General Installation of (4H)-Imidazolone cis-Amide Bioisosteres Along the Peptide Backbone.

Imidazolones represent an important class of heterocycles present in a wide range of pharmaceuticals, metabolites, and bioactive natural products and serve as the active chromophore in green fluorescent protein. Recently, imidazolones have received attention for their ability to act as a nonaromatic amide bond bioisotere which improves pharmacological properties. Herein, we present a tandem amidine installation and cyclization with an adjacent ester to yield (4H)-imidazolone products. Using amino acid building blocks, we can access the first examples of α-chiral imidazolones that have been previously inaccessible. Additionally, our method is amenable to on-resin installation which can be seamlessly integrated into existing solid-phase peptide synthesis protocols. Finally, we show that peptide imidazolones are potent cis-amide bond surrogates that preorganize linear peptides for head-to-tail macrocyclization. This work represents the first general approach to the backbone and side-chain insertion of imidazolone bioisosteres at various positions in linear and cyclic peptides.

Responses of plankton community to threshold metal concentrations of cadmium and lead in a mesocosm experiment at Bay of Bengal.

Metals are essential at trace levels to aquatic organisms for the function of many physiological and biological processes. But their elevated levels are toxic to the ecosystem and even brings about shifts in the plankton population. Threshold limits such as Predicted No Effect Concentration (PNEC - 0.6 µg/l of Cd; 2.7 µg/l of Pb), Criterion Continuous Concentration (CCC - 3.0 µg/l of Cd; 4.5 µg/l of Pb) and Criterion Maximum Concentration (CMC - 23 µg/l of Cd; 130 µg/l of Pb) prescribed for Indian coastal waters were used for the study. Short-term mesocosm experiments (96 h) were conducted in coastal waters of Visakhapatnam to evaluate responses of the planktonic community on exposure to threshold concentrations of cadmium and lead for the first time. Four individual experimental bags of 2500 L capacity (Control, PNEC, CCC & CMC) were used for the deployment and ambient water samples were analysed simultaneously to evaluate the impacts of the threshold levels in the natural waters. Chaetoceros sp. were dominant group in the control system whereas, Prorocentrum sp. Ceratium sp. Tintinopsis sp. Chaetoceros sp. and Skeletonema sp. were major groups in the test bags. Throughout the experiment the phytoplankton community did not show any significant differences with increased nutrients and plankton biomass (Chl-a <8.64 mg/m3). Positive response of plankton community was observed in the experimental bags. High abundance of diatoms were observed in PNEC, CCC & CMC bags at 48 h and the abundance decreased with shift in the species at 72-96 h. The catalase activity in phytoplankton (5.99 nmol/min/ml) and the zooplankton (4.77 nmol/min/ml) showed induction after exposure to PNEC. The present mesocosm study is confirmed that short-term exposure to threshold metal concentration did not affects the phytoplankton community structure in PNEC, but CCC and CMC affects the community structure beyond 24 h. The insights from this study will serve as a baseline information and help develop environmental management tools. We believe that long-term mesocosm experiments would unravel metal detoxification mechanisms at the cellular level and metal transfer rate at higher trophic levels in real-world environment.

Declining Trend in Antimicrobial Sensitivity in Respiratory Tract Bacterial Pathogens against Commonly Used Drugs at a Tertiary Care Hospital.

OBJECTIVES: Antimicrobial resistance (AMR) is a major health issue. To determine trends in bacterial organisms in respiratory tract infections (RTIs) and their antibiotic sensitivity at a tertiary care center in India, we performed this study. METHODS: Successive samples received from January 2017 to December 2021 from the respiratory tract (sputum, endotracheal secretion, and bronchoalveolar lavage) from intensive care units and medical inpatients were processed for bacterial growth. The identification of isolates and antibiotic sensitivity patterns was performed using an automated VITEK-2 system. Descriptive statistics are reported. RESULTS: We received 7,204 respiratory samples. Significant bacterial growth was in 3,000 (41.6%), and 2,992 (41.5%) were gram-negative. Klebsiella pneumoniae was the most prevalent, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Enterobacter aerogenes. Increasing secular trends were observed for Klebsiella and Pseudomonas and declining trends for Acinetobacter and Escherichia (p < 0.05). Antimicrobial sensitivity patterns showed that Klebsiella, Pseudomonas, Acinetobacter, E. coli, and Enterobacter had a high sensitivity with colistin and polymyxin (99-100%). Moderate sensitivity was observed with carbapenems (Acinetobacter: 47.5%, Enterobacter: 62.0%, Escherichia: 76.5%, Klebsiella: 72.3%, Pseudomonas: 66.7%) and tigecycline (Acinetobacter: 50.4%, Enterobacter: 68.0%, Escherichia: 81.1%, Klebsiella: 66.6%, Pseudomonas: 0%). Aminoglycosides had <50% sensitivity for various organisms, and <25% sensitivity was observed with third-generation cephalosporins and quinolones. Trend analysis showed persistent sensitivity of various pathogenic bacteria to colistin and polymyxin and declining pharmacological sensitivity in Acinetobacter (carbapenems and tigecycline), Escherichia (carbapenems, quinolones, and tigecycline), Klebsiella (carbapenems, quinolones, aminoglycosides, and tigecycline), and Pseudomonas (carbapenems and aminoglycosides) species (p < 0.05). CONCLUSION: Common respiratory tract gram-negative bacterial pathogens at a tertiary care hospital are K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli. All these bacteria demonstrate high sensitivity only with colistin and polymyxin. Significant AMR is observed to carbapenems, tigecycline, aminoglycosides, and third-generation cephalosporins. Secular trends show declining antimicrobial sensitivity among various bacterial pathogens.

Design, synthesis, and applications of ring-functionalized histidines in peptide-based medicinal chemistry and drug discovery.

Modified and synthetic α-amino acids are known to show diverse applications. Histidine, which possesses numerous applications when subjected to synthetic modifications, is one such amino acid. The utility of modified histidines varies widely from remarkable biological activities to catalysis, and from nanotechnology to polymer chemistry. This renders histidine residue an important place in scientific research. Histidine is a well-studied scaffold and constitutes the active site of various enzymes catalyzing important reactions in the biological systems. A rational modification in histidine structure with a distinctly developed protocol extensively changes its physical and chemical properties. The utilization of modified histidines in search of potent, target selective and proteostable scaffolds is vital in the development of bioactive peptides with enhanced drug-likeliness. This review is a compilation and analysis of reported side-chain ring modifications at histidine followed by applications of ring-modified histidines in the synthesis of various categories of bioactive peptides and peptidomimetics.

Immobilized phytases: an overview of different strategies, support material, and their applications in improving food and feed nutrition.

Phytases are the most widely used food and feed enzymes, which aid in nutritional improvement by reducing anti-nutritional factor. Despite the benefits, enzymes usage in the industry is restricted by several factors such as their short life-span and poor reusability, which result in high costs for large-scale utilization at commercial scale. Furthermore, under pelleting conditions such as high temperatures, pH, and other factors, the enzyme becomes inactive due to lesser stability. Immobilization of phytases has been suggested as a way to overcome these limitations with improved performance. Matrices used to immobilize phytases include inorganic (Hydroxypatite, zeolite, and silica), organic (Polyacrylamide, epoxy resins, alginate, chitosan, and starch agar), soluble matrix (Polyvinyl alcohol), and nanomaterials including nanoparticles, nanofibers, nanotubes. Several surface analysis methods, including thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), and FTIR analysis, have been used to characterize immobilized phytase. Immobilized phytases have been used in a broad range of biotechnological applications such as animal feed, biodegradation of food phytates, preparations of myo-inositol phosphates, and sulfoxidation by vanadate-substituted peroxidase. This article provides information on different matrices used for phytase immobilization from the last two decades, including the process of immobilization and support material, surface analysis techniques, and multifarious biotechnological applications of the immobilized phytases.

Culturing the unculturables: strategies, challenges, and opportunities for gut microbiome study.

Metagenome sequencing techniques revolutionized the field of gut microbiome study. However, it is equipped with experimental and computational biases, which affect the downstream analysis results. Also, live microbial strains are needed for a better understanding of host-microbial crosstalks and for designing next-generation treatment therapies based on probiotic strains and postbiotic molecules. Conventional culturing methodologies are insufficient to get the dark gut matter on the plate; therefore, there is an urgent need to propose novel culturing methods that can fill the limitations of metagenomics. The current work aims to provide a consolidated evaluation of the available methods for host-microbe interaction with an emphasis on in vitro culturing of gut microbes using organoids, gut on a chip, and gut bioreactor. Further, the knowledge of microbial crosstalk in the gut helps us to identify core microbiota, and key metabolites that will aid in designing culturing media and co-culturing systems for gut microbiome study. After the deeper mining of the current culturing methods, we recommend that 3D-printed intestinal cells in a multistage continuous flow reactor equipped with an extended organoid system might be a good practical choice for gut microbiota-based studies.

Functional analysis of metalloenzymes from human gut microbiota and their role in ulcerative colitis.

AIM: Metalloenzymes produced by gut microbiota play an essential role in various physiological processes, and maintains homeostasis of gastrointestinal tract. Our study includes functional analysis of microbial metalloenzymes using metagenomics and metatranscriptomics data from Inflammatory Bowel Disease Multiomics Database. METHODS AND RESULTS: The distance matrix calculated by using metalloenzymes data produced significant results for bacterial taxonomy, with higher variance compared to HMP analysis in both Western and Indian population. Differential gene expression analysis revealed altered expression of ulcerative colitis (UC)-associated enzymes, increased folds changes in Prevotella and Megamonas transcripts; whereas, low transcripts of Alistipes genera. Further, docking and simulation studies performed on screened UC-associated enzymes revealed changes in catalytic efficiency and ligand interacting residues. CONCLUSION: The ß-diversity using microbes containing metalloenzymes suggests considering small group of specific genes or enzymes for understanding the diversity between UC and healthy individuals. The docking and differential gene expression analysis collectively indicate the probable role of metalloenzymes and few UC-associated enzymes in the severity of UC.

Synthetic amino acids-derived peptides target Cryptococcus neoformans by inducing cell membrane disruption.

We investigated synthetic amino acid-based approach to design short peptide-based antibiotics. Tautomerically restricted, amphiphilic 1-aryl-l-histidines along with hydrophobic tryptophan were utilized to synthesize the designed peptides. l-Trp-l-His(1-biphenyl)-NHBzl (12e, IC50 = 1.91 µg/mL; MIC = 3.46 µg/mL) and l-His[1-(4-n-butylphenyl)]-l-Trp-l-His[1-(4-n-butylphenyl)]-NHBzl (16d, IC50 = 1.36 µg/mL; MIC = 2.46 µg/mL) produced potency against Cryptococcus neoformans. Peptides with moderate antibacterial activities (IC50s = 4.40-8.80 µg/mL) were also identified. The mechanism of action and cellular changes revealed that membrane disruption due to interactions of the positively charged peptides with the negatively charged membrane of the cryptococcal cells result in permeabilization, leading to pore formation. The internal localization of the peptides instigated the interactions with DNA causing fragmentation of the genetic material, which together with membrane disruption led to cell death. Flow cytometric analysis points to cells death by apoptotic pathway. Time kill kinetics and synergistic study confirmed the fungicidal nature and synergism with amphotericin B.

Enhanced production and immobilization of phytase from Aspergillus oryzae: a safe and ideal food supplement for improving nutrition.

Microbial phytases are potentially excellent candidates for eliminating anti-nutrient i.e. phytic acid, due to hydrolysis of phospho-monoester linkages present in the phytic acid. An average 2.29-fold increase in phytase production was obtained after statistical optimization in solid-state fermentation. Aspergillus oryzae SBS50 phytase was immobilized on a Ca-alginate matrix with an effectiveness of 53%. Immobilized-phytase retained > 50% activity after recycling for five cycles and also displayed more stability in the presence of organic solvents, metal ions, and detergents as compared to free enzyme. Values of Km and Vmax of immobilized phytase were recorded as 0.66 mM and 666.6 nmol/sec, respectively. Immobilized phytase efficiently hydrolyzed the phytate contents in wheat and pearl millet flours, exhibiting > 70% catalytic activity even after three cycles. Phytase supplementation resulted in the improved nutritional quality of these flours. Furthermore, the safety assessment of the treated and untreated samples reveals the absence of any aflatoxin in the phytase produced by the mould. The results revealed the improved stability of phytase after immobilization and as a safe and significant additive for application in the food industry.

Implementing Mailed Colorectal Cancer Fecal Screening Tests in Real-World Primary Care Settings: Promising Implementation Practices and Opportunities for Improvement.

Colorectal cancer (CRC) screening reduces morbidity and mortality, but screening rates in the USA remain suboptimal. The Colorectal Cancer Control Program (CRCCP) was established in 2009 to increase screening among groups disproportionately affected. The CRCCP utilizes implementation science to support health system change as a strategy to reduce disparities in CRC screening by directing resources to primary care clinics to implement evidence-based interventions (EBIs) proven to increase CRC screening. As COVID-19 continues to impede in-person healthcare visits and compel the unpredictable redirection of clinic priorities, understanding clinics' adoption and implementation of EBIs into routine care is crucial. Mailed fecal testing is an evidence-based screening approach that offers an alternative to in-person screening tests and represents a promising approach to reduce CRC screening disparities. However, little is known about how mailed fecal testing is implemented in real-world settings. In this retrospective, cross-sectional analysis, we assessed practices around mailed fecal testing implementation in 185 clinics across 62 US health systems. We sought to (1) determine whether clinics that do and do not implement mailed fecal testing differ with respect to characteristics (e.g., type, location, and proportion of uninsured patients) and (2) identify implementation practices among clinics that offer mailed fecal testing. Our findings revealed that over half (58%) of clinics implemented mailed fecal testing. These clinics were more likely to have a CRC screening policy than clinics that did not implement mailed fecal testing (p = 0.007) and to serve a larger patient population (p = 0.004), but less likely to have a large proportion of uninsured patients (p = 0.01). Clinics that implemented mailed fecal testing offered it in combination with EBIs, including patient reminders (92%), provider reminders (94%), and other activities to reduce structural barriers (95%). However, fewer clinics reported having the leadership support (58%) or funding stability (29%) to sustain mailed fecal testing. Mailed fecal testing was widely implemented alongside other EBIs in primary care clinics participating in the CRCCP, but multiple opportunities for enhancing its implementation exist. These include increasing the proportion of community health centers/federally qualified health centers offering mailed screening; increasing the proportion that provide pre-paid return mail supplies with the screening kit; increasing the proportion of clinics monitoring both screening kit distribution and return; ensuring patients with abnormal tests can obtain colonoscopy; and increasing sustainability planning and support.

Nanoarchitectonics of Three-Dimensional Carbon Nanofiber-Supported Hollow Copper Sulfide Spheres for Asymmetric Supercapacitor Applications.

Three-dimensional carbon nanofiber (3D-CNF)-supported hollow copper sulfide (HCuS) spheres were synthesized by the facile hydrothermal method. The morphology of the as-synthesized HCuS@3D-CNF composite clearly revealed that the 3D-CNFs act as a basement for HCuS spheres. The electrochemical performance of as-synthesized HCuS@3D-CNFs was evaluated by cyclic voltammetry (CV) tests, gravimetric charge-discharge (GCD) tests, and Nyquist plots. The obtained results revealed that the HCuS@3D-CNFs exhibited greater areal capacitance (4.6 F/cm2) compared to bare HCuS (0.64 F/cm2) at a current density of 2 mA/cm2. Furthermore, HCuS@3D-CNFs retained excellent cyclic stability of 83.2% after 5000 cycles. The assembled asymmetric device (HCuS@3D-CNFs//BAC) exhibits an energy density of 0.15 mWh/cm2 with a working potential window of 1.5 V in KOH electrolyte. The obtained results demonstrate that HZnS@3D-CNF nanoarchitectonics is a potential electrode material for supercapacitor applications.

Money Matters: A Three-Step Process for Using Budget Data in Program Evaluation to Assess the Design and Management of a Novel Public Health Program.

We applied a three-step process, abstracting and analyzing program budgets to examine how Colorectal Cancer Control Program (CRCCP) awardees are structuring their programs and to assess the fidelity of program design to the CRCCP public health model. We reviewed 23 state, one tribal organization, and six university awardee budgets. We assessed resource allocations, staffing structures, and contracted partners and their activities. Awardees allocated 83% of all funds to contracts and personnel. Program managers were the most budgeted personnel type across three measures: number of people, full-time equivalency, and personnel costs. Awardees not only contracted with health care systems and clinics (39% of all contracts) but also contracted other partner types. Contractors were mainly funded to implement evidence-based interventions (25%) and conduct evaluation (24%). Program design varied among awardees in the number of staff (0-22), number of full-time equivalencies (0-5.4), and the number of contracts (1-11) budgeted. State awardees budgeted more resources to contracts, compared with university awardees (57% vs. 31%), while universities budgeted more for total personnel costs (41% vs. 30%). We learned that awardees designed their programs with fidelity to the CRCCP model. Although implementation approaches varied, overall results suggest implementation requires a combination of internal capacities and contracted partners. Budgets provide opportunities to use already existing program data to evaluate program design, partnerships, and planned activities.

Greater COVID-19 Severity and Mortality in Hospitalized Patients in the Delta-phase Compared to the Others: A Single Center Prospective Registry.

BACKGROUND AND OBJECTIVE: To compare clinical and laboratory features, and outcomes in the second COVID-19 phase (delta variant) with the first and third phases in India we performed a registry-based study. METHODS: Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were recruited over the study period from March 2020 to July 2022. In the first phase (wild type, March-December 2020) of the 7,476 suspected, 1,395 (18.7%) were positive and 863 (61.8%) were hospitalized, in the second phase (delta, January-July 2021) out of 8,680 suspected, 1,641 (19.4%) tested positive and 388 (23.6%) were hospitalized, and in the third phase (omicron, January-July 2022) out of 5,188 suspected patients, 886 (17.1%) tested positive and 94 (10.6%) were hospitalized. We compared details of admission clinical and laboratory features and in-hospital management and outcomes in the three phases. RESULTS: A total of 2,352 patients were recruited. The majority of the patients were men, aged <45 years were 20% and about 20% of patients had hypertension, diabetes, and cardiovascular diseases. Patients in the second phase had significantly more cough, fever, shortness of breath, and lower oxygen saturation (SpO2) at admission and also had more lymphopenia, C-reactive proteins (CRPs), interleukin-6, ferritin, lactic dehydrogenase, and transaminases than patients in the other two phases. In the second vs the first and third phases, the requirement of supplementary oxygen (47.9 vs 33.1 and 23.4%), proning (89.2 vs 37.1 and 5.3%), high flow nasal oxygen (15.7 vs 8.71 and 5.3%), noninvasive ventilation (14.4 vs 9.1 and 11.7%), invasive ventilation (16.2 vs 9.1 and 9.6%), steroids (94.1 vs 83.4 and 37.2%), remdesivir (91.2 vs 73.8 and 39.4%), and anticoagulants (94.3 vs 83.0 and 61.7%) was significantly more (p < 0.001). The median length of stay in days [interquartile range (IQR)] was longer in the second phase [8 (6-10)] vs the first [7 (5-10)] and the third phase [4 (3-6) days]. The intensive care unit (ICU) stay in the second phase [9 (5-13) days] was also significantly more than the first [6 (2-10)] and third [0 (0-3)] phases (p <0.001). Overall, in-hospital deaths occurred in 176 patients (12.8%). Deaths were significantly higher in the second phase (19.3%), compared to the first (11.0%) and the third (3.3%) phases (p <0.01). We also observed that greater disease severity at presentation was associated with higher mortality in all the phases. CONCLUSION: This study shows that COVID-19 patients that were hospitalized in the second (delta) phase of the epidemic had more severe disease compared to the first and third phases. In the second phase of patients, there was a significantly higher duration of hospitalization, ICU hospitalization, greater oxygen requirement, noninvasive and invasive ventilatory support, and more deaths.

A General Strategy to Install Amidine Functional Groups Along the Peptide Backbone.

Amidines are a structural surrogate for peptide bonds, yet have received considerably little attention in peptides due to limitations in existing methods to access them. The synthetic strategy developed in this study represents the first robust and general procedure for the introduction of amidines into the peptide backbone. We exploit and further develop the utility and efficiency of thioimidate protecting groups as a means to side-step reactivity that ultimately renders existing methods unsuitable for the installation of amidines along the main-chain of peptides. This work is significant because it describes a generally applicable path to access unexplored peptide designs and architectures for new therapeutics made possible by the unique properties of amidines.

Proteomic, biochemical, histopathological, and elevated plus maze analysis reveals the gut damaging role of ketoprofen with Yersinia enterocolitica and altered behavior in Wistar rats.

The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is known to damage the intestinal epithelial cells (IECs) that play numerous important roles, including nutrient absorption and barrier protection. In the current study, we determined the effect of ketoprofen on the rat gut when administered with Yersinia enterocolitica. On performing the label-free quantitation of the rat gut proteins, the expression of 494 proteins out of 1628 proteins was altered, which has a profound effect on NF-kB signaling pathway, immune system, dysbiosis, and gut injury. Further, the biochemical [enhanced malondialdehyde (MDA) & hepatic enzyme activities and reduced serotonin & antioxidants levels i.e., catalase (CAT) and superoxide dismutase (SOD)] and histopathological analysis suggested the significant damage in treated rats, compared to control rats. Lastly, the elevated plus maze (EPM) study confirmed high levels of anxiety in treated rats in comparison to the control group. Altogether, results suggest that the co-administration of ketoprofen with Y. enterocolitica damages gut, alters hepatic enzyme activities, and affects behavioral responses in the treated rats.

Balancing reactive oxygen species generation by rebooting gut microbiota.

Reactive oxygen species (ROS; free radical form O2 •- , superoxide radical; OH• , hydroxyl radical; ROO• , peroxyl; RO• , alkoxyl and non-radical form 1 O2 , singlet oxygen; H2 O2 , hydrogen peroxide) are inevitable companions of aerobic life with crucial role in gut health. But, overwhelming production of ROS can cause serious damage to biomolecules. In this review, we have discussed several sources of ROS production that can be beneficial or dangerous to the human gut. Micro-organisms, organelles and enzymes play crucial role in ROS generation, where NOX1 is the main intestinal enzyme, which produce ROS in the intestine epithelial cells. Previous studies have reported that probiotics play significant role in gut homeostasis by checking the ROS generation, maintaining the antioxidant level, immune system and barrier protection. With current knowledge, we have critically analysed the available literature and presented the outcome in the form of bubble maps to suggest that the probiotics help in controlling the ROS-specific intestinal diseases, such as inflammatory bowel disease (IBD) and colon cancer. Finally, it has been concluded that rebooting of the gut microbiota with probiotics, postbiotics or faecal microbiota transplantation (FMT) can have crucial implications in the structuring of gut communities for the personalized management of the gastrointestinal (GI) diseases.

Salt-tolerant PGPR strain Priestia endophytica SK1 promotes fenugreek growth under salt stress by inducing nitrogen assimilation and secondary metabolites.

AIMS: Soil salinity is a huge obstacle in crop production worldwide. Saline soil can reduce active chemical contents in medicinal plants of the Leguminosae family through crippled normal nodule function. Intensive efforts are underway to improve yield and medicinal value of leguminous herbs under salt stress condition by using benign microbes. Here, an attempt was made to explore the salt-tolerant bacteria associated with rhizosphere of fenugreek plant (Trigonella foenum-graecum L.) and to evaluate their impact on host plant growth and metabolite of pharmaceutical importance. METHODS AND RESULTS: A salt-tolerant plant growth promoting rhizobacterial (PGPR) strain Priestia endophytica SK1 isolated from fenugreek rhizospheric soil, which increased biomass and metabolite content in plants grown under saline stress. SK1 bacterial application induced nodule formation and enhanced nitrogen and phosphorus content under salt (100 mM NaCl) stress as compared to control plants. H2 O2 production and lipid peroxidation as a measure of stress were observed high in control plants, while a reduction in these parameters was observed in plants inoculated with SK1. In addition, a significant effect was found on the phenolic compounds and trigonelline content in fenugreek plant inoculated with SK1 bacterium. An increased trigonelline content of about 54% over uninoculated control was recorded under salt stress. CONCLUSION: The results of this study revealed that the application of salt-tolerant PGPR strain P. endophytica SK1 induced nitrogen fixation machinery that leads to alleviate salt stress and improved the biosynthesis of trigonelline content in fenugreek. SIGNIFICANCE OF THE STUDY: This study extends our understanding on the significance of rhizosphere microbiome and their beneficial role in plant health under environmental stress to promote agro-eco-farming practices.

Fungal secondary metabolites in food and pharmaceuticals in the era of multi-omics.

Fungi produce several bioactive metabolites, pigments, dyes, antioxidants, polysaccharides, and industrial enzymes. Fungal products are also the primary sources of functional food and nutrition, and their pharmacological products are used for healthy aging. Their molecular properties are validated through the use of recent high-throughput genomic, transcriptomic, and metabolomic tools and techniques. Together, these updated multi-omic tools have been used to study fungal metabolites structure and their mode of action on biological and cellular processes. Diverse groups of fungi produce different proteins and secondary metabolites, which possess tremendous biotechnological and pharmaceutical applications. Furthermore, its use and acceptability can be accelerated by adopting multi-omics, bioinformatics, and machine learning tools that generate a huge amount of molecular data. The integration of artificial intelligence and machine learning tools in the era of omics and big data has opened up a new outlook in both basic and applied researches in the area of nutraceuticals and functional food and nutrition. KEY POINTS: • Multi-omic tool helps in the identification of novel fungal metabolites • Intra-omic data from genomics to bioinformatics • Novel metabolites and application in human health.

Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics.

Probiotics have been considered as an economical and safe alternative for the treatment of a large number of chronic diseases and improvement of human health. They are known to modulate the host immunity and protect from several infectious and non-infectious diseases. The colonization, killing of pathogens and induction of host cells are few of the important probiotic attributes which affect several functions of the host. In addition, prebiotics and non-digestible food substances selectively promote the growth of probiotics and human health through nutrient enrichment, and modulation of gut microbiota and immune system. This review highlights the role of probiotics and prebiotics alone and in combination (synbiotics) in the modulation of immune system, treatment of infections, management of inflammatory bowel disease and cancer therapy. KEY POINTS: • Probiotics and their derivatives against several human diseases. • Prebiotics feed probiotics and induce several functions in the host. • Discovery of novel and biosafe products needs attention for human health.

Evaluating Uptake of Evidence-Based Interventions in 355 Clinics Partnering With the Colorectal Cancer Control Program, 2015-2018.

PURPOSE AND OBJECTIVES: Colorectal cancer screening rates remain suboptimal in the US. The Colorectal Cancer Control Program (CRCCP) of the Centers for Disease Control and Prevention (CDC) seeks to increase screening in health system clinics through implementation of evidence-based interventions (EBIs) and supporting activities (SAs). This program provided an opportunity to assess the uptake of EBIs and SAs in 355 clinics that participated from 2015 to 2018. INTERVENTION APPROACH: The 30 funded awardees of CRCCP partnered with clinics to implement at least 2 of 4 EBIs that CDC prioritized (patient reminders, provider reminders, reducing structural barriers, provider assessment and feedback) and 4 optional strategies that CDC identified as SAs (small media, professional development and provider education, patient navigation, and community health workers). EVALUATION METHODS: Clinics completed 3 annual surveys to report uptake, implementation, and integration and perceived sustainability of the priority EBIs and SAs. RESULTS: In our sample of 355 clinics, uptake of 4 EBIs and 2 SAs significantly increased over time. By year 3, 82% of clinics implemented patient reminder systems, 88% implemented provider reminder systems, 82% implemented provider assessment and feedback, 76% implemented activities to reduce structural barriers, 51% implemented provider education, and 84% used small media. Most clinics that implemented these strategies (>90%) considered them fully integrated into the health system or clinic operations and sustainable by year 3. Fewer clinics used patient navigation (30%) and community health workers (19%), with no increase over the years of the study. IMPLICATIONS FOR PUBLIC HEALTH: Clinics participating in the CRCCP reported high uptake and perceived sustainability of EBIs that can be integrated into electronic medical record systems but limited uptake of patient navigation and community health workers, which are uniquely suited to reduce cancer disparities. Future research should determine how to promote uptake and assess cost-effectiveness of CRCCP interventions.