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Toroidal dipole response in metamaterials was usually based on a complex structure with special arrangements or symmetries. In this paper, we propose an asymmetric double-disk metamaterial to numerically and experimentally demonstrate the toroidal dipole response in microwave frequency range. When the upper disk has an offset angle θ ranging from 0 to 100 degrees with respect to the lower one, the toroidal dipole resonance always plays the decisive role, which has been proved by calculating the scattered power in terms of the multipole scattering theory. Besides, the dependence of toroidal dipole response on structural parameters has been explored. Our works enrich the research of toroidal moment and, meanwhile, present more application potentials in meta-devices from microwave to optical regime.

Background Toxoplasma gondii is an intracellular protozoan that can infect humans and other animals, including cattle. Cattle are one of the world’s main sources of meat, and people who consume raw or undercooked meat and milk of cattle infected with T. gondii can become infected. In this study, a total of 5292 dairy cattle serum samples, collected from 17 cities (Henan Province, China) from January 2015 to September 2017, were screened for antibodies against T. gondii. Results Antibodies to T. gondii were found in 1.93% (102/5292) (95% CI, 1.56–2.30) of dairy cattle using a modified agglutination test (cut-off 1:100). The results showed that geographic location and season may be risk factors for T. gondii infection of cattle (P

A bi-layer continuous omega-shaped metamaterial was proposed and fabricated to measure the asymmetric transmission (AT) effect of a linearly polarized light at near-infrared region. The metamaterial was fabricated by the electron-beam lithography method, and the AT effect was demonstrated by the difference between total transmittances in the two opposite propagation directions for x-/y-polarized incident light. The experimental results were confirmed by the full-wave simulated results. Importantly, we also experimentally demonstrated that the AT effect is robust against the misalignments between the first and the second omega-shaped layers. Accordingly, the successfully prepared sample and its characterization provide a bright future for applications in light-controlled switchers and optical diodes in on-chip optical systems and information communication systems.

Survival and outcome of cardiac arrest (CA) are dismal despite improvements in cardiopulmonary resuscitation (CPR). Salvianolic acid B (Sal B), extracted from Salvia miltiorrhiza, has been investigated for its cardioprotective properties in cardiac remodeling and ischemic heart disease, but less is known about its role in CA. The aim of this study was to learn whether Sal B improves cardiac and neurologic outcomes after CA/CPR in mice. Female C57BL/6 mice were subjected to eight minutes of CA induced by an intravenous injection of potassium chloride (KCl), followed by CPR. After 30 seconds of CPR, mice were blindly randomized to receive either Sal B (20 mg/kg) or vehicle (normal saline) intravenously. Hemodynamic variables and indices of left ventricular function were determined before CA and within three hours after CPR, the early postresuscitation period. Sal B administration resulted in a remarkable decrease in the time required for the return of spontaneous circulation (ROSC) in animals that successfully resuscitated compared to the vehicle-treated mice. Myocardial performance, including cardiac output and left ventricular systolic (dp/dtmax) and diastolic (dp/dtmin) function, was clearly ameliorated within three hours of ROSC in the Sal B-treated mice. Moreover, Sal B inhibited CA/CPR-induced cardiomyocyte apoptosis and preserved mitochondrial morphology and function. Mechanistically, Sal B dramatically promoted Nrf2 nuclear translocation through the downregulation of Keap1, which resulted in the expression of antioxidant enzymes, including HO-1 and NQO1, thereby counteracted the oxidative damage in response to CA/CPR. The aforementioned antiapoptotic and antioxidant effects of Sal B were impaired in the setting of gene silencing of Nrf2 with siRNA in vitro model. These improvements were associated with better neurological function and increased survival rate (75% vs. 40%, p<0.05) up to 72 hours postresuscitation. Our findings suggest that the administration of Sal B improved cardiac function and neurological outcomes in a murine model of CA via activating the Nrf2 antioxidant signaling pathway, which may represent a novel therapeutic strategy for the treatment of CA.

Regulation of STAT3 activation is critical for normal and malignant hematopoietic cell proliferation. Here, we have reported that the endogenous transmembrane protein upstream-of-mTORC2 (UT2) negatively regulates activation of STAT3. Specifically, we determined that UT2 interacts directly with GP130 and inhibits phosphorylation of STAT3 on tyrosine 705 (STAT3Y705). This reduces cytokine signaling including IL6 that is implicated in multiple myeloma and other hematopoietic malignancies. Modulation of UT2 resulted in inverse effects on animal survival in myeloma models. Samples from multiple myeloma patients also revealed a decreased copy number of UT2 and decreased expression of UT2 in genomic and transcriptomic analyses, respectively. Together, these studies identify a transmembrane protein that functions to negatively regulate cytokine signaling through GP130 and pSTAT3Y705 and is molecularly and mechanistically distinct from the suppressors of cytokine signaling (SOCS) family of genes. Moreover, this work provides evidence that perturbations of this activation-dampening molecule participate in hematologic malignancies and may serve as a key determinant of multiple myeloma pathophysiology. UT2 is a negative regulator shared across STAT3 and mTORC2 signaling cascades, functioning as a tumor suppressor in hematologic malignancies driven by those pathways.

The structural features of Zhundong subbituminous coal (ZSBC) were investigated by ruthenium ion-catalyzed oxidation (RICO) and subsequent analyses with a gas chromatograph/mass spectrometer and an atmospheric-pressure solid analysis probe/time of flight-mass spectrometer (ASAP/TOF-MS). The results suggest that condensed aromatic rings linked by short polymethylene bridged linkages, long side chains, and oxygen-containing groups are predominant in ZSBC. Aliphatic bridged linkages connecting 3 aromatic rings also exist in ZSBC. Several heterocyclic carboxylic acids were produced from RICO of ZSBC. The heterocyclic moieties include tetrahydrofuran, pyridine, pyrazole, benzo[b]thiophene, and dithiole rings, suggesting the existence of oxygen-, nitrogen-, and sulfur-containing building blocks in ZSBC. According to analysis with ASAP/TOF-MS, a series of heavier arenecarboxylic acids were detected in the products from RICO of ZSBC and aromatic rings of the heavier arenepolycarboxylic acids include naphthalene, biphenyl, anthracene, phenylnaphthalene, and methyl(phenyl)tetrahydroanthracene, implying that ZSBC contains highly condensed aromatic rings. The existence of chlorine- and bromine-containing moieties was confirmed by the identification of chlorine- and bromine-containing species produced from RICO of ZSBC.

Ruthenium ion-catalyzed oxidation (RICO) of Yanshan petroleum coke (YPC) was performed to characterize condensed aromatics and heteroatomic species in YPC. The analysis with gas chromatograph/mass spectrometer mainly offers information on the distributions of side chain groups and bridged linkages, while the analyses with atmospheric pressure solid analysis probe/time-of-flight mass spectrometer and direct analysis in real time ion source coupled to time-of-flight mass spectrometer complement information on heteroatomic species and highly condensed aromatic moieties in YPC. The results indicate that YPC is rich in highly condensed aromatic moieties with tiny portions of alkyl/alkenyl side chains and alkyl/cycloalkyl bridged linkages. The organic oxygen, nitrogen, and sulfur exist in different aromatic rings (including isobenzofuran-1,3-dione, dioxoisoindoline, phenylquinoline, pyridine, and thiophene rings) and different functional groups (including methoxy, epoxy, nitro, and cyano groups). The formation of fluorine- and chlorine-containing species reveals the existence of fluorine- and chlorine-containing moieties in YPC. In addition, a series of heavier arenecarboxylic acids were produced from RICO of YPC. Their possible aromatic rings could be naphthalene, biphenyl, anthracene, phenanthrene, dihydroanthracene, dihydrophenanthrene, phenylnaphthalene, and methyl(phenyl)tetrahydroanthracene, further confirming the existence of highly condensed aromatic rings in YPC. This investigation provides an effective approach both for value-added utilization and for understanding the structural features of YPC.

Elimination of malignant cells is an unmet challenge for most human cancer types even with therapies targeting specific driver mutations. Therefore, a multi-pronged strategy to alter cancer cell biology on multiple levels is increasingly recognized as essential for cancer cure. One such aspect of cancer cell biology is the relative apoptosis resistance of tumor-initiating cells. Here, we provide an overview of the mechanisms affecting the apoptotic process in tumor cells emphasizing the differences in the tumor-initiating or stem-like cells of cancer. Further, we summarize efforts to exploit these differences to design therapies targeting that important cancer cell population.

Production of the cells that ultimately populate the thymus to generate α/β T cells has been controversial, and their molecular drivers remain undefined. Here, we report that specific deletion of bone-producing osteocalcin (Ocn)-expressing cells in vivo markedly reduces T-competent progenitors and thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic T cell precursors and decreased generation of mature T cells occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed on bone marrow Ocn+ cells, and selective depletion of DLL4 from these cells recapitulated the thymopoietic abnormality. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell–based adaptive immunity.

The far-field radiation of a single dipolar emitter can be controlled by coupling to toroidal dipole resonance attached to metallic double flat rings, realizing a conversion from non- to super-radiating. The underlying physical mechanism is the hybridization interference of toroidal and electric dipoles under an asymmetric configuration by introducing a radial displacement of the dipolar emitter. By embedding gain medium in the gap spacer between double flat rings, the directional far-field super-radiating power can achieve a tremendous enhancement with a moderate requirement on the gain coefficient, promoting light-matter interaction manipulation.

The balance between oxidative and non-oxidative glucose metabolism is essential for a number of pathophysiological processes. By deleting enzymes that affect aerobic glycolysis with different potencies, we examine how modulating glucose metabolism specifically affects hematopoietic and leukemic cell populations. We find that deficiency in the M2 pyruvate kinase isoform (PKM2) reduces levels of metabolic intermediates important for biosynthesis and impairs progenitor function without perturbing hematopoietic stem cells (HSC), whereas lactate dehydrogenase-A (LDHA) deletion significantly inhibits the function of both HSC and progenitors during hematopoiesis. In contrast, leukemia initiation by transforming alleles putatively affecting either HSC or progenitors is inhibited in the absence of either PKM2 or LDHA, indicating that the cell state-specific responses to metabolic manipulation in hematopoiesis do not apply to the setting of leukemia. This finding suggests that fine-tuning the level of glycolysis may be therapeutically explored for treating leukemia while preserving HSC function., National Institutes of Health (U.S.) (Grants P30CA147882 and R01CA168653), Smith Family Foundation, Burroughs Wellcome Fund, Virginia and D.K. Ludwig Fund for Cancer Research, Damon Runyon Cancer Research Foundation

Three catalysts were prepared by impregnating the same volume of pentachloroantimony (PCA), trimethylsilyl trifluoromethanesulfonate (TMSTFMS), or isometric PCA and TMSTFMA into an activated carbon (AC). Di(1-naphthyl)methane (DNM) was used as a coal-related model compound to evaluate their catalytic activity. The results show that C ar C alk bond in DNM can be specifically cleaved over each catalyst to afford naphthalene and 1-methylnaphthalene under pressurized hydrogen at temperatures up to 300 °C, but as a new solid acid (NSA), PCA–TMSTFMS/AC is significantly more active for DNM hydrocracking than the other two catalysts. FTIR and SEM analyses reveal the strong interactions among PCA, TMSTFMS, and the AC in the NSA. NH 3 -TPD analysis suggests that the NSA should exhibit appreciably stronger acidity than the other two catalysts. The strong interactions may result in the appreciably stronger acidity of the NSA than that of the other two catalysts and thereby facilitate DNM hydrocracking. It is presumed that H 2 was heterolytically cleaved to immobile H − and mobile H + . The addition of mobile H + to ipso -position of DNM should be crucial step for DNM hydrocracking.

The generation of a B cell repertoire involves producing and subsequently purging autoreactive B cells. Receptor editing, clonal deletion and anergy are key mechanisms of central B cell tolerance. Somatic mutation of antigen-activated B cells within the germinal center produces a second wave of autoreactivity; but the regulatory mechanisms that operate at this phase of B cell activation are poorly understood. We recently identified a post germinal center tolerance checkpoint, where receptor editing is re-induced to extinguish autoreactivity that is generated by somatic hypermutation. Re-induction of the recombinase genes RAG1 and RAG2 in antigen-activated B cells requires antigen to engage the B cell receptor and IL-7 to signal through the IL-7 receptor. We demonstrate that this process requires IL-6 to upregulate IL-7 receptor expression on post germinal center B cells. Diminishing IL-6 by blocking antibody or haplo-insufficiency leads to reduced expression of the IL-7 receptor and RAG and increased titers of anti-DNA antibodies following immunization with a peptide mimetope of DNA. The dependence on IL-6 to initiate receptor editing is B cell intrinsic. Interestingly, estradiol decreases IL-6 expression thereby increasing the anti-DNA response. Our data reveal a novel regulatory cascade to control post germinal center B cell autoreactivity.

How self tolerance is maintained during B cell development in the bone marrow has been a focal area of study in immunology. Receptor editing, anergy and clonal deletion all play important roles in the regulation of autoimmunity in the immature population. The mechanisms of tolerance induction in the periphery, however, are less well characterized. Overexpression of the apoptosis inhibitor Bcl-2 rescues autoreactive B cells from deletion and can contribute to the development of autoimmune disease in certain genetic backgrounds. Using a peptide induced autoimmunity model, we recently identified a peripheral tolerance checkpoint in antigen-activated B cells that have undergone class switching and somatic hypermutation. At this checkpoint, receptor editing, induced by antigen engagement, dampened the autoantibody response. In this study, we show that receptor editing fails to be induced in antigen activated DNA-reactive B cells that overexpress Bcl-2 (Bcl-2 Tg). The failure to induce RAG and receptor editing is likely due, at least partially, to the lack of self antigen. First, the levels of circulating DNA and of apoptotic bodies in the spleen of Bcl-2 Tg mice are significantly lower than in control mice. Second, in Bcl-2 Tg mice, RAG can be induced in a population of antigen-activated B cells by providing exogenous soluble antigen. These data suggest that, in addition to its anti-apoptotic activity, Bcl-2 may indirectly inhibit tolerance induction in B cells acquiring anti-nuclear antigen reactivity after peripheral activation by limiting the availability of self antigen.

We present an unsupervised segmentation algorithm for fully polarimetric synthetic aperture radar (PolSAR) data by using the mean shift clustering. The previous work using the span values of the PolSAR data as the features in the mean shift clustering, however, does not sufficiently exploit the full information contained in the polarimetric covariance matrix. When considering the polarimetric covariance matrices as the feature vectors, the traditional mean shift clustering in the Euclidean space is not applicable anymore, since these matrices do not form a Euclidean space. We first show that by regarding each Hermitian positive definite polarimetric covariance matrix at per pixel as a tensor, the tensor space can be represented as a Riemannian manifold. Then, the mean shift clustering is extended to the Riemannian manifold to explain the theoretical meanings of the tensor clustering and a practical segmentation algorithm based on the metric lying on the manifold is proposed. Experimental results using the real fully PolSAR data and simulated data verify the effectiveness of the proposed method.

Autoantibodies clearly contribute to tissue inflammation in systemic lupus erythematosus. In order to therapeutically target B cells making pathogenic autoantibodies, it is necessary to identify their phenotype. It is also important to understand the defects in B cell repertoire selection that permit pathogenic autoreactive B cells to enter the immunocompetent B cell repertoire. We present the data that both marginal zone and follicular B cells can produce pathogenic autoantibodies. Moreover, we discuss how B cell survival and maturation are regulated centrally prior to antigen activation and in the periphery after antigen activation to form the repertoire that generates the spectrum of circulating antibodies.

Toroidal dipolar response in a metallic metastructure, composed of double flat rings, is utilized to manipulate the radiation pattern of a single dipolar emitter (e.g., florescent molecule/atom or quantum dot). Strong Fano-type radiation spectrum can be obtained when these two coupling dipoles are spatially overlapped, leading to significant radiation suppression (so-called nonradiating source) attributed to the dipolar destructive interference. Moreover, this nonradiating configuration will become a directionally super-radiating nanoantenna after a radial displacement of the emitter with respect to the toroidal flat-ring geometry, which emits linearly polarized radiation with orders of power enhancement in a particular orientation. The demonstrated radiation characteristics from a toroidal-dipole-mediated dipolar emitter indicate a promising manipulation capability of the dipolar emission source by intriguing toroidal dipolar response.

Due to metal losses in plasmonic metamaterials, high-refractive-index dielectrics are promising to improve optical performances of their metallic counterparts. In this paper, a LiTaO(3) microtube metamaterial is numerically investigated to explore the toroidal dipolar resonance based on the multipole expansion theory. The local field strength probed on the central axis of the microtube is greatly enhanced for the toroidal dipolar mode, forming a strong hot spot concentrated in the deep-subwavelength scale. Furthermore, we also show the influences of geometrical parameter on the quality (Q) factor of the toroidal mode. The high Q factor and strongly concentrated field strength in the toroidal microtube metamaterial offer application potentials such as sensing, energy havesting, particle trapping, and nonlinear optical effects.

In this paper, the infinite-length metallic bar is folded to a continuous omega-shaped resonator and then arranged as a bi-layer metamaterial, which presents a hybrid resonance and a Fabry-Perot-like cavity mode. The asymmetric transmission (AT) for linearly polarized light is powerfully enhanced at a near-infrared regime by strongly coupling the hybrid resonance to the cavity, with the maximum value of the high-efficiency AT effect reaching 0.8 at around 1364 nm. At this near-infrared band, such a high-efficiency AT effect has never been realized previously by a bi-layer metamaterial. More importantly, we demonstrate that our design is robust to the misalignments, which greatly decreases the difficulties in sample fabrications. Accordingly, the proposed omega-shaped metamaterial provides potential applications in designing polarization filters, polarization switches, and other nano-devices.

Transient left ventricular dysfunction can occur after hypothermic, hyperkalemic cardioplegic arrest and is associated with decreased beta-adrenergic receptor responsiveness. Occupancy of the beta-adrenergic receptor activates adenylate cyclase, which phosphorylates the L-type Ca2+ channel-enhancing myocyte contractility. The goal of this study was to identify potential mechanisms that contribute to the defects in the beta-adrenergic receptor signaling cascade after cardioplegic arrest.Isolated left ventricular porcine myocytes were assigned to one of two treatment groups: (1) cardioplegic arrest (24 mEq/L K+, 4 degrees C x 2 hours, then 5 minutes in 37 degrees C cell media; n = 130) or (2) normothermic control (cell media, 37 degrees C x 2 hours; n = 222). Myocyte contractility was assessed at baseline and after either beta-adrenergic receptor occupancy (25 nmol/L isoproterenol [INN: isoprenaline]), activation of adenylate cyclase (0.5 mumol forskolin), or direct activation of the L-type Ca(2+)-channel (10 nmol/L or 100 nmol/L (-)BayK 8644).Myocyte velocity of shortening (micron/sec) was increased with beta-adrenergic receptor occupancy or direct adenylate cyclase stimulation compared with baseline in the normothermic group (187.3 +/- 6.9, 181.7 +/- 10.2, and 73.9 +/- 2.9, respectively; p0.0001) and after cardioplegic arrest (128.6 +/- 8.9, 124.3 +/- 9.4, and 46.1 +/- 2.6, respectively; p0.0001). However, the response after cardioplegic arrest was significantly reduced compared with normothermic values under all conditions (p = 0.012). Direct activation of the L-type Ca(2+)-channel, which eliminates beta-adrenergic receptor-dependent events, increased myocyte contractility in the normothermic group (161.90 +/- 12.0, p0.0001) and after cardioplegic arrest (92.78 +/- 6.8, p0.0001), but the positive inotropic response appeared reduced compared with normothermic control values (p = 0.003).These findings suggest that contributory mechanisms for the reduced beta-adrenergic receptor-mediated response after hypothermic, hyperkalemic cardioplegic arrest lie downstream from these specific components of the transduction pathway and likely include defects in Ca2+ homeostasis, myofilament Ca2+ sensitivity, or both.

Optical forces can be enhanced by surface plasmon resonances with various interesting characteristics. Here, we numerically calculated the optical forces enhanced by a new kind of toroidal dipolar resonance in a double-disk metastructure. The results show that this kind of optical force is competitive with ordinary plasmonic forces and typically can reach-182.5pNμm2mW-1. Influences of geometric parameters are discussed for the enhancement characteristic of optical force. Finally, we make a contrastive investigation on the optical trapping characteristic on a 5-nm-diameter nanoparticle, and show that the unique annular trapping region can be utilized for nanoscale applications.

Autoreactive B cells are regulated in the BM during development through mechanisms, including editing of the B cell receptor (BCR), clonal deletion, and anergy. Peripheral B cell tolerance is also important for protection from autoimmune damage, although the mechanisms are less well defined. Here we demonstrated, using a mouse model of SLE-like serology, that during an autoimmune response, RAG was reinduced in antigen-activated early memory or preplasma B cells. Expression of RAG was specific to antigen-reactive B cells, required the function of the IL-7 receptor (IL-7R), and contributed to maintenance of humoral tolerance. We also showed that soluble antigen could diminish a non-autoreactive antibody response through induction of BCR revision. These data suggest that tolerance induction operates in B cells at a postactivation checkpoint and that BCR revision helps regulate autoreactivity generated during an ongoing immune response.

Information about the impending collision of an approaching object can be specified by visual and auditory means. We examined the discrimination thresholds for vision, audition, and vision/audition combined, in the processing of time-to-collision (TTC) of an approaching object. The stimulus consisted of a computer simulated car approaching on a flat ground towards the participants which disappeared at a certain point before collision. After the presentation of two approaching movements in succession, participants pressed a button to indicate which of the two movements would result in the car colliding with the viewpoint sooner from the moment it disappeared. The results demonstrated that most participants were sensitive to TTC information provided by a visual source, but not when provided by an auditory source. That said, auditory information provided effective static distance information. When both sources of information were combined, participants used the most accurate source of information to make their judgments.

Campylobacter jejuni is a food-borne bacterial pathogen that possesses two distinct hemoglobins, encoded by the ctb and cgb genes. The former codes for a truncated hemoglobin (Ctb) in group III, an assemblage of uncharacterized globins in diverse clinically and technologically significant bacteria. Here, we show that Ctb purifies as a monomeric, predominantly oxygenated species. Optical spectra of ferric, ferrous, O(2)- and CO-bound forms resemble those of other hemoglobins. However, resonance Raman analysis shows Ctb to have an atypical nu(Fe)(-)(CO) stretching mode at 514 cm(-)(1), compared to those of the other truncated hemoglobins that have been characterized so far. This implies unique roles in ligand stabilization for TyrB10, HisE7, and TrpG8, residues highly conserved within group III truncated hemoglobins. Because C. jejuni is a microaerophile, and a ctb mutant exhibits O(2)-dependent growth defects, one of the hypothesized roles of Ctb is in the detoxification, sequestration, or transfer of O(2). The midpoint potential (E(h)) of Ctb was found to be -33 mV, but no evidence was obtained in vitro to support the hypothesis that Ctb is reducible by NADH or NADPH. This truncated hemoglobin may function in the facilitation of O(2) transfer to one of the terminal oxidases of C. jejuni or, instead, facilitate O(2) transfer to Cgb for NO detoxification.

How glucose is metabolized can influence cell function, but whether differences in glucose metabolism reflect, or dictate, cell state is not clear and is of particular interest given the association of cancer with aerobic glycolysis. Studies on cancer cell lines have indicated that increased glucose uptake with lactate production regardless of oxygen concentration, a phenomenon also known as the Warburg effect, is promoted in part by expression of the M2 isoform of pyruvate kinase (PKM2) and the muscle form of lactate dehydrogenase A (LDHA). Normal somatic cells thought to also preferentially use glycolytic metabolism are tissue stem cells, particularly the self-renewing hematopoietic stem cells (HSC) resident in the hypoxic microenvironment of the bone marrow. It remains to be defined, however whether proliferating hematopoietic progenitor cells rely on aerobic glycolysis and whether malignant and normal hematopoietic cells are dependent on the same metabolic regulation. We observed that PKM2 and LDHA are the predominant isoforms expressed by all BM hematopoietic cells. To further understand the role of glycolytic metabolism in hematopoiesis and hematological malignancy, we utilized a mouse strain that allows conditional deletion of the PKM2 specific exon 10. Deletion of PKM2 in hematopoetic cells leads to expression of PKM1, accompanied with partial inhibition of lactate production and decreased glycolytic intermediates in the hematopoietic stem/progenitor cell (HSPC) population. Loss of PKM2 compromises the long-term repopulation capacity of HSPCs as revealed by serial transplantation assay. Interestingly, the repopulating defects resulting from PKM2 depletion appear to involve progenitors, perhaps due to inadequate biomass generation necessary for robust cell proliferation. To confirm that the effect of PKM2 deletion on HSPC function is due to metabolic changes rather than other putative PKM2 functions, we engineered a mouse strain that allowed conditional knockout of LDHA to more potently impair aerobic glycolysis. LDHA deletion completely inhibited lactate production, enhanced ROS levels in hematopoietic cells and impaired long-term BM repopulating activity. In contrast to PKM2 deletion that affects progenitor but not stem cells, LDHA depletion impacts both stem cell maintenance and progenitor cell proliferation. Deletion of either PKM2 or LDHA markedly suppressed leukemia initiation by either putative stem cell (BCR-ABL) or progenitor (MLL-AF9) transforming alleles. Therefore, modulating aeroblic glycolysis has effects on normal hematopoietic cells that depend upon cell state and negatively impacts leukemic growth regardless of cell state. The differential sensitivity of normal and malignant cells to modulation of aerobic glycolysis suggests a potential therapeutic opportunity for leukemia intervention. Disclosures: No relevant conflicts of interest to declare.

Background Transcutaneous acupoint electrical stimulation (TAES) as a needleless acupuncture has the same effect like traditional manual acupuncture. The combination of TAES and anesthesia has been proved valid in enhancing the anesthetic effects but its mechanisms are still not clear. Methods In this study, we investigated the effect of TAES on anesthesia with an electroencephalogram (EEG) oscillation analysis on surgery patients anesthetized with propofol, a widely-used anesthetic in clinical practice. EEG was continuously recorded during light and deep propofol sedation (target-controlled infusion set at 1.0 and 3.0 μg/mL) in ten surgery patients with pituitary tumor excision. Each concentration of propofol was maintained for 6 min and TAES was given at 2–4 min. The changes in EEG power spectrum at different frequency bands (delta, theta, alpha, beta, and gamma) and the coherence of different EEG channels were analyzed. Results Our result showed that, after TAES application, the EEG power increased at alpha and beta bands in light sedation of propofol, but reduced at delta and beta bands in deep propofol sedation (p