The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1-6. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions.

Microbial carbon use efficiency promotes global soil carbon storage.

Soils store more carbon than other terrestrial ecosystems1,2. How soil organic carbon (SOC) forms and persists remains uncertain1,3, which makes it challenging to understand how it will respond to climatic change3,4. It has been suggested that soil microorganisms play an important role in SOC formation, preservation and loss5-7. Although microorganisms affect the accumulation and loss of soil organic matter through many pathways4,6,8-11, microbial carbon use efficiency (CUE) is an integrative metric that can capture the balance of these processes12,13. Although CUE has the potential to act as a predictor of variation in SOC storage, the role of CUE in SOC persistence remains unresolved7,14,15. Here we examine the relationship between CUE and the preservation of SOC, and interactions with climate, vegetation and edaphic properties, using a combination of global-scale datasets, a microbial-process explicit model, data assimilation, deep learning and meta-analysis. We find that CUE is at least four times as important as other evaluated factors, such as carbon input, decomposition or vertical transport, in determining SOC storage and its spatial variation across the globe. In addition, CUE shows a positive correlation with SOC content. Our findings point to microbial CUE as a major determinant of global SOC storage. Understanding the microbial processes underlying CUE and their environmental dependence may help the prediction of SOC feedback to a changing climate.

Automated iterative Csp3-C bond formation.

Fully automated synthetic chemistry would substantially change the field by providing broad on-demand access to small molecules. However, the reactions that can be run autonomously are still limited. Automating the stereospecific assembly of Csp3-C bonds would expand access to many important types of functional organic molecules1. Previously, methyliminodiacetic acid (MIDA) boronates were used to orchestrate the formation of Csp2-Csp2 bonds and were effective building blocks for automating the synthesis of many small molecules2, but they are incompatible with stereospecific Csp3-Csp2 and Csp3-Csp3 bond-forming reactions3-10. Here we report that hyperconjugative and steric tuning provide a new class of tetramethyl N-methyliminodiacetic acid (TIDA) boronates that are stable to these conditions. Charge density analysis11-13 revealed that redistribution of electron density increases covalency of the N-B bond and thereby attenuates its hydrolysis. Complementary steric shielding of carbonyl π-faces decreases reactivity towards nucleophilic reagents. The unique features of the iminodiacetic acid cage2, which are essential for generalized automated synthesis, are retained by TIDA boronates. This enabled Csp3 boronate building blocks to be assembled using automated synthesis, including the preparation of natural products through automated stereospecific Csp3-Csp2 and Csp3-Csp3 bond formation. These findings will enable increasingly complex Csp3-rich small molecules to be accessed via automated assembly.

GGA1 interacts with the endosomal Na+/H+ Exchanger NHE6 governing localization to the endosome compartment.

Mutations in the endosomal Na+/H+ exchanger (NHE6) cause Christianson Syndrome (CS), an X-linked neurological disorder. NHE6 functions in regulation of endosome acidification and maturation in neurons. Using yeast two-hybrid screening with the NHE6 carboxyl-terminus as bait, we identify Golgi-associated, Gamma adaptin ear containing, ARF binding protein 1 (GGA1) as an interacting partner for NHE6. We corroborated the NHE6-GGA1 interaction using: co-immunoprecipitation (co-IP); over-expressed constructs in mammalian cells; and co-IP of endogenously-expressed GGA1 and NHE6 from neuroblastoma cells, as well as from mouse brain. We demonstrate that GGA1 interacts with organellar NHEs (NHE6, NHE7 and NHE9), and that there is significantly less interaction with cell-surface localized NHEs (NHE1 and NHE5). By constructing hybrid NHE1/NHE6 exchangers, we demonstrate that the cytoplasmic tail of NHE6 interacts most strongly with GGA1. We demonstrate the co-localization of NHE6 and GGA1 in cultured, primary hippocampal neurons, using super-resolution microscopy. We test the hypothesis that the interaction of NHE6 and GGA1 functions in the localization of NHE6 to the endosome compartment. Using subcellular fractionation experiments, we show that NHE6 is mis-localized in GGA1 knockout cells, wherein we find less NHE6 in endosomes, but more NHE6 transport to lysosomes, and more Golgi retention of NHE6, with increased exocytosis to the surface plasma membrane. Consistent with NHE6 mis-localization, and Golgi retention, we find the intra-luminal pH in Golgi to be alkalinized in GGA1-null cells. Our study demonstrates a new interaction between NHE6 and GGA1 which functions in the localization of this intra-cellular NHE to the endosome compartment.

Dysregulation of the chromatin environment leads to differential alternative splicing as a mechanism of disease in a human model of autism spectrum disorder.

Autism spectrum disorder (ASD) affects 1 in 44 children. Chromatin regulatory proteins are overrepresented among genes that contain high risk variants in ASD. Disruption of the chromatin environment leads to widespread dysregulation of gene expression, which is traditionally thought of as a mechanism of disease pathogenesis associated with ASD. Alternatively, alterations in chromatin dynamics could also lead to dysregulation of alternative splicing, which is understudied as a mechanism of ASD pathogenesis. The anticonvulsant valproic acid (VPA) is a well-known environmental risk factor for ASD that acts as a class I histone deacetylase inhibitor. However, the precise molecular mechanisms underlying defects in human neuronal development associated with exposure to VPA are understudied. To dissect how VPA exposure and subsequent chromatin hyperacetylation influence molecular signatures involved in ASD pathogenesis, we conducted RNA sequencing (RNA-seq) in human cortical neurons that were treated with VPA. We observed that differentially expressed genes (DEGs) were enriched for mRNA splicing, mRNA processing, histone modification and metabolism related gene sets. Furthermore, we observed widespread increases in the number and the type of alternative splicing events. Analysis of differential transcript usage (DTU) showed that exposure to VPA induces extensive alterations in transcript isoform usage across neurodevelopmentally important genes. Finally, we find that DEGs and genes that display DTU overlap with known ASD-risk genes. Altogether, these findings suggest that, in addition to differential gene expression, changes in alternative splicing correlated with alterations in the chromatin environment could act as an additional mechanism of disease in ASD.

Sialic acids on B cells are crucial for their survival and provide protection against apoptosis.

Sialic acids (Sias) on the B cell membrane are involved in cell migration, in the control of the complement system and, as sialic acid-binding immunoglobulin-like lectin (Siglec) ligands, in the regulation of cellular signaling. We studied the role of sialoglycans on B cells in a mouse model with B cell-specific deletion of cytidine monophosphate sialic acid synthase (CMAS), the enzyme essential for the synthesis of sialoglycans. Surprisingly, these mice showed a severe B cell deficiency in secondary lymphoid organs. Additional depletion of the complement factor C3 rescued the phenotype only marginally, demonstrating a complement-independent mechanism. The B cell survival receptor BAFF receptor was not up-regulated, and levels of activated caspase 3 and processed caspase 8 were high in B cells of Cmas-deficient mice, indicating ongoing apoptosis. Overexpressed Bcl-2 could not rescue this phenotype, pointing to extrinsic apoptosis. These results show that sialoglycans on the B cell surface are crucial for B cell survival by counteracting several death-inducing pathways.

Proteomic profiling of antibiotic-resistant Escherichia coli GW-AmxH19 isolated from hospital wastewater treated with physical plasma.

Microorganisms which are resistant to antibiotics are a global threat to the health of humans and animals. Wastewater treatment plants are known hotspots for the dissemination of antibiotic resistances. Therefore, novel methods for the inactivation of pathogens, and in particular antibiotic-resistant microorganisms (ARM), are of increasing interest. An especially promising method could be a water treatment by physical plasma which provides charged particles, electric fields, UV-radiation, and reactive species. The latter are foremost responsible for the antimicrobial properties of plasma. Thus, with plasma it might be possible to reduce the amount of ARM and to establish this technology as additional treatment stage for wastewater remediation. However, the impact of plasma on microorganisms beyond a mere inactivation was analyzed in more detail by a proteomic approach. Therefore, Escherichia coli GW-AmxH19, isolated from hospital wastewater in Germany, was used. The bacterial solution was treated by a plasma discharge ignited between each of four pins and the liquid surface. The growth of E. coli and the pH-value decreased during plasma treatment in comparison with the untreated control. Proteome and antibiotic resistance profile were analyzed. Concentrations of nitrite and nitrate were determined as long-lived indicative products of a transient chemistry associated with reactive nitrogen species (RNS). Conversely, hydrogen peroxide served as indicator for reactive oxygen species (ROS). Proteome analyses revealed an oxidative stress response as a result of plasma-generated RNS and ROS as well as a pH-balancing reaction as key responses to plasma treatment. Both, the generation of reactive species and a decreased pH-value is characteristic for plasma-treated solutions. The plasma-mediated changes of the proteome are discussed also in comparison with the Gram-positive bacterium Bacillus subtilis. Furthermore, no effect of the plasma treatment, on the antibiotic resistance of E. coli, was determined under the chosen conditions. The knowledge about the physiological changes of ARM in response to plasma is of fundamental interest to understand the molecular basis for the inactivation. This will be important for the further development and implementation of plasma in wastewater remediation.

Cu-Catalyzed Amination of Base-Sensitive Aryl Bromides and the Chemoselective N- and O-Arylation of Amino Alcohols.

We report a general and functional-group-tolerant method for the Cu-catalyzed amination of base-sensitive aryl bromides including substrates possessing acidic functional groups and small five-membered heteroarenes. The results presented herein substantially expand the scope of Cu-catalyzed C-N coupling reactions. The combination of L8, an anionic N1,N2-diarylbenzene-1,2-diamine ligand, along with the mild base NaOTMS leads to the formation of a stable yet reactive catalyst that resists deactivation from coordination to heterocycles or charged intermediates. This system enables the use of low catalyst and ligand loadings. Exploiting the differences in nucleophile deprotonation in C-O and C-N coupling reactions catalyzed by Cu·L8 we developed a method to chemoselectively N- and O-arylate a variety of amino alcohol substrates. Employing NaOt-Bu as the base resulted exclusively in C-O coupling when the amino alcohols featured primary alcohols and more hindered amines or aniline groups. Utilizing NaOTMS enabled the ability to override the steric-based selectivity of these reactions completely and exclusively promoted C-N coupling regardless of the structure of the amino alcohol. The ability to invert the observed chemoselectivity is distinct from previously described methods that require protecting group manipulations or rely entirely on steric effects to control reactivity. These results substantially improve the scope of Cu-catalyzed C-N coupling reactions using N1,N2-diarylbenzene-1,2-diamine ligands and introduce a new chemoselective method to arylate amino alcohols.

Tracking of Cardiorespiratory Fitness from Childhood to Mid-adulthood.

High cardiorespiratory fitness (CRF) in adulthood is important for survival from major chronic diseases and preserving good health. We examined how childhood CRF tracks, or persists, into adulthood. Among a cohort of 748 school children followed over 34 years, we found child CRF correlated with young- (r = 0.30) and mid-adulthood (r = 0.16) CRF.

Late transplant-associated thrombotic microangiopathy verified in bone marrow biopsy specimens is associated with chronic GVHD and viral infections.

OBJECTIVES: To describe late transplant-associated thrombotic microangiopathy (TA-TMA) as chronic endothelial complication in bone marrow (BM) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: BM specimens along with conventional diagnostic parameters were assessed in 14 single-institutional patients with late TA-TMA (more than 100 days after HCST), including 11 late with history of early TA-TMA, 10 with early TA-TMA (within 100 days), and 12 non TA-TMA patients. Three non-HSCT patients served as control. The time points of BM biopsy were +1086, +798, +396, and +363 days after HSCT, respectively. RESULTS: Late TA-TMA patients showed an increase of CD34+ and von Willebrand Factor (VWF)+ microvascular endothelial cells with atypical VWF+ conglomerates forming thickened VWF+ plaque sinus in the BM compared to patients without late TA-TMA and non-HSCT. Severe chronic (p = .002), steroid-refractory GVHD (p = .007) and reactivation of HHV6 (p = .002), EBV (p = .003), and adenovirus (p = .005) were pronounced in late TA-TMA. Overall and relapse-free survival were shorter in late TA-TMA than in patients without late TA-TMA (5-year OS and RFS: 78.6% vs. 90.2%, 71.4% vs. 86.4%, respectively). CONCLUSION: Chronic allo-immune microangiopathy in BM associated with chronic, steroid-refractory GVHD and/or viral infections are key findings of late, high-risk TA-TMA, which deserves clinical attention.

The Obese Taste Bud study: Objectives and study design.

AIMS: Taste modifies eating behaviour, impacting body weight and potentially obesity development. The Obese Taste Bud (OTB) Study is a prospective cohort study launched in 2020 at the University of Leipzig Obesity Centre in cooperation with the HI-MAG Institute. OTB will test the hypothesis that taste cell homeostasis and taste perception are linked to obesity. Here, we provide the study design, data collection process and baseline characteristics. MATERIALS AND METHODS: Participants presenting overweight, obesity or normal weight undergo taste and smell tests, anthropometric, and taste bud density (TBD) assessment on Day 1. Information on physical and mental health, eating behaviour, physical activity, and dental hygiene are obtained, while biomaterial (saliva, tongue swap, blood) is collected in the fasted state. Further blood samples are taken during a glucose tolerance test. A stool sample is collected at home prior to Day 2, on which a taste bud biopsy follows dental examination. A subsample undergoes functional magnetic resonance imaging while exposed to eating-related cognitive tasks. Follow-up investigations after conventional weight loss interventions and bariatric surgery will be included. RESULTS: Initial results show that glycated haemoglobin levels and age are negatively associated with TBD, while an unfavourable metabolic profile, current dieting, and vegan diet are related to taste perception. Olfactory function negatively correlates with age and high-density lipoprotein cholesterol. CONCLUSION: Initial findings suggest that metabolic alterations are relevant for taste and smell function and TBD. By combining omics data from collected biomaterial with physiological, metabolic and psychological data related to taste perception and eating behaviour, the OTB study aims to strengthen our understanding of taste perception in obesity.

Youth Exposure and Response to the FDA Health Warning Label on Electronic Cigarettes Packaging: Policy Implications.

INTRODUCTION: Youth represent a high-priority group for e-cigarette health communication. This study examined youth exposure to the Food and Drug Administration (FDA) e-cigarette warning label over 4 years and its association with change in youth harm perception and intention. AIMS AND METHODS: We pooled data from the 2018-2021 National Youth Tobacco Survey (age 10-17; n = 67 159). Participants were divided into four groups: never users (58.5%), susceptible nonusers (16.3%), former users (12.7%), and current users (12.5%). We examined the prevalence, time-trend, correlates, and association of youth exposure to the warning with addictiveness and harm perception, intention to use e-cigarettes, and intention to quit all tobacco products. RESULTS: Only 24.5% of youth were exposed to the warning. Exposure increased from 14.9% in 2018 to 30.8% in 2019, then declined to 25.2% in 2021. Hispanic (adjusted odds ratio (aOR) = 0.76 [95% CI = 0.641 to 0.89]) and non-Hispanic black current users (0.53 [0.40 to 0.69]) were less likely to be exposed to the warning than white current users. Youth exposure was positively associated with a higher perception of e-cigarette addictiveness (1.12 [1.04 to 1.19]) and intention to quit all tobacco products (1.28 [1.13 to 1.46]). However, exposure was negatively associated with harm perception (0.91 [0.85 to 0.96]) and the intention to use e-cigarettes among e-cigarette nonusers (2.38 [1.99 to 2.84]). CONCLUSIONS: The decline in youth exposure to the warning indicates wear-out effects. Strengthening the label by using compelling designs, adding themes on e-cigarette harm to youth, periodically rotating warning content, and using culturally tailored messaging may improve its impact on youth and address racial/ethnic disparities. IMPLICATIONS: The FDA e-cigarette label reached only 24.5% of youth, and exposure to the warning declined to indicate wear-out effects. Exposure was significantly lower among minorities. Exposure was associated with a higher perception of e-cigarette addictiveness and intention to quit all tobacco products. Still, it did not increase harm perception or reduce intention to use e-cigarettes among nonusers. Strengthening the label by using more compelling designs, including diverse themes focusing on e-cigarette harm relevant to youth, and periodically rotating warning content may improve its impact on youth. Continued surveillance of the implementation of e-cigarette policies is needed to ensure that they equally affect youth across racial/ethnic subpopulations.

Who tests for lead and why? A 10-year analysis of blood lead screening, follow-up and CNS outcomes in a statewide US healthcare system.

OBJECTIVES: This study aims to determine (1) which providers in US healthcare systems order lead tests, why and at what frequency and (2) whether current patient population lead levels are predictive of clinical outcomes. METHODS: Retrospective medical record study of all blood lead tests in the Medical University of South Carolina healthcare system 2012-2016 and consequent evidence of central nervous system (CNS)-related disease across a potential 10-year window (2012-2022). RESULTS: Across 4 years, 9726 lead tests resulted for 7181 patients (49.0% female; 0-94 years), representing 0.2% of the hospital population. Most tests were for young (76.6%≤age 3) and non-Hispanic black (47.2%) and Hispanic (26.7%) patients. A wide variety of providers ordered tests; however, most were ordered by paediatrics, psychiatry, internal medicine and neurology. Lead levels ranged from ≤2.0 µg/dL (80.8%) to ≥10 µg/dL (0.8%; max 36 µg/dL). 201 children (3.1%) had initial lead levels over the reference value for case management at the time (5.0 µg/dL). Many high level children did not receive follow-up testing in the system (36.3%) and those that did often failed to see levels fall below 5.0 µg/dL (80.1%). Non-Hispanic black and Hispanic patients were more likely to see lead levels stay high or go up over time. Over follow-up, children with high lead levels were more likely to receive new attention-deficit/hyperactivity disorder and conduct disorder diagnoses and new psychiatric medications. No significant associations were found between lead test results and new CNS diagnoses or medications among adults. CONCLUSIONS: Hospital lead testing covers a small portion of patients but includes a wide range of ages, presentations and provider specialities. Lack of lead decline among many paediatric patients suggests there is room to improve provider guidance around when to test and follow-up.

Building consensus on a set of ENDS-specific pictorial health warnings: a Delphi study among a tobacco control expert panel.

BACKGROUND: This study reports on the development of pictorial health warning labels for electronic nicotine delivery system (ENDS) using the Delphi approach with a panel of tobacco control experts. Twenty-four evidence-based ENDS-specific warnings corresponding to three themes (toxicity, health risks and specific harm) were developed and used in the Delphi study. METHODS: We conducted a three-round online Delphi study among 60 experts (55% female) between June 2022 and April 2023. We balanced the panel in areas of expertise and positions relevant to ENDS (risks, benefits). In round 1, participants rated the warnings on attention, relevance to evidence and perceived effectiveness (harm perception, motivation to quit) and provided suggestions for improvement. In rounds 2 and 3, participants ranked the revised warnings based on importance in each theme. We assessed levels of agreement between participants using interquartile deviations and medians. RESULTS: Warnings in theme 1, toxicity, received the highest ratings for perceived effectiveness on harm perception and encouraging quitting ENDS (p<0.05). Experts recommended using clear and affirmative text paired with emotion-provoking pictures and avoiding the rare side effects of ENDS. Most of the top-ranked warnings were from theme 3, ENDS-specific harm, pertained to lung damage, dual use of ENDS and cigarettes, nicotine addiction among youth, anti-ENDS industry sentiment and toxicity. DISCUSSION: This study developed 24 evidence-based ENDS health warning labels using a systematic process that included several rounds of expert panel feedback. These warnings can be used to advance ENDS prevention and tobacco control policies and further target different populations.

Evaluation of the National Cancer Institute (NCI) Pathway to Independence Award (K99/R00) Program.

The National Cancer Institute (NCI) K99/R00 award is intended to help postdoctoral scholars transition in a timely manner to research independence and to foster their development of an impactful cancer research program that is competitive for subsequent independent funding. Here we analyzed factors that impact peer review outcomes and evaluated whether NCI K99/R00 awardees have achieved the goals of the K99/R00 funding mechanism. Our analysis of the K99/R00 review criterion scores demonstrates that while all review criterion scores are positively correlated with the overall impact score, the Research Plan criterion is the strongest predictor of the overall impact score and funding outcomes. In addition, our analysis shows the NCI K99/R00 award facilitated the successful transition of postdoctoral scholars to research independence and enhanced the likelihood of K99/R00 awardees to secure subsequent R01-equivalent NIH grant support although not in an accelerated fashion as originally intended. An NCI K99/R00 award was not determined to be a prerequisite to obtain a faculty position, but for some awardees, it was an asset in that transition. Our results suggest that the NCI K99/R00 award is an important component for training and retention of the next generation of independent cancer researchers and to increasing the percentage of women and promoting the diversity of the cancer research workforce.

Aromas: Lovely to Smell and Nice Solvents for Polyphenols? Curcumin Solubilisation Power of Fragrances and Flavours.

Natural aromas like cinnamaldehyde are suitable solvents to extract curcuminoids, the active ingredients found in the rhizomes of Curcuma longa L. In a pursuit to find other nature-based solvents, capable of solving curcumin, forty fragrances and flavours were investigated in terms of their solubilisation power. Aroma compounds were selected according to their molecular structure and functional groups. Their capabilities of solving curcumin were examined by UV-Vis spectroscopy and COSMO-RS calculations. The trends of these calculations were in accordance with the experimental solubilisation trend of the solubility screening and a list with the respective curcumin concentrations is given; σ-profiles and Gibbs free energy were considered to further investigate the solubilisation process of curcumin, which was found to be based on hydrogen bonding. High curcumin solubility was achieved in the presence of solvent (mixtures) with high hydrogen-bond-acceptor and low hydrogen-bond-donor abilities, like γ- and δ-lactones. The special case of DMSO was also examined, as the highest curcumin solubility was observed with it. Possible specific interactions of selected aroma compounds (citral and δ-hexalactone) with curcumin were investigated via 1H NMR and NOESY experiments. The tested flavours and fragrances were evaluated regarding their potential as green alternative solvents.

Room-Temperature Copper-Catalyzed Etherification of Aryl Bromides.

We disclose the development of a Cu-catalyzed C-O coupling method utilizing a new N1,N2-diarylbenzene-1,2-diamine ligand, L8. Under optimized reaction conditions, structurally diverse aryl and heteroaryl bromides underwent efficient coupling with a variety of alcohols at room temperature using an L8-based catalyst. Notably, the L8-derived catalyst exhibited enhanced activity when compared to the L4-based system previously disclosed for C-N coupling, namely the ability to functionalize aryl bromides containing acidic functional groups. Mechanistic studies demonstrate that C-O coupling utilizing L8 ⋅ Cu involves rate-limiting alkoxide transmetallation, resulting in a mechanism of C-O bond formation that is distinct from previously described Pd-, Cu-, or Ni-based systems. This lower energy pathway leads to rapid C-O bond formation; a 7-fold increase relative to what is seen with other ligands. The results presented in this report overcome limitations in previously described C-O coupling methods and introduce a new ligand that we anticipate may be useful in other Cu-catalyzed C-heteroatom bond-forming reactions.

Stereocontrolled Radical Thiophosphorylation.

The first practical, fully stereoselective P(V)-radical hydrophosphorylation is presented herein by using simple, limonene-derived reagent systems. A set of reagents have been developed that upon radical initiation react smoothly with olefins and other radical acceptors to generate P-chiral products, which can be further diversified (with conventional 2e- chemistry) to a range of underexplored bioisosteric building blocks. The reactions have a wide scope with excellent chemoselectivity, and the unexpected stereochemical outcome has been supported computationally and experimentally. Initial ADME studies are suggestive of the promising properties of this rarely explored chemical space.

Threshold behavior and tunability of a diffusive random laser.

In this study, it is shown that the dynamics of the lasing threshold and the intensity saturation of a diffusive random laser can be visualized by one spectral feature: the peak wavelength shift (tunability). The varied ink concentration and pump energy were utilized to experimentally induce the peak shift and the lasing threshold dynamics. It was found that the peak wavelength progressively turns from blueshift to redshift upon crossing the lasing threshold. A unique random laser threshold regime instead of a threshold point is revealed. This threshold regime was also compared with those deduced from the replica symmetry breaking and the Lévy statistics, both are the state-of-the-art methods to predict the behavior of a complex system. All three results show the high agreement in terms of unveiling the lasing nature of the random lasers.