Structural Diversity in 2-(2-Aminoethyl)pyridine-Based Lead Iodide Hybrids.

While 2D metal-organic hybrids have emerged as promising solar absorbers due to their improved moisture stability, their inferior transport properties limit their potential translation into devices. We report a new hybrid containing 2-(2-ammonioethyl)pyridine [(2-AEP)+], forming a 2D hybrid with the composition (2-AEP)2PbI4. The organic bilayer comprises of (2-AEP)+, which is arranged in a face-to-face stacking that promotes π-π interactions between neighboring pyridyl rings. We also demonstrate the structural diversity of 2-(2-aminoethyl)pyridine-based lead iodide hybrids in solution-processed films. This report highlights the importance of solution-processing conditions in trying to obtain single-phase films of hybrids containing dibasic organic species.

It's time to broaden what we consider a 'blue carbon ecosystem'.

Photoautotrophic marine ecosystems can lock up organic carbon in their biomass and the associated organic sediments they trap over millennia and are thus regarded as blue carbon ecosystems. Because of the ability of marine ecosystems to lock up organic carbon for millennia, blue carbon is receiving much attention within the United Nations' 2030 Agenda for Sustainable Development as a nature-based solution (NBS) to climate change, but classically still focuses on seagrass meadows, mangrove forests, and tidal marshes. However, other coastal ecosystems could also be important for blue carbon storage, but remain largely neglected in both carbon cycling budgets and NBS strategic planning. Using a meta-analysis of 253 research publications, we identify other coastal ecosystems-including mud flats, fjords, coralline algal (rhodolith) beds, and some components or coral reef systems-with a strong capacity to act as blue carbon sinks in certain situations. Features that promote blue carbon burial within these 'non-classical' blue carbon ecosystems included: (1) balancing of carbon release by calcification via carbon uptake at the individual and ecosystem levels; (2) high rates of allochthonous organic carbon supply because of high particle trapping capacity; (3) high rates of carbon preservation and low remineralization rates; and (4) location in depositional environments. Some of these features are context-dependent, meaning that these ecosystems were blue carbon sinks in some locations, but not others. Therefore, we provide a universal framework that can evaluate the likelihood of a given ecosystem to behave as a blue carbon sink for a given context. Overall, this paper seeks to encourage consideration of non-classical blue carbon ecosystems within NBS strategies, allowing more complete blue carbon accounting.

Including Methane Emissions from Agricultural Ponds in National Greenhouse Gas Inventories.

Agricultural ponds are a significant source of greenhouse gases, contributing to the ongoing challenge of anthropogenic climate change. Nations are encouraged to account for these emissions in their national greenhouse gas inventory reports. We present a remote sensing approach using open-access satellite imagery to estimate total methane emissions from agricultural ponds that account for (1) monthly fluctuations in the surface area of individual ponds, (2) rates of historical accumulation of agricultural ponds, and (3) the temperature dependence of methane emissions. As a case study, we used this method to inform the 2024 National Greenhouse Gas Inventory reports submitted by the Australian government, in compliance with the Paris Agreement. Total annual methane emissions increased by 58% from 1990 (26 kilotons CH4 year-1) to 2022 (41 kilotons CH4 year-1). This increase is linked to the water surface of agricultural ponds growing by 51% between 1990 (115 kilo hectares; 1,150 km2) and 2022 (173 kilo hectares; 1,730 km2). In Australia, 16,000 new agricultural ponds are built annually, expanding methane-emitting water surfaces by 1,230 ha yearly (12.3 km2 year-1). On average, the methane flux of agricultural ponds in Australia is 0.238 t CH4 ha-1 year-1. These results offer policymakers insights into developing targeted mitigation strategies to curb these specific forms of anthropogenic emissions. For instance, financial incentives, such as carbon or biodiversity credits, can mobilize widespread investments toward reducing greenhouse gas emissions and enhancing the ecological and environmental values of agricultural ponds. Our data and modeling tools are available on a free cloud-based platform for other countries to adopt this approach.

Transbronchial cryobiopsy followed by as-needed surgical lung biopsy versus immediate surgical lung biopsy for diagnosing interstitial lung disease (the COLD study): a randomised controlled trial.

BACKGROUND: An adequate diagnosis for interstitial lung disease (ILD) is important for clinical decision making and prognosis. In most patients with ILD, an accurate diagnosis can be made by clinical and radiological data assessment, but in a considerable proportion of patients, a lung biopsy is required. Surgical lung biopsy (SLB) is the most common method to obtain tissue, but it is associated with high morbidity and even mortality. More recently, transbronchial cryobiopsy has been introduced, with fewer adverse events but a lower diagnostic yield than SLB. The aim of this study is to compare two diagnostic strategies: a step-up strategy (transbronchial cryobiopsy, followed by SLB if the cryobiopsy is insufficiently informative) versus immediate SLB. METHODS: The COLD study was a multicentre, randomised controlled trial in six hospitals across the Netherlands. We included patients with ILD with an indication for lung biopsy as assessed by a multidisciplinary team discussion. Patients were randomly assigned in a 1:1 ratio to the step-up or immediate SLB strategy, with follow-up for 12 weeks from the initial procedure. Patients, clinicians, and pathologists were not masked to the study treatment. The primary endpoint was unexpected chest tube drainage, defined as requiring any chest tube after transbronchial cryobiopsy, or prolonged (>24 h) chest tube drainage after SLB. Secondary endpoints were diagnostic yield, in-hospital stay, pain, and serious adverse events. A modified intention-to-treat analysis was performed. This trial is registered with the Dutch Trial Register, NL7634, and is now closed. FINDINGS: Between April 8, 2019, and Oct 24, 2021, 122 patients with ILD were assessed for study participation; and 55 patients were randomly assigned to the step-up strategy (n=28) or immediate SLB (n=27); three patients from the immediate SLB group were excluded. Unexpected chest tube drainage occurred in three of 28 patients (11%; 95% CI 4-27%) in the step-up group, and the number of patients for whom the chest tube could not be removed within 24 h was 11 of 24 patients (46%; 95% CI 2-65%) in the SLB group, with an absolute risk reduction of 35% (11-56%; p=0·0058). In the step-up strategy, the multidisciplinary team diagnostic yield after transbronchial cryobiopsy alone was 82% (64-92%), which increased to 89% (73-96%) when subsequent SLB was performed after inconclusive transbronchial cryobiopsy. In the immediate surgery strategy, the multidisciplinary team diagnostic yield was 88% (69-97%). Total in-hospital stay was 1 day (IQR 1-1) in the step-up group versus 5 days (IQR 4-6) in the SLB group. One (4%) serious adverse event occurred in step-up strategy versus 12 (50%) in the immediate SLB strategy. INTERPRETATION: In ILD diagnosis, if lung tissue assessment is required, a diagnostic strategy starting with transbronchial cryobiopsy, followed by SLB when transbronchial cryobiopsy is inconclusive, appears to result in a significant reduction of patient burden and in-hospital stay with a similar diagnostic yield versus immediate SLB. FUNDING: Netherlands Organisation for Health Research and Development (ZonMW) and Amsterdam University Medical Centers.

Chemotherapy and the Extra-Tumor Immune Microenvironment: EXTRA-TIME.

SUMMARY: Understandably, conventional therapeutic strategies have focused on controlling primary tumors. We ask whether the cost of such strategies is actually an increased likelihood of metastatic relapse.

Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses.

Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three-SARS, SARS-CoV-2 and MERS-are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.

Clostridioides difficile infection is associated with differences in transcriptionally active microbial communities.

Clostridioides difficile infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut microbiome dysbiosis is known to be important to CDI. To the best of our knowledge, metatranscriptomics (MT) has only been used to characterize gut microbiome composition and function in one prior study involving CDI patients. Therefore, we utilized MT to investigate differences in active community diversity and composition between CDI+ (n = 20) and CDI- (n = 19) samples with respect to microbial taxa and expressed genes. No significant (Kruskal-Wallis, p > 0.05) differences were detected for richness or evenness based on CDI status. However, clustering based on CDI status was significant for both active microbial taxa and expressed genes datasets (PERMANOVA, p ≤ 0.05). Furthermore, differential feature analysis revealed greater expression of the opportunistic pathogens Enterocloster bolteae and Ruminococcus gnavus in CDI+ compared to CDI- samples. When only fungal sequences were considered, the family Saccharomycetaceae expressed more genes in CDI-, while 31 other fungal taxa were identified as significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) associated with CDI+. We also detected a variety of genes and pathways that differed significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) based on CDI status. Notably, differential genes associated with biofilm formation were expressed by C. difficile. This provides evidence of another possible contributor to C. difficile's resistance to antibiotics and frequent recurrence in vivo. Furthermore, the greater number of CDI+ associated fungal taxa constitute additional evidence that the mycobiome is important to CDI pathogenesis. Future work will focus on establishing if C. difficile is actively producing biofilms during infection and if any specific fungal taxa are particularly influential in CDI.

Activation of Cryptic Donor Splice Sites within the UDP-Glucuronosyltransferase (UGT)1A First-Exon Region Generates Variant Transcripts That Encode UGT1A Proteins with Truncated Aglycone-Binding Domains.

The human UDP-glucuronosyltransferases (UGTs) have crucial roles in metabolizing and clearing numerous small lipophilic compounds. The UGT1A locus generates nine UGT1A mRNAs, 65 spliced transcripts, and 34 circular RNAs. In this study, our analysis of published UGT-RNA capture sequencing (CaptureSeq) datasets identified novel splice junctions that predict 24 variant UGT1A transcripts derived from ligation of exon 2 to unique sequences within the UGT1A first-exon region using cryptic donor splice sites. Of these variants, seven (1A1_n1, 1A3_n3, 1A4_n4, 1A5_n1, 1A8_n2, 1A9_n2, 1A10_n7) are predicted to encode UGT1A proteins with truncated aglycone-binding domains. We assessed their expression profiles and deregulation in cancer using four RNA sequencing (RNA-Seq) datasets of paired normal and cancerous drug-metabolizing tissues from large patient cohorts. Variants were generally coexpressed with their canonical counterparts with a higher relative abundance in tumor than in normal tissues. Variants showed tissue-specific expression with high interindividual variability but overall low abundance. However, 1A8_n2 showed high abundance in normal and cancerous colorectal tissues, with levels that approached or surpassed canonical 1A8 mRNA levels in many samples. We cloned 1A8_n2 and showed expression of the predicted protein (1A8_i3) in human embryonic kidney (HEK)293T cells. Glucuronidation assays with 4-methylumbelliferone (4MU) showed that 1A8_i3 had no activity and was unable to inhibit the activity of 1A8_i1 protein. In summary, the activation of cryptic donor splice sites within the UGT1A first-exon region expands the UGT1A transcriptome and proteome. The 1A8_n2 cryptic donor splice site is highly active in colorectal tissues, representing an important cis-regulatory element that negatively regulates the function of the UGT1A8 gene through pre-mRNA splicing. SIGNIFICANT STATEMENT: The UGT1A locus generates nine canonical mRNAs, 65 alternately spliced transcripts, and 34 different circular RNAs. The present study reports a series of novel UDP-glucuronosyltransferase (UGT)1A variants resulting from use of cryptic donor splice sites in both normal and cancerous tissues, several of which are predicted to encode variant UGT1A proteins with truncated aglycone-binding domains. Of these, 1A8_n2 shows exceptionally high abundance in colorectal tissues, highlighting its potential role in the first-pass metabolism in gut through the glucuronidation pathway.

Two-Coordinate Thermally Activated Delayed Fluorescence Coinage Metal Complexes: Molecular Design, Photophysical Characters, and Device Application.

Since the emergence of the first green light emission from a fluorescent thin-film organic light emitting diode (OLED) in the mid-1980s, a global consumer market for OLED displays has flourished over the past few decades. This growth can primarily be attributed to the development of noble metal phosphorescent emitters that facilitated remarkable gains in electrical conversion efficiency, a broadened color gamut, and vibrant image quality for OLED displays. Despite these achievements, the limited abundance of noble metals in the Earth's crust has spurred ongoing efforts to discover cost-effective electroluminescent materials. One particularly promising avenue is the exploration of thermally activated delayed fluorescence (TADF), a mechanism with the potential to fully harness excitons in OLEDs. Recently, investigations have unveiled TADF in a series of two-coordinate coinage metal (Cu, Ag, and Au) complexes. These organometallic TADF materials exhibit distinctive behavior in comparison to their organic counterparts. They offer benefits such as tunable emissive colors, short TADF emission lifetimes, high luminescent quantum yields, and reasonable stability. Impressively, both vacuum-deposited and solution-processed OLEDs incorporating these materials have achieved outstanding performance. This review encompasses various facets on two-coordinate TADF coinage metal complexes, including molecular design, photophysical characterizations, elucidation of structure-property relationships, and OLED applications.

Using waste biomass to produce 3D-printed artificial biodegradable structures for coastal ecosystem restoration.

The loss of ecosystem functions and services caused by rapidly declining coastal marine ecosystems, including corals and bivalve reefs and wetlands, around the world has sparked significant interest in interdisciplinary methods to restore these ecologically and socially important ecosystems. In recent years, 3D-printed artificial biodegradable structures that mimic natural life stages or habitat have emerged as a promising method for coastal marine restoration. The effectiveness of this method relies on the availability of low-cost biodegradable printing polymers and the development of 3D-printed biomimetic structures that efficiently support the growth of plant and sessile animal species without harming the surrounding ecosystem. In this context, we present the potential and pathway for utilizing low-cost biodegradable biopolymers from waste biomass as printing materials to fabricate 3D-printed biodegradable artificial structures for restoring coastal marine ecosystems. Various waste biomass sources can be used to produce inexpensive biopolymers, particularly those with the higher mechanical rigidity required for 3D-printed artificial structures intended to restore marine ecosystems. Advancements in 3D printing methods, as well as biopolymer modifications and blending to address challenges like biopolymer solubility, rheology, chemical composition, crystallinity, plasticity, and heat stability, have enabled the fabrication of robust structures. The ability of 3D-printed structures to support species colonization and protection was found to be greatly influenced by their biopolymer type, surface topography, structure design, and complexity. Considering limited studies on biodegradability and the effect of biodegradation products on marine ecosystems, we highlight the need for investigating the biodegradability of biopolymers in marine conditions as well as the ecotoxicity of the degraded products. Finally, we present the challenges, considerations, and future perspectives for designing tunable biomimetic 3D-printed artificial biodegradable structures from waste biomass biopolymers for large-scale coastal marine restoration.

A universal molecular control for DNA, mRNA and protein expression.

The expression of genes encompasses their transcription into mRNA followed by translation into protein. In recent years, next-generation sequencing and mass spectrometry methods have profiled DNA, RNA and protein abundance in cells. However, there are currently no reference standards that are compatible across these genomic, transcriptomic and proteomic methods, and provide an integrated measure of gene expression. Here, we use synthetic biology principles to engineer a multi-omics control, termed pREF, that can act as a universal molecular standard for next-generation sequencing and mass spectrometry methods. The pREF sequence encodes 21 synthetic genes that can be in vitro transcribed into spike-in mRNA controls, and in vitro translated to generate matched protein controls. The synthetic genes provide qualitative controls that can measure sensitivity and quantitative accuracy of DNA, RNA and peptide detection. We demonstrate the use of pREF in metagenome DNA sequencing and RNA sequencing experiments and evaluate the quantification of proteins using mass spectrometry. Unlike previous spike-in controls, pREF can be independently propagated and the synthetic mRNA and protein controls can be sustainably prepared by recipient laboratories using common molecular biology techniques. Together, this provides a universal synthetic standard able to integrate genomic, transcriptomic and proteomic methods.

Exhaled breath analyses for bronchial thermoplasty in severe asthma patients.

BACKGROUND: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma. Although multiple trials have demonstrated clinical improvement after BT, optimal patient selection remains a challenge and the mechanism of action is incompletely understood. The aim of this study was to examine whether exhaled breath analysis can contribute to discriminate between BT-responders and non-responders at baseline and to explore pathophysiological insights of BT. METHODS: Exhaled breath was collected from patients at baseline and six months post-BT. Patients were defined as responders or non-responders based on a half point increase in asthma quality of life questionnaire scores. Gas chromatography-mass spectrometry was used for volatile organic compounds (VOCs) detection and analyses. Analytical workflow consisted of: 1) detection of VOCs that differentiate between responders and non-responders and those that differ between baseline and six months post-BT, 2) identification of VOCs of interest and 3) explore correlations between clinical biomarkers and VOCs. RESULTS: Data was available from 14 patients. Nonanal, 2-ethylhexanol and 3-thujol showed a significant difference in intensity between responders and non-responders at baseline (p = 0.04, p = 0.01 and p = 0.03, respectively). After BT, no difference was found in the compound intensity of these VOCs. A negative correlation was observed between nonanal and IgE and BALF eosinophils (r = -0.68, p < 0.01 and r = -0.61, p = 0.02 respectively) and 3-thujol with BALF neutrophils (r = -0.54, p = 0.04). CONCLUSIONS: This explorative study identified discriminative VOCs in exhaled breath between BT responders and non-responders at baseline. Additionally, correlations were found between VOC's and inflammatory BALF cells. Once validated, these findings encourage research in breath analysis as a non-invasive easy to apply technique for identifying airway inflammatory profiles and eligibility for BT or immunotherapies in severe asthma.

Temporal patterns of osteoclast formation and activity following withdrawal of RANKL inhibition.

Rebound bone loss following denosumab discontinuation is an important clinical challenge. Current treatment strategies to prevent this fail to suppress the rise and overshoot in osteoclast-mediated bone resorption. In this study, we use a murine model of denosumab treatment and discontinuation to show the temporal changes in osteoclast formation and activity during RANKL inhibition and withdrawal. We show that the cellular processes that drive the formation of osteoclasts and subsequent bone resorption following withdrawal of RANKL inhibition precede the rebound bone loss. Furthermore, a rise in serum TRAP and RANKL levels is detected before markers of bone turnover used in current clinical practice. These mechanistic advances may provide insight into a more defined window of opportunity to intervene with sequential therapy following denosumab discontinuation.

Stopping denosumab, a medication commonly used to improve bone mass by blocking formation of bone resorbing osteoclasts, leads to a rebound loss in the bone which was gained during treatment. Current strategies to prevent this bone loss fail in most cases as they are unable to prevent the rise and overshoot in bone resorption by osteoclasts. Thie stems from an incomplete understanding of how osteoclasts behave during denosumab treatment and after treatment is discontinued. We use a mouse model of this phenomenon to show how osteoclast formation and activity changes throughout this process. We show that increases in the processes that drive the formation of osteoclasts can be detected in the circulation before bone loss occurs. These findings could therefore provide insight into a targeted 'window of opportunity' to intervene and prevent the rebound bone loss following stopping denosumab in patients.

Plastic Paradox in Blue Carbon Ecosystems.

Plastics are rapidly accumulating in blue carbon ecosystems, i.e., mangrove forests, tidal marshes, and seagrass meadows. Accumulated plastic is diverted from the ocean, but the extent and nature of impacts on blue carbon ecosystem processes, including carbon sequestration, are poorly known. Here, we explore the potential positive and negative consequences of plastic accumulation in blue carbon ecosystems. We highlight the effects of plastic accumulation on organic carbon stocks and sediment biogeochemistry through microbial metabolism. The notion of beneficial plastic accumulation in blue carbon ecosystems is controversial, yet considering the alternative impacts of plastics on oceanic and aboveground environments, this may be the "lesser of evils". Using environmental life cycle impact assessment, we propose a research framework to address the potential positive and negative impacts of plastic accumulation in blue carbon ecosystems. Considering the multifaceted benefits, we prioritize expanding and managing blue carbon ecosystems, which may help with ecosystem conservation, as well as mitigating the negative effects of plastic.

Correlation between Serum Biomarkers and Lung Ultrasound in COVID-19: An Observational Study.

Serum biomarkers and lung ultrasound are important measures for prognostication and treatment allocation in patients with COVID-19. Currently, there is a paucity of studies investigating relationships between serum biomarkers and ultrasonographic biomarkers derived from lung ultrasound. This study aims to assess correlations between serum biomarkers and lung ultrasound findings. This study is a secondary analysis of four prospective observational studies in adult patients with COVID-19. Serum biomarkers included markers of epithelial injury, endothelial dysfunction and immune activation. The primary outcome was the correlation between biomarker concentrations and lung ultrasound score assessed with Pearson's (r) or Spearman's (rs) correlations. Forty-four patients (67 [41-88] years old, 25% female, 52% ICU patients) were included. GAS6 (rs = 0.39), CRP (rs = 0.42) and SP-D (rs = 0.36) were correlated with lung ultrasound scores. ANG-1 (rs = -0.39) was inversely correlated with lung ultrasound scores. No correlations were found between lung ultrasound score and several other serum biomarkers. In patients with COVID-19, several serum biomarkers of epithelial injury, endothelial dysfunction and immune activation correlated with lung ultrasound findings. The lack of correlations with certain biomarkers could offer opportunities for precise prognostication and targeted therapeutic interventions by integrating these unlinked biomarkers.

Freshwater wetland restoration and conservation are long-term natural climate solutions.

Freshwater wetlands have a disproportionately large influence on the global carbon cycle, with the potential to serve as long-term carbon sinks. Many of the world's freshwater wetlands have been destroyed or degraded, thereby affecting carbon-sink capacity. Ecological restoration of degraded wetlands is thus becoming an increasingly sought-after natural climate solution. Yet the time required to revert a degraded wetland from a carbon source to sink remains largely unknown. Moreover, increased methane (CH4) and nitrous oxide (N2O) emissions might complicate the climate benefit that wetland restoration may represent. We conducted a global meta-analysis to evaluate the benefits of wetland restoration in terms of net ecosystem carbon and greenhouse gas balance. Most studies (76 %) investigated the benefits of wetland restoration in peatlands (bogs, fens, and peat swamps) in the northern hemisphere, whereas the effects of restoration in non-peat wetlands (freshwater marshes, non-peat swamps, and riparian wetlands) remain largely unexplored. Despite higher CH4 emissions, most restored (77 %) and all natural peatlands were net carbon sinks, whereas most degraded peatlands (69 %) were carbon sources. Conversely, CH4 emissions from non-peat wetlands were similar across degraded, restored, and natural non-peat wetlands. When considering the radiative forcings and atmospheric lifetimes of the different greenhouse gases, the average time for restored wetlands to have a net cooling effect on the climate after restoration is 525 years for peatlands and 141 years for non-peat wetlands. The radiative benefit of wetland restoration does, therefore, not meet the timeframe set by the Paris Agreement to limit global warming by 2100. The conservation and protection of natural freshwater wetlands should be prioritised over wetland restoration as those ecosystems already play a key role in climate change mitigation.

Projecting the Future Registered Nurse Workforce After the COVID-19 Pandemic.

Importance: Health care delivery systems rely on a well-prepared and adequately sized registered nurse (RN) workforce. The US RN workforce decreased by more than 100 000 in 2021 during the COVID-19 pandemic-a far greater single-year drop than observed over the past 4 decades. The implication for the longer-term growth of the RN workforce is unknown. Objective: To describe recent trends in RN employment through 2023 and forecast the growth of the RN workforce through 2035. Design, Setting, and Participants: Descriptive analysis of recent trends since the start of the COVID-19 pandemic in RN employment using data from the US Bureau of the Census Current Population Survey and including employed RNs aged 23 to 69 years from 1982 through 2023, and retrospective cohort analysis of employment trends by birth year and age to project the age distribution and employment of RNs through 2035. Main Outcome and Measures: Annual full-time equivalent (FTE) employment of RNs by age, demographics, and sector of employment; forecast of RN workforce by age through 2035. Results: The final sample included 455 085 RN respondents aged 23 to 69 years. After a sharp decline in 2021, RN employment recovered, and the total number of FTE RNs in 2022 and 2023 was 6% higher than in 2019 (3.35 million vs 3.16 million, respectively). Using data on employment, education, and population through 2022, the size of the RN workforce was projected to increase by roughly 1.2 million FTEs to 4.56 million by 2035, close to prepandemic forecasts. Growth will be driven primarily by RNs aged 35 to 49 years, who are projected to compose nearly half (47%) of the RN workforce in 2035, up from 38% in 2022. Conclusions and Relevance: In this study, the rebound in the total size of the US RN workforce during 2022 and 2023 indicates that the earlier drop in RN employment during the first 2 years of the COVID-19 pandemic was likely transitory. Updated forecasts of the future RN workforce are very close to those made before the pandemic.