Whole-genome profiling of DNA methylation and hydroxymethylation identifies distinct regulatory programs among innate lymphocytes.

Innate lymphocytes encompass a diverse array of phenotypic identities with specialized functions. DNA methylation and hydroxymethylation are essential for epigenetic fidelity and fate commitment. The landscapes of these modifications are unknown in innate lymphocytes. Here, we characterized the whole-genome distribution of methyl-CpG and 5-hydroxymethylcytosine (5hmC) in mouse innate lymphoid cell 3 (ILC3), ILC2 and natural killer (NK) cells. We identified differentially methylated regions (DMRs) and differentially hydroxymethylated regions (DHMRs) between ILC and NK cell subsets and correlated them with transcriptional signatures. We associated lineage-determining transcription factors (LDTFs) with demethylation and demonstrated unique patterns of DNA methylation/hydroxymethylation in relationship to open chromatin regions (OCRs), histone modifications and TF-binding sites. We further identified an association between hydroxymethylation and NK cell superenhancers (SEs). Using mice lacking the DNA hydroxymethylase TET2, we showed the requirement for TET2 in optimal production of hallmark cytokines by ILC3s and interleukin-17A (IL-17A) by inflammatory ILC2s. These findings provide a powerful resource for studying innate lymphocyte epigenetic regulation and decode the regulatory logic governing their identity.

A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages.

Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex. Deletion of the transcription factor SMAD4 in microglia and embryonic-derived BAMs using Crybb1-Cre caused a developmental arrest of microglia, which instead acquired a BAM specification signature. By contrast, the development of genuine BAMs remained unaffected. Our results reveal that SMAD4 drives a transcriptional and epigenetic program that is indispensable for the commitment of brain macrophages to the microglia fate and highlight Crybb1-Cre as a tool for targeting embryonic brain macrophages.

MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells.

Natural killer (NK) cells are cytotoxic type 1 innate lymphoid cells (ILCs) that defend against viruses and mediate anti-tumor responses, yet mechanisms controlling their development and function remain incompletely understood. We hypothesized that the abundantly expressed microRNA-142 (miR-142) is a critical regulator of type 1 ILC biology. Interleukin-15 (IL-15) signaling induced miR-142 expression, whereas global and ILC-specific miR-142-deficient mice exhibited a cell-intrinsic loss of NK cells. Death of NK cells resulted from diminished IL-15 receptor signaling within miR-142-deficient mice, likely via reduced suppressor of cytokine signaling-1 (Socs1) regulation by miR-142-5p. ILCs persisting in Mir142-/- mice demonstrated increased expression of the miR-142-3p target αV integrin, which supported their survival. Global miR-142-deficient mice exhibited an expansion of ILC1-like cells concurrent with increased transforming growth factor-ß (TGF-ß) signaling. Further, miR-142-deficient mice had reduced NK-cell-dependent function and increased susceptibility to murine cytomegalovirus (MCMV) infection. Thus, miR-142 critically integrates environmental cues for proper type 1 ILC homeostasis and defense against viral infection.

The epithelial C15ORF48/miR-147-NDUFA4 axis is an essential regulator of gut inflammation, energy metabolism, and the microbiome.

Chronic inflammation is epidemiologically linked to the pathogenesis of gastrointestinal diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, our understanding of the molecular mechanisms controlling gut inflammation remains insufficient, hindering the development of targeted therapies for IBD and CRC. In this study, we uncovered C15ORF48/miR-147 as a negative regulator of gut inflammation, operating through the modulation of epithelial cell metabolism. C15ORF48/miR-147 encodes two molecular products, C15ORF48 protein and miR-147-3p microRNA, which are predominantly expressed in the intestinal epithelium. C15ORF48/miR-147 ablation leads to gut dysbiosis and exacerbates chemically induced colitis in mice. C15ORF48 and miR-147-3p work together to suppress colonocyte metabolism and inflammation by silencing NDUFA4, a subunit of mitochondrial complex IV (CIV). Interestingly, the C15ORF48 protein, a structural paralog of NDUFA4, contains a unique C-terminal α-helical domain crucial for displacing NDUFA4 from CIV and its subsequent degradation. NDUFA4 silencing hinders NF-κB signaling activation and consequently attenuates inflammatory responses. Collectively, our findings have established the C15ORF48/miR-147-NDUFA4 molecular axis as an indispensable regulator of gut homeostasis, bridging mitochondrial metabolism and inflammation.

microRNA-142 guards against autoimmunity by controlling Treg cell homeostasis and function.

Regulatory T (Treg) cells are critical in preventing aberrant immune responses. Posttranscriptional control of gene expression by microRNA (miRNA) has recently emerged as an essential genetic element for Treg cell function. Here, we report that mice with Treg cell-specific ablation of miR-142 (hereafter Foxp3CremiR-142fl/fl mice) developed a fatal systemic autoimmune disorder due to a breakdown in peripheral T-cell tolerance. Foxp3CremiR-142fl/fl mice displayed a significant decrease in the abundance and suppressive capacity of Treg cells. Expression profiling of miR-142-deficient Treg cells revealed an up-regulation of multiple genes in the interferon gamma (IFNγ) signaling network. We identified several of these IFNγ-associated genes as direct miR-142-3p targets and observed excessive IFNγ production and signaling in miR-142-deficient Treg cells. Ifng ablation rescued the Treg cell homeostatic defect and alleviated development of autoimmunity in Foxp3CremiR-142fl/fl mice. Thus, our findings implicate miR-142 as an indispensable regulator of Treg cell homeostasis that exerts its function by attenuating IFNγ responses.

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4+ eosinophils unique to the small intestine.

C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile. Clec4a4+ eosinophils expressed high levels of aryl hydrocarbon receptor (Ahr), which drove the expression of Clec4a4 as well as other immunomodulatory features, such as PD-L1. The abundance of Clec4a4+ eosinophils was dependent on dietary AHR ligands, increased with aging, and declined in inflammatory conditions. Mice lacking AHR in eosinophils expanded innate lymphoid cells of type 2 and cleared Nippostrongylus brasiliensis infection more effectively than did wild-type mice. These results highlight the heterogeneity of eosinophils in response to tissue cues and identify a unique AHR-dependent subset of eosinophils in the small intestine with an immunomodulatory profile.

Cytosolic DNA initiates a vicious circle of aging-related endothelial inflammation and mitochondrial dysfunction via STING: the inhibitory effect of Cilostazol.

Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.

The impact of selected methodological factors on data collection outcomes in observational studies of device-measured physical behaviour in adults: A systematic review.

BACKGROUND: Accelerometer measures of physical behaviours (physical activity, sedentary behaviour and sleep) in observational studies offer detailed insight into associations with health and disease. Maximising recruitment and accelerometer wear, and minimising data loss remain key challenges. How varying methods used to collect accelerometer data influence data collection outcomes is poorly understood. We examined the influence of accelerometer placement and other methodological factors on participant recruitment, adherence and data loss in observational studies of adult physical behaviours. METHODS: The review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA). Observational studies of adults including accelerometer measurement of physical behaviours were identified using database (MEDLINE (Ovid), Embase, PsychINFO, Health Management Information Consortium, Web of Science, SPORTDiscus and Cumulative Index to Nursing & Allied Health Literature) and supplementary searches to May 2022. Information regarding study design, accelerometer data collection methods and outcomes were extracted for each accelerometer measurement (study wave). Random effects meta-analyses and narrative syntheses were used to examine associations of methodological factors with participant recruitment, adherence and data loss. RESULTS: 123 accelerometer data collection waves were identified from 95 studies (92.5% from high-income countries). In-person distribution of accelerometers was associated with a greater proportion of invited participants consenting to wear an accelerometer (+ 30% [95% CI 18%, 42%] compared to postal distribution), and adhering to minimum wear criteria (+ 15% [4%, 25%]). The proportion of participants meeting minimum wear criteria was higher when accelerometers were worn at the wrist (+ 14% [ 5%, 23%]) compared to waist. Daily wear-time tended to be higher in studies using wrist-worn accelerometers compared to other wear locations. Reporting of information regarding data collection was inconsistent. CONCLUSION: Methodological decisions including accelerometer wear-location and method of distribution may influence important data collection outcomes including recruitment and accelerometer wear-time. Consistent and comprehensive reporting of accelerometer data collection methods and outcomes is needed to support development of future studies and international consortia. Review supported by the British Heart Foundation (SP/F/20/150002) and registered (Prospero CRD42020213465).

Association between device-measured stepping behaviors and cardiometabolic health markers in middle-aged women: The Australian Longitudinal Study on Women's Health.

The associations between different types and contexts of stepping behaviors and cardiometabolic (CM) health markers are unclear. This study aimed to examine the associations of daily total, walking, stair, incidental and purposeful steps with cardiometabolic risk. A total of 943 women (mean age ± SD = 44.1 ± 1.6 years) from the Australian Longitudinal Study on Women's Health (ALSWH) were included in this cross-sectional study. Daily total, walking, stair, incidental, and purposeful steps were measured using thigh-worn accelerometry. Outcomes comprised of CM markers of adiposity, blood pressure, resting heart rate, lipids, glycaemia, and the composite CM score. We used generalized linear modeling and multiple linear regression to assess the associations. We observed that all stepping behaviors were beneficial to CM health, for example, compared to the lowest quartile (Q1), the change of the composite CM score across low to high quartile of purposeful steps was -0.12 (Q2, 95% CI: -0.41, 0.17), -0.16 (Q3, -0.46, 0.14), and -0.36 (Q4, -0.66, -0.05). Stair steps showed linear associations with blood pressure and adiposity biomarkers, for example, the change of quartile of waist circumference was -1.45 cm (Q2, -4.35, 1.44), -3.56 cm (Q3, -6.52, -0.60), and -7.08 cm (Q4, -10.31, -3.86). Peak 30-min walking intensity showed independent association with adiposity biomarkers (p linear < 0.001 and p = 0.002 for waist circumference and BMI, respectively). Our study showed that all stepping forms were beneficial to CM health. Higher stair steps and peak 30-min walking cadence were associated with a steep decline of adiposity biomarkers. Purposeful steps showed more consistent associations with CM biomarkers than incidental steps.

Comparison of AngioJet Thrombectomy System Versus Suction Catheter with the Adjunct of Catheter-Directed Thrombolysis for Lower Extremity Deep Venous Thrombosis.

BACKGROUND: This study aims to investigate the value of the AngioJet thrombectomy system with adjunct of catheter-directed thrombolysis (CDT) in treating lower extremity deep venous thrombosis (LEDVT). METHODS: 48 patients who were clinically confirmed LEDVT and treated by percutaneous mechanical thrombectomy (PMT) combined with CDT, were included in this retrospective study (AJ-CDT, n = 33; Suction-CDT, n = 15). Baseline characteristics, clinical outcomes and surveillance data were reviewed and analyzed. RESULTS: The overall clot reduction rate of AJ-CDT group was significantly higher than that of Suction-CDT group (77.86% vs 64.47%, P = .027). The CDT therapeutic time (5.75 ± 3.04 vs 7.67 ± 2.82 days, P = .045) and urokinase dosage (3.63 ± 2.16 vs 5.76 ± 2.12 million IU, P = .003) were lower in AJ-CDT group, respectively. There was statistical significance in the transient hemoglobinuria between 2 groups (72.73% vs 6.67%, P < .001). At postoperative 48 hours, the serum creatinine (Scr) value was higher in AJ-CDT group compared to Suction-CDT group statistically (78.56 ± 32.16 vs 60.21 ± 15.72 µmol/l, P = .049). However, the incidence of acute kidney injury (AKI) and uric acid (UA) concentration at postoperative 48 hours between these 2 groups were no statistical difference. There was no statistical significance in the Villalta score and post-thrombosis syndrome (PTS) incidence during postoperative follow-up. CONCLUSIONS: AngioJet thrombectomy system is more effective for the treatment of LEDVT by providing a higher clot reduction rate with shorter thrombolytic time and lower thrombolytic drug dosage. However, the device-related potential risk of renal function injury should be taken appropriate precautions.

Insulative Ion-Conducting Lithium Selenide as the Artificial Solid-Electrolyte Interface Enabling Heavy-Duty Lithium Metal Operations.

The deployment of Li metal batteries has been significantly tethered by uncontrollable lithium dendrite growth, especially in heavy-duty operations. Herein, we implement an in situ surface transformation tactic exploiting the vapor-phase solid-gas reaction to construct an artificial solid-electrolyte interphase (SEI) of Li2Se on Li metal anodes. The conformal Li2Se layer with high ionic diffusivity but poor electron conductivity effectively restrains the Li/Li+ redox conversion to the Li/Li2Se interface, and further renders a smooth and chunky Li deposition through homogenized Li+ flux and promoted redox kinetics. Consequently, the as-fabricated Li@Li2Se electrodes demonstrate superb cycling stability in symmetric cells at both high capacity and current density. The merits of inhibited dendrite growth and side reactions on the stabilized Li@Li2Se anode are further manifested in Li-O2 batteries, greatly extending the cycling stability and energy efficiency.

An Integrated Study on the Fading Mechanism of Malachite Green Industrial Dye for the Marquisette Curtain in the Studio of Cleansing Fragrance, the Palace Museum (Beijing).

Historical marquisette curtains were composed of lightweight fabrics, woven in an open-mesh and leno-type weave, usually made of silk, and found in Qing imperial buildings. As panel curtains, they were exposed to light, and so underwent fading. This study investigated the manufacturing technology and fading mechanism of dyed marquisette fabric from the Studio of Cleansing Fragrance, the Palace Museum (Beijing). The technological aspects were identified. The types of weave, fiber, and adhesive used to fix the curtain to the wooden frame were identified through microscopic observation and infrared spectroscopy. A color change characterization was performed based on UV-visible diffuse reflectance spectra. The textile colorant was identified as malachite green (MG), and its degradation by light was subsequently studied by dynamic photolysis experiments in a kinetic solution for the rapid exploration of by-products. The main degradation pathways were thus identified and the factors responsible for the induced color changes were discussed. A comparison of the liquid chromatography-mass spectrometry (LC-MS) results of the products derived from the photolysis method as well as of the samples extracted from the object allowed for the identification of the presence of different degradation pathways in the faded and unfaded parts of the textile. A metabolomics analysis was applied to account for the differences in the degradation pathways.

A "Blockchain" Synergy in Conductive Polymer-Filled Metal-Organic Frameworks for Dendrite-Free Li Plating/Stripping with High Coulombic Efficiency.

The performance of lithium-metal batteries is severely hampered by uncontrollable dendrite growth and volume expansion on the metal anodes. Inspired by the "blockchain" concept in data mining, here we utilize a conductive polymer-filled metal-organic framework (MOF) as the lithium host, in which polypyrrole (PPy) serves as the "chain" to interlink Li "blocks" stored in the MOF pores. While the N-rich PPy guides fast Li+ infiltration/extrusion and serves as the nucleation sites for isotropic Li growth, the MOF pores compartmentalize bulk Li deposition for 3D matrix Li storage, leading to low-barrier and dendrite-free Li plating/stripping with superb Coulombic efficiency. The as-fabricated lithium-metal anodes operate over 700 cycles at 5 mA cm-2 in symmetric cells, and 800 cycles at 1 C in full cells with a per-cycle capacity loss of only 0.017 %. This work might open a new chapter for Li-metal anode construction by introducing the concept of "blockchain" management of Li plating/stripping.

Impact of Cardiovascular Diseases on COVID-19: A Systematic Review.

In December 2019, pneumonia of unknown cause broke out, and currently more than 150 countries around the world have been affected. Globally, as of 5: 46 pm CET, 6 November 2020, the World Health Organization (WHO) had reported 48 534 508 confirmed cases of COVID-19, including 1 231 017 deaths. The novel coronavirus disease (COVID-19) outbreak, caused by the SARS-CoV-2 virus, is the most important medical challenge in decades. Previous research mainly focused on the exploration of lung changes. However, with development of the disease and deepening research, more and more patients showed cardiovascular diseases, even in those without respiratory symptoms, and some researchers have found that underlying cardiovascular diseases increase the risk of infection. Although the related mechanism is not thoroughly studied, based on existing research, we speculate that the interaction between the virus and its receptor, inflammatory factors, various forms of the stress response, hypoxic environment, and drug administration could all induce the development of cardiac adverse events. Interventions to control these pathogenic factors may effectively reduce the occurrence of cardiovascular complications. This review summarizes the latest research on the relationship between COVID-19 and its associated cardiovascular complications, and we also explore possible mechanisms and treatments.

Performance evaluation of medical service for breast cancer patients based on diagnosis related groups.

BACKGROUND: To evaluate the performance of medical service for patients with breast cancer in Henan Province, China, using diagnosis related groups (DRGs) indicators and to provide data to inform practices and policies for the prevention and control of breast cancer. METHODS: The data were collected from the front pages of medical records (FPMR) of all hospitals above class II that admitted breast cancer patients in Henan Province between 2016 and 2019. Breast cancer patients were the subjects in our study. China DRGs (CN-DRGs) was used as a risk adjustment tool. Three indicators, including the case mix index (CMI), number of DRGs, and total weight, were used to evaluate the range of available services for patients with breast cancer, while indicators including the charge efficiency index (CEI), time efficiency index (TEI) and inpatient mortality of low-risk group cases (IMLRG) were used to evaluate medical service efficiency and medical safety. RESULTS: Between 2016 and 2019, there were 103,760 patients with breast cancer. The total weight increased over the study period at an average annual rate of 21.71%. The TEI decreased over the study period by 15.60%. The CEI exhibited an increasing trend, but the average annual rate of increase was small (2.94%). The IMLRP was 0.02, 0, 0 and 0.01% in 2016, 2017, 2018 and 2019, respectively. CONCLUSION: The performance of medical service improved between 2016 and 2019 for breast cancer patients discharged from study hospitals in Henan Province. The main area of improvement was in the range of available services, but medical institutions must still make efforts to improve the efficiency of medical services and ensure medical safety. DRGs is an effective evaluation tool.

[Clinical features of very preterm infants with prelabor rupture of membranes and predictive factors for major adverse outcomes].

OBJECTIVE: To study the clinical features of very preterm infants with prelabor rupture of membranes (PROM) and predictive factors for early-onset sepsis (EOS) and death. METHODS: A retrospective analysis was performed for the clinical data of the very preterm infants with PROM (with a gestational age of < 32 weeks) who were admitted to the neonatal intensive care unit from January 2018 to May 2020. According to the time from membrane rupture to delivery, the infants were divided into four groups: < 18 hours (n=107), 18 hours to < 3 days (n=111), 3 days to < 14 days (n=144), and ≥ 14 days (n=37). According to the presence or absence of EOS, the infants were divided into EOS (n=42) and non-EOS groups (n=357). According to the survival state, the infants were divided into a survival group (n=359) and a death group (n=40). Clinical features were analyzed for very preterm infants with different times of PROM. A multivariate logistic regression analysis was used to investigate the predictive factors for EOS and death in very preterm infants with PROM. RESULTS: There was no significant difference in the incidence rates of major neonatal complications and mortality rate among the very preterm infants with different times of PROM (P > 0.05). Birth weight < 1 000 g (OR=4.353, P=0.042), grade Ⅲ amniotic fluid contamination (OR=4.132, P=0.032), and grade Ⅲ-Ⅳ respiratory distress syndrome (RDS) (OR=2.528, P=0.021) were predictive factors for EOS in very preterm infants with PROM. Lower birth weights (< 1 000 g or 1 000-1 499 g; OR=11.267 and 3.456 respectively; P=0.004 and 0.050 respectively), grade Ⅲ-Ⅳ RDS (OR=5.572, P < 0.001), and neonatal sepsis (OR=2.631, P=0.012) were predictive factors for death in very preterm infants with PROM. CONCLUSIONS: Prolonged PROM does not increase the incidence of neonatal complications and mortality in very preterm infants. Adverse outcomes of very preterm infants with PROM are mainly associated with lower birth weights, lung immaturity, and systemic infection.

Chalcogenide Photonic Crystals Fabricated by Soft Imprint-Assisted Photodoping of Silver.

This work presents a low-cost, large-scale nanofabrication approach that combines imprint lithography and silver doping (IL-SD) to pattern chalcogenide glass (ChG) films for realizing IR devices. The IL-SD method involves controled photodoping of silver (Ag) atoms into ChG films and selective removing of undoped ChG. For photodoping of Ag, an Ag-coated elastomer stamp is brought in contact with the ChG film and exposed to ultraviolet light, and subsequently, the Ag atoms are photo-dissolved into the ChG film following the nanopatterns on the elastomer stamp. Due to the high wet-etching selectivity of the undoped ChG to Ag-doped one, the ChG film can be precisely patterned with a spatial resolution on the order of a few tens of nanometers. Also, by controling the lateral diffusion of Ag atoms during ultraviolet exposure, it is possible to adjust the size of the final patterns formed in the ChG film. As an application demonstration of the IL-SD process, the As2 S3 -based near-infrared photonic crystals (PhCs) in the wavelength range and flexible midinfrared PhCs are formed, and their optical resonances are investigated. The IL-SD process enables the low-cost fabrication of ChG nanostructures on different substrate materials and gives a great promise to realize various IR devices.

miR-146a-Traf6 regulatory axis controls autoimmunity and myelopoiesis, but is dispensable for hematopoietic stem cell homeostasis and tumor suppression.

microRNA-146a (miR-146a) has been previously implicated as an essential molecular brake, preventing immune overreaction and malignant transformation by attenuating NF-κB signaling, putatively via repression of the Traf6 and Irak1 genes. The exact contribution of miR-146a-mediated silencing of these genes to the control of immune activation is currently unknown. Therefore, we defined the role of the miR-146a-Traf6 signaling axis in the regulation of immune homeostasis using a genetic epistasis analysis in miR-146a-/- mice. We have uncovered a surprising separation of functions at the level of miR-146a targets. Lowering the Traf6 gene dose and consequent attenuation of NF-κB activation rescued several significant miR-146a-/- phenotypes, such as splenomegaly, aberrant myeloproliferation, and excessive inflammatory responses. In contrast, decreasing Traf6 expression had no effect on the development of the progressive bone marrow failure phenotype, as well as lymphomagenesis in miR-146a-/- mice, indicating that miR-146a controls these biological processes through different molecular mechanisms.

Functional MYB transcription factor encoding gene AN2 is associated with anthocyanin biosynthesis in Lycium ruthenicum Murray.

BACKGROUND: Lycium ruthenicum Murray is an important economic plant in China and contains higher levels of anthocyanins in its fruits than other Lyciums. However, the genetic mechanism of anthocyanin production in this plant is unknown. RESULTS: Based on previous transcriptome analysis, LrAN2 and LbAN2, encoding MYB transcription factors, were isolated from L. ruthenicum and L. barbarum, respectively. Both genes contained two introns, encoded 257 amino acids with two-Aa difference, and carried the unabridged HTH-MYB, MYB-like DNA-binding, and SANT domains. In the phylogenetic trees, LrAN2 and LbAN2 were found to be closely related to NtAN2, which regulates anthocyanin biosynthesis in tobacco. Overexpression of LrAN2 and LbAN2 induced anthocyanin biosynthesis in all tissues of tobacco. The anthocyanin content in the leaves of transgenic lines with LbAN2 was lower than LrAN2. It indicated that the function of LbAN2 was weaker than LrAN2. The AN2 transcript could be detected only in the fruits of L. ruthenicum and increased during fruit development, accompanied by anthocyanin accumulation. In natural population, the alleles LrAN2 and LrAN2 were associated strictly with L. ruthenicum and L. barbarum, respectively. Moreover, an AN2 genetic diversity study suggested that Lyciums with yellow, white, purple, and jujube red fruits were derived from L. ruthenicum. CONCLUSIONS: Two AN2 alleles, from L. ruthenicum and L. barbarum, were functional MYB transcriptor regulating anthocyanin biosynthesis. The functional diversity and high expression level of LrAN2 could be the reason for high anthocyanin content in the fruit of L. ruthenicum. Lyciums with yellow, white, purple, and jujube red fruits were derived from L. ruthenicum based on AN2 sequence diversity. The results may be advantageous in identifying new varieties and breeding new cultivars.

Anti-chromatic dispersion transmission of frequency and bandwidth-doubling dual-chirp microwave waveform.

A photonic approach to realizing anti-chromatic dispersion transmission for a frequency and bandwidth-doubling dual-chirp microwave waveform is proposed and experimentally demonstrated. The system has no requirement on polarization devices or optical filters for only the integrated dual-drive dual-parallel Mach-Zehnder modulator employed. To overcome chromatic dispersion, the carrier frequency suppression approach is proposed. The anti-chromatic dispersion process is accomplished in a central station and independent to carrier frequency, fiber length, and dispersion coefficients. An experiment is conducted to verify the analysis. Dual-chirp waveforms at 13 GHz with a bandwidth of 0.8 GHz and time duration of 1 µs are obtained. After 25 km fiber transmission, the proposed approach shows a relatively flat curve in a frequency-power diagram, while the normally carrier-suppressed double-sideband modulation method experiences a significant power fading for fiber dispersion.