METI: deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics.

Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance of METI on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. We also conduct a quantitative comparison of METI with existing clustering and cell deconvolution tools, demonstrating METI's robust and consistent performance.

Comprehensive molecular characterization of collecting duct carcinoma for therapeutic vulnerability.

Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

Neoplastic ICAM-1 protects lung carcinoma from apoptosis through ligation of fibrinogen.

Intercellular cell adhesion molecule-1 (ICAM-1) is frequently overexpressed in non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the mechanism underlying the negative effects of neoplastic ICAM-1 remains obscure. Herein, we demonstrate that the survival of NSCLC cells but not normal human bronchial epithelial cells requires an anti-apoptosis signal triggered by fibrinogen γ chain (FGG)-ICAM-1 interaction. ICAM-1-FGG ligation preserves the tyrosine phosphorylation of ICAM-1 cytoplasmic domain and its association with SHP-2, and subsequently promotes Akt and ERK1/2 activation but suppresses JNK and p38 activation. Abolishing ICAM-1-FGG interaction induces NSCLC cell death by activating caspase-9/3 and significantly inhibits tumor development in a mouse xenograft model. Finally, we developed a monoclonal antibody against ICAM-1-FGG binding motif, which blocks ICAM-1‒FGG interaction and effectively suppresses NSCLC cell survival in vitro and tumor growth in vivo. Thus, suppressing ICAM-1-FGG axis provides a potential strategy for NSCLC targeted therapy.

Cumulative effects of fish disturbance and vegetative propagules reduce the growth advantage of Vallisneria natans.

Benthivorous fish disturbance and density-dependent competition from adjacent macrophytes are two important biotic factors that significantly impact the growth of submerged macrophyte pioneer species, which is crucial for the success of eutrophication lake restoration. We conducted an outdoor mesocosm experiment to explore the individual and combined effects of these two factors on water quality and the growth of Vallisneria natans. The experiment involved two levels of fish (Misgurnus anguillicaudatus) disturbance crossed with two levels of Hydrilla verticillata vegetative propagule (shoot) intensity. The results showed that fish disturbance significantly increased the water column total nitrogen (TN), ammonia nitrogen (N-NH4), total phosphorus (TP), and phosphate­phosphorus (P-PO4). V. natans exhibited restricted plant height elongation and decreased soluble carbohydrate (SC) and starch concentration in fish treatments. Fish disturbance inhibited the growth advantage of V. natans by increasing the extinction coefficient of the water column. There was no statistical significance in total biomass between the two macrophytes in increased vegetative propagule and fish treatments. H. verticillata exhibited a higher relative growth rate (RGR) and summed dominance ratio (SDR3) than V. natans in four treatments and the treatment with three shoots of H. verticillata and one M anguillicaudatus, respectively. Fish disturbance and vegetative propagules showed cumulative effects that negatively affected the RGR_V.H (V. natans relative to H. verticillata). Our findings indicated that benthivorous fish disturbance and vegetative propagules could individually and cumulatively reduce the growth advantage of the pioneer species, V. natans. Our study sheds light on the accumulated effects of multiple disturbances that simultaneously occur in lakes, which holds theoretical and practical importance for lake restoration efforts.

Localized and delocalized topological modes of heat.

The topological physics has sparked intensive investigations into topological lattices in photonic, acoustic, and mechanical systems, powering counterintuitive effects otherwise inaccessible with usual settings. Following the success of these endeavors in classical wave dynamics, there has been a growing interest in establishing their topological counterparts in diffusion. Here, we propose an additional real-space dimension in diffusion, and the system eigenvalues are transformed from "imaginary" to "real." By judiciously tailoring the effective Hamiltonian with coupling networks, localized and delocalized topological modes are realized in heat transfer. Simulations and experiments in active thermal lattices validate the effectiveness of the proposed theoretical strategy. This approach can be applied to establish various topological lattices in diffusion systems, offering insights into engineering topologically protected edge states in dynamic diffusive scenarios.

Von Willebrand factor exacerbates heart failure through formation of neutrophil extracellular traps.

BACKGROUND AND AIMS: Heart failure (HF) is a leading cause of mortality worldwide and characterized by significant co-morbidities and dismal prognosis. Neutrophil extracellular traps (NETs) aggravate inflammation in various cardiovascular diseases; however, their function and mechanism of action in HF pathogenesis remain underexplored. This study aimed to investigate the involvement of a novel VWF-SLC44A2-NET axis in HF progression. METHODS: NET levels were examined in patients with HF and mouse models of transverse aortic constriction (TAC) HF. PAD4 knockout mice and NET inhibitors (GSK-484, DNase I, NEi) were used to evaluate the role of NETs in HF. RNA sequencing was used to investigate the downstream mechanisms. Recombinant human ADAMTS13 (rhADAMTS13), ADAMTS13, and SLC44A2 knockouts were used to identify novel upstream factors of NETs. RESULTS: Elevated NET levels were observed in patients with HF and TAC mouse models of HF. PAD4 knockout and NET inhibitors improved the cardiac function. Mechanistically, NETs induced mitochondrial dysfunction in cardiomyocytes, inhibiting mitochondrial biogenesis via the NE-TLR4-mediated suppression of PGC-1α. Furthermore, VWF/ADAMTS13 regulated NET formation via SLC44A2. Additionally, sacubitril/valsartan amplifies the cardioprotective effects of the VWF-SLC44A2-NET axis blockade. CONCLUSIONS: This study established the role of a novel VWF-SLC44A2-NET axis in regulating mitochondrial homeostasis and function, leading to cardiac apoptosis and contributing to HF pathogenesis. Targeting this axis may offer a potential therapeutic approach for HF treatment.

Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity.

Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8+CD44+CD62L+ central memory T cells into CD8+CD44-CD62L- T cells, designated as inter-organ migratory T cells (TIM cells). TIM cells move from the BM to the intestine by upregulating integrin ß7 and downregulating C-X-C motif chemokine receptor 3 during leukaemogenesis. Upon immunogenic chemotherapy, these BM-derived TIM cells return from the intestine to the BM through integrin α4-vascular cell adhesion molecule 1 interaction. Blocking C-X-C motif chemokine receptor 3 function boosts the immune response against leukaemia by enhancing T cell trafficking. This phenomenon can also be observed in patients with leukaemia. In summary, we identify an unrecognized intestine-BM trafficking circuit of T cells that contributes to the antitumour effects of immunogenic chemotherapy.

Redox/pH Dual-Responsive Fluorescent Nanoparticles for Intelligent Pesticide Release and Visualization in Gray Mold Disease Synergistic Control.

An intelligent delivery nanoformulation could enhance the utilization efficacy, uptake, and translocation of pesticides in plants. Herein, a redox/pH-triggered and fluorescent smart delivery nanoformulation was designed and constructed by using hollow mesoporous organosilica nanoparticles (HMONs) and ZnO quantum dots as the nanocarrier and capping agent, respectively. Boscalid was further loaded to generate Boscalid@HMONs@ZnO with a loading rate of 9.8% for controlling Botrytis cinerea (B. cinerea). The quantity of boscalid released by Boscalid@HMONs@ZnO in a glutathione environment or at pH 3.0 was 1.3-fold and 1.9-fold higher than that in a neutral condition. Boscalid@HMONs@ZnO has 1.7-fold the toxicity index of boscalid technical against B. cinerea in antifungal experiments. Pot experiments revealed that the efficacy of Boscalid@HMONs@ZnO was significantly enhanced more than 1.27-fold compared to commercially available water-dispersible granules of boscalid. Due to the fluorescence properties of Boscalid@HMONs@ZnO, pesticide transport's real-time monitoring of pesticide translocation in tomato plants could be observed by confocal laser scanning microscopy. Fluorescence images revealed that HMONs@ZnO had been effectively transported via treated leaves or roots in tomato plants. This research showed the successful application of HMONs@ZnO as a nanocarrier for controlling disease and offered an effective avenue to explore the real-time tracking of pesticide translocation in plants.

Successfully saving a child with destuctive iliac artery damage by hybrid surgery.

Non-iatrogenic trauma of the iliac artery is rarely reported but is always life-threatening. In this report, we describe the case of a child with complete transection and partial disappearance of the iliac artery caused by bicycle handlebar impalement. He experienced catastrophic hemorrhage, malignant arrhythmia, and difficulty in exploring transected vessel stumps. Aggressive infusion, blood transfusion in time, and pediatric vascular characteristics help delay the deterioration during anesthesia induction. Eventually he was successfully rescued by performing interventional balloon occlusion and open revascularization after more than 7 h post-trauma. A series of interventions and precautionary methods may benefit such severely injured patients; thus, these methods should be highlighted.

CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway.

INTRODUCTION: The diversity in microglial phenotypes and functions following traumatic brain injury (TBI) is poorly characterized. The aim of this study was to explore precise targets for improving the prognosis of TBI patients from a microglial perspective. OBJECTIVES: To assess whether the prognosis of TBI can be improved by modulating microglia function. RESULTS: In CD300LF-deficient mice, we observed an increase in glial cell proliferation, more extensive neuronal loss, and worsened neurological function post-TBI. Transcriptomic comparisons between CD300LF-positive and CD300LF-negative microglia illuminated that the neuroprotective role of CD300LF is principally mediated by the inhibition of the STING signaling pathway. In addition, this protective effect can be augmented using the STING pathway inhibitor C-176. CONCLUSIONS: Our research indicates that CD300LF reduces neuroinflammation and promotes neurological recovery after TBI, and that microglia are integral to the protective effects of CD300LF in this context. In summary, our findings highlight CD300LF as a critical molecular regulator modulating the adverse actions of microglia following acute brain injury and propose a novel therapeutic approach to enhance outcomes for patients with TBI.

Low-intensity pulsed ultrasound improves myocardial ischaemia‒reperfusion injury via migrasome-mediated mitocytosis.

During myocardial ischaemia‒reperfusion injury (MIRI), the accumulation of damaged mitochondria could pose serious threats to the heart. The migrasomes, newly discovered mitocytosis-mediating organelles, selectively remove damaged mitochondria to provide mitochondrial quality control. Here, we utilised low-intensity pulsed ultrasound (LIPUS) on MIRI mice model and demonstrated that LIPUS reduced the infarcted area and improved cardiac dysfunction. Additionally, we found that LIPUS alleviated MIRI-induced mitochondrial dysfunction. We provided new evidence that LIPUS mechanical stimulation facilitated damaged mitochondrial excretion via migrasome-dependent mitocytosis. Inhibition the formation of migrasomes abolished the protective effect of LIPUS on MIRI. Mechanistically, LIPUS induced the formation of migrasomes by evoking the RhoA/Myosin II/F-actin pathway. Meanwhile, F-actin activated YAP nuclear translocation to transcriptionally activate the mitochondrial motor protein KIF5B and Drp1, which are indispensable for LIPUS-induced mitocytosis. These results revealed that LIPUS activates mitocytosis, a migrasome-dependent mitochondrial quality control mechanism, to protect against MIRI, underlining LIPUS as a safe and potentially non-invasive treatment for MIRI.

Ca2+ transients on the T cell surface trigger rapid integrin activation in a timescale of seconds.

One question in lymphocyte homing is how integrins are rapidly activated to enable immediate arrest of fast rolling lymphocytes upon encountering chemokines at target vascular beds given the slow chemokine-induced integrin inside-out activation. Herein we demonstrate that chemokine CCL25-triggered Ca2+ influx induces T cell membrane-proximal external Ca2+ concentration ([Ca2+]ex) drop in 6 s from physiological concentration 1.2 mM to 0.3 mM, a critical extracellular Ca2+ threshold for inducing αLß2 activation, triggering rapid αLß2 activation and T cell arrest before occurrence of αLß2 inside-out activation. Talin knockdown inhibits the slow inside-out activation of αLß2 but not [Ca2+]ex drop-triggered αLß2 quick activation. Blocking Ca2+ influx significantly suppresses T cell rolling-to-arrest transition and homing to skin lesions in a mouse psoriasis model, thus alleviating skin inflammation. [Ca2+]ex decrease-triggered rapid integrin activation bridges the gap between initial chemokine stimulation and slow integrin inside-out activation, ensuring immediate lymphocyte arrest and subsequent diapedesis on the right location.

Neutrophil-derived migrasomes are an essential part of the coagulation system.

Migrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these migrasomes adsorb and enrich coagulation factors on the surface. Moreover, they are highly enriched with adhesion molecules, which enable them to preferentially accumulate at sites of injury, where they trigger platelet activation and clot formation. Depletion of neutrophils, or genetic reduction of the number of these migrasomes, significantly decreases platelet plug formation and impairs coagulation. These defects can be rescued by intravenous injection of purified neutrophil-derived migrasomes. Our study reveals neutrophil-derived migrasomes as a previously unrecognized essential component of the haemostasis system, which may shed light on the cause of various coagulation disorders and open therapeutic possibilities.

Effects of different plasma treatments on bonding properties of zirconia.

This in vitro study was to evaluate the effect of different non-thermal atmospheric pressure plasma (NTP) on shear bond strength (SBS) between yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) and self-adhesive resin cement. In this study, The Y-TZP specimens were divided into 4 groups according to the surface treatment methods as follows: Control (no surface treatment), Sb (Sandblasting), AP(argon NTP), and CP(20 % oxygen and 80 % argon combination NTP). Y-TZP specimens were randomly selected from each group to observe and test the following indexes: scanning electron microscope to observe the surface morphology; atomic force microscope to detect the surface roughness; contact angle detector to detect the surface contact angle; energy spectrometer to analyze the surface elements. Then, resin cement (Rely X-U200) was bonded to human isolated teeth with Y-TZP specimens to measure SBS. The results showed that for the SE test, the NTP group was significantly higher than the control group (p < 0.05). The results of the SBS test showed that the SBS values of the NTP group were significantly higher than those of the other groups, regardless of the plasma treatment (p < 0.05). However, there was no significant difference between groups AP and CP in a test of SBS (p > 0.05). This study shows that non-thermal atmospheric pressure plasma can improve the shear bond strength of Y-TZP by increasing the surface energy. The addition of oxygen ratio to argon is more favorable to increase the shear bond strength and is worth further investigation.

Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

Characteristics and seasonal variations of cirrus clouds from ground-based lidar and satellite observations over Shouxian Area, China.

This study investigates the macroscopic and optical properties of cirrus clouds in the 32N region from July 2016 to May 2017, leveraging data from ground-based lidar observations and CALIOP to overcome the inconsistencies in detected cirrus cloud samples. Through extensive data analysis, statistical characteristics of cirrus clouds were discerned, revealing lidar ratio values of 28.5 ± 10.8 from ground-based lidar and 27.4 ± 11.2 from CALIOP. Validation with a decade of CALIOP data (2008-2018) confirmed these findings, presenting a consistent lidar ratio of 27.4 ± 12.0. A significant outcome of the analysis was the identification of a positive correlation between the lidar ratio and cloud centroid temperature, indicating a gradual decrease in the lidar ratio as temperatures dropped. The study established a fundamental consistency in their macroscopic properties, including cloud base height, cloud top height, cloud thickness, cloud centroid height, and cloud centroid temperature. The results for ground-based lidar (CALIOP) are: 10.0 ± 2.1 km (10.0 ± 2.2 km), 11.8 ± 2.1 km (11.5 ± 2.3 km), 1.87 ± 0.83 km (1.52 ± 0.71 km), and 10.5 ± 2.2 km, -46.9 ± 9.7°C (-47.1 ± 10.0°C).These properties exhibited seasonal variations, with cirrus clouds reaching higher altitudes in summer and lower in winter, influenced by the height of the tropopause. The optical properties of cirrus clouds were also analyzed, showing an annual average optical depth of 0.31 ± 0.35 for ground-based lidar and 0.32 ± 0.44 for CALIOP. The study highlighted the distribution of subvisible, thin, and thick cirrus clouds, with a notable prevalence of subvisible clouds during summer, suggesting their frequent formation above 14 km. Furthermore, the study observed linear growth in geometric thickness and optical depth up to 2.5 km from CALIOP and 2.9 km from ground-based lidar. Maximum optical depth was observed at cloud centroid temperatures of -35°C for CALIOP and -40°C for ground-based lidar, with optical depth decreasing as temperatures fell. This suggests that fully glaciated cirrus clouds exhibit the highest optical depth at warmer temperatures, within the complete glaciation temperature range of -35°C to -40°C.

CG001, a C3b-targeted complement inhibitor, blocks 3 complement pathways: development and preclinical evaluation.

ABSTRACT: Excessively activated or dysregulated complement activation may contribute to the pathogenesis of a wide range of human diseases, thus leading to a surge in complement inhibitors. Herein, we developed a human-derived and antibody-like C3b-targeted fusion protein (CRIg-FH-Fc) x2, termed CG001, that could potently block all 3 complement pathways. Complement receptor of the immunoglobulin superfamily (CRIg) and factor H (FH) bind to distinct sites in C3b and synergistically inhibit complement activation. CRIg occupancy in C3b prevents the recruitment of C3 and C5 substrates, whereas FH occupancy in C3b accelerates the decay of C3/C5 convertases and promotes the factor I-mediated degradation and inactivation of C3b. CG001 also showed therapeutic effects in alternative pathways-induced hemolytic mouse and classical pathways-induced mesangial proliferative glomerulonephritis rat models. In the pharmacological/toxicological evaluation in rats and cynomolgus monkeys, CG001 displayed an antibody-like pharmacokinetic profile, a convincing complement inhibitory effect, and no observable toxic effects. Therefore, CG001 holds substantial potential for human clinical studies.

Remarkable Toughening of Plastic with Monodispersed Nano-CaCO3: From Theoretical Predictions to Experimental Validation.

The structure-property relationship of poly(vinyl chloride) (PVC)/CaCO3 nanocomposites is investigated by all-atom molecular dynamics (MD) simulations. MD simulation results indicate that the dispersity of nanofillers, interfacial bonding, and chain mobility are imperative factors to improve the mechanical performance of nanocomposites, especially toughness. The tensile behavior and dissipated work of the PVC/CaCO3 model demonstrate that 12 wt % CaCO3 modified with oleate anion and dodecylbenzenesulfonate can impart high toughness to PVC due to its good dispersion, favorable interface interaction, and weak migration of PVC chains. Under the guidance of MD simulation, we experimentally prepared a transparent PVC/CaCO3 nanocomposite with good mechanical properties by in situ polymerization of monodispersed CaCO3 in vinyl chloride monomers. Interestingly, experimental tests indicate that the optimum toughness of a nanocomposite (a 368% increase in the elongation at break and 204% improvement of the impact strength) can be indeed realized by adding 12 wt % CaCO3 modified with oleic acid and dodecylbenzenesulfonic acid, which is remarkably consistent with the MD simulation prediction. In short, this work provides a proof-of-concept of using MD simulation to guide the experimental synthesis of PVC/CaCO3 nanocomposites, which can be considered as an example to develop other functional nanocomposites.

CDK4/6 inhibition augments anti-tumor efficacy of XPO1 inhibitor selinexor in natural killer/T-cell lymphoma.

XPO1 is an attractive and promising therapeutic target frequently overexpressed in multiple hematological malignancies. The clinical use of XPO1 inhibitors in natural killer/T-cell lymphoma (NKTL) is not well documented. Here, we demonstrated that XPO1 overexpression is an indicator of poor prognosis in patients with NKTL. The compassionate use of the XPO1 inhibitor selinexor in combination with chemotherapy showed favorable clinical outcomes in three refractory/relapsed (R/R) NKTL patients. Selinexor induced complete tumor regression and prolonged survival in sensitive xenografts but not in resistant xenografts. Transcriptomic profiling analysis indicated that sensitivity to selinexor was correlated with deregulation of the cell cycle machinery, as selinexor significantly suppressed the expression of cell cycle-related genes. CDK4/6 inhibitors were identified as sensitizers that reversed selinexor resistance. Mechanistically, targeting CDK4/6 could enhance the anti-tumor efficacy of selinexor via the suppression of CDK4/6-pRb-E2F-c-Myc pathway in resistant cells, while selinexor alone could dramatically block this pathway in sensitive cells. Overall, our study provids a preclinical proof-of-concept for the use of selinexor alone or in combination with CDK4/6 inhibitors as a novel therapeutic strategy for patients with R/R NKTL.

Salinity decline promotes growth and harmful blooms of a toxic alga by diverting carbon flow.

Global climate change intensifies the water cycle and makes freshest waters become fresher and vice-versa. But how this change impacts phytoplankton in coastal, particularly harmful algal blooms (HABs), remains poorly understood. Here, we monitored a coastal bay for a decade and found a significant correlation between salinity decline and the increase of Karenia mikimotoi blooms. To examine the physiological linkage between salinity decreases and K. mikimotoi blooms, we compare chemical, physiological and multi-omic profiles of this species in laboratory cultures under high (33) and low (25) salinities. Under low salinity, photosynthetic efficiency and capacity as well as growth rate and cellular protein content were significantly higher than that under high salinity. More strikingly, the omics data show that low salinity activated the glyoxylate shunt to bypass the decarboxylation reaction in the tricarboxylic acid cycle, hence redirecting carbon from CO2 release to biosynthesis. Furthermore, the enhanced glyoxylate cycle could promote hydrogen peroxide metabolism, consistent with the detected decrease in reactive oxygen species. These findings suggest that salinity declines can reprogram metabolism to enhance cell proliferation, thus promoting bloom formation in HAB species like K. mikimotoi, which has important ecological implications for future climate-driven salinity declines in the coastal ocean with respect to HAB outbreaks.