Mesenchymal stem cells： a new strategy for immunosuppression and tissue repair

Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.

Efficient Micropropagation of Chestnut Hybrids(Castanea spp.)Using Modified Woody Plant Medium and Zeatin Riboside

The chestnuts genus(Castanea spp.)is comprised of economically important trees native to the Northern hemisphere that are used as food and hardwood timber.Here,a very efficient method for micropropagation of European×Japanese chestnut hybrids(Castanea sativa×C.crenata)is described.Woody Plant Medium was used as the basal medium.In vitro shoots of four rootstock cultivars were micropropagated without shoot-tip necrosis on multiplication medium containing 5.7 or 11.4μmol·L^(−1)zeatin riboside,and were rooted on rooting medium containing 2.46μmol·L^(−1)indolebutyric acid.Monthly shootmultiplication rates for each cultivarwere 2–5 folds.In vitro rooting percentages for four cultivars were 87%for‘Maraval’,67%for‘Marigoule’,93%for‘Marsol’,and 97%for‘Précoce Migoule’.Within a 5 week period,80%–95%of rooted shoots were successfully acclimated under high humidity conditions after they were planted in either soil or rockwool.

N-glucosyltransferase GbNGT1 from ginkgo complements the auxin metabolic pathway

As auxins are among the most important phytohormones,the regulation of auxin homeostasis is complex.Generally,auxin conjugates,especially IAA glucosides,are predominant at high auxin levels.Previous research on terminal glucosylation focused mainly on the O-position,while IAA-N-glucoside and IAA-Asp-N-glucoside have been neglected since their discovery in 2001.In our study,IAA-Asp-N-glucoside was found to be specifically abundant(as high as 4.13 mg/g)in the seeds of 58 ginkgo cultivars.Furthermore,a novel N-glucosyltransferase,termed GbNGT1,was identified via differential transcriptome analysis and in vitro enzymatic testing.It was found that GbNGT1 could catalyze IAA-Asp and IAA to form their corresponding N-glucosides.The enzyme was demonstrated to possess a specific catalytic capacity toward the N-position of the IAA-amino acid or IAA from 52 substrates.Docking and site-directed mutagenesis of this enzyme confirmed that the E15G mutant could almost completely abolish its N-glucosylation ability toward IAA-Asp and IAA in vitro and in vivo.The IAA modification of GbNGT1 and GbGH3.5 was verified by transient expression assay in Nicotiana benthamiana.The effect of GbNGT1 on IAA distribution promotes root growth in Arabidopsis thaliana.

Electrochemically Active Phosphotungstic Acid Assisted Prevention of Graphene Restacking for High-Capacitance Supercapacitors

Direct reduction of graphene oxide usually leads to the agglomeration of the as-generated graphene sheets,thus suppressing the surface exposed for energy storage.Herein,graphene oxide was reduced by a one-pot hydrothermal process in the presence of an electrochemically active phosphotungstic acid to produce three-dimensional porous phosphotungstic acid/reduced graphene oxide composites.Phosphotungstic acid molecules were found to be uniformly anchored on the surface of reduced graphene oxide sheets through the electrostatic interaction to prevent the reduced graphene oxide sheets from restacking.

The APETALA2–MYBL2 module represses proanthocyanidin biosynthesis by affecting formation of the MBW complex in seeds of Arabidopsis thaliana

Proanthocyanidins(PAs)are the second most abundant plant phenolic natural products.PA biosynthesis is regulated by the well-documented MYB/bHLH/WD40(MBW)complex,but how this complex itself is regu-lated remains ill dened.Here,in situ hybridization and b-glucuronidase staining show that APETALA2(AP2),a well-dened regulator offlower and seed development,is strongly expressed in the seed coat endothelium,where PAs accumulate.AP2 negatively regulates PA content and expression levels of key PA pathway genes.AP2 activates MYBL2 transcription and interacts with MYBL2,a key suppressor of the PA pathway.AP2 exerts its function by directly binding to the AT-rich motifs near the promoter region of MYBL2.Molecular and biochemical analyses revealed that AP2 forms AP2–MYBL2–TT8/EGL3 com-plexes,disrupting the MBW complex and thereby repressing expression of ANR,TT12,TT19,and AHA10.Genetic analyses revealed that AP2 functions upstream of MYBL2,TT2,and TT8 in PA regulation.Our work reveals a new role of AP2 as a key regulator of PA biosynthesis in Arabidopsis.Overall,this study sheds new light on the comprehensive regulation network of PA biosynthesis as well as the dual regulatory roles of AP2 in seed development and accumulation of major secondary metabolites in Arabidopsis.

Pirh2 mediates the sensitivity of myeloma cells to bortezomib via canonical NF-κB signaling pathway

Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma （MM）. While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 （Pirh2） in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor- kappaB （NF-κB） p65, pp65, plKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of plKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, plKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF- κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.

High levels of serum IL-10 indicate disease progression,extramedullary involvement,and poor prognosis in multiple myeloma

Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins(M protein),leading to bone destruction,hypercalcemia,anemia,and renal insufficiency(Alexandrakis et al.,2015;Yang et al.,2018).Since a large number of new drugs,represented by proteasome inhibitors and immunomodulators,have been successfullyused to treat MM.

Platinum nanoparticles supported MoS2 nanosheet for simultaneous detection of dopamine and uric acid

Herein, platinum nanoparticles-decorated molybdenum disulfide （PtNPs@MoS2） nanocomposite has been synthesized via a microwave-assisted hydrothermal method, which was characterized by transmission electron microscopy （TEM） and powder X-ray diffraction （XRD）. This MoSz-based nanocomposite modified glass carbon electrode （PtNPs@MoSz/GCE） exhibited excellent electrocatalytic activity toward dopamine （DA） and uric acid （UA） due to their synergistic effect. Two well-defined oxidation peaks of DA and UA were obtained at PtNPs@MoS2/GCE with a large peak separation of 160 mV （DA-UA）, sug- gesting that the modified electrode could individually or simultaneously analyze DA and AA. Under the optimal conditions, the peak currents of DA and UA were linearly dependent on their concentrations in the range of 0.5-150 and 5-1000 gmol/L with detection limit of 0.17 and 0.98 gmol/L, respectively. The proposed MoSz-based sensor can also be employed to examine DA and UA in real samples with satisfactory results. Therefore, the PtNPs@MoS2 nanocomposite might offer a good possibil- ity for electrochemical sensing and other electrocatalytic applications.