Distributed shape detection for an acoustic sensitive optical cable with DAS.

Acoustic sensitive optical cables (ASOCs) and their shape detection are vital in underwater acoustic monitoring, and a distributed ASOC shape detection method is demonstrated with distributed acoustic sensing (DAS) technology. The accurate three-dimensional (3D) position of each ASOC unit is obtained from DAS signals and the prior position information of auxiliary acoustic sources by using a proposed adaptive peak allocation algorithm. Preliminary work has demonstrated single-point 3D localization and distributed ASOC shape detection, and the error is 6.53 cm. To the best of our knowledge, it is the first time that distributed ASOC shape detection is achieved with DAS. This method will promote the development of ASOC applications, such as underwater target detection and towed array correction.

Integrated Optical Waveguide Electric Field Sensors Based on Bismuth Germanate.

Bismuth germanate (Bi4Ge3O12, BGO) is a widely used optical sensing material with a high electro-optic coefficient, ideal for optical electric field sensors. Achieving high precision in electric field sensing requires fabricating optical waveguides on BGO. Traditional waveguide writing methods face challenges with this material. This study explores using femtosecond laser writing technology for preparing waveguides on BGO, leveraging ultrafast optical fields for superior material modification. Our experimental analysis shows that a cladding-type waveguide, written with a femtosecond laser at 200 kHz repetition frequency and 10.15 mW average power (pulse energy of 50.8 nJ), exhibits excellent light-guiding characteristics. Simulations of near-field optical intensity distribution and refractive index variations using the refractive index reconstruction method demonstrate that the refractive index modulation ensures single-mode transmission and effectively confines light to the core layer. In situ refractive index characterization confirms the feasibility of fabricating a waveguide with a refractive index reduction on BGO. The resulting waveguide has a loss per unit length of approximately 1.2 dB/cm, marking a successful fabrication. Additionally, we design an antenna electrode, analyze sensor performance indicators, and integrate a preparation process plan for the antenna electrode. This achievement establishes a solid experimental foundation for future studies on BGO crystal waveguides in electric field measurement applications.

Distributed fiber mountain seismic monitoring and steady-state analysis under natural earthquakes.

Mountain dynamic response monitoring plays important roles in geological disaster evolution monitoring and warning. A distributed mountain seismic monitoring and steady-state analysis method is demonstrated with distributed acoustic sensing (DAS) and a natural earthquake stimulus. In the field test, the seismic detection capability is first verified by comparing the recorded seismic waveforms from DAS and existing seismic stations. The vibration signal difference between steady-state and unsteady-state mountain parts is apparent; the operational modal analysis method is utilized to extract the response difference and to monitor the disaster evolution process. The proposed method has many advantages, including being easy to deploy, all-weather online monitoring, etc. It is believed that the proposed method will broaden the DAS application scope and promote the development of geological disaster early warning such as landslides and collapses.

Chrysin sensitizes osteosarcoma cells against TRAIL-induced apoptosis.

Identifying novel curative and preventive approaches that can specifically target the osteosarcoma cells (OS) without affecting the normal cells is appreciable. The aim of this study is to investigate the combined effect of chrysin as an apigenin analog with high therapeutic potential and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the treatment of Saos-2 and MG-63 cells. Cell viability were determined using MTT method. The rate of apoptosis was assessed by enzyme-linked immunosorbent assay (ELISA) cell death assay and caspase 8 activity assays. The messenger RNA (mRNA) and protein evaluation of candidate genes include Bcl-2, XIAP, c-IAP1, c-IAP2, and c-FLIP were accomplished before and after the treatment by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. Our results showed that chrysin synergistically increased the cytotoxic effects of TRAIL as follows: Chrysin plus TRAIL > TRAIL > Chrysin. Chrysin could sensitize both cells against the TRAIL-induced apoptosis, amplify the caspase 8 activity and this outcome is achieved by decreasing the expression levels of antiapoptotic genes. Our findings suggest that Chrysin can sensitize the OS cell lines against TRAIL through induction of the death receptor pathway. Moreover, the combinational therapy of these agents might be the promising therapeutic regimen for improving the clinical efficacy of TRAIL-induced apoptosis in patients with OS.

Heterogeneous Variations on Historical and Future Trends of CO2 and Multiple Air Pollutants from the Cement Production Process in China: Emission Inventory, Spatial-Temporal Characteristics, and Scenario Projections.

Cement production is a major contributor to carbon dioxide (CO2) and multiple hazardous air pollutant (HAP) emissions, threatening climate mitigation and urban/regional air quality improvement. In this study, we established a comprehensive emission inventory by coupling the unit-based bottom-up and mass balance methods, revealing that emissions of most HAPs have been remarkably controlled. However, an increasing 6.0% of atmospheric mercury emissions, as well as 14.1 and 23.7% of fuel-related and process-related CO2 emission growth were witnessed unexpectedly. Industrial adjustment policies have imposed a great impact on the spatiotemporal changes in emission characteristics. Monthly emissions of CO2 and multiple HAPs decreased from December to February due to the "staggered peak production," especially in northern China after implementing the intensified action plan for air pollution control in winter. Upgrading environmental technologies and adjusting capacity structures are identified as dominant driving forces for reducing HAP emissions. Besides, energy intensity improvement can help offset some of the impact caused by the increase in clinker/cement production. Furthermore, scenario analysis results show that ultra-low emission and low-carbon technology transformation constitute the keys to achieve the synergic reduction of CO2 and multiple HAP emissions in the future.

Pomegranate peel polyphenols interaction with intestinal flora and its metabolic transformation.

1. Pomegranate peel polyphenols (PPPs) have anti-oxidation, anti-atherosclerosis, anti-obesity effects, and so on. However, few studies have been conducted on the absorption and transformation of pomegranate polyphenols in the gut and the biologically active forms that ultimately work in the body.2. In this study, PPPs (300 mg/kg/day) was given to normal rats and relatively sterile rats by gavage respectively. The relatively sterile rats were obtained by neomycin sulphate (250 mg/kg/day) gavage to rats. The purpose of this study is to elaborate on the relationship between intestinal flora and polyphenol metabolism of pomegranate peel and to quantitatively analyse the transformation process of its metabolite urolithin in rats.3. The results showed that decreased bacterial diversity could significantly reduce the abundance of PPPs metabolites in faeces and urine in relatively sterile rats. PPPs can regulate intestinal flora structure, significantly enhance the content of Clostrida Firmicutes (P < 0.05), and effectively promote acetic acid, propionic acid, butyric acid, iso-butyric acid and valeric acid production in the rat (P < 0.05 or P < 0.01 or P < 0.001). PPPs can significantly elevate the relative proportion of Ruminococcaceae (P < 0.05). Ruminococcaceae_NK4A214_group, Ruminococcaceae_UCG-014 and Ruminococcaceae_UCG-005 can promote the metabolic transformation of PPPs and make the utilisation of Urolithin A more effective.

Distributed optical fiber hydrophone based on Φ-OTDR and its field test.

In this letter, a distributed optical fiber hydrophone (DOFH) based on Φ-OTDR is demonstrated and tested in the field. The specially designed sensitized optical cable with sensitivity up to -146 dB rad/µPa/m is introduced, and an array signal processing model for DOFH is constructed to analyze the equivalence and specificity of the distributed array of acoustic sensors. In the field test, a 104-meter-long optical cable and a Φ-OTDR system based on heterodyne coherent detection (Het Φ-OTDR) is utilized, and underwater acoustic signal spatial spectrum estimation, beamforming and motion trajectory tracking with high accuracy can be realized. As far as we know, this is the first report on the field trial of DOFH based on Φ-OTDR. The DOFH has the potential to achieve an array range of tens of kilometers, with elements spaced up to the meter level and flexible configuration, which has a broad application prospect for marine acoustic detection.

High SNR Φ-OTDR with Multi-Transverse Modes Heterodyne Matched-Filtering Technology.

Phase-sensitive optical time domain reflectometer (Φ-OTDR) has attracted attention in scientific research and industry because of its distributed dynamic linear response to external disturbances. However, the signal-to-noise ratio (SNR) of Φ-OTDR is still a limited factor by the weak Rayleigh Backscattering coefficient. Here, the multi-transverse modes heterodyne matched-filtering technology is proposed to improve the system SNR. The capture efficiency and nonlinear threshold are increased with multiple transverse modes in few-mode fibers; the incident light energy is permitted to be enlarged by a wider probe pulse by using heterodyne matched-filtering without spatial resolution being deteriorated. As far as we know, this is the first time that both multi-transverse modes integration method and digital heterodyne matched filtering method have been used to improve the SNR of Φ-OTDR simultaneously. Experimental results show that the noise floor is reduced by 11.4 dB, while the target signal is kept. We believe that this proposed method will help DAS find important applications in marine acoustic detection and seismic detection.

Multi-source aliasing suppression for distributed fiber acoustic sensing with directionally coherent enhancement technology.

Distributed fiber acoustic sensing (DAS) can detect almost all disturbances along the sensing fiber and is widely applied. However, the signals from multiple adjacent disturbance sources are superimposed, according to the sensing principle. A directionally coherent enhancement technology is demonstrated for DAS to suppress multi-source aliasing in air. In preliminary works, two situations are considered for feasibility verification. The submerged weak target signal is effectively extracted from strong broadband noise, and two different same-frequency signals from two sources are separately rebuilt with the same detected signal. As far as we know, this is the first time that the directionally coherent enhancement is proposed for DAS and the multi-source aliasing is suppressed. This technique will help DAS find new important foreground in acoustic detection of large-scale plants with many similar noisy devices, including discharge detection in high voltage substations and acoustic emission flaw detection in mechanical factories.

Reciprocal Regulation of Glycolysis-Driven Th17 Pathogenicity and Regulatory T Cell Stability by Cdc42.

A balance between Th17 cells and regulatory T cells (Tregs) is important for host immunity and immune tolerance. The underlying molecular mechanisms remain poorly understood. Here we have identified Cdc42 as a central regulator of Th17/Treg balance. Deletion of Cdc42 in T cells enhanced Th17 differentiation but diminished induced Treg differentiation and suppressive function. Treg-specific deletion of Cdc42 decreased natural Tregs but increased effector T cells including Th17 cells. Notably, Cdc42-deficient Th17 cells became pathogenic associated with enhanced glycolysis and Cdc42-deficient Tregs became unstable associated with weakened glycolytic signaling. Inhibition of glycolysis in Cdc42-deficient Th17 cells diminished their pathogenicity and restoration of glycolysis in Cdc42-deficient Tregs rescued their instability. Intriguingly, Cdc42 deficiency in T cells led to exacerbated wasting disease in mouse models of colitis and Treg-specific deletion of Cdc42 caused early, fatal lymphoproliferative diseases. In summary, we show that Cdc42 is a bona fide regulator of peripheral tolerance through suppression of Th17 aberrant differentiation/pathogenicity and promotion of Treg differentiation/stability/function involving metabolic signaling and thus Cdc42 pathway might be harnessed in autoimmune disease therapy.

Prior Toxoplasma Gondii Infection Ameliorates Liver Fibrosis Induced by Schistosoma Japonicum through Inhibiting Th2 Response and Improving Balance of Intestinal Flora in Mice.

Schistosomiasis is an immunopathogenic disease in which a T helper (Th) cell type 2-like response plays vital roles. Hepatic fibrosis is its main pathologic manifestations, which is the leading cause of hepatic cirrhosis. Co-infections of Schistosoma japonicum (Sj) with other pathogens are frequently encountered but are easily ignored in clinical studies, and effective therapeutic interventions are lacking. In this study, we explored the effect of Toxoplasma gondii (Tg) prior infection on Th1/Th2 response, community shifts in gut microbiome (GM), and the pathogenesis of schistosomiasis in murine hosts. Mice were prior infected with Tg before Sj infection. The effects of co-infection on Th1/Th2 response and hepatic fibrosis were analyzed. Furthermore, we investigated this issue by sequencing 16S rRNA from fecal specimens to define the GM profiles during co-infection. Tg prior infection markedly reduced the granuloma size and collagen deposit in livers against Sj infection. Prior infection promoted a shift toward Th1 immune response instead of Th2. Furthermore, Tg infection promoted the expansion of preponderant flora and Clostridiaceae was identified as a feature marker in the GM of the co-infection group. Redundancy analysis (RDA)/canonical correspondence analysis (CCA) results showed that liver fibrosis, Th1/Th2 cytokines were significantly correlated (P < 0.05) with the GM compositions. Tg infection inhibits hepatic fibrosis by downregulating Th2 immune response against Sj infection, and further promotes the GM shifts through "gut-liver axis" in the murine hosts. Our study may provide insights into potential anti-fibrosis strategies in co-infection individuals.

Rational targeting Cdc42 restrains Th2 cell differentiation and prevents allergic airway inflammation.

BACKGROUND: Asthma is an allergic airway inflammation-driven disease that affects more than 300 million people world-wide. Targeted therapies for asthma are largely lacking. Although asthma symptoms can be prevented from worsening, asthma development cannot be prevented. Cdc42 GTPase has been shown to regulate actin cytoskeleton, cell proliferation and survival. OBJECTIVES: To investigate the role and targeting of Cdc42 in Th2 cell differentiation and Th2-mediated allergic airway inflammation. METHODS: Post-thymic Cdc42-deficient mice were generated by crossing Cdc42flox/flox mice with dLckicre transgenic mice in which Cre expression is driven by distal Lck promoter. Effects of post-thymic Cdc42 deletion and pharmacological targeting Cdc42 on Th2 cell differentiation were evaluated in vitro under Th2-polarized culture conditions. Effects of post-thymic Cdc42 deletion and pharmacological targeting Cdc42 on allergic airway inflammation were evaluated in ovalbumin- and/or house dust mite-induced mouse models of asthma. RESULTS: Post-thymic deletion of Cdc42 led to reduced peripheral CD8+ T cells and attenuated Th2 cell differentiation, with no effect on closely related Th1, Th17 and induced regulatory T (iTreg) cells. Post-thymic Cdc42 deficiency ameliorated allergic airway inflammation. The selective inhibition of Th2 cell differentiation by post-thymic deletion of Cdc42 was recapitulated by pharmacological targeting of Cdc42 with CASIN, a Cdc42 activity-specific chemical inhibitor. CASIN also alleviated allergic airway inflammation. CASIN-treated Cdc42-deficient mice showed comparable allergic airway inflammation to vehicle-treated Cdc42-deficient mice, indicative of negligible off-target effect of CASIN. CASIN had no effect on established allergic airway inflammation. CONCLUSION AND CLINICAL RELEVANCE: Cdc42 is required for Th2 cell differentiation and allergic airway inflammation, and rational targeting Cdc42 may serve as a preventive but not therapeutic approach for asthma control.

PKCλ/ι regulates Th17 differentiation and house dust mite-induced allergic airway inflammation.

Asthma is a chronic airway inflammation in which Th2 and Th17 cells play critical roles in its pathogenesis. We have reported that atypical protein kinase (PKC) λ/ι is a new regulator for Th2 differentiation and function. However, the role of PKCλ/ι for Th17 cells remains elusive. In this study, we explored the effect of PKCλ/ι on Th17 cells in the context of ex vivo cell culture systems and an in vivo murine model of allergic airway inflammation with the use of activated T cell-specific conditional PKCλ/ι-deficient mice. Our findings indicate that PKCλ/ι regulates Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-21 and IL-22, were inhibited from PKCλ/ι-deficient T cells under non-skewing or Th17-skewing culture conditions. Moreover, the impaired Th17 differentiation and function by the PKCλ/ι-deficiency was associated with the downregulation of Stat3 and Rorγt, key Th17 transcription factors. We developed a model of Th17 and neutrophil-involved allergic airway inflammation by intratracheal inoculation of house dust mites. PKCλ/ι-deficiency significantly inhibited airway inflammations. The infiltrating cells in the lungs and bronchoalveolar lavage fluids were significantly reduced in conditional PKCλ/ι-deficient mice. Th17 effector cytokines were reduced in the bronchoalveolar lavage fluids and lungs at protein and mRNA levels. Thus, PKCλ/ι emerges as a critical regulator of Th17 differentiation and allergic airway hyperresponsiveness.

RhoA orchestrates glycolysis for TH2 cell differentiation and allergic airway inflammation.

BACKGROUND: Mitochondrial metabolism is known to be important for T-cell activation. However, its involvement in effector T-cell differentiation has just begun to gain attention. Importantly, how metabolic pathways are integrated with T-cell activation and effector cell differentiation and function remains largely unknown. OBJECTIVE: We sought to test our hypothesis that RhoA GTPase orchestrates glycolysis for TH2 cell differentiation and TH2-mediated allergic airway inflammation. METHODS: Conditional RhoA-deficient mice were generated by crossing RhoA(flox/flox) mice with CD2-Cre transgenic mice. Effects of RhoA on TH2 differentiation were evaluated based on in vitro TH2-polarized culture conditions and in vivo in ovalbumin-induced allergic airway inflammation. Cytokine levels were measured by using intracellular staining and ELISA. T-cell metabolism was measured by using the Seahorse XF24 Analyzer and flow cytometry. RESULTS: Disruption of RhoA inhibited T-cell activation and TH2 differentiation in vitro and prevented the development of allergic airway inflammation in vivo, with no effect on TH1 cells. RhoA deficiency in activated T cells led to multiple defects in metabolic pathways, such as glycolysis and oxidative phosphorylation. Importantly, RhoA couples glycolysis to TH2 cell differentiation and allergic airway inflammation through regulating IL-4 receptor mRNA expression and TH2-specific signaling events. Finally, inhibition of Rho-associated protein kinase, an immediate downstream effector of RhoA, blocked TH2 differentiation and allergic airway inflammation. CONCLUSION: RhoA is a key component of the signaling cascades leading to TH2 differentiation and allergic airway inflammation at least in part through control of T-cell metabolism and the Rho-associated protein kinase pathway.

Gene targeting RhoA reveals its essential role in coordinating mitochondrial function and thymocyte development.

Thymocyte development is regulated by complex signaling pathways. How these signaling cascades are coordinated remains elusive. RhoA of the Rho family small GTPases plays an important role in actin cytoskeleton organization, cell adhesion, migration, proliferation, and survival. Nonetheless, the physiological function of RhoA in thymocyte development is not clear. By characterizing a conditional gene targeting mouse model bearing T cell deletion of RhoA, we show that RhoA critically regulates thymocyte development by coordinating multiple developmental events. RhoA gene disruption caused a strong developmental block at the pre-TCR checkpoint and during positive selection. Ablation of RhoA led to reduced DNA synthesis in CD4(-)CD8(-), CD4(+)CD8(-), and CD4(-)CD8(+) thymocytes but not in CD4(+)CD8(+) thymocytes. Instead, RhoA-deficient CD4(+)CD8(+) thymocytes showed an impaired mitosis. Furthermore, we found that abrogation of RhoA led to an increased apoptosis in all thymocyte subpopulations. Importantly, we show that the increased apoptosis was resulted from reduced pre-TCR expression and increased production of reactive oxygen species (ROS), which may be because of an enhanced mitochondrial function, as manifested by increased oxidative phosphorylation, glycolysis, mitochondrial membrane potential, and mitochondrial biogenesis in RhoA-deficient thymocytes. Restoration of pre-TCR expression or treatment of RhoA-deficient mice with a ROS scavenger N-acetylcysteine partially restored thymocyte development. These results suggest that RhoA is required for thymocyte development and indicate, to our knowledge, for the first time that fine-tuning of ROS production by RhoA, through a delicate control of metabolic circuit, may contribute to thymopoiesis.

NBR1 is a new PB1 signalling adapter in Th2 differentiation and allergic airway inflammation in vivo.

Allergic airway inflammation is a disease in which T helper 2 (Th2) cells have a critical function. The molecular mechanisms controlling Th2 differentiation and function are of paramount importance in biology and immunology. Recently, a network of PB1-containing adapters and kinases has been shown to be essential in this process owing to its function in regulating cell polarity and the activation of critical transcription factors. Here, we show in vivo data showing that T-cell-specific NBR1-deficient mice show impaired lung inflammation and have defective Th2 differentiation ex vivo with alterations in T-cell polarity and the selective inhibition of Gata3 and nuclear factor of activated T c1 activation. These results establish NBR1 as a novel PB1 adapter in Th2 differentiation and asthma.

Emissions of volatile organic compounds from Chinese coal-fired power plants: Characteristics, source profile, inventories, and impacts.

Volatile organic compounds (VOCs) are key precursors for secondary organic aerosols (SOA) and ozone, imposing severe impacts on human health and environment. Considering the massive coal consumption, coal fired power plants (CFPPs) in China are non-negligible VOCs contributors, whose emission characteristics remain inadequately understood. Here, we investigated emission characteristics of 117 VOCs by field tests in four typical CFPPs, and a latest localized CFPPs source profile was compiled by integrating literature reviews. Then speciated-VOCs emission inventories for 2018-2022 were established based on dynamic emission factors and unit-level activity data. The results suggested that oxygenated VOCs (OVOCs) constituted the dominant group (76.5 %), with propionaldehyde (32.0 %) and formaldehyde (24.5 %) being the predominant species. OVOCs (93.2 %) and aromatics (77.4 %) were identified as the primary contributors to ozone and SOA, respectively. Driven by both the rise in coal consumption and technological advancements, nationwide VOCs emissions decreased from 83,393 t in 2018 to 53,251 t in 2022. Regional disparities and varying rates of decline in provincial emissions were evident, with VOCs emissions predominantly concentrated in northern and eastern provinces. Neimenggu, Shandong, Shanxi, Jiangsu, and Guangdong were identified as the top five provinces with the highest emissions. We believe this study would be conducive to a more comprehensive understanding and effective control of VOCs emissions from CFPPs in China.

Few-shot disease recognition algorithm based on supervised contrastive learning.

Diseases cause crop yield reduction and quality decline, which has a great impact on agricultural production. Plant disease recognition based on computer vision can help farmers quickly and accurately recognize diseases. However, the occurrence of diseases is random and the collection cost is very high. In many cases, the number of disease samples that can be used to train the disease classifier is small. To address this problem, we propose a few-shot disease recognition algorithm that uses supervised contrastive learning. Our algorithm is divided into two phases: supervised contrastive learning and meta-learning. In the first phase, we use a supervised contrastive learning algorithm to train an encoder with strong generalization capabilities using a large number of samples. In the second phase, we treat this encoder as an extractor of plant disease features and adopt the meta-learning training mechanism to accomplish the few-shot disease recognition tasks by training a nearest-centroid classifier based on distance metrics. The experimental results indicate that the proposed method outperforms the other nine popular few-shot learning algorithms as a comparison in the disease recognition accuracy over the public plant disease dataset PlantVillage. In few-shot potato leaf disease recognition tasks in natural scenarios, the accuracy of the model reaches the accuracy of 79.51% with only 30 training images. The experiment also revealed that, in the contrastive learning phase, the combination of different image augmentation operations has a greater impact on model. Furthermore, the introduction of label information in supervised contrastive learning enables our algorithm to still obtain high accuracy in few-shot disease recognition tasks with smaller batch size, thus allowing us to complete the training with less GPU resource compared to traditional contrastive learning.

Solving variability: Accurately extracting feature components from ballistocardiograms.

Objective: A ballistocardiogram (BCG) is a vibration signal generated by the ejection of the blood in each cardiac cycle. The BCG has significant variability in amplitude, temporal aspects, and the deficiency of waveform components, attributed to individual differences, instantaneous heart rate, and the posture of the person being measured. This variability may make methods of extracting J-waves, the most distinct components of BCG less generalizable so that the J-waves could not be precisely localized, and further analysis is difficult. This study is dedicated to solving the variability of BCG to achieve accurate feature extraction. Methods: Inspired by the generation mechanism of the BCG, we proposed an original method based on a profile of second-order derivative of BCG waveform (2ndD-P) to capture the nature of vibration and solve the variability, thereby accurately localizing the components especially when the J-wave is not prominent. Results: In this study, 51 recordings of resting state and 11 recordings of high-heart-rate from 24 participants were used to validate the algorithm. Each recording lasts about 3 min. For resting state data, the sensitivity and positive predictivity of proposed method are: 98.29% and 98.64%, respectively. For high-heart-rate data, the proposed method achieved a performance comparable to those of low-heart-rate: 97.14% and 99.01% for sensitivity and positive predictivity, respectively. Conclusion: Our proposed method can detect the peaks of the J-wave more accurately than conventional extraction methods, under the presence of different types of variability. Higher performance was achieved for BCG with non-prominent J-waves, in both low- and high-heart-rate cases.

Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis.

mTOR integrates signals from nutrients and growth factors to control protein synthesis, cell growth, and survival. Although mTOR has been established as a therapeutic target in hematologic malignancies, its physiological role in regulating hematopoiesis remains unclear. Here we show that conditional gene targeting of mTOR causes bone marrow failure and defects in multi-lineage hematopoiesis including myelopoiesis, erythropoiesis, thrombopoiesis, and lymphopoiesis. mTOR deficiency results in loss of quiescence of hematopoietic stem cells, leading to a transient increase but long-term exhaustion and defective engraftment of hematopoietic stem cells in lethally irradiated recipient mice. Furthermore, ablation of mTOR causes increased apoptosis in lineage-committed blood cells but not hematopoietic stem cells, indicating a differentiation stage-specific function. These results demonstrate that mTOR is essential for hematopoietic stem cell engraftment and multi-lineage hematopoiesis.