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[Display omitted] • SLF from WEEE can be transformed into a feedstock material for recycling. • base metals (Cu, Pb, Zn) and precious metals are concentrated in the solid product. • Continuous pyrolysis evidenced a substantial reduction of mass (50%) in the SLF. • Pyrolytic carbon from SLF can be used as reducing agent in the copper industry. • Continuous technology minimized oil production while maximizing permanent gas. The surge in Waste Electrical and Electronic Equipment (WEEE) generation, reaching 53.6 million metric tons (Mt) in 2019, demands efficient recycling solutions. This study focuses on the Shredder Light Fraction (SLF), a material stream derived from the mechanical pre-processing of WEEE, which is considered "municipal waste". SLF constitutes 4.2% of the output material and is rich in metals like copper, tin, lead, zinc, silver, and gold. Pyrolysis treatment was applied to SLF, enabling recyclability. Both batch and continuous setups were employed for materials flow analysis and technical evaluation of the resource potential. The research evaluates the impact of pyrolysis technology on solid fraction metal content and pyrolysis gas/oil energy potential. Scaling up the process addressed material heterogeneity and increased the reliability of the obtained results. An innovative pyrometallurgical extraction approach was suggested, to recover valuable metals in SLF which otherwise could be lost via energy recovery methods. The resulting solid product after pyrolysis showed enriched concentrations of copper, zinc, lead, and precious metals with concentrations acceptable for industrial use. Additionally, it displayed reduced mass and diminished hazardous constituents. The non-condensable gas, rich in hydrogen, carbon monoxide, and methane, exhibited potential as an alternative energy source or reducing agent in the metallurgical sector. This research advances metal recycling from SLF, offering valuable insights for environmental impact mitigation as waste was transformed into a valuable by-product for potential use in the copper industry. [ABSTRACT FROM AUTHOR]

[Display omitted] Albuterol is the drug most widely used as asthma treatment among African Americans despite having a lower bronchodilator drug response (BDR) than other populations. Although BDR is affected by gene and environmental factors, the influence of DNA methylation is unknown. This study aimed to identify epigenetic markers in whole blood associated with BDR, study their functional consequences by multi-omic integration, and assess their clinical applicability in admixed populations with a high asthma burden. We studied 414 children and young adults (8-21 years old) with asthma in a discovery and replication design. We performed an epigenome-wide association study on 221 African Americans and replicated the results on 193 Latinos. Functional consequences were assessed by integrating epigenomics with genomics, transcriptomics, and environmental exposure data. Machine learning was used to develop a panel of epigenetic markers to classify treatment response. We identified 5 differentially methylated regions and 2 CpGs genome-wide significantly associated with BDR in African Americans located in FGL2 (cg08241295, P = 6.8 × 10−9) and DNASE2 (cg15341340, P = 7.8 × 10−8), which were regulated by genetic variation and/or associated with gene expression of nearby genes (false discovery rate < 0.05). The CpG cg15341340 was replicated in Latinos (P = 3.5 × 10−3). Moreover, a panel of 70 CpGs showed good classification for those with response and nonresponse to albuterol therapy in African American and Latino children (area under the receiver operating characteristic curve for training, 0.99; for validation, 0.70-0.71). The DNA methylation model showed similar discrimination as clinical predictors (P >.05). We report novel associations of epigenetic markers with BDR in pediatric asthma and demonstrate for the first time the applicability of pharmacoepigenetics in precision medicine of respiratory diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS. Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data. In nasal and saliva samples, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 ≤ P ≤.037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 ≤ P ≤.046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 × 10−12 ≤ FDR ≤ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (AUC training : 0.82 and AUC validation : 0.77). The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite receipt of ICS. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the effects of the addition of EGTA to vitrification solutions and a post-warming recovery period supplemented with 1 μM resveratrol on meiotic spindle integrity, mitochondrial activity, ATP content, reactive oxygen species (ROS) levels, and developmental potential of partially denuded, vitrified-warmed bovine oocytes. Results of microtubule distribution and chromosomal arrangement indicated that resveratrol supplementation, irrespective to EGTA addition, reduced the incidence of abnormal meiotic spindles to similar levels of the control group. Mitochondrial membrane potential was similar in all groups, but ATP content was negatively affected by the vitrification-warming procedure and failed to recover after 4 h of post-warming culture. Resveratrol caused the reduction of ROS to lower levels of the control group, and showed the lowest ROS levels when combined with EGTA treatment. Oocytes in all vitrification groups presented lower developmental potential when compared to fresh oocytes. However, oocytes that underwent vitrification supplemented with EGTA and post-warming culture along with resveratrol showed higher developmental competence compared with vitrified-warmed oocytes not supplemented with resveratrol. The results of our study indicate that submitting vitrified-warmed, partially denuded bovine oocytes to a post-warming recovery period supplemented with 1 μM resveratrol improves vitrification outcomes. However, the benefits of EGTA on vitrification and warming of bovine oocytes need to be further investigated. • Post-warming incubation with 1 μM resveratrol recovers meiotic spindle morphology. • Post-warming recovery with resveratrol significantly reduces reactive oxygen species. • Resveratrol supplementation significantly increases cleavage and 8-cell embryo rates. • EGTA supplementation to vitrification solutions should be further studied. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the effects of vitrification on the meiotic spindle and mitochondrial function of bovine oocytes submitted to different times of post-warming culture. Partially denuded cumulus-oocyte complexes were vitrified at different maturation times (18-, 20-, and 24-h) using a two-step cryoprotectant addition protocol and submitted to 6-, 4-, or 0-h of post-warming extended culture in maturation medium. Microtubule configuration and chromosomal arrangement were analyzed after 0- and 6-h of extended culture, whereas mitochondrial membrane potential and ATP content were measured at 0-, 4-, and 6-h of post-warming recovery. Results of meiotic spindle integrity revealed that vitrified-warmed oocytes that underwent 6-h of culture had similar incidence of normal microtubule configuration and chromosomal arrangement as compared to fresh oocytes, but higher than oocytes in the vitrification control group (no culture). Mitochondrial membrane potential was not different in all the vitrification groups, but the oocytes that were cultured for 4-h after warming had similar levels compared to fresh oocytes. ATP concentration in all vitrification groups was lower than the control group. However, oocytes cultured for 6-h had the lowest rate of ATP depleted oocytes among the vitrification groups. The results of this study indicate that extended culture after warming promotes the recovery of the meiotic spindle and, to some extent, mitochondrial function of vitrified-warmed metaphase II bovine oocytes. • Vitrification negatively affects meiotic spindle morphology and mitochondrial function of vitrified-warmed oocytes. • Extended culture for 6-h recovered metaphase plate integrity of vitrified-warmed oocytes. • Extended culture reduces the rates of ATP depletion in vitrified oocytes. • Post-warming incubation for 4-h recovered mitochondrial membrane potential to similar levels of fresh oocytes. [ABSTRACT FROM AUTHOR]

Highlights: • For NMC, LFP, and pouch cells, combustion produces more off-gas than pyrolysis. • Penetration without TR produces less than 20% of the offgas during combustion. • Most toxic gases are: HF, COF 2 , acrolein, CO, formaldehyde, HCl, and electrolyte. • Off-gases generated during thermal and mechanical treatment are of acute toxicity. • For one single LFP cell, space of 379 m3 is required to ensure a safety environment. Abstract Recycling of Li-ion batteries (LIBs) is becoming an urgent issue. However, the chemical composition and the hazard of off-gas produced during the recycling process still remain unclarified due to the complicated reactions during thermal runaway (TR). In order to meet the legislative requirements to carry out an environmentally friendly recycling, this manuscript aims to undertake quantitative analysis and toxicity evaluation of the off-gas produced in mechanical treatment and thermal treatment of LIBs. The measurements were carried out by online Fourier transform infrared spectroscopy (FTIR) and ion chromatograph (IC). The volume of total off-gas was calculated and its toxicity was evaluated by USA's Protective Action Criteria. The influences of treatment method, state-of-charge (SOC), atmosphere, and type of cathode were investigated. [ABSTRACT FROM AUTHOR]

Satisfactory pregnancy rates can now be achieved following the cryopreservation of large equine embryos. Nonetheless, its wide application might be limited by the fact that the cryopreservation of large equine embryos requires a specialized micromanipulation equipment and micromanipulation/vitrification skills. Alternatives should be developed to increase its utilization and widespread application in the commercial equine industry. To determine if large equine embryos are able to remain viable during transport from farms to specialized centers for embryo cryopreservation, we evaluated pregnancy rates following the low-temperature storage of large equine embryos before vitrification. Grade 1 embryos (n = 37) were randomly assigned to six treatments consisting of day of collection (Day 7 or 8 after ovulation) and cooling for 0, 12, or 24 hours before vitrification in a factorial design. Pregnancy rates of Day 7 embryos cooled for 12 and 24 hours were 55.5% and 75%, respectively. Pregnancy rates of Day 8 embryos cooled for 12 and 24 hours were 0 and 16.6%, respectively. Day 7 cooled embryos resulted in higher pregnancy rate compared with Day 8 cooled embryos (64.7% and 7.7%, respectively; P < .05). Pregnancy rate comparison of cooled embryos grouped by diameter showed that embryos <550 μm resulted in a higher pregnancy rate compared with embryos >550 μm (71.4% and 12.5% respectively; P < .05). In conclusion, Day 7 equine embryos up to 550 μm can be cooled to temperatures of 9–12°C for 12 or 24 hours before vitrification and result in satisfactory pregnancy rates. [ABSTRACT FROM AUTHOR]

Alveolar epithelial type 2 (AT2) cells harbor the facultative progenitor capacity in the lung alveolus to drive regeneration after lung injury. Using single-cell transcriptomics, software-guided segmentation of tissue damage, and in vivo mouse lineage tracing, we identified the grainyhead transcription factor cellular promoter 2-like 1 (Tfcp2l1) as a regulator of this regenerative process. Tfcp2l1 loss in adult AT2 cells inhibits self-renewal and enhances AT2-AT1 differentiation during tissue regeneration. Conversely, Tfcp2l1 blunts the proliferative response to inflammatory signaling during the early acute injury phase. Tfcp2l1 temporally regulates AT2 self-renewal and differentiation in alveolar regions undergoing active regeneration. Single-cell transcriptomics and lineage tracing reveal that Tfcp2l1 regulates cell fate dynamics across the AT2-AT1 differentiation and restricts the inflammatory program in murine AT2 cells. Organoid modeling shows that Tfcp2l1 regulation of interleukin-1 (IL-1) receptor expression controlled these cell fate dynamics. These findings highlight the critical role Tfcp2l1 plays in balancing epithelial cell self-renewal and differentiation during alveolar regeneration. [Display omitted] • Tfcp2l1 maintains temporal and spatial AT2 self-renewal during lung regeneration • Tfcp2l1 regulates AT2-AT1 cell differentiation in regional zones of active regeneration • Tfcp2l1 dampens the early response to the inflammatory milieu through control of Il1r1 Cardenas-Diaz et al. use single-cell transcriptomics, software-guided segmentation of tissue damage, and mouse lineage tracing to interrogate the role of Tfcp2l1 in alveolar type 2 cells during lung regeneration. Tfcp2l1 regulates cell fate dynamics across AT2-AT1 differentiation and restricts the inflammatory program in murine AT2 cells. [ABSTRACT FROM AUTHOR]

Pregnancy rates after cryopreservation of large equine blastocyst stage embryos have remained lower than other domesticated livestock species. It is generally accepted that the embryonic capsule is the primary barrier to cryoprotectant entry into the embryo proper and techniques need to be developed to circumvent this obstacle. Therefore, the objective of this study was to develop an efficient Day 8 equine embryo cryopreservation protocol through blastocyst micromanipulation and vitrification. Grade 1 and 2 embryos recovered from mares (n = 15) 8 days after ovulation were used in these experiments. In experiment 1, the effect of either one- or two-puncture treatments before aspiration of blastocoel fluid and exposure to vitrification solutions was evaluated. No difference was detected in mean embryo volume across treatment groups after exposure to vitrification solutions or after 1, 24, 48, and 72 hours of culture. Percent of embryos re-expanding at 24 hours and percent of embryos showing diameter increase at 48 and 72 hours during in vitro culture were 100%, 83%, and 75% compared with 93%, 67%, and 50% for one- and two-puncture treatment groups, respectively. Capsule loss was 25% for one-puncture and 50% for two-puncture treatment groups. In experiment 2, no difference was detected in mean embryo volume for indirect introduction (aspiration of blastocoel fluid + equilibration) and direct introduction (injection of cryoprotectant into blastocoel cavity) treatment groups, after exposure to dilution solution or to culture medium. There was no difference in mean embryo volume for the indirect and direct introduction treatment groups after 1, 24, 48, and 72 hours of culture. Percent of embryos re-expanding at 24 hours and percent of embryos showing diameter increases at 48 and 72 hours during in vitro culture were 100%, 76.9%, and 69.2%, respectively, for both treatment groups. Those embryos subjected to the direct introduction treatment had a higher (P = 0.05) percent capsule loss (70%) compared with the indirect introduction treatment group (31%). The pregnancy rate after transfer of vitrified expanded Grade 1 blastocysts using the indirect introduction method was 83% (5/6). Three pregnancies were allowed to continue to term and resulted in the birth of three healthy foals. The vitrification protocol used in this study has the potential to become a key tool for the successful cryopreservation of equine expanded blastocysts. [ABSTRACT FROM AUTHOR]

There is an urgent need for antivirals to treat the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify new candidates, we screen a repurposing library of ∼3,000 drugs. Screening in Vero cells finds few antivirals, while screening in human Huh7.5 cells validates 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we find that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we find nine drugs are antiviral in respiratory cells, seven of which have been used in humans, and three are US Food and Drug Administration (FDA) approved, including cyclosporine. We find that the antiviral activity of cyclosporine is targeting Cyclophilin rather than calcineurin, revealing essential host targets that have the potential for rapid clinical implementation. [Display omitted] • 3,000 compounds screened in two cell types against SARS-CoV-2 • Entry pathways are distinct in hepatocyte Huh7.5 and respiratory Calu-3 cells • Only nine compounds that are active in Huh7.5 cells are active in Calu-3 cells • Cyclosporin and cyclophilin inhibitors block SARS-CoV-2 infection in diverse cells There is an urgent need for antivirals to treat the newly emerged SARS-CoV-2. Dittmar et al. find nine host-directed drugs are antiviral in respiratory cells, seven of which have been given to humans, and three are FDA approved. We show host targets that have the potential for rapid clinical implementation. [ABSTRACT FROM AUTHOR]

Alveolar epithelial cell fate decisions drive lung development and regeneration. Using transcriptomic and epigenetic profiling coupled with genetic mouse and organoid models, we identified the transcription factor Klf5 as an essential determinant of alveolar epithelial cell fate across the lifespan. We show that although dispensable for both adult alveolar epithelial type 1 (AT1) and alveolar epithelial type 2 (AT2) cell homeostasis, Klf5 enforces AT1 cell lineage fidelity during development. Using infectious and non-infectious models of acute respiratory distress syndrome, we demonstrate that Klf5 represses AT2 cell proliferation and enhances AT2-AT1 cell differentiation in a spatially restricted manner during lung regeneration. Moreover, ex vivo organoid assays identify that Klf5 reduces AT2 cell sensitivity to inflammatory signaling to drive AT2-AT1 cell differentiation. These data define the roll of a major transcriptional regulator of AT1 cell lineage commitment and of the AT2 cell response to inflammatory crosstalk during lung regeneration. [Display omitted] • Klf5 maintains AT1 cell lineage fidelity during development • Loss of Klf5 perturbs spatiotemporal AT2 cell fate choice after acute lung injury • Klf5 represses AT2 cell sensitivity to inflammatory signaling Liberti et al. show that Klf5 is required to maintain alveolar epithelial type 1 (AT1) versus type 2 (AT2) cell fate during murine lung development. Furthermore, they demonstrate that Klf5 represses adult AT2 cell responsiveness to inflammatory signaling to inhibit proliferation and promote differentiation during lung regeneration after acute injury. [ABSTRACT FROM AUTHOR]