Screening Level Research Articles

Risk of Bleeding and Thrombosis with CAR T-Cell Therapy: A Scoping Review

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is emerging as a novel and revolutionary therapy in the treatment of relapsed or refractory lymphoma and other hematological malignancies. Patients with hematological malignancies are at risk of bleeding and thrombosis due to multiple risks factors. As there is an ongoing exploration of the incidence and characteristics of bleeding and thrombosis after CAR T-cell therapy, there is no existing published data that incorporates both peer-reviewed and non-peer-reviewed literature. Aim: Assess the risk of bleeding and thrombosis in CAR T-cell recipients for hematological malignancies. Method: We conducted a systematic literature search in MEDLINE, EMBASE, and CENTRAL electronic databases from inception to October 2022 using a combination of subject headings and text words. We included studies that assessed thrombotic and bleeding complications in patients eighteen or older who underwent CAR T-cell therapy for a hematologic malignancy. Our search strategy yielded 14 studies in the form of abstracts and full-text articles. The review process consisted of two levels of screening: (1) a title and abstract review and (2) a full-text review. Result: Of 3354 records, we included 14 studies based on our inclusion criteria [figure 1]. Majorities of the studies were retrospective. Most of the patients in these studies received CAR T-cell therapy for refractory diffuse large B-cell lymphoma. Patients received at least 2 lines of therapy or more before CAR T-cell treatment. Different types of CAR T-cell therapy were used. Based on the included studies, the risk of bleeding was higher than thrombosis [figure 2]. Bleeding sites were variable, but gastrointestinal (GI) bleeding was predominant. In Ma et al, GI bleeding occurred in 11 (42.3%) patients. In Qi et al and Johnsrud et al, bleeding occurred in 44 (11%) and 12 (9.4%) patients respectively. Variable sites of thrombosis were noticed. In Hashmi et al incidence of thrombosis was 10.8%. Although there are some risk factors associated with bleeding and thrombosis in this population, the exact mechanism is still unknown. We think future studies to determine the exact mechanism of this toxicity and to assess the underlying risk factors would be crucial to decrease morbidity and mortality in this population and to develop risk assessment tools.

Association of health insurance coverage disruptions and breast, colorectal, and cervical cancer screening.

116 Background: Health insurance coverage is critical for ensuring access to recommended health care in the United States. This study investigates the effects of insurance coverage disruptions on receipt of breast, colorectal, and cervical cancer screenings. Methods: We identified adults <65 years eligible for breast, cervical and/or colorectal cancer screening from the 2015, 2019, and 2021 National Health Interview Survey (years cancer control supplements fielded). Adults were categorized into 5 groups based on insurance type at survey and prior coverage disruptions (lack of insurance during prior 12 months): private, with and without disruption; public, with and without disruption; and uninsured. Screening outcomes included: 1) past-year screening and 2) guideline-concordant screening, defined from the US Preventive Services Task Force guidelines available at the time of each survey. Separate multivariate logistic regression models were used to evaluate the associations of insurance coverage disruptions and cancer screening. Results: We identified 12,121 women aged 50-64 years eligible for breast cancer screening, 23,490 people aged 50-64 years eligible for colorectal cancer screening, and 33,391 women aged 21-64 years eligible for cervical cancer screening. Compared to people with continuous private or public coverage, people with coverage disruptions were less likely to receive past-year or guideline-concordant cancer screening (Table). People without health insurance coverage had the lowest level of screening. Among people with private coverage, disruptions were associated with lower guideline-concordant screening across all three cancer types in adjusted analyses (breast: AOR: 0.45, 95% confidence interval (CI): (0.32, 0.63); colorectal: 0.49 (0.39, 0.62); cervical: 0.70 (0.58,0.84)); among people with public coverage, disruptions were associated with lower guideline-concordant breast cancer screening (AOR: 0.39 (0.23, 0.65)). Conclusions: Health insurance coverage disruptions were associated with lower past-year and guideline-concordant breast, colorectal, and cervical cancer screening. Findings underscore the importance of stable health insurance coverage as part of a comprehensive approach to improve cancer screening rates and early detection of cancers when treatment is most effective.[Table: see text]

Using a Reanalysis-Driven Land Surface Model for Initialization of a Numerical Weather Prediction System

Abstract Realistic initialization of the land surface is important to produce accurate NWP forecasts. Therefore, making use of available observations is essential when estimating the surface state. In this work, sequential land surface data assimilation of soil variables is replaced with an offline cycling method. To obtain the best possible initial state for the lower boundary of the NWP system, the land surface model is rerun between forecasts with an analyzed atmospheric forcing. We found a relative reduction of 2-m temperature root-mean-square errors and mean errors of 6% and 12%, respectively, and 4.5% and 11% for 2-m specific humidity. During a convective event, the system was able to produce useful (fractions skill score greater than the uniform forecast) forecasts [above 30 mm (12 h)−1] down to a 100-km length scale where the reference failed to do so below 200 km. The different precipitation forcing caused differences in soil moisture fields that persisted for several weeks and consequently impacted the surface fluxes of heat and moisture and the forecasts of screen level parameters. The experiments also indicate diurnal- and weather-dependent variations of the forecast errors that give valuable insight on the role of initial land surface conditions and the land–atmosphere interactions in southern Scandinavia.

Screening levels of TCS-172 NaI(Tl) survey meters used for direct thyroid measurements in nuclear disasters.

It is a challenging task to establish a feasible and robust method for the population monitoring of individuals' thyroid exposure following an accidental intake of radioiodines in a nuclear emergency, because of the time restriction. The authors previously proposed a method for such monitoring to obtain as many reliable human data as possible and one of the components is simplified measurements by conventional NaI(Tl) survey meters that are intended to be used for the initial triage to identify significantly exposed individuals and get an overall picture of the exposure levels in a target population in a timely manner. This study determined screening levels (SLs) for a conventional NaI(Tl) survey meter (model TCS-172, Hitachi, Japan) using the conversion factor (131I kBq in the thyroid per μSv h-1) that were obtained from experiments and simulations with age-specific phantoms. The results demonstrated that the derived SLs for 100mSv thyroid equivalent dose were as follows: 0.2μSvh-1 (SL1) for the age group≤5-y-olds, 0.5μSvh-1 (SL2) for the 10- and 15-y-old age groups and 1.0μSvh-1 (SL3) for adults. These SLs would be reasonably available within 1week after the intake of 131I on the safe side.

Environmental Pollution Assessment of Heavy Metals in Soils and Crops in Xinping Area of Yunnan Province, China

With the development of the economy and society, the environmental problems caused by heavy metals have always been the focus of attention. Strong concern has been recently shown for the heavy metal pollution of soils in southwestern China. The heavy metals of surface soils in the Xinping area of Yunnan province, China are surveyed along with some crop samples. There are 3312 surface soils and 95 crop samples collected in about 370 square kilometers. Heavy metals including As, Cd, Cr, Hg, and Pb and pH are analyzed. New single and integrated pollution indices of heavy metals for soils (PI and PIn) and crops (PIc and PInc) based on Chinese criteria (GB15618-2018 and GB2762-2022) are described and presented here and used to assess the pollution status of heavy metals. The results indicate that the background level of surface soils is about 62.1%, the screening level is about 33.4%, and the intervention level is about 4.5%, which is mainly a result from Cr and spatially coincides with the peridotite rock, indicating a geogenic pollution source. Most crop samples are not contaminated with heavy metals. Comparing the results of the two integrated pollution indices between soils and crops, two inconsistent assessments are observed. One is that some contaminated crops are growing in unpolluted areas (or Type I) and the other is that some uncontaminated crops are growing in polluted areas (or Type II). This indicates a new challenge between the assessment criteria on soils and crops.

Primary prevention of hepatic encephalopathy post-TIPS: A systematic review and meta-analysis.

Transjugular intrahepatic portosystemic shunt (TIPS) can be an effective treatment for cirrhotic patients who develop variceal bleeding and ascites. However, TIPS placement is associated with an increased risk of developing hepatic encephalopathy (HE). Recently, there have been efforts to use the typical medical therapies prophylactically in patients undergoing TIPS placement to prevent post-TIPS HE. We conducted literature searches in MEDLINE, Embase, CINAHL, Scopus, and Cochrane to examine studies that use prophylactic medical therapy for preventing post-TIPS HE. A narrative synthesis and grading of recommendations assessment assessment were done for all studies. Meta-analysis was performed for eligible studies using the Mantel-Haenszel method random-effects model. Nine hundred twenty-one articles were screened and 5 studies were included in the study after 2 levels of screening. The medications studied were rifaximin, lactulose, lactitol, L-Ornithine-L-aspartate (LOLA), albumin, and combination therapies. Narrative results showed that lactulose, lactitol, LOLA and albumin prophylaxis were not associated with reduction in HE occurrence or mortality. A combination of rifaximin and lactulose was found to be associated with lower occurrence of HE, and the results were not different when LOLA was added. Meta-analysis (n = 3) showed that rifaximin treatment was not associated with changes in HE occurrences. In conclusion, a vast majority of medications were not found to be effective post-TIPS HE prophylaxis when used alone. A rifaximin and lactulose combination therapy may be beneficial. Overall, there is significant limitation in the current data and more studies are needed to yield more robust meta-analysis results in the future.

Processes for identifying caregivers and screening for caregiver and patient distress in community oncology: results from WF-1803CD.

Despite their vital roles, informal caregivers of adult cancer patients are commonly overlooked in cancer care. This study describes processes for identifying cancer caregivers and processes for distress screening and management among caregivers and patients in the understudied community oncology setting. Supportive care leaders from the National Cancer Institute Community Oncology Research Program practices completed online survey questions regarding caregiver identification, caregiver and patient distress screening, and distress management strategies. We described practice group characteristics and prevalence of study outcomes. Multivariable logistic regression explored associations between practice group characteristics and caregiver identification in the electronic health record (EHR). Most (64.9%, 72 of 111) supportive care leaders reported routine identification and documentation of informal caregivers; 63.8% record this information in the EHR. Only 16% routinely screen caregivers for distress, though 92.5% screen patients. Distress management strategies for caregivers and patients are widely available, yet only 12.6% are routinely identified and screened and had at least 1 referral strategy for caregivers with distress; 90.6% are routinely screened and had at least 1 referral strategy for patients. Practices with a free-standing outpatient clinic (odds ratio [OR] = 0.29, P = .0106) and academic affiliation (OR = 0.01, P = .04) were less likely to identify and document caregivers in the EHR. However, higher oncologist volume was associated with an increased likelihood of recording caregiver information in the EHR (OR = 1.04, P = .02). Despite high levels of patient distress screening and management, few practices provide comprehensive caregiver engagement practices. Existing patient engagement protocols may provide a promising platform to build capacity to better address caregiver needs.

What evidence exists on the ecological and physical effects of built structures in shallow, tropical coral reefs? A systematic map protocol

BackgroundShallow, tropical coral reefs face compounding threats from habitat degradation due to coastal development and pollution, impacts from storms and sea-level rise, and pulse disturbances like blast fishing, mining, dredging, and ship groundings that reduce coral reefs’ height and variability. One approach toward restoring coral reef structure from these threats is deploying built structures. Built structures range from engineered modules and repurposed materials to underwater sculptures and intentionally placed natural rocks. Restoration practitioners and coastal managers increasingly consider incorporating built structures, including nature-based solutions, into coral reef-related applications. Yet, synthesized evidence on the ecological and physical performance of built structure interventions across a variety of contexts (e.g., restoration, coastal protection, mitigation, tourism) is not readily available to guide decisions. To help inform management decisions, here we aim to document the global evidence base on the ecological and physical performance of built structures in shallow (≤ 30 m) tropical (35° N to 35° S latitude) coral ecosystems. The collated evidence base on use cases and associated ecological and physical outcomes of built structure interventions can help inform future consideration of built structures in reef restoration design, siting, and implementation.MethodTo discover evidence on the performance of built structures in coral reef-related applications, such as restoration, mitigation, and coastal protection, primary literature will be searched across indexing platforms, bibliographic databases, open discovery citation indexes, a web-based search engine, a novel literature discovery tool, and organizational websites. The geographic scope of the search is global, and there is no limitation to temporal scope. Primary literature will be screened first at the level of title and abstract and then at the full text level against defined eligibility criteria for the population, intervention, study type, and outcomes of interest. Metadata will be extracted from studies that pass both screening levels. The resulting data will be analyzed to determine the distribution and abundance of evidence. Results will be made publicly available and reported in a systematic map that includes a narrative description, identifies evidence clusters and gaps, and outlines future research directions on the use of built structures in coral reef-related applications.

Longitudinal Measurement Invariance of CCAPS-34 Scores with a Large University Sample

Objective Counseling Center Assessment of Psychological Symptoms (CCAPS-34) scores were studied for longitudinal bias-free construct evidence. Method A sample of 4,696 university students referred to a university counseling center were assessed twice for evidence of longitudinal measurement invariance. Results Adequate or marginal longitudinal measurement invariance (LMI) of all subscales except for Eating Concerns was confirmed. Coefficients alpha and omega suggested that the internal consistencies for both initial and subsequent administrations were largely adequate for screening level test scores (≥ .80), except for the Hostility and Alcohol Use subscales (≥ .73). Second session effect sizes (Cohen’s d) were small but detectable and statistically significant for most subscales (-0.02–.17). Conclusions Counselors can use most CCAPS-34 subscale scores for tracking psychological symptoms and constructs over time with confidence. The Generalized Anxiety, Social Anxiety, Academic Concerns, and Alcohol Use subscales can be used with great confidence. Some confidence is warranted from the LMI evidence when using the Depression and Hostility subscales, but caution in warranted when using the Eating Concerns subscale.

The application potential and direction of artificial intelligence in the prevention and treatment of glaucoma

The rapid iteration of artificial intelligence (AI) technology has driven the development of intelligent ophthalmology, with enormous potential for application in the regional screening, precise diagnosis, and disease progression prediction of intractable blinding diseases, particularly glaucoma. Aiming to encourage collaborative discussions among ophthalmologists, this article elucidates the application potential and direction of AI in the prevention and treatment of glaucoma from the aspects of enhancing glaucoma screening and diagnosis levels through AI, promoting initiatives for the application of AI, and exploring the prospects of AI.

Re: Genetically Adjusted PSA Levels for Prostate Cancer Screening

Re: Genetically Adjusted PSA Levels for Prostate Cancer Screening

On-Surface Synthesis of Graphene Nanoribbons with Atomically Precise Structural Heterogeneities and On-Site Characterizations.

Graphene nanoribbons (GNRs) are strips of graphene, with widths of a few nanometers, that are promising candidates for future applications in nanodevices and quantum information processing due to their highly tunable structure-dependent electronic, spintronic, topological, and optical properties. Implantation of periodic structural heterogeneities, such as heteroatoms, nanopores, and non-hexagonal rings, has become a powerful manner for tailoring the designer properties of GNRs. The bottom-up synthesis approach, by combining on-surface chemical reactions based on rationally designed molecular precursors and in situ tip-based microscopic and spectroscopic techniques, promotes the construction of atomically precise GNRs with periodic structural modulations. However, there are still obstacles and challenges lying on the way toward the understanding of the intrinsic structure-property relations, such as the strong screening and Fermi level pinning effect of the normally used transition metal substrates and the lack of collective tip-based techniques that can cover multi-internal degrees of freedom of the GNRs. In this Perspective, we briefly review the recent progress in the on-surface synthesis of GNRs with diverse structural heterogeneities and highlight the structure-property relations as characterized by the noncontact atomic force microscopy and scanning tunneling microscopy/spectroscopy. We furthermore motivate to deliver the need for developing strategies to achieve quasi-freestanding GNRs and for exploiting multifunctional tip-based techniques to collectively probe the intrinsic properties.

Screening level approach to support companies in making safe and sustainable by design decisions at the early stages of innovation

Screening level approach to support companies in making safe and sustainable by design decisions at the early stages of innovation

Checklists for interpreting chest radiographs: a scoping review protocol

IntroductionWhat is known about checklists for interpreting chest radiographs? The question will guide the development of the inclusion criteria for the scoping review. Breaking down the scoping review question will allow the evaluation of inclusion and exclusion criteria for the protocol. The eligibility of the proposed research question will be assessed using the Population or Participants, Concept and Context (PCC) framework.BackgroundX-ray reporting can be standardised using checklists. Checklists may reduce the time needed to produce a comprehensive X-ray report and improve the quality and consistency of detecting abnormalities on chest radiographs. This scoping review aims to map the available literature on what is known about checklists for interpreting chest radiographs.MethodsWe will follow the methodological framework for scoping reviews originally described by Arksey and O’Malley. The scoping review will include articles that describe checklists for reducing diagnostic errors, checklists for analysing chest radiographs, checklists for identifying abnormalities on chest radiographs and checklists for reporting chest radiographs in all settings. Search terms are chest radiographs, checklists, and chest X-rays. We will search for peer-reviewed articles and grey literature including dissertations and theses. We will search online databases including Ovid Medline and Ebscohost, to identify articles published in English from 1994 to 2022. The searched articles will undergo two levels of screening, first the title and abstract screening, then a full-text screening by two reviewers. Data from the selected articles will be extracted, using a tested extraction form and charted using the Joanna Briggs Institute guidelines.ResultsThe results will be collated, summarised and discussed including any limitations of the included articles. The articles will be summarised in a table, as well as narratively. The distribution of studies will be summarised quantitatively and the numerical analysis will provide an overview and identify knowledge gaps. Content analysis will map different checklists available for chest interpretation.DiscussionThe results of the scoping review will be used to develop a checklist that will be used by medical doctors in collaboration with radiographers working in settings where there are no radiologists on-site, for interpreting chest radiographs.Systematic review registrationScoping review protocol registered with Open Science Framework on 27 July 2022. Registration https://doi.org/10.17605/OSF.IO/JS5PQ

Environmental hazards of WELGRO® Cu+Zn: A nano-enabled fertilizer

Nanoagrochemicals have the potential to revolutionize agriculture towards a precision farming system, able to reduce application rates and consequently their environmental footprint, while keeping efficacy. Several nanoagrochemicals (including nanopesticides (Npes) and nanofertilizers (Nfer)) are already commercialized but the environmental risk assessment of these advanced materials is often lacking. In the present study, we studied the commercial fertilizer WELGRO® Cu + Zn and assessed its ecotoxicity to the soil invertebrate species Enchytraeus crypticus (Oligochaeta), further comparing it to its individual active substances CuO and ZnO. To get a comprehensive picture of possible effects, we used four types of highly relevant tests in LUFA 2.2 soil: 1) avoidance behaviour (2 days), 2) reproduction (OECD standard, 28 d), 3) its extension (56 d), and 4) the full life cycle (FLC) (46 d) – this high level of hazard screening allows for increased interpretation. The results confirmed the nano-features of WELGRO® and a higher toxicity than the mixture of the individual components CuO + ZnO. E. crypticus avoided the soil spiked with WELGRO® and CuO + ZnO, this being the most sensitive endpoint - avoidance behaviour. Both WELGRO® and the active substances were little to non-toxic based on the OECD standard test. However, the toxicity dramatically increased in the tests focussing on longer-term sustainability measures, i.e., 56 days, ca. 170 for WELGRO®. This seems related to the nano-features of WELGRO®, e.g., slow release of ions from the nanoparticles throughout time. The FLCt results showed WELGRO® affected hatching and juveniles’ survival, being these the most sensitive life stages. Hence, under actual real world field usage scenarios, i.e., based on the recommended application rates, nanoenabled WELGRO® can affect oligochaete populations like enchytraeids, both via the immediate avoidance behaviour and also via prolonged exposure periods.

Effects on Cancer Prevention from the COVID-19 Pandemic.

The COVID-19 pandemic led to disruption of health services around the world, including cancer services. We carried out a narrative review of the effect of the pandemic on cancer prevention services, including screening. Services were severely affected in the early months of the pandemic, and in some areas are still recovering. Large numbers of additional cancers or additional late-stage cancers have been predicted to arise over the coming years as a result of this disruption. To minimize the effects on cancer outcomes, it is necessary to return as quickly as possible to prepandemic levels of screening and prevention activity or indeed to exceed these levels. The recovery of services should address health inequalities.

A Critical Review of Amphibian Per- and Polyfluoroalkyl Substance Ecotoxicity Research Studies: Identification of Screening Levels in Water and Other Useful Resources for Site-Specific Ecological Risk Assessments.

With the goal of aiding risk assessors conducting site-specific risk assessments at per- and polyfluoroalkyl substance (PFAS)-contaminated sites, this critical review synthesizes information on the ecotoxicity of PFAS to amphibians in 10 amphibian species and 16 peer-reviewed publications. The studies in this review consisted of spiked-PFAS chronic toxicity experiments with perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and 6:2 fluorotelomer sulfonate (6:2 FTS) that evaluated apical endpoints typical of ecological risk-based decision making (survival, growth, and development). Body mass was the most sensitive endpoint, showing clear and biologically meaningful population level adverse effect sizes (≥20% adverse effects). From these results, we recommend chronic no observed effect concentration (NOEC) screening levels of 590 µg/L for PFOS and 130 µg/L for PFOA. At or above recommended chronic lowest observed effect concentration screening levels of 1100 µg/L PFOS and 1400 µg/L PFOA, there is an increased chance of adverse biologically relevant chronic effects. Biologically relevant adverse effects were not observed for PFHxS and 6:2 FTS, so unbounded NOECs of 1300 µg/L PFHxS and 1800 µg/L 6:2 FTS are recommended. Screening levels are also provided for the concentration of PFAS in an amphibian diet, amphibian tissue, and moss substrate. In addition, we recommend bioconcentration factors that can be useful to predict concentrations of PFAS in amphibians using concentrations in water; these values are useful for food web modeling to understand risks to vertebrate wildlife that prey on amphibians. Overall, the present study provides a guide to the wealth of ecotoxicological research on PFAS conducted by our research group and highlights the need for additional work that would improve the understanding of chemical risks to amphibians. Environ Toxicol Chem 2023;00:1-13. © 2023 SETAC.

Predictions of PFAS regional-scale atmospheric deposition and ambient air exposure

Per- and polyfluoroalkyl substances (PFAS) are a large class of human-made compounds that have contaminated the global environment. One environmental entry point for PFAS is via atmospheric emission. Air releases can impact human health through multiple routes, including direct inhalation and contamination of drinking water following air deposition. In this work, we convert the reference dose (RfD) underlying the United States Environmental Protection Agency's GenX drinking water Health Advisory to an inhalation screening level and compare to predicted PFAS and GenX air concentrations from a fluorochemical manufacturing facility in Eastern North Carolina. We find that the area around the facility experiences ~15 days per year of GenX concentrations above the inhalation screening level we derive. We investigate the sensitivity of model predictions to assumptions regarding model spatial resolution, emissions temporal profiles, and knowledge of air emission chemical composition. Decreasing the chemical specificity of PFAS emissions has the largest impact on deposition predictions with domain-wide total deposition varying by as much as 250 % for total PFAS. However, predicted domain-wide mean and median air concentrations varied by <18 % over all scenarios tested for total PFAS. Other model features like emission temporal variability and model spatial resolution had weaker impacts on predicted PFAS deposition.

The worm Adult Activity Test (wAAT): A de novo mathematical model for detecting acute chemical effects in Caenorhabditis elegans.

We have adapted a semiautomated method for tracking Caenorhabditis elegans spontaneous locomotor activity into a quantifiable assay by developing a sophisticated method for analyzing the time course of measured activity. The 16-h worm Adult Activity Test (wAAT) can be used to measure C. elegans activity levels for efficient screening for pharmacological and toxicity-induced effects. As with any apical endpoint assay, the wAAT is mode of action agnostic, allowing for detection of effects from a broad spectrum of response pathways. With caffeine as a model mild stimulant, the wAAT showed transient hyperactivity followed by reversion to baseline. Mercury chloride (HgCl2 ) produced an early dose-response hyperactivity phase followed by pronounced hypoactivity, a behavior pattern we have termed a toxicant "escape response." Methylmercury chloride (meHgCl) produced a similar pattern to HgCl2 , but at much lower concentrations, a weaker hyperactivity response, and more pronounced hypoactivity. Sodium arsenite (NaAsO2 ) and dimethylarsinic acid (DMA) induced hypoactivity at high concentrations. Acute toxicity, as measured by hypoactivity in C. elegans adults, was ranked: meHgCl > HgCl2 > NaAsO2 = DMA. Caffeine was not toxic with the wAAT at tested concentrations. Methods for conducting the wAAT are described, along with instructions for preparing C. elegans Habitation Medium, a liquid nutrient medium that allows for developmental timing equivalent to that found with C. elegans grown on agar with OP50 Escherichia coli feeder cultures. A de novo mathematical parametric model for adult C. elegans activity and the application of this model in ranking exposure toxicity are presented.

Site Mutation Improves the Expression and Antimicrobial Properties of Fungal Defense.

Although antimicrobial peptides (AMPs) have highly desirable intrinsic characteristics in their commercial product development as new antimicrobials, the limitations of AMPs from experimental to scale development include the low oral bioavailability, and high production costs due to inadequate in vitro/in vivo gene expression- and low scale. Plectasin has good bactericidal activity against Staphylococcus and Streptococcus, and the selective bactericidal activity greatly reduces the damage to the micro-ecosystem when applied in vivo. However, its expression level was relatively low (748.63 mg/L). In view of these situations, this study will optimize and modify the structure of Plectasin, hoping to obtain candidates with high expression, no/low toxicity, and maintain desirable antibacterial activity. Through sequence alignment, Plectasin was used as a template to introduce the degenerate bases, and the screening library was constructed. After three different levels of screening, the candidate sequence PN7 was obtained, and its total protein yield in the supernatant was 5.53 g/L, with the highest value so far for the variants or constructs from the same ancestor source. PN7 had strong activity against several species of Gram-positive bacteria (MIC value range 1~16 μg/mL). It was relatively stable in various conditions in vitro; in addition, the peptide showed no toxicity to mice for 1 week after intraperitoneal injection. Meanwhile, PN7 kills Staphylococcus aureus ATCC 43300 with a mode of a quicker (>99% S. aureus was killed within 2 h, whereas vancomycin at 2× MIC was 8 h.) and longer PAE period. The findings indicate that PN7 may be a novel promising antimicrobial agent, and this study also provides a model or an example for the design, modification, or reconstruction of novel AMPs and their derivatives.