Novel indicators to better monitor the collection and recovery of (critical) raw materials in WEEE: Focus on screens.

Currently, in the European Union (EU), e-waste chain performance is assessed by technical indicators that aim to ensure system compliance with collection and recovery targets set by the WEEE Directive. This study proposes indicators to improve WEEE flow monitoring beyond the current overall weight-based approach, including complementary flows and treatment performance. A case study focused on the screen category in France is presented. In 2017, the collection rate of cathode-ray tube screens (CRT) was 68%, while for flat panel display (FPD) generated only 14% was collected. CRT screens have less precious and critical materials than FDP. Thus, elements like cobalt and gold highly concentrated in FPD, have a collection rate two to four times lower than elements such as copper (37%) which represents a high proportion in CRTs. Recycling is the main treatment in France. Nevertheless, the recycling rate per element varies significantly due to the low collection, and also the lack of technology and/or secondary raw materials market. The elements with higher recycling rates are base metals such as copper (28%), followed by precious metals like silver (23%), and gold (13%). Except for palladium, the recycling rate of the critical raw materials targeted in the study ranged from 6% (cobalt) to 0% (e.g. neodymium and indium). The results stress the need for indicators to support the development of WEEE chain from waste management to secondary (critical) raw materials suppliers.

Oxidative damage in metal fragment-embedded Sprague-Dawley rat gastrocnemius muscle.

Injuries suffered in armed conflicts often result in wounds with embedded metal fragments. Standard surgical guidance has been to leave fragments in place except under certain circumstances; meaning that individuals may carry these retained fragments for their lifetime. Because of advancements in weapon design and the use of improvised explosive devices, the list of metals that could be found in a wound is extensive. In most cases the toxicological properties of these metals when embedded in the body are not known. To assess the potential damage embedded metals may cause to surrounding tissue, we utilized a rodent model to investigate the effect of a variety of military-relevant metals on markers of oxidative damage. The metals tested included tungsten, nickel, cobalt, iron, copper, aluminum, lead, and depleted uranium. Herein we report our findings on creatine kinase activity, lipid and protein oxidation, total antioxidant capacity, and glutathione levels in gastrocnemius homogenates from Sprague-Dawley rats surgically implanted with metal pellets for periods up to 12 months. Not all embedded metals affected the measured markers equally. However, metal-associated effects were seen at various times for muscle and serum creatinine levels, protein oxidation, total antioxidant capacity, and glutathione levels. No metal-induced effects on lipid peroxidation were observed. Taken together, these data suggest that subtle oxidative damage may be occurring in the muscle surrounding an embedded metal and indicates the need for medical surveillance of those individuals wounded by metal shrapnel.

Advances in the development of biodegradable coronary stents: A translational perspective.

Implantation of cardiovascular stents is an important therapeutic method to treat coronary artery diseases. Bare-metal and drug-eluting stents show promising clinical outcomes, however, their permanent presence may create complications. In recent years, numerous preclinical and clinical trials have evaluated the properties of bioresorbable stents, including polymer and magnesium-based stents. Three-dimensional (3D) printed-shape-memory polymeric materials enable the self-deployment of stents and provide a novel approach for individualized treatment. Novel bioresorbable metallic stents such as iron- and zinc-based stents have also been investigated and refined. However, the development of novel bioresorbable stents accompanied by clinical translation remains time-consuming and challenging. This review comprehensively summarizes the development of bioresorbable stents based on their preclinical/clinical trials and highlights translational research as well as novel technologies for stents (e.g., bioresorbable electronic stents integrated with biosensors). These findings are expected to inspire the design of novel stents and optimization approaches to improve the efficacy of treatments for cardiovascular diseases.

Roles and current applications of S-nitrosoglutathione in anti-infective biomaterials.

Bacterial infections can compromise the physical and biological functionalities of humans and pose a huge economical and psychological burden on infected patients. Nitric oxide (NO) is a broad-spectrum antimicrobial agent, whose mechanism of action is not affected by bacterial resistance. S-nitrosoglutathione (GSNO), an endogenous donor and carrier of NO, has gained increasing attention because of its potent antibacterial activity and efficient biocompatibility. Significant breakthroughs have been made in the application of GSNO in biomaterials. This review is based on the existing evidence that comprehensively summarizes the progress of antimicrobial GSNO applications focusing on their anti-infective performance, underlying antibacterial mechanisms, and application in anti-infective biomaterials. We provide an accurate overview of the roles and applications of GSNO in antibacterial biomaterials and shed new light on the avenues for future studies.

Single domain antibodies derived from ancient animals as broadly neutralizing agents for SARS-CoV-2 and other coronaviruses.

With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.

Increase of Cardiometabolic Biomarkers Among Vehicle Inspectors Exposed to PM0.25 and Compositions.

BACKGROUND: Exposure to particulate matter (PM) emitted from vehicle exhaust might disrupt systemic function and elevate the risk of cardiovascular disease. In this study, we examined the changes of cardiometabolic biomarkers among vehicle inspectors exposed daily to PM0.25 and components. METHODS: This cross-sectional study was conducted at two vehicle inspection centers, Pulogadung and Ujung Menteng, located in East Jakarta, Indonesia. The exposed respondents were 43 workers from vehicle inspection centers, and the unexposed group consisted of 22 staff officers working in the same locations. Vehicle exhaust particulate matter was measured for eight hours using a Leland Legacy personal pump attached to a Sioutas Cascade Impactor. The used filters were 25 and 37-mm quartz filters. The particulate matter concentration was analyzed using a gravimetric method, whereas trace elements were analyzed using energy dispersive X-ray fluorescence. An EEL Smoke Stain Reflectometer analyzed black carbon. RESULTS: The personal exposure concentrations of PM0.25 were 10.4-fold higher than those in unexposed groups. Calcium and sulfur were the major components in the obtained dust, and their levels were 3.3- and 7.2-fold higher, respectively, in the exposed group. Based on an independent-samples t-test, high-density lipoprotein, triglyceride, HbA1c, total immunoglobulin E, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and nitric oxide levels were significantly different between the groups. CONCLUSIONS: In summary, it was suggested that PM0.25 exposure from vehicle exhaust might affect cardiometabolic biomarkers change.

Health risk assessment of Cd, Cr, Cu, Ni and Pb in the muscle, liver and gizzard of hen's marketed in East of Iran.

The present study aimed to determine the average concentration of some metals, including cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni) and lead (Pb) in the chicken, hen's liver, and gizzard in the east of Iran. Estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI) and carcinogenic risk (CR) were calculated. In this cross-sectional study, fifty one samples including chicken, hen's liver and gizzard were obtained from Birjand, Iran. Measurement of Cd, Cr, Cu, Ni, and Pb was carried out by using an Inductively Coupled Plasma-Optic Emission Spectroscopy (ICP-OES). All of the measured metals were detected in 100 % of the samples. The metals had a different distribution pattern. The highest concentration of Cd and Cu was in the liver samples while the Cr and Ni had the highest levels in the chicken. Pb concentration was at the highest level in the gizzard. The least amount of Cr, Ni, and Pb was found in the liver while Cu had the least content in the muscle. EDI had an acceptable level, but the highest daily intake of all studied metals was through muscle. Cr had the highest THQ and it was more than one in the meat. HI in chicken was more than one. Liver and gizzard of hens had a neglectable HI. CR was neglectable in the case of both Cd and Pb, but it was considerable for Cr and Ni. The consumption of chicken in both adults and children may pose a significant health risk for consumers.

Effect of embedded metal fragments on urinary metal levels and kidney biomarkers in the Sprague-Dawley rat.

BACKGROUND: Wounds with embedded metal fragments are an unfortunate consequence of armed conflicts. In many cases the exact identity of the metal(s) and their long-term health effects, especially on the kidney, are not known. AIM OF STUDY: The aim of this study was to quantitate the urinary levels of metals solubilized from surgically implanted metal pellets and to assess the effect of these metals on the kidney using a battery of biomarker assays. MATERIALS AND METHODS: Using a rodent model system developed in our Institute to simulate embedded fragment injuries, eight metals considered likely components of an embedded fragment wound were individually implanted into the gastrocnemius muscle of male Sprague-Dawley rats. The rats were followed for 12 months post-implantation with urine collected prior to surgery then at 1-, 3-, 6-, 9-, and 12-months post-implantation to provide a within-subjects cohort for examination. Urinary metal levels were determined using inductively coupled plasma-mass spectrometry and urinary biomarkers assessed using commercially available kits to determine metal-induced kidney effects. RESULTS: With few exceptions, most of the implanted metals rapidly solubilized and were found in the urine at significantly higher levels than in control animals as early as 1-month post-implantation. Surprisingly, many of the biomarkers measured were decreased compared to control at 1-month post-implantation before returning to normal at the later time points. However, two metals, iron and depleted uranium, showed increased levels of several markers at later time points, yet these levels also returned to normal as time progressed. CONCLUSION: This study showed that metal pellets surgically implanted into the leg muscle of Sprague-Dawley rats rapidly solubilized with significant levels of the implanted metal found in the urine. Although kidney biomarker results were inconsistent, the changes observed along with the relatively low amounts of metal implanted, suggest that metal-induced renal effects need to be considered when caring for individuals with embedded metal fragment wounds.

Endocytosis of nutrient transporters in fungi: The ART of connecting signaling and trafficking.

Plasma membrane transporters play pivotal roles in the import of nutrients, including sugars, amino acids, nucleobases, carboxylic acids, and metal ions, that surround fungal cells. The selective removal of these transporters by endocytosis is one of the most important regulatory mechanisms that ensures a rapid adaptation of cells to the changing environment (e.g., nutrient fluctuations or different stresses). At the heart of this mechanism lies a network of proteins that includes the arrestin-related trafficking adaptors (ARTs) which link the ubiquitin ligase Rsp5 to nutrient transporters and endocytic factors. Transporter conformational changes, as well as dynamic interactions between its cytosolic termini/loops and with lipids of the plasma membrane, are also critical during the endocytic process. Here, we review the current knowledge and recent findings on the molecular mechanisms involved in nutrient transporter endocytosis, both in the budding yeast Saccharomyces cerevisiae and in some species of the filamentous fungus Aspergillus. We elaborate on the physiological importance of tightly regulated endocytosis for cellular fitness under dynamic conditions found in nature and highlight how further understanding and engineering of this process is essential to maximize titer, rate and yield (TRY)-values of engineered cell factories in industrial biotechnological processes.

Promotion of cadmium uptake and cadmium-induced toxicity by the copper transporter CTR1 in HepG2 and ZFL cells.

Cadmium (Cd2+) is considered a human carcinogen as it causes oxidative stress and alters DNA repair responses. However, how Cd2+ is taken up by cells remains unclear. We hypothesized that Cd2+ could be transported into cells via a membrane copper (Cu) transporter, CTR1. CTR1 expression was not affected by Cd2+ exposure at the mRNA or protein level. Stable cell lines overexpressing either hCTR1, in the human liver cell line HepG2, or zCTR1, in the zebrafish liver cell line ZFL, were created to study their responses to Cd2+ insult. It was found that both HepG2 and ZFL cells overexpressing CTR1 had higher Cd2+ uptake and thus became sensitive to Cd2+. In contrast, hCTR1 knockdown in HepG2 cells led to a reduced uptake of Cd2+, making the cells relatively resistant to Cd2+. Localization studies revealed that hCTR1 had a clustered pattern after Cd2+ exposure, possibly in an attempt to reduce both Cd2+ uptake and Cd2+-induced toxicity. These in vitro results indicate that CTR1 can transport Cd2+ into the cell, resulting in Cd2+ toxicity.

Oxidative stress and apoptotic effects of copper and cadmium in the zebrafish liver cell line ZFL.

Copper (Cu) and cadmium (Cd) are widely used in industrial activities, resulting in Cu and Cd contamination in aquatic systems worldwide. Although Cu plays an essential role in many biological functions, an excessive amount of the metal causes cytotoxicity. In contrast, Cd is a non-essential metal that usually co-exists with Cu. Together, they cause oxidative stress in cells, leading to cell damage. These metal ions are also believed to cause cell apoptosis. In this study, we used a zebrafish liver cell line, ZFL, to study combined Cu and Cd cytotoxicity. Although Cd is more toxic than Cu, both were found to regulate the expression of oxidative stress related genes, and neither significantly altered the activity of oxidative stress related enzymes. Co-exposure tests with the antioxidant N-acetyl-l-cysteine and the Cu chelator bathocuproinedisulfonic acid disodium salt demonstrated that Cd toxicity was due to the oxidative stress caused by Cu, and that Cu at a low concentration could in fact exert an antioxidant effect against the oxidative stress in ZFL. Excessive Cu concentration triggered the expression of initiator caspases (caspase 8 and caspase 9) but suppressed that of an executioner caspase (caspase 3), halting apoptosis. Cd could only trigger the expression of initiator caspases; it could not halt apoptosis. However, a low concentration of Cu reduced the mitochondrial superoxide level, suppressing the Cd-induced apoptotic effects in ZFL.

Effects of soil properties on accumulation characteristics of copper, manganese, zinc, and cadmium in Chinese turnip.

Clarifying the mechanisms of heavy metal (HM) accumulation and translocation from soil-root-leaf is crucial to coping with soil HM pollution. In this study, we analysed copper (Cu), manganese (Mn), zinc (Zn) and cadmium (Cd) accumulation characteristics in Chinese turnips and the effect of soil physicochemical properties on both HM accumulation and translocation. Our results indicate that Chinese turnips absorb and translocate Mn, Zn, and Cd at much higher levels than they do Cu. When we measured bioconcentration factors in Chinese turnips for different HMs in the same soil, we found Chinese turnip capacities for HM accumulation decrease from Zn > Mn > Cd > Cu. In addition, the translocation factor for these HMs decreases from Mn > Cd > Zn > Cu. Correlation analysis indicates that soil pH and various soil components are either negatively or positively correlated with Mn, Zn, and Cd accumulation; also, soil properties are correlated with Mn translocation from root to leaf. These findings may help evaluate HM accumulation and translocation mechanisms as well as artificially regulate HM uptake levels from soils to turnips.

Wilson's Disease: Clinical Practice Guidelines of the Indian National Association for Study of the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the Movement Disorders Society of India.

Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system - Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties.

Bombesin functionalized 64Cu-copper sulfide nanoparticles for targeted imaging of orthotopic prostate cancer.

Aim: To synthesize and evaluate the imaging potential of Bom-PEG-[64Cu]CuS nanoparticles (NPs) in orothotopic prostate tumor. Materials & methods: [64Cu]CuS NPs were synthesized in aqueous solution by 64CuCl2 and Na2S reaction. Then PEG linker with or without bombesin peptide were conjugated to the surface of [64Cu]CuS NPs to produce Bom-PEG-[64Cu]CuS and PEG-[64Cu]CuS NPs. These two kinds of NPs were used for testing specific uptake in prostate cancer cells in vitro and imaging of orthotopic prostate tumor in vivo. Results: Bom-PEG-[64Cu]CuS and PEG-[64Cu]CuS NPs were successfully synthesized with core diameter of approximately 5 nm. Radioactive cellular uptake revealed that Bom-PEG-[64Cu]CuS was able to specifically bind to prostate cancer cells, and the microPET-CT imaging indicated clear visualization of orthotopic prostate tumors. Conclusion: Radiolabeled Bom-PEG-[64Cu]CuS NPs have potential as an ideal agent for orthotopic prostate tumor imaging by microPET-CT.

Effects of steaming on contaminants of emerging concern levels in seafood.

Seafood consumption is a major route for human exposure to environmental contaminants of emerging concern (CeCs). However, toxicological information about the presence of CeCs in seafood is still insufficient, especially considering the effect of cooking procedures on contaminant levels. This study is one among a few who evaluated the effect of steaming on the levels of different CeCs (toxic elements, PFCs, PAHs, musk fragrances and UV-filters) in commercially relevant seafood in Europe, and estimate the potential risks associated with its consumption for consumers. In most cases, an increase in contaminant levels was observed after steaming, though varying according to contaminant and seafood species (e.g. iAs, perfluorobutanoate, dibenzo(ah)anthracene in Mytilus edulis, HHCB-Lactone in Solea sp., 2-Ethylhexyl salicylate in Lophius piscatorius). Furthermore, the increase in some CeCs, like Pb, MeHg, iAs, Cd and carcinogenic PAHs, in seafood after steaming reveals that adverse health effects can never be excluded, regardless contaminants concentration. However, the risk of adverse effects can vary. The drastic changes induced by steaming suggest that the effect of cooking should be integrated in food risk assessment, as well as accounted in CeCs regulations and recommendations issued by food safety authorities, in order to avoid over/underestimation of risks for consumer health.

Nitric oxide overcomes Cd and Cu toxicity in in vitro-grown tobacco plants through increasing contents and activities of rubisco and rubisco activase.

Toxic heavy metals such as cadmium (Cd) and copper (Cu) are global problems that are a growing threat to the environment. Despite some heavy metals are required for plant growth and development, others are considered toxic elements and do not play any known physiological role in plant cells. Elevated doses of Cd or Cu cause toxicity in plants and generate damages due to the stress condition and eventually cause a significant reduction in quantity and quality of crop plants. The nitric oxide (NO) donor sodium nitroprusside (SNP) is reported to alleviate the toxicity of some heavy metals like Cd and Cu. In the current study, the role of NO in alleviating stresses of Cd and Cu was investigated in in vitro-grown tobacco (Nicotiana tabacum) Based on plant growth, total chlorophyll contents, contents and activities of rubisco and rubisco activase. According to the results of this study, the growth and total chlorophyll contents of Cd/Cu stressed plants were hugely decreased in the absence of SNP, while the supplementation of SNP resulted in a significant increase of both fresh weight and total chlorophyll contents. Remarkable reductions of Rubisco and rubisco activase contents and activities were observed in Cd and Cu-induced plants. SNP supplementation showed the highest contents and activities of rubisco and rubisco activase compared to the control and Cu/Cd-stressed plants. Taken together, our findings suggest that SNP could play a protective role in regulation of plant responses to abiotic stresses such as Cd and Cu by enhancing Rubisco and Rubisco activase.

Regulation of Cu delivery to chloroplast proteins.

Plastocyanin is a copper (Cu)-requiring protein that functions in photosynthetic electron transport in the thylakoid lumen of plants. To allow plastocyanin maturation, Cu must first be transported into the chloroplast stroma by means of the PAA1/HMA6 transporter and then into the thylakoid lumen by the PAA2/HMA8 transporter. Recent evidence indicated that the chloroplast regulates Cu transport into the thylakoids via Clp protease-mediated turnover of PAA2/HMA8. Here we present further genetic evidence that this regulatory mechanism for the adjustment of intra-cellular Cu distribution depends on stromal Cu levels. A key transcription factor mediating Cu homeostasis in plants is SQUAMOSA promoter binding protein-like7 (SPL7). SPL7 transcriptionally regulates Cu homeostasis when the nutrient becomes limiting by up-regulating expression of Cu importers at the cell membrane, and down-regulating expression of seemingly non-essential cuproproteins. It was proposed that this latter mechanism favors Cu delivery to the chloroplast. We propose a 2-tiered system which functions to control plant leaf Cu homeostasis: SPL7 dependent transcriptional regulation of cuproproteins, and PAA2/HMA8 turnover by the Clp system, which is independent on SPL7.

Metals in obex and retropharyngeal lymph nodes of Illinois white-tailed deer and their variations associated with CWD status.

Prion proteins (PrP(C)) are cell membrane glycoproteins that can be found in many cell types, but specially in neurons. Many studies have suggested PrP(C)'s participation in metal transport and cellular protection against stress in the central nervous system (CNS). On the other hand PrP(Sc), the misfolded isoform of PrP(C) and the pathogenic agent in transmissible spongiform encephalopathies (TSE), has been associated with brain metal dyshomeostasis in prion diseases. Thus, changes in metal concentration associated with protein misfolding and aggregation have been reported for human and animal prion diseases, as well as for other neurodegenerative disorders, such as Parkinson's and Alzheimer's disease. The use of metal concentrations in tissues as surrogate markers for early detection of TSEs has been suggested. Studies on the accumulation of metals in free-ranging white-tailed deer have not been conducted. This study established concentrations of copper, iron, manganese, and magnesium in 2 diagnostic tissues used for CWD testing (obex and retropharyngeal lymph nodes (RLN)). We compared these concentrations between tissues and in relation to CWD status. We established reference intervals (RIs) for these metals and explored their ability to discriminate between CWD-positive and CWD-negative animals. Our results indicate that independent of CWD status, white-tailed deer accumulate higher concentrations of Fe, Mn and Mg in RLN than in obex. White-tailed deer infected with CWD accumulated significantly lower concentrations of Mn and Fe than CWD-negative deer. These patterns differed from other species infected with prion diseases. Overlapping values between CWD positive and negative groups indicate that evaluation of these metals in obex and RLN may not be appropriate as a diagnostic tool for CWD infection in white-tailed deer. Because the CWD-negative deer were included in constructing the RIs, high specificities were expected and should be interpreted with caution. Due to the low sensitivity derived from the RIs, we do not recommend using metal concentrations for disease discrimination.