Discovering targeted inhibitors for Escherichia coli efflux pump fusion proteins using computational and structure-guided approaches.

Multidrug resistance pathogens causing infections and illness remain largely untreated clinically. Efflux pumps are one of the primary processes through which bacteria develop resistance by transferring antibiotics from the interior of their cells to the outside environment. Inhibiting these pumps by developing efficient derivatives appears to be a promising strategy for restoring antibiotic potency. This investigation explores literature-reported inhibitors of E. coli efflux pump fusion proteins AcrB-AcrA and identify potential chemical derivatives of these inhibitors to overcome the limitations. Using computational and structure-guided approaches, a study was conducted with the selected inhibitors (AcrA:25-AcrB:59) obtained by data mining and their derivatives (AcrA:857-AcrB:3891) to identify their inhibitory effect on efflux pump using virtual screening, molecular docking and density functional theory (DFT) calculations. The finding indicates that Compound 2 (ZINC000072136376) has shown better binding and a significant inhibitory effect on AcrA, while Compound 3 (ZINC000072266819) has shown stronger binding and substantial inhibition effect on both non-mutant and mutated AcrB subunits. The identified derivatives could exhibit a better inhibitor and provide a potential approach for restoring the actions of resistant antibiotics.

4-Methylbenzylidene camphor induced neurobehavioral toxicity in zebrafish (Danio rerio) embryos.

4-Methylbenzylidene camphor (4-MBC) is a widely used organic UV filter in personal care products. Extensive use of 4-MBC and its frequent detection in aquatic ecosystems defile the biota with muscular and neuronal impairments. This study investigates the neurobehavioral toxicity of 4-MBC using Danio rerio as a model organism. Embryos were exposed semi-statically to 4-MBC at 5, 50, and 500 µg/L concentrations for 10-day post fertilization (dpf). Embryos exhibited a significant thigmotaxis and decreased startle touch response with altered expression of nervous system mRNA transcripts on 5 & 10 dpf. Compared to the sham-exposed group, 4-MBC treated larvae exhibited changes in the expression of shha, ngn1, mbp, elavl3, α1-tubulin, syn2a, and gap43 genes. Since ngn1 induction is mediated by shh signaling during sensory neuron specification, the elevated protein expression of NGN1 indicates 4-MBC interference in the sonic hedgehog signaling pathway. This leads to sensory neuron impairment and function such as 'sense' as evident from reduced touch response. In addition, larval brain histology with a reduced number of cells in the Purkinje layer emblazing the defunct motor coordination. Predictive toxicity study also showed a higher affinity of 4-MBC to modeled Shh protein. Thus, the findings of the present work highlighted that 4-MBC is potential to induce developmental neurotoxicity at both behavioral and molecular functional perspectives, and developing D. rerio larvae could be considered as a suitable alternate animal model to assess the neurological dysfunction of organic UV filters.

Computational Risk Assessment of Persistence, Bioaccumulation, and Toxicity of Novel Flame-Retardant Chemicals.

Novel brominated flame retardants (NBFRs) have emerged as chemicals of environmental concern, as they have been widely used as an alternative to polybrominated diphenyl ethers (PBDEs). Considering the similar structural features of NBFRs and PBDEs necessitates a comprehensive investigation to understand the physicochemical relationships of these compounds and their ability to alter biological functions. In this study, we investigated the persistent nature of NBFRs in terms of thyroid-disrupting potential by understanding the structure-stability aspects using density functional theory (DFT)-based reactivity parameters and interactions via molecular docking and molecular dynamics (MD) simulations. The results indicate that the DFT-based stability descriptor (chemical hardness) is associated with the persistent nature of NBFRs. The computed molecular interaction profile revealed prominent interactions between thyroid receptor-ß (TR-ß) and NBFRs. Stable trajectory and interactions with TR-ß were obtained with ATE, p-TBX, PBT, PBEB, and TBBPA-DBPE during 100 ns of MD simulation. The results of these studies have suggested that the presence of a higher number of halogenated atoms increases the stability vis-à-vis the persistence and endocrine disruption potential of NBFRs.

Are drains useful in eTEP ventral hernia repairs? An AWR surgical collaborative (AWRSC) retrospective study.

BACKGROUND: Drain practices in minimally invasive retromuscular ventral hernia repairs have largely been transferred over from open surgery without significant review. We wished to evaluate the role of drains in these repairs. METHODS: Using the Abdominal Wall Reconstruction Surgical Collaborative (AWRSC) registry, patients with ventral hernias who underwent enhanced-view totally extraperitoneal (eTEP) repairs between February 2016 and September 2019 were evaluated. Patients with contamination or active infection within the surgical field, those who underwent an emergent or hybrid repair, or received a concomitant procedure were excluded. Propensity score matching based on the defect size, previous hernia repair status, and the use of posterior component separation (PCS) was used to match patients with drains to patients without drains. We evaluated 180-day outcomes in terms of SSIs, SSOs, and recurrence. RESULTS: 308 patients met the inclusion criteria. After propensity score matching, 48 patients with drains and 72 without drains were included in the analysis cohort. Those with drains were older with a greater likelihood of an incisional hernia, but were broadly similar for other relevant demographic and hernia-related variables. While there was no difference in the incidence of SSOs and SSIs between the two groups, we report a higher risk of SSOs needing procedural intervention (SSOPI) and recurrence, with a lengthened hospital stay in the cohort that received surgical drains. CONCLUSION: The use of surgical drains in "clean" eTEP repairs of ventral hernias appears to be common, with a selection bias for more complex cases. Based on our analysis, we found the use of drains was associated with longer hospital stays. The use of drains did not change the likelihood of suffering an SSI or SSO. However, the incidence of SSOPIs was higher despite the use of drains, which raises questions about their protective role in these repairs.

Integrated QSAR and Adverse Outcome Pathway Analysis of Chemicals Released on 3D Printing Using Acrylonitrile Butadiene Styrene.

Additive manufacturing commonly known as 3D printing has numerous applications in several domains including material and biomedical technologies and has emerged as a tool of capabilities by providing fast, highly customized, and cost-effective solutions. However, the impact of the printing materials and chemicals present in the printing fumes has raised concerns about their adverse potential affecting humans and the environment. Thus, it is necessary to understand the properties of the chemicals emitted during additive manufacturing for developing safe and biocompatible fibers having controlled emission of fumes including its sustainable usage. Therefore, in this study, we have developed a computational predictive risk-assessment framework on the comprehensive list of chemicals released during 3D printing using the acrylonitrile butadiene styrene (ABS) filament. Our results showed that the chemicals present in the fumes of the ABS-based fiber used in additive manufacturing have the potential to lead to various toxicity end points such as inhalation toxicity, oral toxicity, carcinogenicity, hepatotoxicity, and teratogenicity. Moreover, because of their absorption, distribution in the body, metabolism, and excretion properties, most of the chemicals exhibited a high absorption level in the intestine and the potential to cross the blood-brain barrier. Furthermore, pathway analysis revealed that signaling like alpha-adrenergic receptor signaling, heterotrimeric G-protein signaling, and Alzheimer's disease-amyloid secretase pathway are significantly overrepresented given the identified target proteins of these chemicals. These findings signify the adversities associated with 3D printing fumes and the necessity for the development of biodegradable and considerably safer fibers for 3D printing technology.

FOCUS-DB: An Online Comprehensive Database on Food Additive Safety.

Processing and packaging food has greatly exaggerated the use of food additives in different types of food products. Safety assessment to determine the pharmacokinetic and toxicological properties of food additives is imperative and experimentally challenging. Several resources of food additives properties have been collated; however, information remains partial, scattered, and not readily accessible, particularly for food safety. To address the concern related to the potential health hazard of food additives, we have developed the Food-Additive-Consumption-Safety Database (FOCUS-DB). Presently, the database comprises 2885 food additives, distributed into 18 categories with 40,800 collected data points, 89,435 predicted data points, and 14,425 external links. The dynamic web interface of the FOCUS-DB resource enables a risk assessment of additives, their approval status in various regulatory authorities, physicochemical properties, acceptable daily intake, GHS signals, biological pathways, predicted pharmacokinetic parameters, and various toxicity endpoint values. FOCUS-DB supports the exploration of food additives; it is beneficial for both the regulatory authorities and industries to optimize the usage limits of the additives and formulations. This database is a promising tool that helps understand the relationship between food additives and toxicity, which could be used to develop a future food safety framework.

Extended View: Totally Extra Peritoneal (e-TEP) Approach for Ventral and Incisional Hernia-Early results from a single center.

BACKGROUND: Laparoscopy for ventral hernia repair is now an established technique with its proven benefits of less pain, early recovery, low-recurrence rate as compared to open repair. Several techniques have been described such as IPOM, MILOS, TES, EMILOS, SCOLA, e-TEP. e-TEP was originally conceptualized as an alternative approach to inguinal hernia in difficult cases (obese, previous scars) and for training surgery residents. Application of this approach for ventral hernia repair has recently been reported by few surgeons. We present our experience of e-TEP approach for ventral hernia from a tertiary care center in South India over one year duration. MATERIALS AND METHODS: Electronically maintained data of patients who underwent e-TEP for ventral hernia during a period of November 2017 to November 2018 was reviewed retrospectively. Their demographic data, intraoperative details, postoperative complications and follow up data for a period of 6 months was noted. RESULTS: 171 patients underwent e-TEP approach ventral hernia repair. Mean age was 49.34 ± 10.75 years with hypertension being most common comorbidity. Mean BMI was 29.2 ± 4.1 kg/m2. Mean defect area was 51.35 ± 45.09 cm2 and mean mesh size used was 397.56 ± 208.83 cm2. Fifty patients required TAR. Mean duration of surgery was 176.75 ± 62.42 min and blood loss was 78.7 ± 24.4 ml. Mean length of stay was 2.18 ± 1.27 days. Seven cases had paralytic ileus, 5 cases had surgical site infection, and 3 cases had recurrence at 6 months follow up. CONCLUSION: e-TEP is a minimally invasive approach which is safe, feasible and also avoids placement of mesh in peritoneal cavity. Since it is a relatively new approach it requires further studies for standardization of techniques, criteria for patient selection and to study long-term outcomes.

A comparative prospective study of short-term outcomes of extended view totally extraperitoneal (e-TEP) repair versus laparoscopic intraperitoneal on lay mesh (IPOM) plus repair for ventral hernia.

BACKGROUND: Currently, minimally invasive approach is preferred for the treatment of ventral hernias. After the introduction of extended view totally extraperitoneal (e-TEP) technique, there has been a constant debate over the choice of better approach. In this study, we compare the short-term outcomes of e-TEP and laparoscopic IPOM Plus repair for ventral hernias. METHODS: This is a comparative, prospective single-center study done at GEM Hospital and research center Coimbatore, India from July 2018 to July 2019. All patients who underwent elective ventral hernia surgery with defect size of 2 to 6 cm were included. Patient demographics, hernia characteristics, operative and perioperative findings, and postoperative complications were systematically recorded and analyzed. RESULTS: We evaluated 92 cases (n = 92), 46 in each group. Mean age, sex, BMI, location of hernia, primary and incisional hernia, and comorbidity were comparable in both the groups. Mean defect size for IPOM Plus and e-TEP was 4 cm and 3.89 cm, respectively. Operative time was significantly higher for e-TEP, while postoperative pain (VAS), analgesic requirement, and postoperative hospital stay were significantly less as compared to IPOM Plus. However, 2 cases (4.35%) of e-TEP had recurrence but none in IPOM Plus group. CONCLUSION: e-TEP is an evolving procedure and comparable to IPOM Plus in terms of postoperative pain, analgesic requirement, cost of mesh, and length of hospital stay. More randomized controlled and multicentric studies are required with longer follow-up to validate our findings.

Laparoscopic Roux-en Y duodenojejunostomy: A safe and physiological treatment for symptomatic annular pancreas in adults.

Background: Annular pancreas is a rare, congenital, rotational anomaly of pancreas, seen usually in newborns who present with features of duodenal obstruction. However, in adults, only 24% of cases are present with duodenal obstruction. Surgery remains the procedure of choice in patients in whom symptoms can be attributed to duodenal obstruction and the goal of surgery is to relieve obstruction by bypassing the annulus. Laparoscopic Roux-en Y duodenostomy (DJ) is our preferred bypass approach for this condition. Literature search revealed that very few case reports have been published about laparoscopic management of annular pancreas, especially about duodenojejunal anastomosis. We present our experience in the laparoscopic management of symptomatic annular pancreas in adults and technique of the laparoscopic Roux-en Y DJ for annular pancreas. Materials and Methods: Between 1996 and 2016, a total of six adult patients underwent laparoscopic management for symptomatic annular pancreas. The demographic, perioperative and follow-up details were documented. Results: All surgeries were successfully performed by laparoscopic approach with no conversion to open. Five cases underwent Roux-en Y DJ and one underwent gastrojejunostomy. No major perioperative events occurred. The mean length of hospital stay was 5.6 days. Five out of six patients were followed up for 24 months, and no symptom recurrence was seen. Conclusion: Laparoscopic Roux-en Y duodenojejunostomy could be used as a safe and physiological treatment for annular pancreas in adult patients and should be preferred for the treatment of duodenal obstruction due to annular pancreas.

Laparoscopic management of solid pseudo papillary neoplasm of pancreas in tertiary care center from south India.

BACKGROUND: Solid pseudo papillary neoplasm (SPN) of the pancreas which predominantly affects young women is a relatively indolent entity with favorable prognosis. Resection through minimal access approach helps to achieve better short term benefits. The aim of this study is to describe our experience in laparoscopic management of this disease. METHODS: A retrospective review of our prospectively maintained database revealed that 17 patients with SPN were managed with surgical resection between March 2009 and October 2016. The clinical data of these patients were then analyzed. RESULTS: Among the 17 cases of SPN, 14 were females and 3 were males. The mean age at presentation was 26.1 years (11-46 years). The most common presenting symptom was an abdominal pain (n = 10; 58.8%). A tumor was incidentally detected in 5 patients. The neoplasm was localized in the pancreatic head/neck in 6 patients and in the body/tail in 11. The median diameter of the tumors was 7.5 cm (2-13 cm). Five patients underwent pancreaticoduodenectomy, 10 had distal pancreatectomy, while median pancreatectomy or enucleation was performed in one each. All the patients were offered laparoscopic surgery; one distal pancreatectomy was converted to open in view of bleeding. The median length of stay was 7 days (5-28 days). The patients were followed up for a median period of 31 months (3-62 months). CONCLUSION: SPN is a rare neoplasm with low malignant potential and has an excellent prognosis. In our experience, laparoscopic surgical resection is safe and feasible, even for larger lesions.

Efficient biomass pretreatment using ionic liquids derived from lignin and hemicellulose.

Ionic liquids (ILs), solvents composed entirely of paired ions, have been used in a variety of process chemistry and renewable energy applications. Imidazolium-based ILs effectively dissolve biomass and represent a remarkable platform for biomass pretreatment. Although efficient, imidazolium cations are expensive and thus limited in their large-scale industrial deployment. To replace imidazolium-based ILs with those derived from renewable sources, we synthesized a series of tertiary amine-based ILs from aromatic aldehydes derived from lignin and hemicellulose, the major by-products of lignocellulosic biofuel production. Compositional analysis of switchgrass pretreated with ILs derived from vanillin, p-anisaldehyde, and furfural confirmed their efficacy. Enzymatic hydrolysis of pretreated switchgrass allowed for direct comparison of sugar yields and lignin removal between biomass-derived ILs and 1-ethyl-3-methylimidazolium acetate. Although the rate of cellulose hydrolysis for switchgrass pretreated with biomass-derived ILs was slightly slower than that of 1-ethyl-3-methylimidazolium acetate, 90-95% glucose and 70-75% xylose yields were obtained for these samples after 72-h incubation. Molecular modeling was used to compare IL solvent parameters with experimentally obtained compositional analysis data. Effective pretreatment of lignocellulose was further investigated by powder X-ray diffraction and glycome profiling of switchgrass cell walls. These studies showed different cellulose structural changes and differences in hemicellulose epitopes between switchgrass pretreatments with the aforementioned ILs. Our concept of deriving ILs from lignocellulosic biomass shows significant potential for the realization of a "closed-loop" process for future lignocellulosic biorefineries and has far-reaching economic impacts for other IL-based process technology currently using ILs synthesized from petroleum sources.

Management of gastric leaks after laparoscopic sleeve gastrectomy for morbid obesity: A tertiary care experience and design of a management algorithm.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed 'standalone' bariatric procedure in India. Staple line gastric leaks occur infrequently but cause significant and prolonged morbidity. The aim of this retrospective study was to analyse the management of patients with a gastric leak after LSG for morbid obesity at our institution. PATIENTS AND METHODS: From February 2008 to 2014, 650 patients with different degrees of morbid obesity underwent LSG. Among these, all those diagnosed with a gastric leak were included in the study. Patients referred to our institution with gastric leak after LSG were also included. The time of presentation, site of leak, investigations performed, treatment given and time of closure of all leaks were analysed. RESULTS: Among the 650 patients who underwent LSG, 3 (0.46%) developed a gastric leak. Two patients were referred after LSG was performed at another institution. The mean age was 45.60 ± 15.43 years. Mean body mass index (BMI) was 44.79 ± 5.35. Gastric leak was diagnosed 24 h to 7 months after surgery. One was early, two were intermediate and two were late leaks. Two were type I and three were type II gastric leaks. Endoscopic oesophageal stenting was used variably before or after re-surgery. Re-surgery was performed in all and included stapled fistula excision (re-sleeve), suture repair only or with conversion to roux-en-Y gastric bypass or fistula jujenostomy. There was no mortality. CONCLUSION: Leakage closure time may be shorter with intervention than expectant management. Sequence and choice of endoscopic oesophageal stenting and/or surgical re-intervention should be individualized according to clinical presentation.

Comparison of weight loss outcomes 1 year after sleeve gastrectomy and Roux-en-Y gastric bypass in patients aged above 50 years.

INTRODUCTION: Safe, effective weight loss with resolution of comorbidities has been convincingly demonstrated with bariatric surgery in the aged obese. They, however, lose less weight than younger individuals. It is not known if degree of weight loss is influenced by the choice of bariatric procedure. The aim of this study was to compare the degree of weight loss between laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in patients above the age of 50 years at 1 year after surgery. MATERIALS AND METHODS: A retrospective analysis was performed of all patients more than 50 years of age who underwent LSG or LRYGB between February 2012 and July 2013 with at least 1 year of follow-up. Data evaluated at 1 year included age, sex, weight, body mass index (BMI), mean operative time, percentage of weight loss and excess weight loss, resolution/remission of diabetes, morbidity and mortality. RESULTS: Of a total of 86 patients, 54 underwent LSG and 32 underwent LRYGB. The mean percentage of excess weight loss at the end of 1 year was 60.19 ± 17.45 % after LSG and 82.76 ± 34.26 % after LRYGB (P = 0.021). One patient developed a sleeve leak after LSG, and 2 developed iron deficiency anaemia after LRYGB. The remission/improvement in diabetes mellitus and biochemistry was similar. CONCLUSION: LRYGB may offer better results than LSG in terms of weight loss in patients over 50 years of age.

Review of various liver retraction techniques in single incision laparoscopic surgery for the exposure of hiatus.

BACKGROUND: The main aspect of concern for upper GI procedures has been the retraction of the liver especially large left lobes as commonly encountered in Bariatric surgery. Not doing so would compromise the view of the hiatus, hence theoretically reducing the quality of the surgery and increasing the possibility of complications. The aim of this study was to review the various liver retraction techniques in single incision surgery being done at our institute and analyze them. MATERIAL AND METHODS: A retrospective study of the various techniques and a subsequent analysis was made based on advantages and disadvantages of each method. Objectively a quantitative measure of hiatal exposure was done using a scoring system based on the grade of exposure after reviewing the surgical videos. From January 2011 to January 2013 total 104 patients underwent single incision surgery with the various liver retraction techniques with following grades of exposure -liver suspension tube technique with naso gastric tubing (2.11) and with corrugated drain (2.09) needlescopic method (1.2), Umbilical tape sling (1.95), crural stitch method (2.5). Needeloscopic method has the best grade of exposure and is the easiest to start with. The average time to create the liver retraction was 2.8 to 8.6 min.There was no procedure related morbidity or mortality. CONCLUSIONS: The mentioned liver retraction techniques are cost effective and easy to learn. We recommend using these techniques to have a good exposure of hiatus, without compromising the safety of surgery in single incision surgery.

Laparoscopic central pancreatectomy: Our technique and long-term results in 14 patients.

INTRODUCTION: Conventional pancreatic resections may be unnecessary for benign tumours or for tumours of low malignant potential located in the neck and body of pancreas. Such extensive resections can place the patient at increased risk of developing postoperative exocrine and endocrine insufficiency. Central pancreatectomy is a plausible surgical option for the management of tumours located in these locations. Laparoscopic approach seems appropriate for such small tumours situated deep in the retroperitoneum. AIMS: To assess the technical feasibility, safety and long-term results of laparoscopic central pancreatectomy in patients with benign and low malignant potential tumours involving the neck and body of pancreas. SETTINGS AND DESIGN: This study was an observational study which reports a single-centre experience with laparoscopic central pancreatectomy over a 9-year period. MATERIALS AND METHODS: 14 patients underwent laparoscopic central pancreatectomy from October 2004 to September 2013. These included patients with tumours located in the neck and body of pancreas that were radiologically benign-looking tumours of less than 3 cm in size. STATISTICAL ANALYSIS USED: The statistical analysis was done using GraphPad Prism software. RESULTS: The mean age of patients was 48.93 years. The mean operative time was 239.7 min. Mean blood loss was 153.2 ml. Mean postoperative ICU stay was 1.2 days and overall mean hospital stay was 8.07 days. There were no mortalities and no major postoperative complications. Margins were negative in all cases and with a median follow-up of 44 months, there was no recurrence. CONCLUSIONS: Laparoscopic central pancreatectomy is a feasible procedure with acceptable morbidity. In the long term, there were no recurrences and pancreatic function was well preserved.

Computational framework for identifying and evaluating mutagenic and xenoestrogenic potential of food additives.

Food additives are chemicals incorporated in food to enhance its flavor, color and prevent spoilage. Some of these are associated with substantial health hazards, including developmental disorders, increase cancer risk, and hormone disruption. Hence, this study aimed to comprehend the in-silico toxicology framework for evaluating mutagenic and xenoestrogenic potential of food additives and their association with breast cancer. A total of 2885 food additives were screened for toxicity based on Threshold of Toxicological Concern (TTC), mutagenicity endpoint prediction, and mutagenic structural alerts/toxicophores identification. Ten food additives were identified as having mutagenic potential based on toxicity screening. Furthermore, Protein-Protein Interaction (PPI) analysis identified ESR1, as a key hub gene in breast cancer. KEGG pathway analysis verified that ESR1 plays a significant role in breast cancer pathogenesis. Additionally, competitive interaction studies of the predicted potential mutagenic food additives with the estrogen receptor-α were evaluated at agonist and antagonist binding sites. Indole, Dichloromethane, Trichloroethylene, Quinoline, 6-methyl quinoline, Ethyl nitrite, and 4-methyl quinoline could act as agonists, and Paraldehyde, Azodicarbonamide, and 2-acetylfuranmay as antagonists. The systematic risk assessment framework reported in this study enables the exploration of mutagenic and xenoestrogenic potential associated with food additives for hazard identification and management.

Cytokines inhibitory mechanism of Prunus domestica L. (Plum) peptides as potential immunomodulators against systemic lupus erythematosus: an in-silico screening.

Natural bioactive peptides exhibit various chemical and structural properties to enhance the immune response against multiple inflammatory and autoimmune related disorders. The immunomodulatory function and bioactivity of seed peptides show the capability for the development of biotherapeutics that could prevent autoimmune diseases. The aim of current study is to determine the immunomodulatory function of bioactive peptides derived from the seed of plum (Prunus domestica L.) by applying various immunoinformatic approaches. A thorough analysis of forty-one peptides was performed including drug likeliness, pharmacokinetic, and bioactivity profiling studies. Further, molecular docking and molecular dynamics (MD) simulations of screened peptides were carried out with the two interleukin targets (IL-17A and IL-23) of systemic lupus erythematosus (SLE). After the systematic screening, four peptides, namely HLLP, LPLL, LPAGV, and NLPL, were found as potential inhibitors against SLE. Additionally, site-directed mutagenesis analysis was conducted to explore the role of essential amino acid residues in the binding pattern/energy change. Computational alanine screening analysis found that CYS123, CYS121 of IL-17A and ASP270, and SER249 of IL-23 as hot spot residues that could play an important role in the inhibition property of screened peptides. Overall, the methodology described in the study can be utilized for developing unique peptide inhibitors that have a preventative role against SLE. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00188-8.

Ecotoxicological impacts of landfill sites: Towards risk assessment, mitigation policies and the role of artificial intelligence.

Waste disposal in landfills remains a global concern. Despite technological developments, landfill leachate poses a hazard to ecosystems and human health since it acts as a secondary reservoir for legacy and emerging pollutants. This study provides a systematic and scientometric review of the nature and toxicity of pollutants generated by landfills and means of assessing their potential risks. Regarding human health, unregulated waste disposal and pathogens in leachate are the leading causes of diseases reported in local populations. Both in vitro and in vivo approaches have been employed in the ecotoxicological risk assessment of landfill leachate, with model organisms ranging from bacteria to birds. These studies demonstrate a wide range of toxic effects that reflect the complex composition of leachate and geographical variations in climate, resource availability and management practices. Based on bioassay (and other) evidence, categories of persistent chemicals of most concern include brominated flame retardants, per- and polyfluorinated chemicals, pharmaceuticals and alkyl phenol ethoxylates. However, the emerging and more general literature on microplastic toxicity suggests that these particles might also be problematic in leachate. Various mitigation strategies have been identified, with most focussing on improving landfill design or leachate treatment, developing alternative disposal methods and reducing waste volume through recycling or using more sustainable materials. The success of these efforts will rely on policies and practices and their enforcement, which is seen as a particular challenge in developing nations and at the international (and transboundary) level. Artificial intelligence and machine learning afford a wide range of options for evaluating and reducing the risks associated with leachates and gaseous emissions from landfills, and various approaches tested or having potential are discussed. However, addressing the limitations in data collection, model accuracy, real-time monitoring and our understanding of environmental impacts will be critical for realising this potential.

Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): an open-source disease-specific drug discovery portal.

Molecular Property Diagnostic Suite (MPDS) was conceived and developed as an open-source disease-specific web portal based on Galaxy. MPDSCOVID-19 was developed for COVID-19 as a one-stop solution for drug discovery research. Galaxy platforms enable the creation of customized workflows connecting various modules in the web server. The architecture of MPDSCOVID-19 effectively employs Galaxy v22.04 features, which are ported on CentOS 7.8 and Python 3.7. MPDSCOVID-19 provides significant updates and the addition of several new tools updated after six years. Tools developed by our group in Perl/Python and open-source tools are collated and integrated into MPDSCOVID-19 using XML scripts. Our MPDS suite aims to facilitate transparent and open innovation. This approach significantly helps bring inclusiveness in the community while promoting free access and participation in software development. Availability & Implementation: The MPDSCOVID-19 portal can be accessed at https://mpds.neist.res.in:8085/.

Galaxy for open-source computational drug discovery solutions.

INTRODUCTION: Drug discovery in academia and industry poses contrasting challenges. While academia focuses on producing new knowledge, industry is keen on product development and success in clinical trials. Galaxy is a web-based open-source computational workbench which is used to analyze large datasets and is customized to integrate analysis and visualization tools in a single framework. Depending on the methodology, one can generate customized and suitable workflows in the Galaxy platform. AREAS COVERED: Herein, the authors appraise the suitability of the Galaxy platform for developing a disease specific web portal called the Molecular Property Diagnostic Suite (MPDS). The authors include their future perspectives in the expert opinion section. EXPERT OPINION: Galaxy is ideally suited for community-based software development as the scripts, tools, and codes developed in the different programming languages can be integrated in an extremely efficient fashion. MPDS puts forth a new approach known as a disease-specific web portal which aims to implement a range of computational methods and algorithms that can be developed and shared freely across the community of computer aided drug design (CADD) scientists.