Low Safety Risk Research Articles

Fast Convergent Antinoise Dual Neural Network Controller With Adaptive Gain for Flexible Endoscope Robots.

Manual rigid endoscopes have defects such as a low efficiency, difficult operation, and safety risks, and the antinoise interference ability, convergence speed, and control accuracy of the neural network control technology for the existing autonomous endoscopes are often ignored. Solving these problems is important for the stable operation of endoscopes. Therefore, a new adaptive fast convergent antinoise dual neural network (AFA-DNN) controller for the visual servo control of ten-degree of freedom flexible endoscope robots (FERs) with physical constraints is proposed in this work. First, the control scheme of the FERs is formulated as a quadratic programming problem, and then, an AFA-DNN visual servo controller is designed for the FERs. The adaptive gains of the controller can accelerate the convergence, improve the antinoise ability, and increase the convergence accuracy of the controller. Then, according to the Lyapunov theory, the fast convergence of the AFA-DNN in finite time is proven for both noise-free and noisy conditions. The experimental results indicate that the FER controlled by the proposed AFA-DNN can accurately track various trajectories and that the AFA-DNN has a better antinoise interference ability, higher convergence accuracy, and faster convergence speed than conventional methods. The convergence speed of the AFA-DNN is increased by a factor of 4.22 by using the adaptive gains. Experiments also indicate that the AFA-DNN remains well functioning under various noise disturbances (such as constant, periodic, linear, and Gaussian noise).

Environmentally-friendly solvent pulping and grafting strategies for better foamability of poly(lactic acid)/agricultural waste biocomposites

In this study, the foamability of poly (lactic acid) (PLA) through a continuous extrusion process was enhanced by using an agricultural waste, environmentally friendly pulping methods, and reactive compatibilization of the lignocellulosic filler with matrix in the extrusion flow field. Both applied solvent-pulping methods by using chemicals with low safety and toxicity risks were considerably successful in purifying the micron-sized cellulosic fibers of rice straw (RS). The interface of PLA matrix with RS pulp fibers was modified by applying reactive compatibilizers containing maleic anhydride (MA) and epoxy functional groups. Both compatibilizers had the ability to simultaneously react with the hydroxyl groups of RS pulp fibers and end groups of PLA chains during the melt-compounding process. As a result of RS pulping and PLA/RS pulp compatibilizing reactions, the processability of PLA in an extrusion foaming process was substantially enhanced, in a way that the void fraction and cell density of PLA foam increased more than seven and two times, respectively. The extruded lightweight all-green biocomposite foams can be applied in construction and packaging applications.

Abstract PO5-27-09: Pharmacological eIF4E inhibition suppresses anti-tumor activity in ER+ breast cancer

Abstract Elevated levels of eukaryotic initiation factor 4E (eIF4E) are found in a broad range of cancers, including breast, and have been associated with aggressive, drug resistant tumors. Furthermore, elevated eIF4E activity is sufficient to cause transformation in various cancers, while inhibition suppresses tumor growth. eIF4E, the main regulator and rate limiting factor of protein synthesis, is the downstream integrator of several important oncogenic signaling pathways (PI3K/AKT/mTOR, Ras/Raf/MEK, and Myc). Activation of eIF4E results in increased protein levels of key proliferation and metabolism proteins such as Cyclin D1 (CCND1) and Ornithine Decarboxylase 1 (ODC1), as well as an overall increase in cellular synthesis machinery, causing cellular growth and proliferation. Here, we describe the development and characterization of novel, potent, and selective eIF4E inhibitors. Compounds from this chemical series have nanomolar activity in multiple biochemical and biophysical m7G cap-competition assays as well as potent inhibition of translation in cellular and biochemical assays. In cells, these compounds rapidly and reversibly decrease protein levels of several oncogenes, including CCND1, leading to a G1 cell cycle arrest. We demonstrate that eIF4E inhibitors cause growth inhibition in a variety of breast cancer cell lines, including ER+ breast cancer. These inhibitors also inhibit growth of breast cancer lines with acquired resistance to Palbociclib with the same potency as the parental cell lines. Additionally, eIF4E inhibition shows an increased sensitivity in resistant cell lines when combined with standard of care (SOC), including Palbociclib. Select analogs from the series demonstrate favorable ADMET/PK properties with good oral bioavailability and low safety risk. Lastly, these compounds have demonstrated near complete tumor growth inhibition in non-breast cancer in vivo models. Ongoing experiments will address in vivo efficacy in ER+ breast cancer in both monotherapy and in combination with SOC. Citation Format: Matthew Friedersdorf, Devon Blake, Sarah Thompson, Krista Marran, Jessica Sorrentino. Pharmacological eIF4E inhibition suppresses anti-tumor activity in ER+ breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-09.

Toxicity Study on Crude Alkaloid Extracts of Houttuyniae herba Based on Zebrafish and Mice.

Houttuyniae herba has a long history of medicinal and edible homology in China. It has the functions of clearing heat and detoxifying, reducing swelling and purulent discharge, diuresis, and relieving gonorrhea. It is mainly distributed in the central, southeastern, and southwestern provinces of China. Houttuyniae herba has been designated by the National Ministry of Health of China as a dual-use plant for both food and medicine. Comprising volatile oils, flavonoids, and alkaloids as its primary constituents, Houttuyniae herba harbors aristolactams, a prominent subclass of alkaloids. Notably, the structural affinity of aristolactams to aristolochic acids is discernible, the latter known for its explicit toxicological effects. Additionally, the safety study on Houttuyniae herba mainly focused on the ethanol, methanol, or aqueous extract. In this study, both zebrafish and mice were used to evaluate the acute toxicity of the total alkaloids extracts from Houttuyniae herba (HHTAE). The zebrafish experiment showed that a high concentration (0.1 mg/mL) of HHTAE had a lethal effect on zebrafish embryos. Furthermore, the mice experiment results showed that, even at a higher dose of 2000 mg/kg, HHTAE was not toxic. In conclusion, HHTAE was of low safety risk.

Comparative Safety of Pulsed Field Ablation and Cryoballoon Ablation Technologies for Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation: A Critical Literature Review and Indirect Treatment Comparison.

Cryoballoon ablation (CBA) is a standard catheter ablation technology with demonstrated clinical effectiveness for the treatment of paroxysmal atrial fibrillation (PAF); however, it can be associated with major adverse events, including phrenic nerve paralysis. Pulsed field ablation (PFA) is a novel, minimally thermal technology with comparable effectiveness and low safety risk. This study aimed to compare the safety profiles of PFA and CBA through critical analyses of the literature and indirect treatment comparisons. Studies were identified by searching the MEDLINE database and the Clinicaltrials.gov registry. Registered clinical trials and/or Food and Drug Administration Investigation Device Exemption (FDA IDE) studies evaluating PFA or CBA in adult patients with drug-refractory PAF between January 2008 and March 2023 were selected. Comparative safety between PFA and CBA was assessed for major and prespecified adverse events. Indirect comparisons were conducted using the proportion of patients experiencing adverse events and confirmed with single-arm meta-analyses and sensitivity analyses. Data were extracted from three PFA publications including a total of 497 patients and six CBA studies including a total of 1113 patients. The analysis revealed that PFA was associated with significantly lower risk of major adverse events {risk difference-4.3% [95% confidence interval (CI)-5.8,-2.8]; risk ratio 0.16 [95% CI 0.07, 0.45]} and prespecified adverse events [risk difference -2.5% (95% CI-4.4,-0.5); risk ratio 0.53 (95% CI 0.31, 0.96)]. Meta-analyses confirmed the lower rate of major adverse events for PFA [0.4% (95% CI 0.0, 1.3)] vs. CBA [5.6% (95% CI 2.6, 8.6)] and prespecified adverse events for PFA [2.7% (95% CI 1.2, 4.1)] vs. CBA [5.8% (95% CI 2.7, 9.0)]. Sensitivity analyses exploring heterogeneity across studies confirmed robustness of the main analyses. The findings of this study show that PFA has a more favorable safety profile than CBA, with significantly lower risks of major and prespecified adverse events. These indirect comparisons help contextualize the safety of PFA compared to CBA for the treatment of drug-refractory PAF in the absence of head-to-head studies.

Safety evaluation of Plukenetia volubilis seeds: a metabolomic profiling and network toxicology approach.

Sacha Inchi (Plukenetia volubilis) seeds and oil have been integrated into daily diets. However, scientific reports have raised concerns regarding potential health risks associated with saponins and alkaloids in this seeds. This study employed a combination analysis using proton-NMR, GC-MS, LC-QTOF, and GNPS molecular networking to evaluate the chemical composition of these seeds. In silico toxicology analysis and in vitro cytotoxicity assays were conducted to investigate the potential toxicity effects of Sacha Inchi seeds and their contained metabolites. The results revealed that major components of these seeds are oils (linoleic, linolenic, and oleic acids) and sugars, with minor amounts of phytosterols and trigonelline, a pyridine alkaloid. GNPS analysis suggested the absence of saponins, instead, it identified trigonelline and a few other nitrogen-containing metabolites (amino acids and oligopeptides). In silico toxicology analysis indicated that this sample did not exhibit toxicity. Furthermore, in vitro cytotoxicity screening demonstrated no cytotoxic effects against NIH-3T3 cells, even at 400 μg mL-1. In general, these findings collectively indicated the absence of saponins, the presence of phytosterols and trigonellin (a pyridine alkaloid), and a low safety risk related to saponin and alkaloid content in the Sacha Inchi seeds.

Effectiveness and safety of apixaban and rivaroxaban vs warfarin in patients with atrial fibrillation and chronic kidney disease.

Randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) included a low proportion of atrial fibrillation (AF) patients with chronic kidney disease (CKD), and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD. In a metanalysis of RCTs and observational studies, DOACs were associated with better efficacy (vs warfarin) in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD. But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD. The effectiveness and safety of DOACs in those patients are still subject to debate. To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population. A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, and death, whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation. Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards. A total of 8899 included patients filled out a new oral anticoagulation therapy claim; 3335 for warfarin and 5564 for DOACs. Compared with warfarin, 15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk. Apixaban 5.0 mg was associated with a lower effectiveness composite risk [Hazard ratio (HR) 0.76; 95% confidence interval (CI): 0.65-0.88] and a similar safety risk (HR 0.94; 95%CI: 0.66-1.35). Apixaban 2.5 mg was associated with a similar effectiveness composite (HR 1.00; 95%CI: 0.79-1.26) and a lower safety risk (HR 0.65; 95%CI: 0.43-0.99. Although, apixaban 5.0 mg was associated with a better effectiveness (HR 0.76; 95%CI: 0.65-0.88), but a similar safety risk profile (HR 0.94; 95%CI: 0.66-1.35). The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality (HR 0.61; 95%CI: 0.43-0.88). In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

Recent Advances of Using Exosomes as Diagnostic Markers and Targeting Carriers for Cardiovascular Disease.

Cardiovascular diseases (CVDs) are the leading cause of human death worldwide. Exosomes act as endogenous biological vectors; they possess advantages of low immunogenicity and low safety risks, also providing tissue selectivity, including the inherent targeting the to heart. Therefore, exosomes not only have been applied as biomarkers for diagnosis and therapeutic outcome confirmation but also showed potential as drug carriers for cardiovascular targeting delivery. This review aims to summarize the progress and challenges of exosomes as novel biomarkers, especially many novel exosomal noncoding RNAs (ncRNAs), and also provides an overview of the improved targeting functions of exosomes by unique engineered approaches, the latest developed administration methods, and the therapeutic effects of exosomes used as the biocarriers of medications for cardiovascular disease treatment. Also, the possible therapeutic mechanisms and the potentials for transferring exosomes to the clinic for CVD treatment are discussed. The advances, in vivo and in vitro applications, modifications, mechanisms, and challenges summarized in this review will provide a general understanding of this promising strategy for CVD treatment.

Achieving High Efficacy and Low Safety Risk by Balancing Pesticide Deposition on Leaves and Fruits of Chinese Wolfberry (Lycium barbarum L.).

Pesticide residue has become the main technical barrier that restricts the export of Chinese wolfberry. Can we achieve high efficacy and low safety risk by balancing pesticide deposition on the leaves and fruits of Chinese wolfberry? In this research, the structural characteristics and wettability of leaves and fruits of Chinese wolfberry at different growth stages were studied. The adaxial and abaxial surfaces of leaves were hydrophobic, whereas the fruit surfaces were hydrophilic. Adding spray adjuvant could increase the retention of droplets on the leaf surfaces of Chinese wolfberry by 52.28-97.89% and reduce the retention on the fruit surfaces by 21.68-42.14%. A structural equation model analysis showed that the adhesion tension was the key factor affecting the retention of the solutions among various interface behaviors. When the concentrations of Silwet618, AEO-5, Gemini 31551, and 1227 were 2-5 times higher than their CMCs, the retention of pesticide solutions (pyraclostrobin and tylophorine) on Chinese wolfberry leaves significantly increased, and the control efficacies on aphids and powdery mildew also dramatically improved (65.90-105.15 and 41.18-133.06%, respectively). Meanwhile, the retention of pesticides on the fruit of Chinese wolfberry was reduced. This study provides new insights into increasing the utilization of pesticides in controlling pests and improving food safety.

Identification of target materials for recycling of solid-state batteries from environmental and economic perspective using information theory entropy

Solid-state batteries (SSBs) are a promising emerging battery technology for electromobility application. Along with new technical opportunities (higher energy density, lower safety risks), they introduce new cell chemistry configurations and novel materials in use. This leads to increased complexity of material composition and may reduce the recyclability of SSBs. To ensure circularity of SSB materials, it is important to consider their recyclability at the early stage of SSB development. This paper proposes an approach for identification of target materials for recycling within three types of SSBs with polymer, oxide and sulfide electrolytes. To consider environmental and economic perspectives, interdependencies of material dilution, their cost and environmental material footprint are analyzed using Sherwood and global warming potential (GWP)-plots. Furthermore, a socio-geopolitical aspect of supply risk is considered as a relevant criterion for targeting materials. Li is identified as the main target material for all considered SSBs and Co as a further one for oxide- and sulfide-based cells. Furthermore, an upscaling scenario to a battery pack considered changes in concentration of target materials and revealed direct recycling of composite cathode LLZO and LCO to be very beneficial. Results of this approach can be used by SSB developers and recyclers in order to strive for holistic design enabling recycling of identified target materials.

Post COVID community based self-care management of disabling osteoarthritis: importance and possible targeted needs

Background: Osteoarthritis, a highly common, disabling joint disease affecting a large number of older adults is presently incurable, and not always amenable to surgery or pharmacologic interventions. Purpose: Further complicated by multiple past and ongoing COVID-19 pandemic issues and disease consequences, the purpose was to examine what current data reveal as to the prevailing epidemiological features of osteoarthritis and its pathology. Another was to review the utility of some non-pharmacological and non-operative treatment strategies that have been advocated for alleviating the pain and disability of this disease in later life. Methods: Building on a 35 year prior review conducted in 2015, this current review was conducted to identify relevant literature published on this topic over the last 5 years, particularly since COVID-19 onset in 2019. Key words included osteoarthritis, COVID-19, prevention, and intervention. Results: As in prior years, osteoarthritis continues to induce considerable physical disability and consistently impedes the attainment of a high life quality for many older adults. Although not studied to any degree, COVID-19 factors may be expected to render further challenges that compound the disease presentation and its mitigation over time, especially among the long COVID affected older adult. In the face of closures, limited resources, and complex disease presentations, it does appear a variety of non-operative and non-pharmacologic approaches may yet influence the disease process and functional outcomes more positively than not with low safety risks. They may help the older adult more effectively even if surgery is indicated and multiple medications are yet required. Conclusion: The application of one or more carefully designed conservative interventions is likely to reduce the functional disability and pain experienced by older people with any form of osteoarthritis, regardless of whether surgical and or pharmacologic strategies are indicated.

A protocol for Removing Environmental Barriers to Independent Living (REBIL): An adapted evidence-based occupational therapy intervention to increase community participation for individuals aging with long-term physical disabilities.

People aging with long-term physical disabilities (PAwLTPD) are living longer and experiencing the challenges of aging, including the onset of secondary and age-related health conditions. PAwLTPD are at high risk of falls, fall injuries, diminished functional abilities, and compromised participation. However, no available programs support PAwLTPD to participate safely at home and in the community. The proposed study is to examine the feasibility and efficacy of an adapted intervention: Removing Environmental Barriers to Independent Living (REBIL). A single-blinded randomized controlled trial (RCT) will be conducted. Participants who are 45-65 years old; self-report difficulty with ≥2 daily activities; have had a physical disability for ≥5 years; and live within 60 miles of the research lab are eligible. All participants will receive an initial in-home evaluation before randomization. The treatment group will receive REBIL (total five visits), which is tailored. The waitlist control group will be offered the same intervention after 6-month follow-up. Expected outcomes are high acceptability, fidelity, and adherence; low safety risk; improved community participation and daily activities performance; and fewer environmental barriers and fall hazards. Findings will serve as preliminary evidence for occupational therapy community practice. Outcomes will also inform future large, pragmatic trials. ClinicalTrials.gov identifier NCT04589988.

Automatic berthing using supervised learning and reinforcement learning

Although various studies have been conducted on automatic berthing, including offline optimization and online control, real-time berthing control remains a difficult problem. Online control methods without reference trajectories are promising for real-time berthing control. We used reinforcement learning (RL), which is a type of machine learning, to obtain an online control law without reference trajectories. As online control for automatic berthing is difficult, obtaining an appropriate control law with naive reinforcement learning is difficult. Furthermore, almost all existing online control methods do not consider port geometries. This study proposes a method for obtaining online berthing control laws by combining supervised learning (SL) and RL. We first trained the controller using offline-calculated trajectories and then further trained it using RL. Owing to the SL process, the proposed method can start the RL process with a good control policy. We evaluated the control law performance of the proposed method in a simulation environment that considered port geometries and wind disturbances. The experimental results show that the proposed method can achieve a higher success rate and lower safety risk than the naive SL and RL algorithms.

An Interdigitated Li‐Solid Polymer Electrolyte Framework for Interfacial Stable All‐Solid‐State Batteries

AbstractAll‐solid‐state lithium metal batteries are prominent candidates for next‐generation batteries with high energy density and low safety risks. However, the traditional planar contact between Li metal and solid‐state electrolytes (SSEs) exhibits substantive void formation and large interfacial morphological fluctuation, causing poor interfacial stability. Here, an interdigitated Li‐solid polymer electrolyte framework (I‐Li@SPE), a pioneering demonstration of 3D interface in polymer‐based all‐solid‐state batteries, is designed, transferring the Li‐SSE interfacial contact from planar to 3D for enhanced interfacial integrity. A smooth and intact 3D Li‐SSE interfacial contact after repeated cycling that precedes planar Li‐SSE contact, is shown. COMSOL simulation indicates I‐Li@SPE reduces local current densities by more than 40% and moderates interfacial variation by more than 50%. As a result, I‐Li@SPE achieves high critical current density of 1 mA cm−2, as well as promising high areal capacity cycling of 4 mAh cm−2 at 0.4 mA cm−2. This work provides a new structure for Li‐SSE composite fabrication and high‐capacity solid‐state Li batteries.

Hernandezine, a natural herbal alkaloid, ameliorates type 2 diabetes by activating AMPK in two mouse models

AMP-activated protein kinase (AMPK) is an effective target for treating diabetes. However, successful drug development is delayed due to issues including toxicity. Plant-derived natural product AMPK activators have emerged as a new way to treat diabetes due to its potential low safety risks. Here, we studied the effect of hernandezine (HER), a natural product derived from Thalictrum, in activating AMPK and treating T2D in mouse models. We tested HER in various cells and tissues, including primary hepatocytes, skeletal myotubes cell lines, as well as major metabolic tissues from diabetic (db/db) and diet-induced obesity (DIO) model mice. The effect of HER on glucose uptake via AMPK in vitro and in vivo was confirmed utilizing cell transfection and adenovirus interference analysis. Tissue staining assessed the effect of HER on adipogenesis. Real-time quantitative polymerase chain reaction (real-time PCR) was applied to verify the effect of HER on transcription factors. Western blot analysis was used to determine the activation of phosphorylated AMPK and ACC pathways. Biochemically, we found that HER prevented pAMPK from dephosphorylation to prolong its activity, disproving previous direct activation model and providing a new model to explain HER-mediated AMPK activation. HER could be orally delivered to animals and has a 3-fold long half-life in vivo as compared to metformin. Importantly, long-term oral HER treatment potently reduced body weight and blood glucose in both type 2 diabetes mullitus (T2DM) mouse models by increasing glucose disposal and reducing lipogenesis, and appeared not to induce cardiac hypertrophy. Natural product HER indirectly activates AMPK by suppressing its dephosphorylation. Oral HER effectively alleviated hyperglycemia and reduced body weight in T2D mouse models, appeared to have a low risk of causing cardiac hypertrophy, and might be a potential therapeutic option for T2DM.

Synthesis of hollow spherical polyaniline by using poly(styrene‐co‐acrylic acid) sphere as the template for high adsorption of Cr(VI)

AbstractSynthesis of hollow spherical polyaniline (HSPANI) with the merits of facile strategy, low cost, low safety risk and high adsorption capacity of Cr(VI) is always a big challenge. In this manuscript, we proposed a facile way to preparation of HSPANI by using the poly(styrene‐co‐acrylic acid) sphere as template. The results indicated that HSPANI was emeraldine comprised of lots of basically uniform hollow spheres, and its average pore diameter was about 300 nm. HSPANI displayed high adsorption capacity of Cr(VI), and its value arrived at 601.3, 347.8, 235 mg g−1 at pH = 1, 2, and 3, respectively, which were high than many other adsorbents. The endothermic, spontaneous and chemical adsorption process was responsible for this adsorption. The Cr(VI) adsorption capacity was significant relied on its pH, contact time, Cr(VI) concentration and adsorption temperature. The adsorption behavior was well agreed with pseudo second‐order equation and Redlich–Peterson isotherm models. HSPANI exhibited remarkable selectivity for adsorption of Cr(VI) even if the K+, Cu2+, NO3− and SO42− were coexisted. HSPANI also displayed excellent regeneration performance. Therefore, this work not only provided a facile way to synthesis of hollow spherical polyaniline, but also supplied a potential adsorbent for adsorption of Cr(VI) from the industrial wastewater.

Browning inhibition of plant extracts on fresh‐cut fruits and vegetables—A review

Fresh-cut fruits and vegetables are prone to browning which leads to quality decline, low acceptability, and food waste. Therefore, it is of great importance to study and alleviate the browning of fresh-cut fruits and vegetables. Plant extracts, rich in bioactive compounds like polyphenols, flavonoids, terpenes, and other active ingredients, exhibit high antioxidant and anti-browning ability. Many traditional physical and chemical methods have been used to prevent browning and were considered to cause high safety risk, off-flavor, and nutrients loss. As an alternative, plant extracts are strongly preferred due to their natural and safe nature. This review systematically summarizes the most recently reported plant extracts on browning inhibition of fresh-cut fruits and vegetables. It elaborates the type, anti-browning ability, extraction, and application techniques of plant extracts on fresh-cut fruits and vegetables. Moreover, the anti-browning mechanism is emphasized. This review provides new insight into the browning control of fresh-cut fruits and vegetables. Novelty impact statement Plant extracts exhibited a potent browning inhibition on fresh-cut fruits and vegetables. They have a wide range of sources, rich bioactive components, low safety risk, less impact on product quality, and higher consumer acceptance compared with the chemical anti-browning agents. The application of plant extracts combined with new extraction techniques has a promising effect on browning inhibition and shelf-life extension of fresh-cut fruits and vegetables. The action mechanism and prospect of plant extracts on browning inhibition of fresh-cut fruits and vegetables are the main focus in this area.

Mechanism of fungal inhibition activity of Nα-lauroyl-L-arginine ethyl ester (LAE) and potential in control of Penicillium expansum on postharvest citrus 'Benimadonna' (Citrus reticulata × Citrus sinensis).

Citrus 'Benimadonna' (Citrus reticulata × Citrus sinensis) is a high-value perishable fruit; thus there is an urgent need for a preservation technology with high effectiveness and low safety risk from industries. Nα-Lauroyl-l-arginine ethyl ester hydrochloride (LAE) was applied to enhance preservability by compounding with natamycin, and a possible fungal inhibition mechanism based on the hypothesis of an impact on the cell membrane by surfactant was investigated. In vitro testing showed that the minimum inhibitory concentration of LAE against Penicillium expansum (PE), isolated as the predominant spoilage-inducing fungus, was 32 mg L-1 and it was partially synergistic with natamycin. Subsequent in vivo testing proved the inhibition capacity. During 90 days' refrigerated preservation, spoilage rate was significantly decreased by preharvest spraying versus control without extra taste loss, and LAE showed an alleviating benefit on total pectin loss. Subsequently, electron microscopic imaging and intracellular protein levels of PE exposed to LAE indicated that LAE stress led to increased permeability and decreased cell integrity. Moreover, peroxidase, superoxide dismutase and catalase revealed that LAE enhanced oxidative stress, while pectinase was antagonized. The present investigation first introduced LAE as a candidate active ingredient for citrus preservative. A theoretical basis was provided for the development of preservation technology for high-value perishable fruit. According to the authors' knowledge this study is the first report on the inhibition mechanism of LAE in terms of oxidative stress. © 2022 Society of Chemical Industry.

Enhancing the Use of Flood Resilient Spatial Planning in Dutch Water Management. A Study of Barriers and Opportunities in Practice

Around the world, deltaic and coastal regions like the Netherlands are facing challenges from climate, change such as sea-level rise as well as more frequent and extreme natural events. Since 2009, the Dutch government has tried to mitigate flood vulnerability by deploying a balanced mix of flood protection measures, resilient spatial planning and crisis management (Multi-Layer Safety). However, recent evaluations have concluded that resilient spatial planning is (too) limitedly applied in practice. This article aims to understand the barriers and opportunities for resilient spatial planning in flood risk management by comparing two cases where resilient spatial planning was opted for: Dordrecht and the IJssel-Vecht Delta. The study suggests a large gap between the wide array of possible measures, and those that are actually realized in practice. Three physical-spatial barriers were identified: maximum flood depths, lack of space, and rigidity of the existing built environment. Additionally, institutional-organizational barriers were found, including: a false, low or non-existent safety perception or risk awareness, and therefore a lack of urgency to act; a lack of political and societal support; a suboptimal collaboration between stakeholders; ambiguity regarding responsibilities; finances and a cost-benefit imbalance; and a lack of human capital. Subsequently, the article explores possibilities to overcome these barriers. Overcoming these barriers can pave pathways for flood resilient spatial planning. The institutional-organizational barriers appear surmountable, whereas the physical-spatial barriers prove to be more problematic and form the most important restrictive factor for resilient spatial planning in flood risk management.

SARS-CoV-2 circulation in Croatian wastewaters and the absence of SARS-CoV-2 in bivalve molluscan shellfish

The circulation of SARS-CoV-2 in the environment has been confirmed numerous times, whilst research on the bioaccumulation in bivalve molluscan shellfish (BMS) has been rather scarce. The present study aimed to fulfil the knowledge gap on SARS-CoV-2 circulation in wastewaters and surface waters in this region and to extend the current knowledge on potential presence of SARS-CoV-2 contamination in BMS. The study included 13 archive wastewater and surface water samples from the start of epidemic and 17 influents and effluents from nine wastewater treatment plants (WWTP) of different capacity and treatment stage, sampled during the second epidemic wave. From that period are the most of 77 collected BMS samples, represented by mussels, oysters and warty venus clams harvested along the Dalmatian coast. All samples were processed according to EN ISO 15216-1 2017 using Mengovirus as a whole process control. SARS-CoV-2 detection was performed by real-time and conventional RT-PCR assays targeting E, N and nsp14 protein genes complemented with nsp14 partial sequencing. Rotavirus A (RVA) real-time RT-PCR assay was implemented as an additional evaluation criterion of virus concentration techniques. The results revealed the circulation of SARS-CoV-2 in nine influents and two secondary treatment effluents from eight WWTPs, while all samples from the start of epidemic (wastewaters, surface waters) were negative which was influenced by sampling strategy. All tertiary effluents and BMS were SARS-CoV-2 negative. The results of RVA amplification were beneficial in evaluating virus concentration techniques and provided insights into RVA dynamics within the environment and community. In conclusion, the results of the present study confirm SARS-CoV-2 circulation in Croatian wastewaters during the second epidemic wave while extending the knowledge on wastewater treatment potential in SARS-CoV-2 removal. Our findings represent a significant contribution to the current state of knowledge that considers BMS of a very low food safety risk regarding SARS-CoV-2.