CD47 serves as a ligand for signaling regulatory protein α (SIRPα) and as a receptor for thrombospondin‐1 (TSP‐1). Although CD47, TSP‐1, and SIRPα are thought to be involved in the clearance of aged ...red blood cells (RBCs), aging‐associated changes in the expression and interaction of these molecules on RBCs have been elusive. Using direct stochastic optical reconstruction microscopy (dSTORM)‐based imaging and quantitative analysis, we can report that CD47 molecules on young RBCs reside as nanoclusters with little binding to TSP‐1, suggesting a minimal role for TSP‐1/CD47 signaling in normal RBCs. On aged RBCs, CD47 molecules decreased in number but formed bigger and denser clusters, with increased ability to bind TSP‐1. Exposure of aged RBCs to TSP‐1 resulted in a further increase in the size of CD47 clusters via a lipid raft‐dependent mechanism. Furthermore, CD47 cluster formation was dramatically inhibited on thbs1−/− mouse RBCs and associated with a significantly prolonged RBC lifespan. These results indicate that the strength of CD47 binding to its ligand TSP‐1 is predominantly determined by the distribution pattern and not the amount of CD47 molecules on RBCs, and offer direct evidence for the role of TSP‐1 in phagocytosis of aged RBCs. This study provides clear nanoscale pictures of aging‐associated changes in CD47 distribution and TSP‐1/CD47 interaction on the cell surface, and insights into the molecular basis for how these molecules coordinate to remove aged RBCs.
On young RBCs (Top), CD47 molecules reside as nanoclusters with minimal binding to TSP‐1 trimmers. On aged RBCs (Bottom), CD47 proteins form bigger and denser clusters and gain increased ability to bind TSP‐1, thus promoting phagocytosis of aged RBCs.
Background： Practice guidelines have recommended cognitive behavioral therapy （CBT） and interpersonal psychotherapy （IPT） as the treatment of choice for major depression disorder （MDD）. However, ...whether one therapy is better than the other remains inconclusive. The aim of this study was to compare the treatment efficacy of the two treatment approaches for MDD. Methods： Using the terms ＂cognitive behavior therapy or cognitive therapy or CBTor CTor cognitive behavioral therapy＂ and ＂interpersonal psychotherapy or IPT,＂ we systematically searched PubMed, Psyclnfo and Chinese National Knowledge Infrastructure databases up to February 2017. The language was restricted to be English and Chinese. Therapeutic outcomes, characteristics, and research quality were then extracted and analyzed independently. In accessing the included studies, we followed the criteria suggested by the Cochrane Handbook for Systematic Reviews of Interventions. Results： Data for 946 patients from 10 randomized controlled trials were included in the study. Methodological quality was not optimal in most trials. Meta-analysis showed a mean difference （MD） of -1.31, 95% confidence interval （CI） （-2.49, -0.12） （P 〈 0.05） in favor of CBT according to the Beck Depression Inventory （BDI）, and however, we did not found any statistically significant difference between CBT and IPT on the Hamilton Rating Scale for depression （HRSD） （MD -0.90, 95% CI -2.18, 0.38）. Subgroup analyses for the studies in which patients were treated only by psychotherapy （MD -1.26, 95% CI -2.78, 0.35） and for those which offered more sessions of therapies （MD -0.82, 95% CI -2.23, 0.59） showed there was no significant difference between CBT and IPT according to BDI. Conclusions： Differences in treatment efficacy seem to vary according to different outcome measures. CBT shows an advantage over IPT for MDD according to BDI, and there is no significant difference between the two according to HRSD. These results should be interpreted with caution.
Alpha‐amylases play essential roles in germination, and the malting and brewing processes, by hydrolyzing starch granules present in the endosperm of barley. Hordeum spontaneum C. Koch, the ...progenitor of cultivated barley that harbors rich genetic diversity, was collected from seven different environments. To investigate the influence of microclimatic ecological divergence on α‐amylase, single nucleotide polymorphisms (SNPs) in amy genes from these populations were determined. A total of 16 and 17 SNPs were detected in the coding sequences of amy1 and amy2, respectively, from the seven wild barley populations. Among these SNPs, three in amy1‐2 and nine in amy2‐2 were significantly associated with ecological factors. The genetic divergence of amy sequences was significantly different among the populations. Natural microclimatic selection was apparently the major evolutionary driving force causing interslope divergence and adaptive evolution of these genes. The genetic variation in amy1‐2 and amy2‐2 was at least partly ecologically determined in these populations, representing adaptive patterns generated by natural selection. The SNPs were apparently generated by natural selection in climatic environmental patterns at both the micro (“Evolution Canyon”) and macro (across Israel, Galilee, and Negev) scales.
As an important herbaceous plant, Scutellaria baicalensis Georgi (Chinese skullcap) is geographically widespread and commonly used throughout the world. In the Chinese medicine market, S. baicalensis ...has been divided into two primary types, “Ku Qin” (WXR) and “Tiao Qin” (TST). Moreover, TST is also divided into different grades according to the diameter of roots. To explore the distribution patterns of the contents of five biologically activate ingredients (FBAI), we used six-year-old cultivated S. baicalensis and analyzed its growth characteristics as well as the quality difference among different types and diameters in roots. Throughout the entire root, we discovered that contents of the FBAI all initially increased and subsequently decreased from the top to the bottom of the roots. The baicalin content of WXR was less than that of TST. On the contrary, the contents of baicalein, wogonin, and oroxylin A in WXR were up to about two times higher than that in TST. We also found that the 0 to 40 cm part of the S. baicalensis root possessed about 87% of the root biomass and about 92% of the contents of the active ingredients.
Five novel donor-acceptor （D-A） conjugated cooligomers （F4B-hP, F5B-hP, F5B21,2-hP, F5B2I,3-hP and F7B21,2-hP） were synthesized. The absorption spectra of the cooligomers cover a wide range from 300 ...nm to 630 nm. The cooligomers could form films featured by alternating D-A lamellar nanostructures with the periods relative to the molecular lengths after thermal annealing or solvent vapor annealing. Single molecule solar cells were fabricated, and FSB-hP exhibited the best device performance. When the film of FSB-hP was thermally annealed, a power conversion efficiency （PCE） of 1.56% was realized. With solvent vapor annealing, the PCE could be further improved to 1.72% with a short-circuit current （J_SC） of 5.76 mA/cm2, an open-circuit voltage （Voc） of 0.87 V and a fill factor （FF） of 0.34.
Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylation-state-specific manner. However, how substrate specificity is determined and how the enzymes ...are regulated were largely unknown. We recently found that ceKDM7A, a PHD- and JmjC domain-containing protein, is a histone demethylase specific for H3K9me2 and H3K27me2, and the PHD finger binding to H3K4me3 guides the demethylation activity in vivo. To provide structural insight into the molecular mechanisms for the enzymatic activity and the function of the PHD finger, we solved six crystal structures of the enzyme in apo form and in complex with single or two peptides containing various combinations of H3K4me3, H3K9me2, and H3K27me2 modifications. The structures indicate that H3K9me2 and H3K27me2 interact with ceKDM7A in a similar fashion, and that the peptide-binding specificity is determined by a network of specific interactions. The geometrical measurement of the structures also revealed that H3K4me3 associated with the PHD finger and H3K9me2 bound to the JmjC domain are from two separate molecules, suggesting a trans-histone peptide-binding mechanism. Thus, our systemic structural studies reveal not only the substrate recognition by the catalytic domain but also more importantly, the molecular mechanism of dual specificity of ceDKM7A for both H3K9me2 and H3K27me2.
Gastric cancer, like all cancers, is considered to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumour suppressor loss. More recently, ...the role of epigenetic change as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes has emerged in many cancer types. The study of DNA methylation changes in gastric cancer has now provided additional clues into the pathogenesis of the disease. E-cadherin as a metastases suppressor is mutationally inactivated in both familial and sporadic forms of gastric cancers. Evidence now suggests that the transcriptional silencing of E-cadherin gene by promotor methylation plays a crucial role in the development and progression of gastric malignancies. In order to further analyze the role of E-cadherin gene promotor methylation in gastric carcinogenesis and progression, we performed the studies of promoter methylation status and protein expression of E-cadherin gene in asso
Background Features of necrotic lesions and various interventions could affect the biomechanics of the femoral head. A three-dimensional finite-element analysis was designed to demonstrate necrotic ...femoral head stress changes with various sizes of necrotic lesions, and evaluate the effect of tantalum rods on preventing femoral head cracking. Methods Femoral computed tomography scans were used to build a normal three-dimensional finite-element femoral head model in a computer. Based on the normal model, necrotic models of different lesion diameters （15 mm, 20 mm and 30 mm） were created, as were the repaired models with tantalum rods for each diameter. After a series of meshing and force loading, the von Mises stress distributions, simulating single-legged stance, and stresses on specific points under loaded conditions were determined for each model. Results Deep exploration into the burdened area of the femoral head indicated that higher stresses to the femoral head were observed with a larger necrotic lesion; the largest stress concentration, 91.3 MPa, was found on the femoral head with a lesion diameter of 30 mm. By contrast, topical stress on the surface of the necrotic regions was lowered following implantation of a tantalum rod, and the changes in stress were significant in models with lesions of 15 mm and 30 mm in diameter, with the best biomechanical benefit from the tantalum rod found with a lesion diameter of 15 mm. Conclusions Femoral heads with larger necrotic lesions usually have a higher stress concentration and a higher risk of collapse. Various sized lesions on the femoral head can benefit from the mechanical support offered by the implantation of a tantalum rod; however, femoral heads with smaller sized lesions may benefit more. A thorough evaluation of the lesion size should be conducted prior to the use of tantalum rod implants in the treatment of femoral head necrosis.
Although B cells play important roles in the humoral immune response and the regulation of adaptive immunity, B cell subpopulations with unique phenotypes, particularly those with non-classical ...immune functions, should be further investigated. By challenging mice with Listeria monocytogenes, Escherichia coli, vesicular stomatitis virus and Toll-like receptor ligands, we identified an inducible CDlla^hi FcγRIII^hi B cell subpopulation that is significantly expanded and produces high levels of IFN-γ during the early stage of the immune response. This subpopulation of B cells can promote macrophage activation via generating IFN-γ, thereby facilitating the innate immune response against intracellular bacterial infection. As this new subpopulation is of B cell origin and exhibits the phenotypic characteristics of B cells, we designated these cells as IFN-γ-producing innate B cells. Dendritic cells were essential for the inducible generation of these innate B cells from the follicular B cells via CD40L-CD40 ligation. Increased Bruton＇s tyrosine kinase activation was found to be responsible for the increased activation of non-canonical NF-κB pathway in these innate B cells after CD40 ligation, with the consequent induction of additional IFN-γ production. The identification of this new population of innate B cells may contribute to a better understanding of B cell functions in anti-infection immune responses and immune regulation.
The Turpan-Hami Basin in eastern Xinjiang is one of the driest regions on Earth and a premier environment to form and preserve nitrate.A large nitrate ore field in this basin was found recently.It is ...estimated there are about 2.5 billion tons of resources of nitrate,and the amount is as much as the Atacama Desert super-scale nitrate deposit in Chile.Nitrate is one of a few minerals with mass-independent fractionation（MIF）,and the oxygen isotope MIF is an effective method to determine the source of nitrate.Theδ~（17）O,δ~（18）O of nitrate were measured by fluorination and thermal decomposition method.The date indicated that this is the first time that oxygen isotope MIF has been located in inland nitrate minerals.The results obtained by two methods are similar,⊿~（17）=δ~（17）O-0.52×δ~（18）O=12‰-17‰.The experiment and observation data proved that oxygen isotope MIF of nitrate are the result of photochemical reactions in the troposphere and stratosphere.Thus, evidence from MIF oxygen isotopic compositions indicate that long term atmospheric deposition of nitrate aerosol particles produced by photochemical reactions is the source of the deposits.
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