Residual Toxicity Research Articles

Transformation behavior of hazardous jarosite into recyclable hematite in a solution with high concentrations of K+ and Na+

Iron in the leaching solution with high K+ and Na+ concentrations was usually precipitated as the typical hazardous and toxic jarosite residues. However, this method of treatment has been greatly restricted by increasingly strict environmental regulations. Here we propose that iron can be precipitated from the solution with high K+ and Na+ concentrations as recyclable hematite products by adjusting the concentration ratio of sodium and potassium ions in the solution. The transformation behavior of jarosite into hematite in high concentration potassium ion and sodium ion solution was explained based on collision theory. The results indicated that in instances where the concentration ratio of Na+/K+ is ≥ 4:1, the iron present in the solution can be effectively precipitated as a recyclable hematite product, as opposed to forming the conventional hazardous jarosite residue, even under conditions where the potassium ion concentration reaches levels as high as 4 g/L. On the other hand, thermodynamic and molecular dynamics simulations indicate that at a temperature of 185 °C, the decomposition transformation of Na-jarosite (32.64 kJ and 7.25 eV) is more energetically advantageous compared to that of K-jarosite (61.07 kJ and 15.31 eV). The results were verified by the leaching solution from smelting industry. The iron content in the residues is above 58%, the sulfur content is below 4%, the zinc content is below 1%, and the total iron concentration in the supernatant is about 4 g/L, reaching the production index of the smelting industry. The green, environmentally friendly, and recyclable separation of iron in a solution with high concentrations of potassium and sodium ions is achieved, which is of great significance for the treatment of iron-containing solution and wastewater in the chemical industry and metallurgy fields.

High-energy emulsification of Allium sativum essential oil boosts insecticidal activity against Planococcus citri with no risk to honeybees

AbstractThe ecotoxicological consequences of synthetic pesticides have encouraged stakeholders to search for eco-friendly pest control tools, like essential oils (EOs). Nano-delivery systems (nanoparticles and nano-emulsions) seem ideal for developing EO-based biopesticides, although production processes should be standardized and implemented. In this study, nano-emulsions loaded with a high amount of Allium sativum L. EO (15%) were developed using different mixed bottom-up/top-down processes. Garlic EO was chemically analyzed by gas chromatography-mass spectrometry (GC-MS) and formulations were physically characterized using Dynamic Light Scattering (DLS) apparatus. The insecticidal activity against Planococcus citri Risso (Hemiptera: Pseudococcidae) and selectivity toward Apis mellifera L. (Hymenoptera: Apidae) worker bees was evaluated. Garlic EO was mainly composed of sulphur components (96.3%), with diallyl disulphide and diallyl trisulphide as the most abundant compounds (37.26% and 28.15%, respectively). Top-down processes could produce stable nano-emulsions with droplet size in the nanometric range (< 200nm) and good polydispersity index (PDI < 0.2). In contrast, the bottom-up emulsion was unstable, and its droplet size was around 500nm after 24 hours. High-energy emulsification processes significantly increased the residual toxicity of garlic EO against 3rd instar P. citri nymphs, whereas the developed formulations were harmless to A. mellifera workers in topical application. This study confirmed that the production process significantly affected the physical properties and efficacy against target pests. The lack of adverse impact on honeybees denotated the potential of these formulations as bioinsecticides in organic and/or IPM programs, although further extended ecotoxicological studies are necessary.

Residual toxicity of pesticide active substance commonly used in tomato crop on the predator Nesidiocoris tenuis (Heteroptera: Miridae)

AbstractNesidiocoris tenuis (Reuter) (Heteroptera Miridae) is a key biological control agent of the tomato leaf miner Tuta absoluta (Meyrick). However, in cases of prey scarcity, this predator switches into a phytophagous pest causing ring injuries in stems of tomato plants. The aim of this study was to assess the side effects of dry residues and explore the presence of target site resistance mutations of 10 insecticides, two bioinsecticides, an acaricide and a fungicide widely applied in IPM, on adults of N. tenuis collected from two different regions of Crete; the Western and the Eastern side of the island during two successive years. Lethal toxicity trials were performed on sprayed tomato stems and toxicity of adults of N. tenuis was recorded 2 h, 7 and 14 days after exposure. At both populations, chlorpyrifos, acetamiprid and thiamethoxam were moderately harmful at the application day and slightly harmful 7 days after the application. Only chlorpyrifos maintained its toxicity for more than 7 days. All the rest tested pesticides (emamectin benzoate, abamectin, chlorantraniliprole+abamectin, chlorantraniliprole, deltamethrin, tebufenpyrad, spinosad, Bacillus thuringiensis var kurstaki, metaflumizone and myclobutanil) were classified as harmless. Additionally, analysis of insecticide target site sequences indicated the absence of resistance mutations in both populations. Overall, our findings illustrate the impact of 15 pesticides and their residual toxicity on the mortality rates of N. tenuis adults.

Risk Assessment of Antibiotics in Agricultural Environment

Antibiotics are widely used in animal husbandry, planting, and aquaculture in agricultural industries. A large amount of the parent antibiotics used are released into the environment through discharge via feces and urine, posing potential risks to human health and ecosystems. It is thus very important to understand how antibiotics in the agricultural environment threaten the ecological environment and human health. Accordingly, risk assessment of antibiotics in the environment has become the research focus in recent years. The aim of this study was to review the risk assessment methods of antibiotics. The results showed that the ecological environment risk has mainly been assessed by the risk quotient (RQ). Predicted no-impact concentrations (PNECs) are an important indicator for ecological environment risk assessment, but a definite value is still controversial. The hazard quotient (HQ) is generally used to assess health risks. At present, it is necessary to clarify the selection of antibiotic exposure pathways and toxicological thresholds. However, neither of these two methods have currently considered either mixed pollution or the risk of antibiotic metabolites. Further analysis indicated that the ecological risks of antibiotics in the water environment and feces/manure/soil environment were widespread, which had an impact on both the soil and water environment. The types of antibiotics with high risk were different for various cultivated types. The factors including test species, testing conditions, calculation methods, and soil types all affected the detection of PNECs. Human health risk caused by dietary intake of antibiotics was minimal, but it cannot be ignored given the seafood consumption in coastal areas. Moreover, quinolones have both high ecological and human health risks in the agricultural environment. Based on the amount of antibiotics in agriculture and the residual concentration or toxicity of antibiotics in the related environment, this study proposed a priority-control list of antibiotics in the agricultural environment and summarized the main problems in the current antibiotic risk assessment. It will provide helpful support for the scientific optimization of antibiotic risk assessment and the effective control of antibiotics in agricultural environments.

A phase 1 single-arm, open-label study of emavusertib (CA-4948) in combination with azacitidine and venetoclax in patients (pts) with acute myeloid leukemia (AML) in complete response (CR) with measurable residual disease (MRD).

TPS6587 Background: Emavusertib is a novel potent oral inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4) with additional inhibitory activity against FMS-like tyrosine kinase 3 (FLT3) and CDC-like kinases (CLK1/2/4). Inhibition of these 3 onco-proteins by emavusertib may address the unmet need for novel therapies in AML. Clinical studies with emavusertib monotherapy have demonstrated a significant reduction in AML blasts with clinical and molecular responses in pts with relapsed or refractory AML (Metzeler 2022). Azacitidine + venetoclax (aza+ven) is an approved therapy for newly diagnosed pts with AML, unfit for intensive chemotherapy. Pre-clinical studies have demonstrated that emavusertib in combination with aza+ven has synergistic and antileukemic effects. In the VIALE-A study, composite CR (CRc) (CR, CRh, or CRi) in the absence of MRD of <1 residual blast/1000 leukocytes (MRD negative [MRD−]) resulted in longer duration of response (DOR), event-free survival, and overall survival (OS) compared with AML pts who achieved CRc but were MRD+ (Pratz, 2022). Therefore, adding emavusertib to aza+ven in CR or CRh, MRD+ pts may convert MRD status without significant toxicity and become a potential new regimen in front-line therapy. Methods: This is a single-arm, open-label Phase 1 study of emavusertib in combination with first line aza+ven in AML pts ≥60 years of age who achieved CR or CRh with MRD+ status based on local testing. The primary objective is to determine a safe and tolerable dosing schedule for the triple combination. Secondary objectives include determining the MRD conversion rate, pharmacokinetics, DOR, and OS. The study will enroll approximately 24 pts at 5 to 10 sites globally. Pts will have received aza+ven as first line therapy and achieved CR or CRh after 1-6 cycles of aza+ven. If MRD status remains positive, emavusertib will be added to the existing aza+ven regimen. Key exclusion criteria include residual toxicities and significant comorbidities. In the first cohort, the starting emavusertib dose is 200 mg BID for 7 days per cycle of 28 days. The duration of emavusertib treatment will extend to 14 and 21 days, in subsequent cohorts. The pts will continue triple treatment (emavusertib+aza+ven) until consent withdrawal, disease progression, intolerable toxicity, or not achieving MRD- after 6 cycles of treatment. Enrollment to cohort 1 began in December 2023. (EU CT Number 2023-505828-58). Clinical trial information: 2023-505828-58.

Residual toxicities of some plant essential oils against Cotton Aphid, Aphis gossypii Glover

Residual toxicities of some plant essential oils against Cotton Aphid, Aphis gossypii Glover

Application of Chitosan as a Coagulant- A Preliminary Review

One of the best water treatment methods is to use coagulant. Coagulation with metal salts like aluminium or iron salt are commercially use in the treatment of turbid sea water today. However, this type of coagulant might leave toxic residue in the treated water since it is made up from metal or inorganic material. Thus it might affect the health if the water is use for drinking and such else. Several studies on synthetic and organic polymer has been carried out in order to identify which polymer can works as a coagulant to replace the use of metal salts. Chitosan is natural polymer that can be used as a coagulant in the treatment of turbid sea water. Chitosan has been used at water purification system for detoxifying water. This might be due to its ability to form bond or coagulate with other particles. It is able to absorbs greases, oil, and other potential toxins and also have relatively lowest toxicity or risk for human since it is an organic. The contamination of water can affect both physical and chemical properties of water. Thus it is essential for the sea water to be treated to remove the turbidity so that the water can be used safely. There are many methods that can be used in the water treatment but may produce different properties of treated water. Some treated water may have poor microbiological quality which is unsafe to be use or consumed by human.

Actinobacteria as Promising Biocontrol Agents for In Vitro and In Planta Degradation and Detoxification of Zearalenone.

Zearalenone (ZEN) is a prevalent mycotoxin found in grains and grain-derived products, inducing adverse health effects in both animals and humans. The in-field application of microorganisms to degrade and detoxify ZEN is a promising strategy to enhance the safety of food and feed. In this study, we investigated the potential of three actinobacterial strains to degrade and detoxify ZEN in vitro and in planta on wheat ears. The residual ZEN concentration and toxicity in the samples were analysed with UHPLC-MS/MS and a bioluminescence BLYES assay, respectively. Streptomyces rimosus subsp. rimosus LMG19352 could completely degrade and detoxify 5 mg/L ZEN in LB broth within 24 h, along with significant reductions in ZEN concentration both in a minimal medium (MM) and on wheat ears. Additionally, it was the only strain that showed a significant colonisation of these ears. Rhodococcus sp. R25614 exhibited partial but significant degradation in LB broth and MM, whereas Streptomyces sp. LMG16995 degraded and detoxified ZEN in LB broth after 72 h by 39% and 33%, respectively. Although all three actinobacterial strains demonstrated the metabolic capability to degrade and detoxify ZEN in vitro, only S. rimosus subsp. rimosus LMG19352 showed promising potential to mitigate ZEN in planta. This distinction underscores the importance of incorporating in planta screening assays for assessing the potential of mycotoxin-biotransforming microorganisms as biocontrol agents.

Kinetics of Vegetable Oils (Rice Bran, Sunflower Seed, and Soybean) Extracted by Pressurized Liquid Extraction in Intermittent Process

The research focuses on optimizing vegetable oil production processes for human consumption, emphasizing green and efficient extraction methods using renewable solvents with minimal toxic residues. Pressurized liquid extraction (PLE), especially with ethanol, is studied for its efficiency and low solvent usage in intermittent processes. By evaluating extraction parameters and kinetics, the study aims to determine optimal conditions for higher extraction rates and yields, providing insights into production costs and other factors. Specifically, the research examines the behavior of extraction kinetics for vegetable oils like rice bran, sunflower seeds, and rolled soybeans. It also seeks to determine mass diffusivity in semi-continuous processes and to model PLE in intermittent processes using Fick’s Law and Mathematica Wolfram Software v11.2. The effective diffusivity (Deff) for rice bran oil in pressurized ethanol varied between 13.09 and 15.70 × 10−12 m2/s, and the Deff value of sunflower seed oil was between 8.10 and 12.60 × 10−12 m2/s. For rolled soybean oil, the Deff value ranged from 17.25 to 31.29 × 10−12 m2/s. The mass diffusivity values of vegetable oils in pressurized ethanol remained within the same order of magnitude. The mass diffusivity for PLE in an intermittent process presented values of 5.97 × 10−12 m2/s for rice bran oil with 3 extraction cycles. The Deff value for sunflower seed oil in pressurized ethanol was 1.38 × 10−12 m2/s, with 4 cycles, and for rolled soybeans, the Deff value was 1.77 × 10−12 m2/s in 3 cycles. The Deff value found in the intermittent extraction process was lower than that in the semi-continuous process. The total solvent renewal in the semi-continuous extraction process significantly impacted the diffusivity values for all extracted oils, as this process utilizes much more solvent compared to the intermittent process for all matrices studied. Various factors, including geometry, average particle diameter, extraction temperature, and rinse solvent volume, can affect the differences in curve behavior between the semi-continuous and intermittent processes. Despite these factors, the intermittent process is considered more viable for implementation due to its favorable economic and environmental characteristics, primarily because it requires a much smaller amount of solvent.

Impact of Plant Extracts on the Pollination Activity of <i>Apis mellifera</i> Linnaeus, 1758 (Hymenoptera: Apidae) on Flowers of Cowpea Variety Feekem, in Dang (Adamaoua, Cameroon)

Synthetic pesticides present worldwide risks of contamination of humans, livestock and the environment due to the strong persistence and the toxic residues in fruits and vegetables. Natural biopesticides of local plant origin present low persistence and are the best alternative for the control of crop pests. In the Adamaoua region (Northern Cameroon), few studies exist concerning effects of botanical pesticides on the behavior of beneficial insects. Studies aimed to draw up a list of pollinating insects on flowers of <i>Vigna unguiculata </i>(L.) Walp., 1843 (Fabales: Fabaceae), in situations of treatment with botanical pesticides compared to the situation of the use of synthetic insecticide and to determine the effect of the biopesticides on the behavior of the main floricultural insects. Field investigations were carried out during two cowpea cultivation campaigns (June to September 2021 and June to October 2022) in Dang (suburb of Ngaoundere) on the effect of leaves extracts of local plant origin on the foraging behavior of <i>Apis mellifera</i> Linnaeus, 1758 (Hymenoptera: Apidae) and the main sap-sucking insect <i>Aphis craccivora </i>Koch, 1854 (Hemiptera: Aphididae). Forty-four cowpea plots of 4x3.5 m each distributed according to the randomized complete block model (four untreated plots as negative control, four plots treated with the synthetic insecticide Parastar (40EC 535/ 10/IN, 20 g/l of imidacloprid and 20 g/l of lamda-cyhalothrin) as positive control, and 36 experimental plots treated with three concentrations (10%, 20% and 30%) of aqueous leaves extract of <i>Calotropis procera</i> (Gentianales: Apocynaceae), <i>Eucalyptus camaldulensis </i>(Myrtales: Myrtaceae), and <i>Tithonia diversifolia</i> (Asterales: Asteraceae) respectively, made it possible to conduct four treatments: (1) flowers left to freely pollination, (2) flowers protected against pollinators, (3) flowers visited exclusively by <i>Ap. mellifera</i> and (4) flowers protected against insects. Among eight species (four orders, four families and seven genera) recorded on the flowers of <i>V. unguiculata</i>, the domestic bee <i>Ap. mellifera</i> was the most common and collected nectar and pollen. The control plots and those treated with 10% or 20% aqueous leaves extracts allowed the bee to carry out its activity. Plots treated with 30% extract of each plant and those treated with the synthetic insecticide Parastar, drastically altered the rhythm and speed of activity in <i>Ap. mellifera</i> foragers. This behavior became less coordinated and slow on treated plants. It would be wise to use 10% or 20% aqueous extracts as botanical insecticides and an alternative to the synthetic insecticide Parastar.

Carbon Emission Pathways of Biodegradable Thermoplastic-based Species in Natural and Simulated Aqueous Conditions

This study assessed the carbon emission pathways of the biodegradation processes of bio-based thermoplastic moieties in two aqueous (surface and simulated marine water) environments and its implications on environmental quality. The physicochemical parameters of the aqueous media were determined using standard methods. The American Society for Testing and Materials’ standard was used to assess amount of CO2 evolved. Cellulose, bioplastic and polyethylene were inserted in two aquatic environments and arranged thrice in a randomized experimental arrangement of 2x4x3. Ultimate biodegradations of the test films were monitored using Scanning Electron Microscopy (SEM). The amount of CO2 evolved was assayed using the titration method. Data obtained were subjected to descriptive and inferential statistical analyses using Statistical Packages for Social Sciences (SPSS) version 25.0. After biodegradation, the initial values of the physicochemical parameters were within recommended values of the WHO standards with slight (less than 2%) differences. Moreover, CO2 captured from the two aqueous conditions were lower than the amount of CO2 evolved in aqueous solution with cellulose which is a natural polymer in this order: 88.725×102 mg from the soaked cellulose samples in marine > 85.215×102 mg of CO2 evolved from cellulose entrenched in surface water > 82.758×102 mg of CO2 evolved from bioplastic soaked in marine water > 82.758×102 mg of CO2 evolved from bioplastic soaked in surface water > 65.046×102 mg of CO2 evolved from polyethylene soaked in marine water > 60.152×102 mg of CO2 evolved from polyethylene soaked in surface water. Moreover, the SEM results revealed high level of biodegradation and growth of biofilm on the biodegradable thermoplastics while the nylon 6 had little or no biofilm growth because of the recalcitrant nature. This study concluded that some biodegradable thermoplastics can biodegrade totally in aquatic environments without the release of greenhouse gases that could threaten the integrity of the aquatic environment as well as the release of toxic residues.

Application of green synthesized Ag and Cu nanoparticles for the control of bruchids and their impact on seed quality and yield in greengram

Storage pests, particularly bruchids, are major biotic constraints causing significant storage losses in pulses. Conventional control methods relying on insecticides and fumigants often lead to food contamination due to toxic pesticide residues and a rapid decline in seed germination. In this investigation, through green nano-technological application, a promising and sustainable alternative for pest management is developed. Silver and copper nanoparticles were synthesized through ocimum leaf extract. The characterization of silver and copper nanoparticles was carried out by UV-spectroscopy, particle size analyzer, scanning electron microscopy, X-ray diffraction, and Fourier-transform infrared. Both the nanoparticles were spherical and crystalline in nature. Greengram seeds were primed with standardized silver and copper nanoparticles at different concentrations (1000, 1500, and 2000 ppm) and compared with castor-treated, deltamethrin-treated, and untreated control seeds for seed quality, growth, and yield. After one month of storage, all the pulse beetles released in different treatments exhibited 100 % mortality, whereas in control, the insects multiplied. At the end of nine months, the control seeds had shown 72 % damage and 39.67 % germination. In contrast, silver nanoparticles at 1000 ppm showed no seed damage and achieved 81.67 % germination, which was on par with copper nanoparticles at 1000 ppm with 79.33 % germination. Seed priming of silver and copper nanoparticles at 1000 ppm also demonstrated superior performance in all the seed quality and biochemical parameters (alpha amylase and catalase) throughout the storage period. Whereas, in the greenhouse experiment, enhanced growth (35.96 cm, 46.48 cm, and 53.00 cm at 30, 60 DAS, and at harvest, respectively) and yield per plant (3.75 g) were significantly higher in plants that were given foliar application with silver nanoparticles at 1000 ppm. Furthermore, foliar application of these nanoparticles at all concentrations (1000, 1500, and 2000 ppm) did not exhibit any adverse effects on soil microbial organisms, as assessed by dehydrogenase enzyme activity. Hence, this research highlights the potential use of silver and copper nanoparticles at 1000 ppm as effective tools for storage pest management and contributing to improved agricultural productivity and sustainability.

Mechanism Analysis of Antimicrobial Peptide NoPv1 Related to Potato Late Blight through a Computer-Aided Study.

Phytophthora infestans (Mont.) de Bary, the oomycotic pathogen responsible for potato late blight, is the most devastating disease of potato production. The primary pesticides used to control oomycosis are phenyl amide fungicides, which cause environmental pollution and toxic residues harmful to both human and animal health. To address this, an antimicrobial peptide, NoPv1, has been screened to target Plasmopara viticola cellulose synthase 2 (PvCesA2) to inhibit the growth of Phytophthora infestans (P. infestans). In this study, we employed AlphaFold2 to predict the three-dimensional structure of PvCesA2 along with NoPv peptides. Subsequently, utilizing computational methods, we dissected the interaction mechanism between PvCesA2 and these peptides. Based on this analysis, we performed a saturation mutation of NoPv1 and successfully obtained the double mutants DP1 and DP2 with a higher affinity for PvCesA2. Meanwhile, dynamics simulations revealed that both DP1 and DP2 utilize a mechanism akin to the barrel-stave model for penetrating the cell membrane. Furthermore, the predicted results showed that the antimicrobial activity of DP1 was superior to that of NoPv1 without being toxic to human cells. These findings may offer insights for advancing the development of eco-friendly pesticides targeting various oomycete diseases, including late blight.

Modification of the incinerator to prevent the emission of toxic air pollutant in biomedical waste incineration process at Base Hospital Udugama

Modification of the incinerator to prevent the emission of toxic air pollutant in biomedical waste incineration process at Base Hospital Udugama

Effectiveness of Soil-amended Biochar in Improving Crop Production, Soil Health and Environmental Aspects

Effectiveness of Soil-amended Biochar in Improving Crop Production, Soil Health and Environmental Aspects

PROSOPIS AFRICANA EXTRACTS AS POTENTIAL NATURAL ALTERNATIVES TO SYNTHETIC ANTIBIOTICS AND A KEY FOR SUSTAINABLE BROILER PRODUCTION: A REVIEW

The chicken sector is more vulnerable to antimicrobial resistance, the buildup of toxic or dangerous residues in meat and eggs and environmental contamination as a result of the widespread and careless use of antibiotics in most nations. Natural solutions, such as medicinal plants, are required to address these issues. These plants have been shown to contain a variety of phytochemicals, including phenols, flavonoids, terpenoids, tannins, alkaloids and saponins. These chemicals endow plants with a multitude of medicinal qualities. One of the many alternatives to antibiotics is Prosopis africana extract, which includes stem bark, leaves, roots and their essential oils. Antioxidant, antibacterial, antifungal, anti-helminthic, antiviral, hepatoprotective, immune-stimulatory and antimicrobial properties are among the many pharmacological activity of P. africana preparations. They are also an abundant supplier of vital minerals and amino acids that support enzyme function and provide defense against the effects of oxidative stress. Using extracts from Prosopis africana is the way forward for effective chicken production, environmental sustainability and food hygiene.

A One Health Epidemiological Approach for Understanding Ticks and Tick-Borne Pathogens.

Background: The control and prevention of ticks and tick borne diseases (TBDs) is often difficult, since it is necessary to disrupt a complex transmission cycle, involving ticks and vertebrate hosts, which interact in a changing environment, driven by constant environmental and ecological changes. Our view is that factors driving the spread of R. microplus are complex and intrinsically interconnected, something that has often been ignored in control strategies. Results: The aim of this review is to analyze the importance of the epidemiological surveillance of ticks and tick-borne diseases (TTBDs) for Public Health, with the One Health approach; emphasizing the knowledge, importance, and distribution of TTBDs. Conclusions: The key points for surveillance, and raising the scope and limitations of surveillance programs, to delay the emergence of acaricide resistance, to reduce toxic residues in food for human consumption and to protect animal, human, and environmental health, from a One Health perspective will require calling producers, veterinarians, academics, pharmaceutical industry, and decision makers to join efforts in order to mitigate the effects of ticks and TBDs affecting the cattle industry in Mexico.

Hierarchically porous coralloid ZnO@Ag microspheres as SERS substrate for highly sensitive malachite green detection

The improper management and unreasonable use of malachite green (MG) in aquatic transportation and large-scale aquaculture pose a significant threat to human health. It is crucial to develop a rapid and reliable approach for detecting MG. In this study, hierarchically porous coralloid ZnO@Ag (C–ZnO@Ag) microspheres were developed as a surface-enhanced Raman scattering (SERS) substrate to detect MG content in water. The hierarchical and porous structure supporting plenty of Ag nanoparticles provides numerous “hot spots” to excite the strong enhanced local electromagnetic field for enlarging the Raman signals of analytes. Moreover, C–ZnO@Ag generates an additional pathway to improve the charge transfer between the substrate and analytes. The manifold mechanisms resulted in the Raman enhancement factor as high as 1.61 × 107 when R6G was selected as the probe. The MG solution at an ultralow concentration of 10−9 M can be successfully identified using the C–ZnO@Ag substrate, which is much lower than the maximum MG residual concentration in water set by the European Union. Therefore, the C–ZnO@Ag substrate has promising opportunities to be applied in rapid SERS-based detection of toxic organic residues.

Thermo-responsive microneedles patch for transdermal drug delivery via squeezing in diabetic foot ulcers

Microneedle (MN) patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide. While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches, it can create toxic chemical residues or require the help of additional devices. Herein, a thermo-responsive microneedles patch (TMN) with high biocompatibility without additional equipment is proposed. The TMN consisted of a bilayer microneedles composed of sodium alginate (SA)-g-poly(N-isopropylacrylamide) layer (SA-g-PNIPAM) loaded with sucrose octasulfate sodium salt (SOS) and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride (TH) and SOS. PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes, and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation. The results showed that the drug release of TMN was significantly faster, with the drug release rate of more than 80% in the 10th h, and the antibacterial rate of TMN could reach 800%. In addition, TMN had good biocompatibility and good healing effects in vivo, which may be helpful for the design of multifunctional dressings in the future.

Dual Deletion of Keap1 and Rbpjκ Genes in Liver Leads to Hepatomegaly and Hypercholesterolemia.

The hepatic deletion of Rbpjκ (RbpjF/F::AlbCre) in the mouse leads to exhibition of the Alagille syndrome phenotype during early postnatal liver development with hyperlipidemia and cholestasis due to attenuated disruption of NOTCH signaling. Given the roles of NRF2 signaling in the regulation of lipid metabolism and bile ductal formation, it was anticipated that these symptoms could be alleviated by enhancing NRF2 signaling in the RbpjF/F::AlbCre mouse by hepatic deletion of Keap1 in compound Keap1F/F::RbpjF/F::AlbCre mice. Unexpectedly, these mice developed higher hepatic and plasma cholesterol levels with more severe cholestatic liver damage during the pre-weaning period than in the RbpjF/F::AlbCre mice. In addition, hypercholesterolemia and hepatic damage were sustained throughout the growth period unlike in the RbpjF/F::AlbCre mouse. These enhanced abnormalities in lipid metabolism appear to be due to NRF2-dependent changes in gene expression related to cholesterol synthetic and subsequent bile acid production pathways. Notably, the hepatic expression of Cyp1A7 and Abcb11 genes involved in bile acid homeostasis was significantly reduced in Keap1F/F::RbpjF/F::AlbCre compared to RbpjF/F::AlbCre mice. The accumulation of liver cholesterol and the weakened capacity for bile excretion during the 3 pre-weaning weeks in the Keap1F/F::RbpjF/F::AlbCre mice may aggravate hepatocellular damage level caused by both excessive cholesterol and residual bile acid toxicity in hepatocytes. These results indicate that a tuned balance of NOTCH and NRF2 signaling is of biological importance for early liver development after birth.