Cell-state-specific metabolic dependency in hematopoiesis and leukemogenesis.

The balance between oxidative and nonoxidative 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 a deficiency in the M2 pyruvate kinase isoform (PKM2) reduces the levels of metabolic intermediates important for biosynthesis and impairs progenitor function without perturbing hematopoietic stem cells (HSCs), whereas lactate dehydrogenase A (LDHA) deletion significantly inhibits the function of both HSCs and progenitors during hematopoiesis. In contrast, leukemia initiation by transforming alleles putatively affecting either HSCs 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 explored therapeutically for treating leukemia while preserving HSC function.

Terahertz polarization conversion and asymmetric transmission based on a liquid crystal integrated EIT metasurface.

We experimentally demonstrate a liquid crystal (LC)-integrated EIT metasurface for active THz polarization conversion and asymmetric transmission. By controlling the LC orientation under static magnetic field anchoring and an adjustable electric field, the device realizes the active control from the OFF state to the ON state, corresponding to the orthogonal polarization excitation modes of the EIT metasurface. Furthermore, based on the different polarization responses at forward and backward incidences, we achieve asymmetric transmission at the EIT peak and two nearby resonances, with its isolation actively manipulated by the external electric field. This study on dynamic polarization conversion and asymmetric transmission by a LC-integrated metasurface offers a promising route for active THz devices, applicable to THz communication, switching, and sensing systems.

Intensity-tunable terahertz bandpass filters based on liquid crystal integrated metamaterials.

In this paper, we demonstrate an intensity-tunable THz bandpass filter by introducing liquid crystal (LC) integrated with asymmetric frequency selective surface (FSS) and subwavelength metal gratings. Here, the tunable THz filter is derived from the inner polarization state conversion in composited devices, and the incident linear polarization can be converted into 90° orthogonal components. By controlling the LC orientation under the applied electric field with the metamaterial electrodes, the polarization conversion process can be actively modulated; thus, the polarization-dependent and tunable THz bandpass filter is achieved. Based on the multilayer design and the inner Fabry-Perot-like resonance mechanism, the LC-integrated metamaterials filter presents better filtering performance than the single FSS filter, and the Q-value is improved from 7.7 to 13.8 at the working frequency. Our simulated work paves the way for the design of new and efficient THz filters.

Enhanced asymmetric transmissions attributed to the cavity coupling hybrid resonance in a continuous omega-shaped metamaterial.

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.

Low prevalence of antibodies against Toxoplasma gondii in dairy cattle from China's central region.

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 < 0.05), and the seroprevalence of T. gondii in cattle along the Yellow River is higher than other areas. CONCLUSIONS: This is the first large-scale investigation on the seroprevalence of T. gondii infection in cattle from Central China. This survey shows that the T. gondii infection rate of dairy cattle is low; however, these findings provide additional information on the epidemiology of Chinese T. gondii. The possibility of dairy cattle exposure to T. gondii in Central China can not be ignored, and the consumption of raw or undercooked beef or milk may pose a risk to human health.

Harnessing the apoptotic programs in cancer stem-like cells.

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.

[Comparative identification studies on wild and cultivated Glycyrrhiza uralensis produced Ningxia based on index components and near-infrared spectroscopy].

This study is to construct a rapid and effective method for identification of wild and cultivated Glycyrrhiza uralensis (hereinafter referred to as Glycyrrhizae Radix et Rhizoma) from Ningxia by comparison of the difference in chromatography identification based on index components and near-infrared spectroscopy identification. HPLC and UV methods were used to determine the content of liquiritin, glycyrrhizate and total flavonoids for 9 wild Glycyrrhizae Radix et Rhizoma and 14 cultivated Glycyrrhizae Radix et Rhizoma samples,and the near-infrared spectroscopy was also,collected. The results illustrated that the chromatography identification based on index components could not identify wild and cultivated Glycyrrhizae Radix et Rhizoma from Ningxia, while near-infrared spectroscopy could quickly and effectively achieve it. It provides an effective method for the growth pattern identification and application of Glycyrrhizae Radix et Rhizoma.

Optical force enhancement and annular trapping by plasmonic toroidal resonance in a double-disk metastructure.

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.

Effect of transcutaneous acupoint electrical stimulation on propofol sedation: an electroencephalogram analysis of patients undergoing pituitary adenomas resection.

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 < 0.001). In addition, the EEG oscillation analysis showed an enhancement of synchronization at low frequencies and a decline in synchronization at high frequencies between different EEG channels in either light or deep propofol sedation. CONCLUSIONS: Our study showed evidence suggested that TAES may have different effects on propofol under light and deep sedation. TAES could enhance the sedative effect of propofol at low concentration but reduce the sedative effect of propofol at high concentration.

[Comparative studies on HPLC fingerprint and near-infrared spectra of cultivated and reference crude Scutellaria baicalensis].

Scutellaria baicalensis is a common and important medicinal plant in China, facing with reducing sharply in wild resources. To meet the needs in Chinese herbwouls medicine market and clinical application, S. baicalensis has been widely cultivated in Ningxia, Hebei, Shanxi, and Gansu et al. HPLC finger-print and near-infrared were studied in the research to evaluate quality difference of S. baicalensis in four districts. The results showed that the similarity of HPLC finger-print of 12 cultivated S. baicalensis and reference crude herb is more than 0.961, and the other is more than 0.983. On the other hand, paired sample t-test indicated there has no significant difference between the common peaks' area of 12 cultivated S. baicalensis and reference crude herb. It was verified that 12 cultivated S. baicalensis has highly consistency with reference crude herb. On the basis of chromatographic finger-print and near-infrared spectrum, the study applied paired sample t-test to verify analysis results, which could avoid erroneous judgment induced by indefinite threshold values in the similarity of chromatographic finger-print and provide reliable basis for the analysis results. Meanwhile, it also provides a new idea for improving the quality control method of Chinese medicinal materials by comparative study about two comprehensive detection means.

[Production regionalization study of Glycyrrhiza uralensis].

The distribution information of Glycyrrhiza uralensis was collected by interview investigation and field survey, and 46 related environmental factors were collected, some kinds of functional chemical constituents of G.uralensis were analyzed. Integrated climate, topography and other related ecological factors, the habitat suitability study was conducted based on Arc geographic information system(ArcGIS),and maximum entropy model. The AUC of ROC curve was both above 0.95, indicating that the predictive results with the maximum model were highly precise. The results showed that 5 major ecological factors have obvious influence on ecology suitability distributions of G. uralensis, including July average temperature, soil sub category, Dec precipitation, vegetation types and standard deviation of seasonal variation in temperature, et al. It is suitable for the living habits of the G. uralensis, adequate light, low rainfall, summer heat and large temperature difference between day and night, which is suitable for distribution in the northern temperate plains and mountains. In addition, the ecological suitability regionalization based on the chemical constituents of G.uralensis also provides a new suitable distribution area other than the traditional distribution area, which provides a scientific basis for the reasonable introduction of G.uralensis.

[Production regionalization study of Lycii Fructus].

The distribution information of Lycii Fructus was collected by interview investigation and field survey, and 46 related environmental factors were collected, some kinds of functional chemical constituents the of Lycii Fructus were analyzed. Integrated climate, topography and other related ecological factors, the habitat suitability study was conducted based on Arc geographic information system(ArcGIS),and maximum entropy model. The AUC of ROC curve was both above 0.95, indicating that the predictive results with the maximum model were highly precise. The results showed that 5 major ecological factors had obvious influence on ecology suitability distributions of Lycii Fructus, including soil pH, soil subclass, vegetation type and in August the average temperature et al. It is suitable for the living habits of the Lycii Fructus, dry, cool weather, more hardy, drought-resistant, alkali soil, which is suitable for distribution in the northern temperate plains. In addition, the ecological suitability regionalization based on the chemical constituents of Lycii Fructus also provides a new suitable distribution area other than the traditional distribution area, which provides a scientific basis for the reasonable introduction of Lycii Fructus.

From non- to super-radiating manipulation of a dipolar emitter coupled to a toroidal metastructure.

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.

Toroidal dipolar response by a dielectric microtube metamaterial in the terahertz regime.

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.

[Inhibitory effect of flavonoids from Glycyrrhiza uralensis on expressions of TGF-ß1 and Caspase-3 in thioacetamide-induced hepatic fibrosis in rats].

OBJECTIVE: To study the inhibitory effect of flavonoids from Glycyrrhiza uralensis on thioacetamide-induced chonic hepatic fibrosis in rats and the effect on the protein expressions of transforming growth factor-ß1 (TGF-ß1) and Caspase-3 in livers. METHOD: Male Sprague-Dawley rats were randomly divided into totally seven groups: the normal control group, the model group, LF groups s (400, 200, 100, 50 mg · kg(-1) · d(-1)) and the silymarin positive control group (30 mg · kg(-1) · d(-1)). The hepatic fibrosis model was induced in the rats through intraperitoneal injection with 3% thioacetamide (TAA) at a dose of 150 mg · kg(-1) body weight twice a week for 12 weeks. During the course, the control group and the model group were orally administered with saline (1 mL · kg(-1) · d(-1)). After the modeling and drug intervention, the pathologic changes and fibrosis in liver tissues were observed by HE staining and Masson's Trichrome staining. The serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and liver hydroxyproline (HYP) contents were assayed by biochemical process. The serum hyaluronic acid (HA) was assessed by radioimmunoassay. In addition, the protein expressions of liver TGF-ß1 and Caspase-3 were examined by immunohistochemical method. The mRNA expression of TGF-ß1 in hepatic tissues was examined by quantitative Real-time PCR analysis. RESULT: Compared with the model group, flavonoids can protect the integrity of the structure of liver tissues, significantly reduce the hepatic cell degeneration and necrosis and the proliferation of fibrous tissues, notably reduce the serum AST, ALT, ALP and HA and HYP in hepatic tissues and down-regulate the protein expressions of liver TGF-ß1 and Caspase-3 and the mRNA expression of TGF-ß1 in hepatic tissues. CONCLUSION: The licorice flavonoids can resist the thioacetamide-induced hepatic fibrosis in rats. Its mechanism may be related to the down-regulation of the protein expressions of TGF-ß1 and Caspase-3.

Raloxifene Prevents Chemically-Induced Ferroptotic Neuronal Death In Vitro and In Vivo.

Ferroptosis, a regulated form of cell death characterized by excessive iron-dependent lipid peroxidation, can be readily induced in cultured cells by chemicals such as erastin and RSL3. Protein disulfide isomerase (PDI) has been identified as an upstream mediator of chemically induced ferroptosis and also a target for ferroptosis protection. In this study, we discovered that raloxifene (RAL), a selective estrogen receptor modulator known for its neuroprotective actions in humans, can effectively inhibit PDI function and provide robust protection against chemically induced ferroptosis in cultured HT22 neuronal cells. Specifically, RAL can bind directly to PDI both in vitro and in intact neuronal cells and inhibit its catalytic activity. Computational modeling analysis reveals that RAL can tightly bind to PDI through forming a hydrogen bond with its His256 residue, and biochemical analysis further shows that when PDI's His256 is mutated to Ala256, RAL loses its inhibition of PDI's catalytic activity. This inhibition of PDI by RAL significantly reduces the dimerization of both the inducible and neuronal nitric oxide synthases and the accumulation of nitric oxide, both of which have recently been shown to play a crucial role in mediating chemically induced ferroptosis through subsequent induction of ROS and lipid-ROS accumulation. In vivo behavioral analysis shows that mice treated with RAL are strongly protected against kainic acid-induced memory deficits and hippocampal neuronal damage. In conclusion, this study demonstrates that RAL is a potent inhibitor of PDI and can effectively prevent chemically induced ferroptosis in hippocampal neurons both in vitro and in vivo. These findings offer a novel estrogen receptor-independent mechanism for RAL's neuroprotective actions in animal models and humans.

IL-6 contributes to an immune tolerance checkpoint in post germinal center B cells.

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.

[Antidepressant activities of flavonoids from Glycyrrhiza uralensis and its neurogenesis protective effect in rats].

Adult rats chronic unpredictable stress model of depression (CUS) was adopted to elucidate the antidepressant pharmacological activity and related neurogenesis protective effect of the total flavonoids extract (licorice flavonoids, LF) from the Glycyrrhiza uralensis Fisch. cultivated locally in Ningxia. The rats were exposed to 9 kinds of unpredictable sequence of stressors and were given flavonoids (300 mg x kg(-1), 100 mg x kg(-1) and 30 mg x kg(-1)) for 28 days. The antidepressant effect was elucidated by open field test, forced swimming test and tail suspension test. The level of serum corticosterone was detected by radioimmunoassay. 5'-Bromo-2'-deoxyuridine (BrdU) labeling experiments was employed to study the neurogenesis protective activities. The flavonoids can increase the sum of line crosses and number of rears, and decrease the number of fecal boli produced in the open field test of the CUS rats. Also the flavonoids can decrease the immobility time in forced swim test as well as in the tail suspension test. In addition, the flavonoids (300 mg x kg(-1)) can decrease the serum corticosterone level of the CUS rats, and increase the number of the new born BrdU positive progenitor cells at the subgranular zone (SGZ) of dentate gyrus (DG) region in hippocampus. The results demonstrated that the total flavonoids extract from the cultivated Glycyrrhiza uralensis Fisch. could produce the anti-depressive effect on chronic unpredictable stress of depression model rats and its mechanism may be associated with its neurogenesis protective effect.

Complete chloroplast genome sequence of Pithecellobium clypearia (Jack) Benth.

Pithecellobium clypearia (Jack) Benth. 1844 belongs to the genus Pithecellobium in the family Fabaceae. The complete chloroplast genome of P. clypearia was sequenced and analyzed by Illumina sequencing in this study. The full length of the complete chloroplast genome is 176,770 bp, containing a pair of inverted repeat regions of 39,693 bp (IRa and IRb) separated by a large single-copy (LSC) region of 92,500 bp and a small single-copy (SSC) region of 4,884 bp. The P. clypearia chloroplast genome encodes 137 genes, comprising 92 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on complete chloroplast genomes revealed that P. clypearia is closely related to Archidendron lucyi and Pithecellobium flexicaule. This study provides useful resources for further study and development of this species.

B cell receptor revision diminishes the autoreactive B cell response after antigen activation in mice.

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.