosa. Based on their toxicological profiles and the average binding energy obtained through molecular docking, azlocillin and moxalactam have emerged as lead antibiotics. The binding energy for the docking of azlocillin and moxalactam with LasA was determined to be -8.2 and -8.6 kcal/mol, respectively. Molecular simulation analysis has confirmed the stable interaction of both these ligands with all three target proteins (LasI, LasA and PqsR) under physiological conditions. The results of this research underscore the effectiveness of azlocillin and moxalactam. These two antibiotics may be repurposed to target the quorum sensing of P. aeruginosa.Communicated by Ramaswamy H. Sarma.

Single-cell lineage capture across genomic modalities with CellTag-multi reveals fate-specific gene regulatory changes.

Complex gene regulatory mechanisms underlie differentiation and reprogramming. Contemporary single-cell lineage-tracing (scLT) methods use expressed, heritable DNA barcodes to combine cell lineage readout with single-cell transcriptomics. However, reliance on transcriptional profiling limits adaptation to other single-cell assays. With CellTag-multi, we present an approach that enables direct capture of heritable random barcodes expressed as polyadenylated transcripts, in both single-cell RNA sequencing and single-cell Assay for Transposase Accessible Chromatin using sequencing assays, allowing for independent clonal tracking of transcriptional and epigenomic cell states. We validate CellTag-multi to characterize progenitor cell lineage priming during mouse hematopoiesis. Additionally, in direct reprogramming of fibroblasts to endoderm progenitors, we identify core regulatory programs underlying on-target and off-target fates. Furthermore, we reveal the transcription factor Zfp281 as a regulator of reprogramming outcome, biasing cells toward an off-target mesenchymal fate. Our results establish CellTag-multi as a lineage-tracing method compatible with multiple single-cell modalities and demonstrate its utility in revealing fate-specifying gene regulatory changes across diverse paradigms of differentiation and reprogramming.

Umbelliferone modulates the quorum sensing and biofilm of Gram - ve bacteria: in vitro and in silico investigations.

In last two decades, the world has seen an exponential increase in the antimicrobial resistance (AMR), making the issue a serious threat to human health. The mortality caused by AMR is one of the leading causes of human death worldwide. Till the end of the twentieth century, a tremendous success in the discovery of new antibiotics was seen, but in last two decades, there is negligible progress in this direction. The increase in AMR combined with slow progress of antibiotic drug discovery has created an urgent demand to search for newer methods of intervention to combat infectious diseases. One of such approach is to look for biofilm and quorum sensing (QS) inhibitors. Plants are excellent source of wide class compounds that can be harnessed to look for the compounds with such properties. This study proves a broad-spectrum biofilm and QS inhibitory potential of umbelliferone. More than 85% reduction in violacein production Chromobacterium violaceum 12472 was found. All tested virulent traits of Pseudomonas aeruginosa PAO1 and Serratia marcescens MTCC 97 were remarkably inhibited that ranged from 56.62% to 86.24%. Umbelliferone also successfully prevented the biofilm of test bacteria at least by 67.68%. Umbelliferone interacted at the active site of many proteins of QS circuit, which led to the mitigation of virulent traits. The stable nature of complexes of umbelliferone with proteins further strengthens in vitro results. After examining the toxicological profile and other drug-like properties, umbelliferone could be potentially developed as new drug to target the infections caused by Gram - ve bacteria.Communicated by Ramaswamy H. Sarma.

Gene regulatory network reconfiguration in direct lineage reprogramming.

In direct lineage conversion, transcription factor (TF) overexpression reconfigures gene regulatory networks (GRNs) to reprogram cell identity. We previously developed CellOracle, a computational method to infer GRNs from single-cell transcriptome and epigenome data. Using inferred GRNs, CellOracle simulates gene expression changes in response to TF perturbation, enabling in silico interrogation of network reconfiguration. Here, we combine CellOracle analysis with lineage tracing of fibroblast to induced endoderm progenitor (iEP) conversion, a prototypical direct reprogramming paradigm. By linking early network state to reprogramming outcome, we reveal distinct network configurations underlying successful and failed fate conversion. Via in silico simulation of TF perturbation, we identify new factors to coax cells into successfully converting their identity, uncovering a central role for the AP-1 subunit Fos with the Hippo signaling effector, Yap1. Together, these results demonstrate the efficacy of CellOracle to infer and interpret cell-type-specific GRN configurations, providing new mechanistic insights into lineage reprogramming.

Personality traits and behaviour biases: the moderating role of risk-tolerance.

The current research tries to contribute to the prospect theory by examining how personality factors affect behaviour biases. Moreover, the study tries to inspect how risk-tolerance behaviour moderates the relationship between personality traits and behavior biases. The research considered a cross-sectional research design to collect responses from 847 individual investors through a questionnaire. The study considered a convenience sampling technique. Further to examine the hypotheses, the study used SEM and PROCESS macro v3.0 for SPSS. The findings of the study suggest that conscientiousness and extroversion traits significantly influence behaviour biases. The findings also explain that neuroticism was associated with herding, disposition, and anchoring bias. The findings confirmed the moderating effect of risk-tolerance on the association between personality traits and behaviour biases. The findings contribute to the existing literature of behaviour finance by focusing on the prospect theory as well as some practical implications for investors and financial advisors. The study suggests to the individual investors with different traits how they can overcome these biases while investing. The study suggests that financial advisors should educate their clients and also establish a lock-gain point and stop-loss point to reduce the effect of such biases. The study also suggests that investment advisors should provide information more efficiently so that investors' portfolios could be amassed into a well-diversified investment and tries to set up efficient approaches associated with investment quality and give swapping options as per their risk-tolerance behavior. The research contributes to behaviour finance literature by signifying the moderation effect of risk tolerance on the association amid personality factors and behavioural biases and how it reduces the influence of biases while taking investment decisions among Indian investors. To the best of our knowledge, this is the first comprehensive study that examines the moderation effect of risk-tolerance among the relationship between personality traits and behaviour biases. Furthermore, it demonstrates that an individual's risk-tolerance enhances their involvement in the decision-making process, allowing them to make the best financial option possible.

Examining ecotourism intention: The role of tourists' traits and environmental concerns.

The study offers new insights by examining the influence of personality traits (extraversion and neuroticism) on tourists' intentions to visit ecotourism sites using the lens of the theory of planned behavior. It also investigates whether environmental knowledge moderates the effect of extraversion, neuroticism, and environmental concern on tourists' ecotourism intentions. We applied structural equation modeling on 350 responses collected through the Amazon M-Turk platform. Results highlight that extroverts are more likely to express ecotourism intentions than neurotic tourists. However, it was also noted that neurotic tourists' intention to visit ecotourism sites could be influenced if their environmental concerns were emphasized. The study offers important new insights to managers, policy-makers, and practitioners about the roles of personality traits, environmental knowledge, and environmental concern vis-a-vis their relative significance in shaping tourists' decision-making and choices for ecotourism sites. As a result, managers/practitioners need to devise specific communication strategies to enhance awareness and a sense of responsibility among neurotic tourists.

Phobic COVID-19 Disorder Scale: Development, Dimensionality, and Item-Structure Test.

Over the century, the world has witnessed a number of pandemics-such as plague, Spanish flu, smallpox, and tuberculosis. Such pandemics have not only resulted in a great loss to human lives but have also affected the economy of many countries. COVID-19, declared as global pandemic by the World Health Organization (WHO), is the latest in this series which has hit the world since the last quarter of 2019. Although a number of scales exist to assess fear and distress of individuals related to COVID-19, it is well articulated in the extant literature that sometimes the proposed scales are context specific and lack applicability in multi-cultural environment as also the factors' structure of the scale are fit from the context of audience from certain geographical regions. Thus, a need was felt to evaluate the FCV-19S and propose and statistically validate a new COVID-19-based scale called Phobic COVID-19 Disorder scale (Phobic-19 scale). A structured e-questionnaire in English was used to collect the data from the respondents. A 12-item, three-dimensional (fear, anxiety, and distress) scale was developed to capture the emotions of general populations towards COVID-19. The study analyzes the dimensionality and item structure of the scale through exploratory factor analysis and further validated with the help of confirmatory factor analysis. The results show that the Phobic-19 scale has a strong internal consistency along with better psychometric characteristics. Mass replication and a large number of empirical research using the Phobic-19 scale would instill confidence amongst scholars and practitioners in the results. The findings also highlight that the results would help to advance our understanding by providing critical information related to COVID-19 and ensure that the scale provides accurate and usable data.

Understanding cornea epithelial stem cells and stem cell deficiency: Lessons learned using vertebrate model systems.

Animal models have contributed greatly to our understanding of human diseases. Here, we focus on cornea epithelial stem cell (CESC) deficiency (commonly called limbal stem cell deficiency, LSCD). Corneal development, homeostasis and wound healing are supported by specific stem cells, that include the CESCs. Damage to or loss of these cells results in blindness and other debilitating ocular conditions. Here we describe the contributions from several vertebrate models toward understanding CESCs and LSCD treatments. These include both mammalian models, as well as two aquatic models, Zebrafish and the amphibian, Xenopus. Pioneering developments have been made using stem cell transplants to restore normal vision in patients with LSCD, but questions still remain about the basic biology of CESCs, including their precise cell lineages and behavior in the cornea. We describe various cell lineage tracing studies to follow their patterns of division, and the fates of their progeny during development, homeostasis, and wound healing. In addition, we present some preliminary results using the Xenopus model system. Ultimately, a more thorough understanding of these cornea cells will advance our knowledge of stem cell biology and lead to better cornea disease therapeutics.

Transcriptional Control of the Oxidative Stress Response and Implications of Using Plant Derived Molecules for Therapeutic Interventions in Cancer.

The oxidative stress response is critical for malignant cells. It plays a dual role by helping cancer cells survive and proliferate but also causing apoptosis and apoptosis-- like cell death. The oxidative stress response is characterized by tight regulation of gene expression by a series of transcription factors (OSRts; oxidative stress response transcription factors). In this communication, we review the role of OSRts, notably NRF2 and p53 as well as other transcription factors that modulate the response. We discuss how hierarchal the oxidative stress response is and controls 'live or die' signals. This is followed by a discussion on how plant-derived molecules, including polyphenols, which are described both as prooxidants and antioxidants within the cancer cells, have been reported to affect the activities of OSRts. Deriving an example from preliminary data from our group, we discuss how plant-derived molecules might modulate the oxidative stress response by causing structural perturbations in the proteinaceous transcription factors, notably Nrf2 and p53. We look at this information in the light of understanding how plant derived molecules may be used as lead compounds to develop modulators of the oxidative stress response.

Accuracy of noncycloplegic photorefraction using Spot photoscreener in detecting amblyopia risk factors in preschool children in an Indian eye clinic.

Purpose: To evaluate the accuracy of Spot photoscreener (PS) as a noncycloplegic photorefractor in detecting amblyopia risk factors (ARFs) in preschool children in an Indian eye clinic setting. Also, to derive appropriate cutoff values for screening to obtain maximum sensitivity and specificity of the device in detecting ARF. Methods: This was a cross-sectional study conducted in the outpatient pediatric eye clinic at a tertiary eye care institute. A Spot PS was used to screen all the children between the ages of 6 months and 5 years that presented to the eye clinic from August 2018 to October 2018. This screening was followed by a complete eye examination, including cycloplegic refraction by a masked examiner. The 2013 American Association for Pediatric Ophthalmology and Strabismus (AAPOS) guidelines were considered the standard cutoff values for clinically significant refractive error in children younger than 5 years of age. Results: The study comprised of 219 children. The Spot PS diagnosed 135 (61.64%) children with ARF as compared with 124 (56.62%) children detected by clinic examination. For ARF detection, the Spot photoscreeneer had 85.48% sensitivity, 69.47% specificity, 78.52% positive predictive value and 78.57% negative predictive value. The sensitivity for detection of strabismus and hypermetropia was very low (42% and 36%, respectively). The 95% limits of agreement ranged from -5.48 to +5.59 diopters (D) with a bias of 0.06 D for spherical equivalent between noncycloplegic photorefraction and cycloplegic refraction. Conclusion: The Spot PS may be used as a screening tool to detect ARF in children younger than 5 years of age keeping its limitations in consideration. However, the performance can be improved by modifying the cutoff values for the referral.

Impact of Citral and Phloretin, Alone and in Combination, on Major Virulence Traits of Streptococcus pyogenes.

Streptococcus pyogenes is well documented as a multi-virulent and exclusively human pathogen. The LuxS-based signaling in these bacteria has a crucial role in causing several infections through pathways that are pathogenic. This study evaluated the individual and synergistic effects of citral and phloretin against S. pyogenes in relation to major virulence traits. The in vitro synergy of citral and phloretin was evaluated by the checkerboard method. The fractional inhibitory concentration (FIC) values were calculated to determine the interactions between the inhibitors. The bacteria's virulence properties were tested in the presence of the molecules, individually as well as in combination. Molecules' cytotoxicity was tested using human tonsil epithelial cells. The synergistic effects of the molecules on the expression of biofilm and quorum sensing genes were tested using quantitative real-time polymerase chain reaction (qRT-PCR). The molecules were also tested for their impact on LuxS protein by molecular docking, modeling, and free-energy calculations. When the two molecules were assessed in combination (synergistic effect, FIC Index of 0.5), a stronger growth inhibitory activity was exhibited than the individual molecules. The cell surface hydrophobicity, as well as genes involved in quorum sensing and biofilm formation, showed greater suppression when the molecules were tested in combination. The in silico findings also suggest the inhibitory potential of the two molecules against LuxS protein. The binding orientation and the binding affinity of citral and phloretin well support the notion that there is a synergistic effect of citral and phloretin. The data reveal the combination of citral and phloretin as a potent antibacterial agent to combat the virulence of S. pyogenes.

Understanding cornea homeostasis and wound healing using a novel model of stem cell deficiency in Xenopus.

Limbal Stem Cell Deficiency (LSCD) is a painful and debilitating disease that results from damage or loss of the Corneal Epithelial Stem Cells (CESCs). Therapies have been developed to treat LSCD by utilizing epithelial stem cell transplants. However, effective repair and recovery depends on many factors, such as the source and concentration of donor stem cells, and the proper conditions to support these transplanted cells. We do not yet fully understand how CESCs heal wounds or how transplanted CESCs are able to restore transparency in LSCD patients. A major hurdle has been the lack of vertebrate models to study CESCs. Here we utilized a short treatment with Psoralen AMT (a DNA cross-linker), immediately followed by UV treatment (PUV treatment), to establish a novel frog model that recapitulates the characteristics of cornea stem cell deficiency, such as pigment cell invasion from the periphery, corneal opacity, and neovascularization. These PUV treated whole corneas do not regain transparency. Moreover, PUV treatment leads to appearance of the Tcf7l2 labeled subset of apical skin cells in the cornea region. PUV treatment also results in increased cell death, immediately following treatment, with pyknosis as a primary mechanism. Furthermore, we show that PUV treatment causes depletion of p63 expressing basal epithelial cells, and can stimulate mitosis in the remaining cells in the cornea region. To study the response of CESCs, we created localized PUV damage by focusing the UV radiation on one half of the cornea. These cases initially develop localized stem cell deficiency characteristics on the treated side. The localized PUV treatment is also capable of stimulating some mitosis in the untreated (control) half of those corneas. Unlike the whole treated corneas, the treated half is ultimately able to recover and corneal transparency is restored. Our study provides insight into the response of cornea cells following stem cell depletion, and establishes Xenopus as a suitable model for studying CESCs, stem cell deficiency, and other cornea diseases. This model will also be valuable for understanding the nature of transplanted CESCs, which will lead to progress in the development of therapeutics for LSCD.

Ascophyllum nodosum-Based Biostimulants: Sustainable Applications in Agriculture for the Stimulation of Plant Growth, Stress Tolerance, and Disease Management.

Abiotic and biotic stresses limit the growth and productivity of plants. In the current global scenario, in order to meet the requirements of the ever-increasing world population, chemical pesticides and synthetic fertilizers are used to boost agricultural production. These harmful chemicals pose a serious threat to the health of humans, animals, plants, and the entire biosphere. To minimize the agricultural chemical footprint, extracts of Ascophyllum nodosum (ANE) have been explored for their ability to improve plant growth and agricultural productivity. The scientific literature reviewed in this article attempts to explain how certain bioactive compounds present in extracts aid to improve plant tolerances to abiotic and/or biotic stresses, plant growth promotion, and their effects on root/microbe interactions. These reports have highlighted the use of various seaweed extracts in improving nutrient use efficiency in treated plants. These studies include investigations of physiological, biochemical, and molecular mechanisms as evidenced using model plants. However, the various modes of action of A. nodosum extracts have not been previously reviewed. The information presented in this review depicts the multiple, beneficial effects of A. nodosum-based biostimulant extracts on plant growth and their defense responses and suggests new opportunities for further applications for marked benefits in production and quality in the agriculture and horticultural sectors.