The impact of nuclear shape on the emergence of the neutron dripline.

Atomic nuclei are composed of a certain number of protons Z and neutrons N. A natural question is how large Z and N can be. The study of superheavy elements explores the large Z limit1,2, and we are still looking for a comprehensive theoretical explanation of the largest possible N for a given Z-the existence limit for the neutron-rich isotopes of a given atomic species, known as the neutron dripline3. The neutron dripline of oxygen (Z = 8) can be understood theoretically as the result of single nucleons filling single-particle orbits confined by a mean potential, and experiments confirm this interpretation. However, recent experiments on heavier elements are at odds with this description. Here we show that the neutron dripline from fluorine (Z = 9) to magnesium (Z = 12) can be predicted using a mechanism that goes beyond the single-particle picture: as the number of neutrons increases, the nuclear shape assumes an increasingly ellipsoidal deformation, leading to a higher binding energy. The saturation of this effect (when the nucleus cannot be further deformed) yields the neutron dripline: beyond this maximum N, the isotope is unbound and further neutrons 'drip' out when added. Our calculations are based on a recently developed effective nucleon-nucleon interaction4, for which large-scale eigenvalue problems are solved using configuration-interaction simulations. The results obtained show good agreement with experiments, even for excitation energies of low-lying states, up to the nucleus of magnesium-40 (which has 28 neutrons). The proposed mechanism for the formation of the neutron dripline has the potential to stimulate further thinking in the field towards explaining nucleosynthesis with neutron-rich nuclei.

Additive impact of soy protein dietary intake and exercise on visceral fat mass reduction and mitochondrial complex I activation in skeletal muscle.

Soy protein has shown remarkable effectiveness in reducing fat mass compared with other protein sources, and exercise has the potential to further enhance this fat loss effect. Previous studies have demonstrated that soy protein intake leads to decreased fatty acid synthesis, which contributes to its fat-loss properties. However, the exact mechanism by which these lipids are consumed remains unclear. To investigate this, we conducted a comprehensive study using C57/BL6 male mice, comparing the effects of soy and casein proteins with and without exercise (Casein-Sed, Casein-Ex, Soy-Sed, and Soy-Ex groups) under high- and low-protein conditions (14% or 40% protein). Our findings revealed that combining soy protein intake with exercise significantly reduced epididymal white adipose tissue (eWAT) weight, particularly in the high-protein diet group. Further analysis revealed that exercise increased the expression of lipid oxidation-regulatory proteins, including mitochondrial oxidative phosphorylation protein (OXPHOS) complexes, in the plantaris muscle regardless of the protein source. Although soy protein intake did not directly affect muscle mitochondrial protein expression, the activity of OXPHOS complex I was additively enhanced by exercise and soy protein under the 40% protein condition. Notably, complex I activity inversely correlated with eWAT weight in the soy protein diet group. These results highlight the potential link between improved complex I activity induced by soy protein and fat mass reduction, which emphasizes the promising benefits of combining soy protein with exercise in promoting fat loss.NEW & NOTEWORTHY The findings revealed that soy protein intake combined with exercise resulted in reduced adipose tissue weight compared with that obtained with casein protein intake. Furthermore, the joint impact of exercise and soy protein consumption resulted in enhanced activity of oxidative phosphorylation protein (OXPHOS) complex I in fast-twitch muscles, which appears to be associated with fat mass reduction. These findings elucidate the potential additive effects of soy protein and exercise on body weight management.

Clonal heamatopoiesis and associated cardiovascular diseases.

Cancer and cardiovascular disease share several risk factors. Clonal heamatopoiesis, a novel risk factor associated with both diseases, has received increasing attention in the fields of cardiology, heamatology and oncology. Clonal heamatopoiesis of indeterminate potential refers to the presence of at least one driver mutation in the heamatopoietic cells of peripheral blood without heamatological malignancy. Clonal heamatopoiesis of indeterminate potential is a common age-related condition that affects up to 60% of individuals aged > 80 years. Importantly, clonal heamatopoiesis of indeterminate potential carriers have a 2- to 4-fold higher risk of developing cardiovascular disease than non-carriers. Therefore, we performed an up-to-date review of clonal heamatopoiesis and its association with various forms of cardiovascular disease, including atherosclerotic disease, heart failure, aortic stenosis and pulmonary hypertension. In addition, we reviewed experimental studies that examined the causality and directionality between clonal heamatopoiesis and cardiovascular disease. Lastly, we discussed future research directions that will aid in the design of personalized therapies and preventive strategies for individuals with clonal heamatopoiesis. This review showed that clonal heamatopoiesis of indeterminate potential is a common condition, especially in older patients, and is associated with an increased risk of cardiovascular disease and worse prognosis. However, further research is needed to determine whether anti-inflammatory therapies or therapies that can reduce or eliminate clone size are effective in preventing cardiovascular disease in patients with clonal heamatopoiesis of indeterminate potential.

Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.

Rationale: Although persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF), mechanisms regulating persistent fibroblast activation in the lungs have not been fully elucidated. Objectives: On the basis of our observation that lung fibroblasts express TBXA2R (thromboxane-prostanoid receptor) during fibrosis, we investigated the role of TBXA2R signaling in fibrotic remodeling. Methods: We identified TBXA2R expression in lungs of patients with IPF and mice and studied primary mouse and human lung fibroblasts to determine the impact of TBXA2R signaling on fibroblast activation. We used TBXA2R-deficient mice and small-molecule inhibitors to investigate TBXA2R signaling in preclinical lung fibrosis models. Measurements and Main Results: TBXA2R expression was upregulated in fibroblasts in the lungs of patients with IPF and in mouse lungs during experimental lung fibrosis. Genetic deletion of TBXA2R, but not inhibition of thromboxane synthase, protected mice from bleomycin-induced lung fibrosis, thereby suggesting that an alternative ligand activates profibrotic TBXA2R signaling. In contrast to thromboxane, F2-isoprostanes, which are nonenzymatic products of arachidonic acid induced by reactive oxygen species, were persistently elevated during fibrosis. F2-isoprostanes induced TBXA2R signaling in fibroblasts and mediated a myofibroblast activation profile due, at least in part, to potentiation of TGF-ß (transforming growth factor-ß) signaling. In vivo treatment with the TBXA2R antagonist ifetroban reduced profibrotic signaling in the lungs, protected mice from lung fibrosis in three preclinical models (bleomycin, Hermansky-Pudlak mice, and radiation-induced fibrosis), and markedly enhanced fibrotic resolution after bleomycin treatment. Conclusions: TBXA2R links oxidative stress to fibroblast activation during lung fibrosis. TBXA2R antagonists could have utility in treating pulmonary fibrosis.

Effects of intake of Lactococcus cremoris subsp. cremoris FC on constipation symptoms and immune system in healthy participants with mild constipation: a double-blind, placebo-controlled study.

This study evaluated the effect of Lactococcus cremoris subsp. cremoris FC (FC) on constipation symptoms and the immune system in healthy participants with mild constipation. Eighty-three participants were randomised into four groups with different doses: 50, 75, and 100 mg of freeze-dried FC (test) or corn starch (placebo). Defaecation frequency significantly increased in all test groups compared to the placebo group. Stool appearance and volume were improved considerably within the groups administered 50 mg and 75 mg of FC. The abundances of total bacteria, Bifidobacterium spp., and Lactobacillus group in the faeces showed increasing trends in the test groups. Regarding immunological parameters, the naive T cell counts in the blood were significantly higher at a dose of 75 mg of FC in the test group than in the placebo group. These results suggest that FC intake improves defaecation and some immunological parameters, especially naive T cell counts, in healthy adults.

[Pharmacologic Therapy for Bone Metastases-Current Strategies and Future Directions].

Bisphosphonates were introduced in the late 1990s to reduce the frequency of skeletal-related events(SREs)in patients with metastatic bone disease. In the 2010s, anti-RANKL antibodies were launched as another type of bone modifying agents(BMA). Both induce osteoclast apoptosis and have been used in Japan for solid tumors with bone metastases and multiple myeloma. In addition to osteoclasts, bone microenvironment includes a wide variety of cells such as osteoblasts, vascular endothelial cells, and immune cells, which spatiotemporally interact with cancer cells, resulting in the colonization of dissociated tumor cells(DTCs). Understanding the pathways and microenvironmental factors through which cancer evolves to promote bone colony formation will lead to better planning of the therapeutic strategies in individual cases and to further elucidation of molecular drivers.

[A new method for measuring spinal kyphosis using CT images and a study of its relationship with reflux esophagitis].

[Purpose] This study aimed to examine the validity and reproducibility of a new quantitative method for measuring spinal kyphosis using computed tomography (CT), and to investigate its relationship with reflux esophagitis. [Method] Using a new method to measure the index of kyphosis in CT images (IKCT), 10 examiners evaluated 10 cases of spinal kyphosis. One examiner measured 47 cases twice and 20 cases were examined to assess the validity with the kyphosis index. A case-control study was conducted on 303 cases of reflux esophagitis, of which 241 were mild and 62 severe. [Results] Regarding IKCT reproducibility, the inter-rater intraclass correlation coefficient was 0.977. The intra-rater intraclass correlation coefficient was 0.974. The correlation index with the kyphosis index was 0.731. A greater IKCT value, not contracting serious atrophic gastritis, and severe hiatal hernia were identified as risk factors for severe reflux esophagitis. [Conclusion] IKCT is a simple and useful method for measuring kyphosis. The prevention of kyphosis can help suppress severe reflux esophagitis.

Lactococcus cremoris subsp. cremoris FC-fermented milk activates protein synthesis and increases skeletal muscle mass in middle-aged mice.

Age-related muscle atrophy is associated with decreased protein anabolic capacity. Dietary intervention is an important strategy for the treatment of age-related muscle atrophy. This study examined the effect of Lactococcus cremoris subsp. cremoris FC-fermented milk on muscle mass and protein anabolic signaling in middle-aged mice. Male C57BL/6J mice (18-month-old) were divided into the control and Lactococcus cremoris subsp. cremoris FC-fermented milk supplementation groups. Mice were administered unfermented or fermented milk (300 µL/day) by gavage every alternate day for 8 weeks; thereafter, muscle weight, protein metabolic signaling factors, and inflammatory factors were investigated. Soleus muscle weight was higher in the fermented milk group than in the control group. Expression of insulin growth factor-1, a typical anabolic factor, and phosphorylation levels of anabolic signaling factors (mTOR and p70S6K) were higher after fermented milk supplementation. Levels of tumor necrosis factor-α, an inhibitor of protein anabolism, were lower in the fermented milk group. These data suggest that the daily intake of Lactococcus cremoris subsp. cremoris FC-fermented milk increased skeletal muscle mass as well as protein synthesis in the middle-aged mice, which may be mediated by reduction in the levels of inflammatory factors. Therefore, accelerated protein synthesis, induced by the consumption of fermented milk, has a potential role in counteracting muscle atrophy.

Evaluation of a new point-of-care quantitative reverse transcription polymerase chain test for detecting severe acute respiratory syndrome coronavirus 2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rapidly spreading worldwide, and the resultant disease, coronavirus disease (COVID-19), has become a global pandemic. Although there are multiple methods for detecting SARS-CoV-2, there are some issues with such tests, including long processing time, expense, low sensitivity, complexity, risk of contamination, and user friendly. This study evaluated the reproducibility and usability of a new point-of-care test (POCT) using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for detecting SARS-CoV-2. METHODS: Samples from 96 patients with suspected SARS-CoV-2 infection were assessed using the real-time qRT-PCR-based POCT and the conventional real-time qRT-PCR method based on the Japanese National Institute of Infectious Diseases guidelines (registration number: jRCT1032200025). RESULTS: The real-time qRT-PCR-based POCT had a positive agreement rate of 90.0% (18/20), a negative agreement rate of 100% (76/76), and a total agreement rate of 97.9% (94/96), and the significantly high score of questionnaire survey (total score p < 0.0001). In the two cases in which real-time qRT-PCR-based POCT results did not match conventional real-time qRT-PCR test results, the SARS-CoV-2 RNA copy numbers were 8.0 copies per test in one case and below the detection limit in the other case when quantified using conventional real-time qRT-PCR. All patients could be triaged within 1 day using the real-time qRT-PCR-based POCT without invalid reports. CONCLUSIONS: The real-time qRT-PCR-based POCT not only had high reproducibility and useability but also allowed rapid patient triage. Therefore, it may be helpful in clinical settings.

Solubilization of poorly water-soluble bioactive molecules in neutral aqueous media by complexation with renatured ß-1,3-1,6-glucan nanoparticles.

The design of scaffolds for solubilizing/dispersing poorly water-soluble bioactive molecules in neutral aqueous media is a major challenge of functional food, pharmaceuticals, and cosmetics development, as highlighted by the plethora of corresponding solubilization/dispersion strategies. Herein, renatured ß-1,3-1,6-glucan (r-glucan) nanoparticles prepared by neutralization of alkali-denatured ß-1,3-1,6-glucan and subsequent centrifugation are used as a host to disperse water-insoluble bioactive molecules (curcumin, all-trans-retinoic acid, and rebamipide) by simple mixing of host and guest solutions. Curcumin in the r-glucan cavity is found to be stacked in the form of J-aggregates and twisted along the helix, and is demonstrated to be retained for significantly longer than curcumin in the corresponding γ-cyclodextrin (γ-CD) complex. Specifically, curcumin incorporated in γ-CD is released within 5.5 hours, whereas that in the r-glucan complex is released very slowly, with 12% of curcumin in the latter complex retained after 31-day incubation at 37°C. Thus, inclusion protocol simplicity and slow release ability make r-glucan nanoparticles a potential carrier scaffold for various applications.

[Cardiac Tamponade as Cardio-Oncologic Emergency Disease].

The causes of cardiac tamponade include neoplastic pericarditis as well as radiation-induced, drug-induced, purulent and iatrogenic pericarditis. Since we can get access to the advanced cancer therapy these days, some of the cardiac tamponade patients can survive longer if we can manage their pericardial effusion well. Here, we will summarize the clinical evidence in cardiac tamponade in patients with malignant tumor, and will discuss about its presentation, diagnosis and management.

Turn-on fluorescence and photodynamic activity of ß-(1,3-1,6)-d-glucan-complexed porphyrin derivatives inside HeLa cells.

Fluorescence intensities of water-soluble ß-(1,3-1,6)-d-glucan (ß-1,3-glucan)-complexed porphyrin derivatives were very weak as a result of self-quenching. However, ß-1,3-glucan-complexed tetra(aminophenyl)porphyrin exhibited 'off-state' to 'on-state' fluorescence switching activity by intracellular uptake. Furthermore, the internalised complex showed a high level of photodynamic activity toward HeLa cells under photoirradiation at long wavelengths.

Contact Sex Pheromone Activity of Synthetic Gomadalactones in Male White-Spotted Longhorn Beetle, Anoplophora malasiaca (Coleoptera: Cerambycidae).

The elytra of females of the white-spotted longhorn beetle, Anoplophora malasiaca (Coleoptera: Cerambycidae), are coated with a contact sex pheromone, which was previously shown to be composed of at least three chemical groups. Individually, the chemical groups had little pheromonal activity, but a blend of all three exhibited activity equal to that of the crude female extract. Two groups are female-specific aliphatic hydrocarbons and ketones, which were previously synthesized and confirmed to elicit mating behavior. The third group consists of three lactones, gomadalactones A, B, and C, whose chemical structures were previously identified. These have now been synthesized, and the contact sex pheromone activities of synthetic gomadalactones A, B, and C, and the diastereomer of gomadalactone C, were tested in bioassays in this study. When tested in combination with synthetic hydrocarbons and ketones at the same doses as found in female elytra extract, the individual gomadalactones and a blend showed potent pheromonal activity equivalent to that of the crude extract of the elytra of female beetles. This completes the identification of the essential components of the contact sex pheromone of A. malasiaca. Redundancy of components in the hydrocarbon and ketone groups required to elicit mating behavior was observed previously, and this was also true for the gomadalactones.

Isolation and characterization of endothelial-to-mesenchymal transition cells in pulmonary arterial hypertension.

Endothelial-to-mesenchymal transition (EndMT) is a process in which endothelial cells lose polarity and cell-to cell contacts, and undergo a dramatic remodeling of the cytoskeleton. It has been implicated in initiation and progression of pulmonary arterial hypertension (PAH). However, the characteristics of cells which have undergone EndMT cells in vivo have not been reported and so remain unclear. To study this, sugen5416 and hypoxia (SuHx)-induced PAH was established in Cdh5-Cre/Gt(ROSA)26Sortm4(ACTB-tdTomato,EGFP)Luo/J double transgenic mice, in which GFP was stably expressed in pan-endothelial cells. After 3 wk of SuHx, flow cytometry and immunohistochemistry demonstrated CD144-negative and GFP-positive cells (complete EndMT cells) possessed higher proliferative and migratory activity compared with other mesenchymal cells. While CD144-positive and α-smooth muscle actin (α-SMA)-positive cells (partial EndMT cells) continued to express endothelial progenitor cell markers, complete EndMT cells were Sca-1-rich mesenchymal cells with high proliferative and migratory ability. When transferred in fibronectin-coated chamber slides containing smooth muscle media, α-SMA robustly expressed in these cells compared with cEndMT cells that were grown in maintenance media. Demonstrating additional paracrine effects, conditioned medium from isolated complete EndMT cells induced enhanced mesenchymal proliferation and migration and increased angiogenesis compared with conditioned medium from resident mesenchymal cells. Overall, these findings show that EndMT cells could contribute to the pathogenesis of PAH both directly, by transformation into smooth muscle-like cells with higher proliferative and migratory potency, and indirectly, through paracrine effects on vascular intimal and medial proliferation.

Endothelial cell-related autophagic pathways in Sugen/hypoxia-exposed pulmonary arterial hypertensive rats.

Pulmonary arterial hypertension (PAH) is characterized by progressive obstructive remodeling of pulmonary arteries. However, no reports have described the causative role of the autophagic pathway in pulmonary vascular endothelial cell (EC) alterations associated with PAH. This study investigated the time-dependent role of the autophagic pathway in pulmonary vascular ECs and pulmonary vascular EC kinesis in a severe PAH rat model (Sugen/hypoxia rat) and evaluated whether timely induction of the autophagic pathway by rapamycin improves PAH. Hemodynamic and histological examinations as well as flow cytometry of pulmonary vascular EC-related autophagic pathways and pulmonary vascular EC kinetics in lung cell suspensions were performed. The time-dependent and therapeutic effects of rapamycin on the autophagic pathway were also assessed. Sugen/hypoxia rats treated with the vascular endothelial growth factor receptor blocker SU5416 showed increased right ventricular systolic pressure (RVSP) and numbers of obstructive vessels due to increased pulmonary vascular remodeling. The expression of the autophagic marker LC3 in ECs also changed in a time-dependent manner, in parallel with proliferation and apoptotic markers as assessed by flow cytometry. These results suggest the presence of cross talk between pulmonary vascular remodeling and the autophagic pathway, especially in small vascular lesions. Moreover, treatment of Sugen/hypoxia rats with rapamycin after SU5416 injection activated the autophagic pathway and improved the balance between cell proliferation and apoptosis in pulmonary vascular ECs to reduce RVSP and pulmonary vascular remodeling. These results suggested that the autophagic pathway can suppress PAH progression and that rapamycin-dependent activation of the autophagic pathway could ameliorate PAH.

Vildagliptin ameliorates pulmonary fibrosis in lipopolysaccharide-induced lung injury by inhibiting endothelial-to-mesenchymal transition.

BACKGROUND: Pulmonary fibrosis is a late manifestation of acute respiratory distress syndrome (ARDS). Sepsis is a major cause of ARDS, and its pathogenesis includes endotoxin-induced vascular injury. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play an important role in pulmonary fibrosis. On the other hand, dipeptidyl peptidase (DPP)-4 was reported to improve vascular dysfunction in an experimental sepsis model, although whether DPP-4 affects EndMT and fibrosis initiation during lipopolysaccharide (LPS)-induced lung injury is unclear. The aim of this study was to investigate the anti-EndMT effects of the DPP-4 inhibitor vildagliptin in pulmonary fibrosis after systemic endotoxemic injury. METHODS: A septic lung injury model was established by intraperitoneal injection of lipopolysaccharide (LPS) in eight-week-old male mice (5 mg/kg for five consecutive days). The mice were then treated with vehicle or vildagliptin (intraperitoneally, 10 mg/kg, once daily for 14 consecutive days from 1 day before the first administration of LPS.). Flow cytometry, immunohistochemical staining, and quantitative polymerase chain reaction (qPCR) analysis was used to assess cell dynamics and EndMT function in lung samples from the mice. RESULTS: Lung tissue samples from treated mice revealed obvious inflammatory reactions and typical interstitial fibrosis 2 days and 28 days after LPS challenge. Quantitative flow cytometric analysis showed that the number of pulmonary vascular endothelial cells (PVECs) expressing alpha-smooth muscle actin (α-SMA) or S100 calcium-binding protein A4 (S100A4) increased 28 days after LPS challenge. Similar increases in expression were also confirmed by qPCR of mRNA from isolated PVECs. EndMT cells had higher proliferative activity and migration activity than mesenchymal cells. All of these changes were alleviated by intraperitoneal injection of vildagliptin. Interestingly, vildagliptin and linagliptin significantly attenuated EndMT in the absence of immune cells or GLP-1. CONCLUSIONS: Inhibiting DPP-4 signaling by vildagliptin could ameliorate pulmonary fibrosis by downregulating EndMT in systemic LPS-induced lung injury.

Formation of ß-(1,3-1,6)-d-glucan-complexed [70]fullerene and its photodynamic activity towards macrophages.

[70]Fullerene was dissolved in water by complexation with ß-1,3-glucan using a mechanochemical high-speed vibration milling apparatus. The photodynamic activity of ß-1,3-glucan-complexed C70 was highly dependent on the expression level of dectin-1 on the cell surfaces of macrophages. The photodynamic activity increased as a result of a synergistic effect between ß-1,3-glucan-complexed 1'-acetoxychavicol acetate and the C70 complex.

Correction: Formation of ß-(1,3-1,6)-d-glucan-complexed [70]fullerene and its photodynamic activity towards macrophages.

Correction for 'Formation of ß-(1,3-1,6)-d-glucan-complexed [70]fullerene and its photodynamic activity towards macrophages' by Atsushi Ikeda et al., Org. Biomol. Chem., 2017, 15, 1990-1997.

Prominin-1/CD133 expression as potential tissue-resident vascular endothelial progenitor cells in the pulmonary circulation.

Pulmonary vascular endothelial cells could contribute to maintain homeostasis in adult lung vasculature. "Tissue-resident" endothelial progenitor cells (EPCs) play pivotal roles in postnatal vasculogenesis, vascular repair, and tissue regeneration; however, their local pulmonary counterparts remain to be defined. To determine whether prominin-1/CD133 expression can be a marker of tissue-resident vascular EPCs in the pulmonary circulation, we examined the origin and characteristics of prominin-1/CD133-positive (Prom1(+)) PVECs considering cell cycle status, viability, histological distribution, and association with pulmonary vascular remodeling. Prom1(+) PVECs exhibited high steady-state transit through the cell cycle compared with Prom1(-) PVECs and exhibited homeostatic cell division as assessed using the label dilution method and mice expressing green fluorescent protein. In addition, Prom1(+) PVECs showed more marked expression of putative EPC markers and drug resistance genes as well as highly increased activation of aldehyde dehydrogenase compared with Prom1(-) PVECs. Bone marrow reconstitution demonstrated that tissue-resident cells were the source of >98% of Prom1(+) PVECs. Immunofluorescence analyses revealed that Prom1(+) PVECs preferentially resided in the arterial vasculature, including the resistant vessels of the lung. The number of Prom1(+) PVECs was higher in developing postnatal lungs. Sorted Prom1(+) PVECs gave rise to colonies and formed fine vascular networks compared with Prom1(-) PVECs. Moreover, Prom1(+) PVECs increased in the monocrotaline and the Su-5416 + hypoxia experimental models of pulmonary vascular remodeling. Our findings indicated that Prom1(+) PVECs exhibited the phenotype of tissue-resident EPCs. The unique biological characteristics of Prom1(+) PVECs predominantly contribute to neovasculogenesis and maintenance of homeostasis in pulmonary vascular tissues.

Endothelial-to-mesenchymal transition in lipopolysaccharide-induced acute lung injury drives a progenitor cell-like phenotype.

Pulmonary vascular endothelial function may be impaired by oxidative stress in endotoxemia-derived acute lung injury. Growing evidence suggests that endothelial-to-mesenchymal transition (EndMT) could play a pivotal role in various respiratory diseases; however, it remains unclear whether EndMT participates in the injury/repair process of septic acute lung injury. Here, we analyzed lipopolysaccharide (LPS)-treated mice whose total number of pulmonary vascular endothelial cells (PVECs) transiently decreased after production of reactive oxygen species (ROS), while the population of EndMT-PVECs significantly increased. NAD(P)H oxidase inhibition suppressed EndMT of PVECs. Most EndMT-PVECs derived from tissue-resident cells, not from bone marrow, as assessed by mice with chimeric bone marrow. Bromodeoxyuridine-incorporation assays revealed higher proliferation of capillary EndMT-PVECs. In addition, EndMT-PVECs strongly expressed c-kit and CD133. LPS loading to human lung microvascular endothelial cells (HMVEC-Ls) induced reversible EndMT, as evidenced by phenotypic recovery observed after removal of LPS. LPS-induced EndMT-HMVEC-Ls had increased vasculogenic ability, aldehyde dehydrogenase activity, and expression of drug resistance genes, which are also fundamental properties of progenitor cells. Taken together, our results demonstrate that LPS induces EndMT of tissue-resident PVECs during the early phase of acute lung injury, partly mediated by ROS, contributing to increased proliferation of PVECs.