Ultralow Catalytic Loading for Optimised Electrocatalytic Performance of AuPt Nanoparticles to Produce Hydrogen and Ammonia.

The hydrogen evolution and nitrite reduction reactions are key to producing green hydrogen and ammonia. Antenna-reactor nanoparticles hold promise to improve the performances of these transformations under visible-light excitation, by combining plasmonic and catalytic materials. However, current materials involve compromising either on the catalytic activity or the plasmonic enhancement and also lack control of reaction selectivity. Here, we demonstrate that ultralow loadings and non-uniform surface segregation of the catalytic component optimize catalytic activity and selectivity under visible-light irradiation. Taking Pt-Au as an example we find that fine-tuning the Pt content produces a 6-fold increase in the hydrogen evolution compared to commercial Pt/C as well as a 6.5-fold increase in the nitrite reduction and a 2.5-fold increase in the selectivity for producing ammonia under visible light excitation relative to dark conditions. Density functional theory suggests that the catalytic reactions are accelerated by the intimate contact between nanoscale Pt-rich and Au-rich regions at the surface, which facilitates the formation of electron-rich hot-carrier puddles associated with the Pt-based active sites. The results provide exciting opportunities to design new materials with improved photocatalytic performance for demanding sustainable energy applications.

The utility of PET imaging in depression.

This educational review article aims to discuss growing evidence from PET studies in the diagnosis and treatment of depression. PET has been used in depression to explore the neurotransmitters involved, the alterations in neuroreceptors, non-neuroreceptor targets (e.g., microglia and astrocytes), the severity and duration of the disease, the pharmacodynamics of various antidepressants, and neurobiological mechanisms of non-pharmacological therapies like psychotherapy, electroconvulsive therapy, and deep brain stimulation therapy, by showing changes in brain metabolism and receptor and non-receptor targets. Studies have revealed alterations in neurotransmitter systems such as serotonin, dopamine, GABA, and glutamate, which are linked to the pathophysiology of depression. Overall, PET imaging has furthered the neurobiological understanding of depression. Despite these advancements, PET findings have not yet led to significant changes in evidence-based practices. Addressing the reasons behind inconsistencies in PET imaging results, conducting large sample size studies with a more standardized methodological approach, and investigating further the genetic and neurobiological aspects of depression may better leverage PET imaging in future studies.

Unearthing who and Y at Harewood Cemetery and inference of George Washington's Y-chromosomal haplotype.

An excavation conducted at Harewood Cemetery to identify the unmarked grave of Samuel Washington resulted in the discovery of burials presumably belonging to George Washington's paternal grandnephews and their mother, Lucy Payne. To confirm their identities this study examined Y-chromosomal, mitochondrial, and autosomal DNA from the burials and a living Washington descendant. The burial's Y-STR profile was compared to FamilyTreeDNA's database, which resulted in a one-step difference from the living descendant and an exact match to another Washington. A more complete Y-STR and Y-SNP profile from the descendant was inferred to be the Washington Y profile. Kinship comparisons performed in relation to the descendant, who is a 4th and 5th degree relative of the putative individuals, resulted in >37,000 overlapping autosomal SNPs and strong statistical support with likelihood ratios exceeding one billion. This study highlights the benefits of a multi-marker approach for kinship prediction and DNA-assisted identification of historical remains.

Observations on the Tritiated Water and TEWL Skin Integrity Tests: Relevance to In Vitro Permeation Testing (IVPT).

BACKGROUND: The in vitro permeation test (IVPT) using ex vivo human skin is a sensitive and robust model system that has been vital in elucidating the fundamental parameters surrounding the absorption of both therapeutic agents and industrial chemicals through skin. FDA and OECD IVPT Guidances recommend that each skin section selected for study should be screened prior to use to ensure that the stratum corneum integrity is retained. Three methods are currently considered acceptable: 1) transepidermal water loss (TEWL), 2) electrical resistance, and 3) tritiated water (3H2O) absorption. METHODS: A retrospective analysis of data from the authors' laboratory has been performed with the objective of addressing a number of questions regarding the 3H2O and TEWL integrity tests, and the population attributes of a large database consisting of 17,330 individual skin sections obtained from 459 skin donors. The applicability and usefulness of these tests, when compared to companion permeation data obtained from 25 topical drug products, has also been examined. RESULTS: Both integrity tests found water permeability to be equal in White and Hispanic races but higher than in Blacks, 3H2O being more discriminating than TEWL. Male skin is more permeable than female and there is a slight decrease in permeability with advancing age in both groups. Correlation between 3H2O absorption and drug absorption revealed a minimal relationship between the two in most cases, the Pearson correlation coefficient ranging from -0.417 to 0.953. Additionally, drug outliers were not always identified with a failing integrity test. CONCLUSION: The results call for a critical reexamination of the value of the 3H2O integrity test, and by extension, TEWL, for use in IVPT studies.

Robotic versus laparoscopic versus open nephrectomy for live kidney donors.

BACKGROUND: Waiting lists for kidney transplantation continue to grow. Live kidney donation significantly reduces waiting times and improves long-term outcomes for recipients. Major disincentives to potential kidney donors are the pain and morbidity associated with surgery. This is an update of a review published in 2011. OBJECTIVES: To assess the benefits and harms of open donor nephrectomy (ODN), laparoscopic donor nephrectomy (LDN), hand-assisted LDN (HALDN) and robotic donor nephrectomy (RDN) as appropriate surgical techniques for live kidney donors. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 31 March 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing LDN with ODN, HALDN, or RDN were included. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Thirteen studies randomising 1280 live kidney donors to ODN, LDN, HALDN, or RDN were included. All studies were assessed as having a low or unclear risk of bias for selection bias. Five studies had a high risk of bias for blinding. Seven studies randomised 815 live kidney donors to LDN or ODN. LDN was associated with reduced analgesia use (high certainty evidence) and shorter hospital stay, a longer procedure and longer warm ischaemia time (moderate certainty evidence). There were no overall differences in blood loss, perioperative complications, or need for operations (low or very low certainty evidence). Three studies randomised 270 live kidney donors to LDN or HALDN. There were no differences between HALDN and LDN for analgesia requirement, hospital stay (high certainty evidence), duration of procedure (moderate certainty evidence), blood loss, perioperative complications, or reoperations (low certainty evidence). The evidence for warm ischaemia time was very uncertain due to high heterogeneity. One study randomised 50 live kidney donors to retroperitoneal ODN or HALDN and reported less pain and analgesia requirements with ODN. It found decreased blood loss and duration of the procedure with HALDN. No differences were found in perioperative complications, reoperations, hospital stay, or primary warm ischaemia time. One study randomised 45 live kidney donors to LDN or RDN and reported a longer warm ischaemia time with RDN but no differences in analgesia requirement, duration of procedure, blood loss, perioperative complications, reoperations, or hospital stay. One study randomised 100 live kidney donors to two variations of LDN and reported no differences in hospital stay, duration of procedure, conversion rates, primary warm ischaemia times, or complications (not meta-analysed). The conversion rates to ODN were 6/587 (1.02%) in LDN, 1/160 (0.63%) in HALDN, and 0/15 in RDN. Graft outcomes were rarely or selectively reported across the studies. There were no differences between LDN and ODN for early graft loss, delayed graft function, acute rejection, ureteric complications, kidney function or one-year graft loss. In a meta-regression analysis between LDN and ODN, moderate certainty evidence on procedure duration changed significantly in favour of LDN over time (yearly reduction = 7.12 min, 95% CI 2.56 to 11.67; P = 0.0022). Differences in very low certainty evidence on perioperative complications also changed significantly in favour of LDN over time (yearly change in LnRR = 0.107, 95% CI 0.022 to 0.192; P = 0.014). Various different combinations of techniques were used in each study, resulting in heterogeneity among the results. AUTHORS' CONCLUSIONS: LDN is associated with less pain compared to ODN and has comparable pain to HALDN and RDN. HALDN is comparable to LDN in all outcomes except warm ischaemia time, which may be associated with a reduction. One study reported kidneys obtained during RDN had greater warm ischaemia times. Complications and occurrences of perioperative events needing further intervention were equivalent between all methods.

Transcriptomic signatures of progression to TB disease among close contacts in Brazil.

BACKGROUND: Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB, so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease. METHODS: Close contacts (≥4 hours exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically-confirmed or clinically-diagnosed pulmonary or extra-pulmonary TB disease through 24 months of follow-up was symptom-triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative PCR. Prognostic performance for incident TB was tested using receiver operating characteristic curve (ROC) analysis at 6, 9, 12, and 24 months of follow-up. RESULTS: Between June 2015 and June 2019, 1,854 close contacts were enrolled; Twenty-five progressed to incident TB, of whom 13 had microbiologically-confirmed disease. Baseline transcriptomic signature scores were measured in 1,789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile (TPP) for a prognostic test through 6 months; three (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the TPP threshold through 12 or more months of follow-up. CONCLUSIONS: Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts, to target preventive therapy administration.

Evaluating ChatGPT-3.5 and ChatGPT-4.0 Responses on Hyperlipidemia for Patient Education.

Introduction Hyperlipidemia is prevalent worldwide and affects a significant number of US adults. It significantly contributes to ischemic heart disease and millions of deaths annually. With the increasing use of the internet for health information, tools like ChatGPT (OpenAI, San Francisco, CA, USA) have gained traction. ChatGPT version 4.0, launched in March 2023, offers enhanced features over its predecessor but requires a monthly fee. This study compares the accuracy, comprehensibility, and response length of the free and paid versions of ChatGPT for patient education on hyperlipidemia. Materials and methods ChatGPT versions 3.5 and 4.0 were prompted in three different ways and 25 questions from the Cleveland Clinic's frequently asked questions (FAQs) on hyperlipidemia. Prompts included no prompting (Form 1), patient-friendly prompting (Form 2), and physician-level prompting (Form 3). Responses were categorized as incorrect, partially correct, or correct. Additionally, the grade level and word count from each response were recorded for analysis. Results Overall, scoring frequencies for ChatGPT version 3.5 were: five (6.67%) incorrect, 18 partially correct (24%), and 52 (69.33%) correct. Scoring frequencies for ChatGPT version 4.0 were: one (1.33%) incorrect, 18 (24.00%) partially correct, and 56 (74.67%) correct. Correct answers did not significantly differ between ChatGPT version 3.5 and ChatGPT version 4.0 (p = 0.586). ChatGPT version 3.5 had a significantly higher grade reading level than version 4.0 (p = 0.0002). ChatGPT version 3.5 had a significantly higher word count than version 4.0 (p = 0.0073). Discussion There was no significant difference in accuracy between the free and paid versions of hyperlipidemia FAQs. Both versions provided accurate but sometimes partially complete responses. Version 4.0 offered more concise and readable information, aligning with the readability of most online medical resources despite exceeding the National Institutes of Health's (NIH's) recommended eighth-grade reading level. The paid version demonstrated superior adaptability in tailoring responses based on the input. Conclusion Both versions of ChatGPT provide reliable medical information, with the paid version offering more adaptable and readable responses. Healthcare providers can recommend ChatGPT as a source of patient education, regardless of the version used. Future research should explore diverse question formulations and ChatGPT's handling of incorrect information.

Impact of Surface Composition Changes on the CO2-Reduction Performance of Au-Cu Aerogels.

Over the past decades, the electrochemical CO2-reduction reaction (CO2RR) has emerged as a promising option for facilitating intermittent energy storage while generating industrial raw materials of economic relevance such as CO. Recent studies have reported that Au-Cu bimetallic nanocatalysts feature a superior CO2-to-CO conversion as compared with the monometallic components, thus improving the noble metal utilization. Under this premise and with the added advantage of a suppressed H2-evolution reaction due to absence of a carbon support, herein, we employ bimetallic Au3Cu and AuCu aerogels (with a web thickness ≈7 nm) as CO2-reduction electrocatalysts in 0.5 M KHCO3 and compare their performance with that of a monometallic Au aerogel. We supplement this by investigating how the CO2RR-performance of these materials is affected by their surface composition, which we modified by systematically dissolving a part of their Cu-content using cyclic voltammetry (CV). To this end, the effect of this CV-driven composition change on the electrochemical surface area is quantified via Pb underpotential deposition, and the local structural and compositional changes are visually assessed by employing identical-location transmission electron microscopy and energy-dispersive X-ray analyses. When compared to the pristine aerogels, the CV-treated samples displayed superior CO Faradaic efficiencies (≈68 vs ≈92% for Au3Cu and ≈34 vs ≈87% for AuCu) and CO partial currents, with the AuCu aerogel outperforming the Au3Cu and Au counterparts in terms of Au-mass normalized CO currents among the CV-treated samples.

Scanning the aged to minimize missed injury: An EAST multicenter study.

BACKGROUND: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a Pan-Scan (Head/C-spine/Torso) or a Selective Scan (Head/C-spine ± Torso). We hypothesized that a patient's initial history and exam could be used to guide imaging. METHODS: We prospectively studied blunt trauma patients aged 65+ at 18 Level I/II trauma centers. Patients presenting >24 h after injury or who died upon arrival were excluded. We collected history and physical elements and final injury diagnoses. Injury diagnoses were categorized into CT body regions of Head/C-spine or Torso (chest, abdomen/pelvis, and T/L spine). Using machine learning and regression modeling as well as a priori clinical algorithms based, we tested various decision rules against our dataset. Our priority was to identify a simple rule which could be applied at the bedside, maximizing sensitivity (Sens) and negative predictive value (NPV) to minimize missed injuries. RESULTS: We enrolled 5,498 patients with 3,082 injuries. Nearly half (47.1%, n = 2,587) had an injury within the defined CT body regions. No rule to guide a Pan-Scan could be identified with suitable Sens/NPV for clinical use. A clinical algorithm to identify patients for Pan-Scan, using a combination of physical exam findings and specific high-risk criteria, was identified and had a Sens of 0.94 and NPV of 0.86 This rule would have identified injuries in all but 90 patients (1.6%) and would theoretically spare 11.9% (655) of blunt trauma patients a torso CT. CONCLUSIONS: Our findings advocate for Head/Cspine CT in all geriatric patients with the addition of torso CT in the setting of positive clinical findings and high-risk criteria. Prospective validation of this rule could lead to streamlined diagnostic care of this growing trauma population. LEVEL OF EVIDENCE: Level 2, Diagnostic Tests or Criteria.

Open-Channel Droplet Microfluidic Platform for Passive Generation of Human Sperm Microdroplets.

Sperm cryopreservation is important for individuals undergoing infertility treatment, and for those who wish to preserve fertility potential, prior to treatments like chemotherapy, radiation therapy, gender-affirming medical interventions, elective fertility delay, or individuals in high-risk professions such as the military. Current methods for sperm cryopreservation result in approximately 30-50% decrease in sperm motility. However, recent studies have shown that ultra-rapid freezing (vitrification) is a valuable approach for maintaining sperm quality after freeze-thawing processes in the clinical laboratory setting and requires submicroliter to microliter volumes. A major challenge for the adoption of vitrification in fertility laboratories is the ability to pipette small volumes of sample. Here, we present a method that leverages open-channel droplet microfluidics to autonomously generate sub-microliter to microliter volumes of purified human sperm samples. Using a novel, open-channel droplet generator, we found no change in sperm movement and kinematic data after exposure to device and reagents in our platform. We conclude that our platform is compatible with human sperm, an important foundation for future implementation of vitrification in fertility laboratories.

ECEIM consensus statement on equine kidney disease.

The aim of this consensus statement is to summarize and appraise scientific evidence and combine this with the clinical experience of a panel of experts to optimize recommendations on how to recognize and manage kidney disease in horses.

Skeletal Muscle Texture Assessment Using Ultrasonography: Comparison with Magnetic Resonance Imaging in Chronic Kidney Disease.

Skeletal muscle dysfunction is common in chronic kidney disease (CKD). Of interest is the concept of "muscle quality," of which measures include ultrasound-derived echo intensity (EI). Alternative parameters of muscle texture, for example, gray level of co-occurrence matrix (GCLM), are available and may circumvent limitations in EI. The validity of EI is limited in humans, particularly in chronic diseases. This study aimed to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Images of the thigh were acquired using a 3 Tesla MRI scanner. Quantification of muscle (contractile), fat (non-contractile), and miscellaneous (connective tissue, fascia) components were estimated. Anatomical rectus femoris cross-sectional area was measured using B-mode 2D ultrasonography. To assess muscle texture, first (i.e., EI)- and second (i.e., GLCM)-order statistical analyses were performed. Fourteen participants with CKD were included (age: 58.0 ± 11.9 years, 50% male, eGFR: 27.0 ± 7.4 ml/min/1.73m2, 55% Stage 4). Higher EI was associated with lower muscle % (quadriceps: ß = -.568, p = .034; hamstrings: ß = -.644, p = .010). Higher EI was associated with a higher fat % in the hamstrings (ß = -.626, p = .017). A higher angular second moment from GLCM analysis was associated with greater muscle % (ß = .570, p = .033) and lower fat % (ß = -.534, p = .049). A higher inverse difference moment was associated with greater muscle % (ß = .610, p = .021 and lower fat % (ß = -.599, p = .024). This is the first study to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Our preliminary findings suggest ultrasound-derived texture analysis provides a novel indicator of reduced skeletal muscle % and thus increased intramuscular fat.

Anticoagulation for post-operative atrial fibrillation after isolated coronary artery bypass grafting: a meta-analysis.

BACKGROUND AND AIMS: This study aimed to evaluate clinical outcomes in patients developing post-operative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and characterize variations in oral anticoagulation (OAC) use, benefits, and complications. METHODS: A systematic search identified studies on new-onset POAF after CABG and OAC initiation. Outcomes included risks of thromboembolic events, bleeding, and mortality. Furthermore, a meta-analysis was conducted on these outcomes, stratified by the use or non-use of OAC. RESULTS: The identified studies were all non-randomized. Among 1 698 307 CABG patients, POAF incidence ranged from 7.9% to 37.6%. Of all POAF patients, 15.5% received OAC. Within 30 days, thromboembolic events occurred at rates of 1.0% (POAF: 0.3%; non-POAF: 0.8%) with 2.0% mortality (POAF: 1.0%; non-POAF: 0.5%). Bleeding rates were 1.1% for POAF patients and 2.7% for non-POAF patients. Over a median of 4.6 years, POAF patients had 1.73 thromboembolic events, 3.39 mortality, and 2.00 bleeding events per 100 person-years; non-POAF patients had 1.14, 2.19, and 1.60, respectively. No significant differences in thromboembolic risks [effect size -0.11 (-0.36 to 0.13)] and mortality [effect size -0.07 (-0.21 to 0.07)] were observed between OAC users and non-users. However, OAC use was associated with higher bleeding risk [effect size 0.32 (0.06-0.58)]. CONCLUSIONS: In multiple timeframes following CABG, the incidence of complications in patients who develop POAF is low. The use of OAC in patients with POAF after CABG is associated with increased bleeding risk.

Artificial Intelligence Helps Pathologists Increase Diagnostic Accuracy and Efficiency in the Detection of Breast Cancer Lymph Node Metastases.

The detection of lymph node metastases is essential for breast cancer staging, although it is a tedious and time-consuming task where the sensitivity of pathologists is suboptimal. Artificial intelligence (AI) can help pathologists detect lymph node metastases, which could help alleviate workload issues. We studied how pathologists' performance varied when aided by AI. An AI algorithm was trained using more than 32 000 breast sentinel lymph node whole slide images (WSIs) matched with their corresponding pathology reports from more than 8000 patients. The algorithm highlighted areas suspicious of harboring metastasis. Three pathologists were asked to review a dataset comprising 167 breast sentinel lymph node WSIs, of which 69 harbored cancer metastases of different sizes, enriched for challenging cases. Ninety-eight slides were benign. The pathologists read the dataset twice, both digitally, with and without AI assistance, randomized for slide and reading orders to reduce bias, separated by a 3-week washout period. Their slide-level diagnosis was recorded, and they were timed during their reads. The average reading time per slide was 129 seconds during the unassisted phase versus 58 seconds during the AI-assisted phase, resulting in an overall efficiency gain of 55% (P<0.001). These efficiency gains are applied to both benign and malignant WSIs. Two of the 3 reading pathologists experienced significant sensitivity improvements, from 74.5% to 93.5% (P≤0.006). This study highlights that AI can help pathologists shorten their reading times by more than half and also improve their metastasis detection rate.

Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone.

BACKGROUND: Bone metastasis is a common consequence of advanced prostate cancer. Bisphosphonates can be used to manage symptoms, but there are currently no curative treatments available. Altered tumour cell glycosylation is a hallmark of cancer and is an important driver of a malignant phenotype. In prostate cancer, the sialyltransferase ST6GAL1 is upregulated, and studies show ST6GAL1-mediated aberrant sialylation of N-glycans promotes prostate tumour growth and disease progression. METHODS: Here, we monitor ST6GAL1 in tumour and serum samples from men with aggressive prostate cancer and using in vitro and in vivo models we investigate the role of ST6GAL1 in prostate cancer bone metastasis. FINDINGS: ST6GAL1 is upregulated in patients with prostate cancer with tumours that have spread to the bone and can promote prostate cancer bone metastasis in vivo. The mechanisms involved are multi-faceted and involve modification of the pre-metastatic niche towards bone resorption to promote the vicious cycle, promoting the development of M2 like macrophages, and the regulation of immunosuppressive sialoglycans. Furthermore, using syngeneic mouse models, we show that inhibiting sialylation can block the spread of prostate tumours to bone. INTERPRETATION: Our study identifies an important role for ST6GAL1 and α2-6 sialylated N-glycans in prostate cancer bone metastasis, provides proof-of-concept data to show that inhibiting sialylation can suppress the spread of prostate tumours to bone, and highlights sialic acid blockade as an exciting new strategy to develop new therapies for patients with advanced prostate cancer. FUNDING: Prostate Cancer Research and the Mark Foundation For Cancer Research, the Medical Research Council and Prostate Cancer UK.

Glycosylated Polyhydroxyproline Is a Potent Antifreeze Molecule.

Molecules that inhibit the growth of ice crystals are highly desirable for applications in building materials, foods, and agriculture. Antifreezes are particularly essential in biomedicine for tissue banking, yet molecules currently in use have known toxic effects. Antifreeze glycoproteins have evolved naturally in polar fish species living in subzero climates, but practical issues with collection and purification have limited their commercial use. Here, we present a synthetic strategy using polymerization of amino acid N-carboxyanhydrides to produce polypeptide mimics of these potent natural antifreeze proteins. We investigated a set of mimics with varied structural properties and identified a glycopolypeptide with potent ice recrystallization inhibition properties. We optimized for molecular weight, characterized their conformations, and verified their cytocompatibility in a human cell line. Overall, we present a material that will have broad applications as a biocompatible antifreeze.

Lipid availability influences ferroptosis sensitivity in cancer cells by regulating polyunsaturated fatty acid trafficking.

Ferroptosis is a form of cell death caused by lipid peroxidation that is emerging as a target for cancer therapy, highlighting the need to identify factors that govern ferroptosis susceptibility. Lipid peroxidation occurs primarily on phospholipids containing polyunsaturated fatty acids (PUFAs). Here, we show that even though extracellular lipid limitation reduces cellular PUFA levels, lipid-starved cancer cells are paradoxically more sensitive to ferroptosis. Using mass spectrometry-based lipidomics with stable isotope fatty acid labeling, we show that lipid limitation induces a fatty acid trafficking pathway in which PUFAs are liberated from triglycerides to synthesize highly unsaturated PUFAs such as arachidonic acid and adrenic acid. These PUFAs then accumulate in phospholipids, particularly ether phospholipids, to promote ferroptosis sensitivity. Therefore, PUFA levels within cancer cells do not necessarily correlate with ferroptosis susceptibility. Rather, how cancer cells respond to extracellular lipid levels by trafficking PUFAs into proper phospholipid pools dictates their sensitivity to ferroptosis.