Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling.

Despite advancements in treating cutaneous melanoma, patients with acral and mucosal (A/M) melanomas still have limited therapeutic options and poor prognoses. We analyzed 156 melanomas (101 cutaneous, 28 acral, and 27 mucosal) using the Foundation One cancer-gene specific clinical testing platform and identified new, potentially targetable genomic alterations (GAs) in specific anatomic sites of A/M melanomas. Using novel pre-clinical models of A/M melanoma, we demonstrate that several GAs and corresponding oncogenic pathways associated with cutaneous melanomas are similarly targetable in A/M melanomas. Other alterations, including MYC and CRKL amplifications, were unique to A/M melanomas and susceptible to indirect targeting using the BRD4 inhibitor JQ1 or Src/ABL inhibitor dasatinib, respectively. We further identified new, actionable A/M-specific alterations, including an inactivating NF2 fusion in a mucosal melanoma responsive to dasatinib in vivo. Our study highlights new molecular differences between cutaneous and A/M melanomas, and across different anatomic sites within A/M, which may change clinical testing and treatment paradigms for these rare melanomas.

Exploring single-cell RNA sequencing as a decision-making tool in the clinical management of Fuchs' endothelial corneal dystrophy.

Single-cell RNA sequencing (scRNA-seq) has enabled the identification of novel gene signatures and cell heterogeneity in numerous tissues and diseases. Here we review the use of this technology for Fuchs' Endothelial Corneal Dystrophy (FECD). FECD is the most common indication for corneal endothelial transplantation worldwide. FECD is challenging to manage because it is genetically heterogenous, can be autosomal dominant or sporadic, and progress at different rates. Single-cell RNA sequencing has enabled the discovery of several FECD subtypes, each with associated gene signatures, and cell heterogeneity. Current FECD treatments are mainly surgical, with various Rho kinase (ROCK) inhibitors used to promote endothelial cell metabolism and proliferation following surgery. A range of emerging therapies for FECD including cell therapies, gene therapies, tissue engineered scaffolds, and pharmaceuticals are in preclinical and clinical trials. Unlike conventional disease management methods based on clinical presentations and family history, targeting FECD using scRNA-seq based precision-medicine has the potential to pinpoint the disease subtypes, mechanisms, stages, severities, and help clinicians in making the best decision for surgeries and the applications of therapeutics. In this review, we first discuss the feasibility and potential of using scRNA-seq in clinical diagnostics for FECD, highlight advances from the latest clinical treatments and emerging therapies for FECD, integrate scRNA-seq results and clinical notes from our FECD patients and discuss the potential of applying alternative therapies to manage these cases clinically.

Health-related quality of life in patients with metastatic basal cell carcinoma treated with cemiplimab: Analysis of a phase 2 trial.

BACKGROUND: A phase 2 cemiplimab study (NCT03132636) demonstrated a 24.1% objective response rate in patients diagnosed with metastatic basal cell carcinoma (mBCC) who were not candidates for continued hedgehog inhibitor (HHI) therapy due to intolerance to previous HHI therapy, disease progression while receiving HHI therapy, or having not better than stable disease on HHI therapy after 9 months. Here, health-related quality of life (QoL) for this patient population is reported. METHODS: Adult patients with mBCC were treated with intravenous cemiplimab at a dose of 350 mg every 3 weeks for 5 treatment cycles of 9 weeks/cycle then 4 treatment cycles of 12 weeks/cycle. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and Day 1 of each cycle. Across Cycles 2 to 9, the overall change from baseline was analyzed using a mixed model with repeated measures. Responder analyses determined clinically meaningful improvement or deterioration (changes ≥10 points) or maintenance across all scales. RESULTS: Patients reported low symptom burden and moderate-to-high functioning at baseline. Maintenance for QLQ-C30 global health status (GHS)/QoL and across all functioning and symptom scales was indicated by overall mean changes from baseline. Clinically meaningful improvement or maintenance was reported at Cycle 2 for GHS/QoL (77%), functioning scales (77% to 86%), and symptom scales (70% to 93%), with similar proportions of improvement or maintenance at Cycles 6 and 9, excluding fatigue. On the Skindex-16, clinically meaningful improvement or maintenance was reported across the emotional, symptom, and functional subscales, in 76%-88% of patients at Cycle 2, which were generally maintained at Cycles 6 and 9. Overall mean changes from baseline showed maintenance across these subscales. CONCLUSIONS: The majority of patients treated with cemiplimab reported improvement or maintenance in GHS/QoL and functioning while maintaining a low symptom burden.

Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma.

PURPOSE: Coblockade of lymphocyte activation gene-3 (LAG-3) and PD-1 receptors could provide significant clinical benefit for patients with advanced melanoma. Fianlimab and cemiplimab are high-affinity, human, hinge-stabilized IgG4 monoclonal antibodies, targeting LAG-3 and PD-1, respectively. We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma. METHODS: Patients with advanced melanoma were eligible for enrollment into four cohorts: three for patients without and one for patients with previous anti-PD-1 therapy in the advanced disease setting. Patients were treated with fianlimab 1,600 mg and cemiplimab 350 mg intravenously once every 3 weeks for up to 51 weeks, with an optional additional 51 weeks if clinically indicated. The primary end point was objective response rate (ORR) per RECIST 1.1 criteria. RESULTS: ORRs were 63% for patients with anti-PD-1-naïve melanoma (cohort-6; n = 40; median follow-up 20.8 months), 63% for patients with systemic treatment-naïve melanoma (cohort-15; n = 40; 11.5 months), and 56% for patients with previous neo/adjuvant treatment melanoma (cohort-16; n = 18, 9.7 months). At a median follow-up of 12.6 months for the combined cohorts (6 + 15 + 16), the ORR was 61.2% and the median progression-free survival (mPFS) 13.3 months (95% CI, 7.5 to not estimated [NE]). In patients (n = 13) with previous anti-PD-1 adjuvant therapy, ORR was 61.5% and mPFS 12 months (95% CI, 1.4 to NE). ORR in patients with previous anti-PD-1 therapy for advanced disease (n = 15) was 13.3% and mPFS 1.5 months (95% CI, 1.3 to 7.7). Treatment-emergent and treatment-related adverse events ≥grade 3 (G3) were observed in 44% and 22% of patients, respectively. Except for increased incidence of adrenal insufficiency (12%-G1-4, 4%-G3-4), no new safety signals were recorded. CONCLUSION: The current results show a promising benefit-risk profile of fianlimab/cemiplimab combination for patients with advanced melanoma, including those with previous anti-PD-1 therapy in the adjuvant, but not advanced, setting.

High-throughput single-cell transcriptomics of bacteria using combinatorial barcoding.

Microbial split-pool ligation transcriptomics (microSPLiT) is a high-throughput single-cell RNA sequencing method for bacteria. With four combinatorial barcoding rounds, microSPLiT can profile transcriptional states in hundreds of thousands of Gram-negative and Gram-positive bacteria in a single experiment without specialized equipment. As bacterial samples are fixed and permeabilized before barcoding, they can be collected and stored ahead of time. During the first barcoding round, the fixed and permeabilized bacteria are distributed into a 96-well plate, where their transcripts are reverse transcribed into cDNA and labeled with the first well-specific barcode inside the cells. The cells are mixed and redistributed two more times into new 96-well plates, where the second and third barcodes are appended to the cDNA via in-cell ligation reactions. Finally, the cells are mixed and divided into aliquot sub-libraries, which can be stored until future use or prepared for sequencing with the addition of a fourth barcode. It takes 4 days to generate sequencing-ready libraries, including 1 day for collection and overnight fixation of samples. The standard plate setup enables single-cell transcriptional profiling of up to 1 million bacterial cells and up to 96 samples in a single barcoding experiment, with the possibility of expansion by adding barcoding rounds. The protocol requires experience in basic molecular biology techniques, handling of bacterial samples and preparation of DNA libraries for next-generation sequencing. It can be performed by experienced undergraduate or graduate students. Data analysis requires access to computing resources, familiarity with Unix command line and basic experience with Python or R.

Reaction Mechanisms of H2S Oxidation by Naphthoquinones.

1,4-naphthoquinones (NQs) catalytically oxidize H2S to per- and polysufides and sulfoxides, reduce oxygen to superoxide and hydrogen peroxide, and can form NQ-SH adducts through Michael addition. Here, we measured oxygen consumption and used sulfur-specific fluorophores, liquid chromatography tandem mass spectrometry (LC-MS/MS), and UV-Vis spectrometry to examine H2S oxidation by NQs with various substituent groups. In general, the order of H2S oxidization was DCNQ ~ juglone > 1,4-NQ > plumbagin >DMNQ ~ 2-MNQ > menadione, although this order varied somewhat depending on the experimental conditions. DMNQ does not form adducts with GSH or cysteine (Cys), yet it readily oxidizes H2S to polysulfides and sulfoxides. This suggests that H2S oxidation occurs at the carbonyl moiety and not at the quinoid 2 or 3 carbons, although the latter cannot be ruled out. We found little evidence from oxygen consumption studies or LC-MS/MS that NQs directly oxidize H2S2-4, and we propose that apparent reactions of NQs with inorganic polysulfides are due to H2S impurities in the polysulfides or an equilibrium between H2S and H2Sn. Collectively, NQ oxidation of H2S forms a variety of products that include hydropersulfides, hydropolysulfides, sulfenylpolysulfides, sulfite, and thiosulfate, and some of these reactions may proceed until an insoluble S8 colloid is formed.

Multiple sclerosis presenting with paroxysmal symptoms: Patients at the limitations of current diagnostic criteria.

Paroxysmal neurological symptoms in patients with multiple sclerosis (MS) have long been acknowledged. However, consideration of whether such symptoms are a clinical attack and sufficient for fulfillment of MS diagnostic criteria has varied as criteria have evolved over time. Previous studies and anecdotal reports indicate that some patients with MS first present with syndromes such as trigeminal neuralgia, Lhermitte's phenomenon, tonic spasm, and seizure years before an attack typical of MS such as optic neuritis or myelitis. We discuss four patients with presumed MS who initially presented with these syndromes with evidence of a corresponding central nervous system (CNS) lesion who, were these symptoms considered an attack, could have been diagnosed with relapsing remitting MS or clinically isolated syndrome. This case series aims to highlight the unmet need for data for such patient presentations and for clinical guidance from future MS diagnostic criteria to optimize care.

Gene expression plasticity facilitates acclimatization of a long-lived Caribbean coral across divergent reef environments.

Local adaptation can increase fitness under stable environmental conditions. However, in rapidly changing environments, compensatory mechanisms enabled through plasticity may better promote fitness. Climate change is causing devastating impacts on coral reefs globally and understanding the potential for adaptive and plastic responses is critical for reef management. We conducted a four-year, three-way reciprocal transplant of the Caribbean coral Siderastrea siderea across forereef, backreef, and nearshore populations in Belize to investigate the potential for environmental specialization versus plasticity in this species. Corals maintained high survival within forereef and backreef environments, but transplantation to nearshore environments resulted in high mortality, suggesting that nearshore environments present strong environmental selection. Only forereef-sourced corals demonstrated evidence of environmental specialization, exhibiting the highest growth in the forereef. Gene expression profiling 3.5 years post-transplantation revealed that transplanted coral hosts exhibited profiles more similar to other corals in the same reef environment, regardless of their source location, suggesting that transcriptome plasticity facilitates acclimatization to environmental change in S. siderea. In contrast, algal symbiont (Cladocopium goreaui) gene expression showcased functional variation between source locations that was maintained post-transplantation. Our findings suggest limited acclimatory capacity of some S. siderea populations under strong environmental selection and highlight the potential limits of coral physiological plasticity in reef restoration.

Detecting defects that reduce breakdown voltage using machine learning and optical profilometry.

Semiconductor wafer manufacturing relies on the precise control of various performance metrics to ensure the quality and reliability of integrated circuits. In particular, GaN has properties that are advantageous for high voltage and high frequency power devices; however, defects in the substrate growth and manufacturing are preventing vertical devices from performing optimally. This paper explores the application of machine learning techniques utilizing data obtained from optical profilometry as input variables to predict the probability of a wafer meeting performance metrics, specifically the breakdown voltage (Vbk). By incorporating machine learning techniques, it is possible to reliably predict performance metrics that cause devices to fail at low voltage. For diodes that fail at a higher (but still below theoretical) breakdown voltage, alternative inspection methods or a combination of several experimental techniques may be necessary.

Single nuclei transcriptomics of the in situ human limbal stem cell niche.

The corneal epithelium acts as a barrier to pathogens entering the eye; corneal epithelial cells are continuously renewed by uni-potent, quiescent limbal stem cells (LSCs) located at the limbus, where the cornea transitions to conjunctiva. There has yet to be a consensus on LSC markers and their transcriptome profile is not fully understood, which may be due to using cadaveric tissue without an intact stem cell niche for transcriptomics. In this study, we addressed this problem by using single nuclei RNA sequencing (snRNAseq) on healthy human limbal tissue that was immediately snap-frozen after excision from patients undergoing cataract surgery. We identified the quiescent LSCs as a sub-population of corneal epithelial cells with a low level of total transcript counts. Moreover, TP63, KRT15, CXCL14, and ITGß4 were found to be highly expressed in LSCs and transiently amplifying cells (TACs), which constitute the corneal epithelial progenitor populations at the limbus. The surface markers SLC6A6 and ITGß4 could be used to enrich human corneal epithelial cell progenitors, which were also found to specifically express the putative limbal progenitor cell markers MMP10 and AC093496.1.

Integrated optical frequency division for microwave and mmWave generation.

The generation of ultra-low-noise microwave and mmWave in miniaturized, chip-based platforms can transform communication, radar and sensing systems1-3. Optical frequency division that leverages optical references and optical frequency combs has emerged as a powerful technique to generate microwaves with superior spectral purity than any other approaches4-7. Here we demonstrate a miniaturized optical frequency division system that can potentially transfer the approach to a complementary metal-oxide-semiconductor-compatible integrated photonic platform. Phase stability is provided by a large mode volume, planar-waveguide-based optical reference coil cavity8,9 and is divided down from optical to mmWave frequency by using soliton microcombs generated in a waveguide-coupled microresonator10-12. Besides achieving record-low phase noise for integrated photonic mmWave oscillators, these devices can be heterogeneously integrated with semiconductor lasers, amplifiers and photodiodes, holding the potential of large-volume, low-cost manufacturing for fundamental and mass-market applications13.

A far-ultraviolet-driven photoevaporation flow observed in a protoplanetary disk.

Most low-mass stars form in stellar clusters that also contain massive stars, which are sources of far-ultraviolet (FUV) radiation. Theoretical models predict that this FUV radiation produces photodissociation regions (PDRs) on the surfaces of protoplanetary disks around low-mass stars, which affects planet formation within the disks. We report James Webb Space Telescope and Atacama Large Millimeter Array observations of a FUV-irradiated protoplanetary disk in the Orion Nebula. Emission lines are detected from the PDR; modeling their kinematics and excitation allowed us to constrain the physical conditions within the gas. We quantified the mass-loss rate induced by the FUV irradiation and found that it is sufficient to remove gas from the disk in less than a million years. This is rapid enough to affect giant planet formation in the disk.

Evaluation of ATNPD Framework and Biofluid Markers to Predict Cognitive Decline in Early Parkinson Disease.

BACKGROUND AND OBJECTIVES: In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-ß-amyloid 1-42 (Aß42), phosphorylated tau 181 (p-tau181), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau181 and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aß42. First, we describe longitudinal trajectories of biofluid markers in PD. Second, we modified the AD ß-amyloid/tau/neurodegeneration (ATN) framework for application in PD (ATNPD) using CSF Aß42 (A), p-tau181 (T), and serum NfL (N) and tested ATNPD prediction of longitudinal cognitive decline in PD. METHODS: Participants were selected from the Parkinson's Progression Markers Initiative cohort, clinically diagnosed with sporadic PD or as controls, and followed up annually for 5 years. Linear mixed-effects models (LMEMs) tested the interaction of diagnosis with longitudinal trajectories of analytes (log transformed, false discovery rate [FDR] corrected). In patients with PD, LMEMs tested how baseline ATNPD status (AD [A+T+N±] vs not) predicted clinical outcomes, including Montreal Cognitive Assessment (MoCA; rank transformed, FDR corrected). RESULTS: Participants were 364 patients with PD and 168 controls, with comparable baseline mean (±SD) age (patients with PD = 62 ± 10 years; controls = 61 ± 11 years]; Mann-Whitney Wilcoxon: p = 0.4) and sex distribution (patients with PD = 231 male individuals [63%]; controls = 107 male individuals [64%]; χ2: p = 1). Patients with PD had overall lower CSF p-tau181 (ß = -0.16, 95% CI -0.23 to -0.092, p = 2.2e-05) and t-tau than controls (ß = -0.13, 95% CI -0.19 to -0.065, p = 4e-04), but not Aß42 (p = 0.061) or NfL (p = 0.32). Over time, patients with PD had greater increases in serum NfL than controls (ß = 0.035, 95% CI 0.022 to 0.048, p = 9.8e-07); slopes of patients with PD did not differ from those of controls for CSF Aß42 (p = 0.18), p-tau181 (p = 1), or t-tau (p = 0.96). Using ATNPD, PD classified as A+T+N± (n = 32; 9%) had worse cognitive decline on global MoCA (ß = -73, 95% CI -110 to -37, p = 0.00077) than all other ATNPD statuses including A+ alone (A+T-N-; n = 75; 21%). DISCUSSION: In patients with early PD, CSF p-tau181 and t-tau were low compared with those in controls and did not increase over 5 years of follow-up. Our study shows that classification using modified ATNPD (incorporating CSF Aß42, CSF p-tau181, and serum NfL) can identify biologically relevant subgroups of PD to improve prediction of cognitive decline in early PD.

A phase 1 study of triple-targeted therapy with BRAF, MEK, and AKT inhibitors for patients with BRAF-mutated cancers.

BACKGROUND: Aberrant PI3K/AKT signaling in BRAF-mutant cancers contributes to resistance to BRAF inhibitors. The authors examined dual MAPK and PI3K pathway inhibition in patients who had BRAF-mutated solid tumors (ClinicalTrials.gov identifier NCT01902173). METHODS: Patients with BRAF V600E/V600K-mutant solid tumors received oral dabrafenib at 150 mg twice daily with dose escalation of oral uprosertib starting at 50 mg daily, or, in the triplet cohorts, with dose escalation of both oral trametinib starting at 1.5 mg daily and oral uprosertib starting at 25 mg daily. Dose-limiting toxicities (DLTs) were assessed within the first 56 days of treatment. Radiographic responses were assessed at 8-week intervals. RESULTS: Twenty-seven patients (22 evaluable) were enrolled in parallel doublet and triplet cohorts. No DLTs were observed in the doublet cohorts (N = 7). One patient had a DLT at the maximum administered dose of triplet therapy (dabrafenib 150 mg twice daily and trametinib 2 mg daily plus uprosertib 75 mg daily). Three patients in the doublet cohorts had partial responses (including one who had BRAF inhibitor-resistant melanoma). Two patients in the triplet cohorts had a partial response, and one patient had an unconfirmed partial response. Pharmacokinetic data suggested reduced dabrafenib and dabrafenib metabolite exposure in patients who were also exposed to both trametinib and uprosertib, but not in whose who were exposed to uprosertib without trametinib. CONCLUSIONS: Concomitant inhibition of both the MAPK and PI3K-AKT pathways for the treatment of BRAF-mutated cancers was well tolerated, leading to objective responses, but higher level drug-drug interactions affected exposure to dabrafenib and its metabolites.

Integrated photonic molecule Brillouin laser with a high-power sub-100-mHz fundamental linewidth.

Photonic integrated lasers with an ultra-low fundamental linewidth and a high output power are important for precision atomic and quantum applications, high-capacity communications, and fiber sensing, yet wafer-scale solutions have remained elusive. Here we report an integrated stimulated Brillouin laser (SBL), based on a photonic molecule coupled resonator design, that achieves a sub-100-mHz fundamental linewidth with greater than 10-mW output power in the C band, fabricated on a 200-mm silicon nitride (Si3N4) CMOS-foundry compatible wafer-scale platform. The photonic molecule design is used to suppress the second-order Stokes (S2) emission, allowing the primary lasing mode to increase with the pump power without phase noise feedback from higher Stokes orders. The nested waveguide resonators have a 184 million intrinsic and 92 million loaded Q, over an order of magnitude improvement over prior photonic molecules, enabling precision resonance splitting of 198 MHz at the S2 frequency. We demonstrate S2-suppressed single-mode SBL with a minimum fundamental linewidth of 71±18 mHz, corresponding to a 23±6-mHz2/Hz white-frequency-noise floor, over an order of magnitude lower than prior integrated SBLs, with an ∼11-mW output power and 2.3-mW threshold power. The frequency noise reaches the resonator-intrinsic thermo-refractive noise from 2-kHz to 1-MHz offset. The laser phase noise reaches -155 dBc/Hz at 10-MHz offset. The performance of this chip-scale SBL shows promise not only to improve the reliability and reduce size and cost but also to enable new precision experiments that require the high-speed manipulation, control, and interrogation of atoms and qubits. Realization in the silicon nitride ultra-low loss platform is adaptable to a wide range of wavelengths from the visible to infrared and enables integration with other components for systems-on-chip solutions for a wide range of precision scientific and engineering applications including quantum sensing, gravitometers, atom interferometers, precision metrology, optical atomic clocks, and ultra-low noise microwave generation.

Testing a computational model for aural detection of aircraft in ambient noise.

Computational models are used to predict the performance of human listeners for carefully specified signal and noise conditions. However, there may be substantial discrepancies between the conditions under which listeners are tested and those used for model predictions. Thus, models may predict better performance than exhibited by the listeners, or they may "fail" to capture the ability of the listener to respond to subtle stimulus conditions. This study tested a computational model devised to predict a listener's ability to detect an aircraft in various soundscapes. The model and listeners processed the same sound recordings under carefully specified testing conditions. Details of signal and masker calibration were carefully matched, and the model was tested using the same adaptive tracking paradigm. Perhaps most importantly, the behavioral results were not available to the modeler before the model predictions were presented. Recordings from three different aircraft were used as the target signals. Maskers were derived from recordings obtained at nine locations ranging from very quiet rural environments to suburban and urban settings. Overall, with a few exceptions, model predictions matched the performance of the listeners very well. Discussion focuses on those differences and possible reasons for their occurrence.

Developing a Toolbox of Antibodies Validated for Array Tomography-Based Imaging of Brain Synapses.

Antibody (Ab)-based imaging techniques rely on reagents whose performance may be application specific. Because commercial antibodies are validated for only a few purposes, users interested in other applications may have to perform extensive in-house antibody testing. Here, we present a novel application-specific proxy screening step to efficiently identify candidate antibodies for array tomography (AT), a serial section volume microscopy technique for high-dimensional quantitative analysis of the cellular proteome. To identify antibodies suitable for AT-based analysis of synapses in mammalian brain, we introduce a heterologous cell-based assay that simulates characteristic features of AT, such as chemical fixation and resin embedding that are likely to influence antibody binding. The assay was included into an initial screening strategy to generate monoclonal antibodies that can be used for AT. This approach simplifies the screening of candidate antibodies and has high predictive value for identifying antibodies suitable for AT analyses. In addition, we have created a comprehensive database of AT-validated antibodies with a neuroscience focus and show that these antibodies have a high likelihood of success for postembedding applications in general, including immunogold electron microscopy. The generation of a large and growing toolbox of AT-compatible antibodies will further enhance the value of this imaging technique.

Metals from spacecraft reentry in stratospheric aerosol particles.

Large increases in the number of low earth orbit satellites are projected in the coming decades [L. Schulz, K.-H. Glassmeier, Adv. Space Res. 67, 1002-1025 (2021)] with perhaps 50,000 additional satellites in orbit by 2030 [GAO, Large constellations of satellites: Mitigating environmental and other effects (2022)]. When spent rocket bodies and defunct satellites reenter the atmosphere, they produce metal vapors that condense into aerosol particles that descend into the stratosphere. So far, models of spacecraft reentry have focused on understanding the hazard presented by objects that survive to the surface rather than on the fate of the metals that vaporize. Here, we show that metals that vaporized during spacecraft reentries can be clearly measured in stratospheric sulfuric acid particles. Over 20 elements from reentry were detected and were present in ratios consistent with alloys used in spacecraft. The mass of lithium, aluminum, copper, and lead from the reentry of spacecraft was found to exceed the cosmic dust influx of those metals. About 10% of stratospheric sulfuric acid particles larger than 120 nm in diameter contain aluminum and other elements from spacecraft reentry. Planned increases in the number of low earth orbit satellites within the next few decades could cause up to half of stratospheric sulfuric acid particles to contain metals from reentry. The influence of this level of metallic content on the properties of stratospheric aerosol is unknown.

Harnessing water fleas for water reclamation: A nature-based tertiary wastewater treatment technology.

Urbanisation, population growth, and climate change have put unprecedented pressure on water resources, leading to a global water crisis and the need for water reuse. However, water reuse is unsafe unless persistent chemical pollutants are removed from reclaimed water. State-of-the-art technologies for the reduction of persistent chemical pollutants in wastewater typically impose high operational and energy costs and potentially generate toxic by-products (e.g., bromate from ozonation). Nature-base solutions are preferred to these technologies for their lower environmental impact. However, so far, bio-based tertiary wastewater treatments have been inefficient for industrial-scale applications. Moreover, they often demand significant financial investment and large infrastructure, undermining sustainability objectives. Here, we present a scalable, low-cost, low-carbon, and retrofittable nature-inspired solution to remove persistent chemical pollutants (pharmaceutical, pesticides and industrial chemicals). We showed Daphnia's removal efficiency of individual chemicals and chemicals from wastewater at laboratory scale ranging between 50 % for PFOS and 90 % for diclofenac. We validated the removal efficiency of diclofenac at prototype scale, showing sustained performance over four weeks in outdoor seminatural conditions. A techno-commercial analysis on the Daphnia-based technology suggested several technical, commercial and sustainability advantages over established and emerging treatments at comparable removal efficiency, benchmarked on available data on individual chemicals. Further testing of the technology is underway in open flow environments holding real wastewater. The technology has the potential to improve the quality of wastewater effluent, meeting requirements to produce water appropriate for reuse in irrigation, industrial application, and household use. By preventing persistent chemicals from entering waterways, this technology has the potential to maximise the shift to clean growth, enabling water reuse, reducing resource depletion and preventing environmental pollution.