Breeding and Promotion of Dunyu 107,a High-yielding and Stable-yielding Maize Variety

Dunyu 107 is a new maize variety bred by the Gansu Dunhuang Seed Group Co.,Ltd.with the self-bred excellent inbred line HA189 as the female parent and HB38 as the male parent.The variety has early maturity,tolerance to dense planting,lodging resistance,good yielding stability,good comprehensive resistance and suitability for mechanized harvesting.It passed the national approval in 2019 and has great market potential and application value.

ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways

Kidney fibrosis is an inevitable result of various chronic kidney diseases(CKDs)and significantly contributes to end-stage renal failure.Currently,there is no specific treatment available for renal fibrosis.ELA13(amino acid sequence:RRCMPLHSRVPFP)is a conserved region of ELABELA in all vertebrates;however,its biological activity has been very little studied.In the present study,we evaluated the therapeutic effect of ELA13 on transforming growth factor-β1(TGF-β1)-treated NRK-52E cells and unilateral ureteral occlusion(UUO)mice.Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum,and reduce the expression of fibrosis biomarkers confirmed by Masson staining,immunohistochemistry,real-time polymerase chain reaction(RT-PCR),and western blot.Inflammation biomarkers were increased after UUO and decreased by administration of ELA13.Furthermore,we found that the levels of essential molecules in the mothers against decapentaplegic(Smad)and extracellular signal-regulated kinase(ERK)pathways were reduced by ELA13 treatment in vivo and in vitro.In conclusion,ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.

Neurokinin-2 receptor antagonist SR48968 induced necroptosis of myeloid leukemia cells by calcium overload-driven reactive oxygen species accumulation

Increasing evidence highlight tachykinin receptors as a prominent player in hematological malignancy.We previously revealed the proto-oncogenic role of neurokinin-1 receptor(NK-1R)in acute myeloid leukemia(AML),1 whereas the role of neurokinin-2 receptor(NK-2R)has not been elucidated.Herein,we found NK-2R was significantly up-regulated in AML patients in The Cancer Genome Atlas databases.This result was further confirmed in blood from AML patients and a range of human leukemia cells.Then,we verified that blocking NK-2R by SR48968 markedly promoted cell death in human myeloid leukemia without cytotoxicity to normal cells.Mechanically,we uncovered that SR48968 induced cytotoxicity through necroptosis mediated by calcium overload-driven reactive oxygen species(ROS)accumulation.In summary,our results propose that NK-2R antagonist SR48968 may be used as a new therapeutic approach for myeloid leukemia.

Therapeutic peptides: current applications and future directions

Peptide drug development has made great progress in the last decade thanks to new production,modification,and analytic technologies.Peptides have been produced and modified using both chemical and biological methods,together with novel design and delivery strategies,which have helped to overcome the inherent drawbacks of peptides and have allowed the continued advancement of this field.

The antimicrobial peptide YD attenuates inflammation via miR-155 targeting CASP12 during liver fibrosis

The antimicrobial peptide APKGVQGPNG(named YD),a natural peptide originating from Bacillus amyloliquefaciens CBSYD1,exhibited excellent antibacterial and antioxidant properties in vitro.These characteristics are closely related to inflammatory responses which is the central trigger for liverfibrosis.However,the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied.In this study,we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of a-smooth muscle actin and collagen I in carbon tetrachloride-induced mice.Then we found that YD inhibited the level of miR-155,which plays an important role in inflammation and liver fibrosis.Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155.We demonstrate that YD signifi-cantly decreases the contents of inflammatory cytokines and suppresses the NF-k B signaling pathway.Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation,the downregulated levels of inflammatory cytokines,and the inactivation of the NF-k B pathways.Collectively,our study indicates that YD reduces inflammation throughthe mi R-155 e Casp12 e NF-k B axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.

Therapeutic potential for targeting Annexin A1 in fibrotic diseases

Annexin A1,a well-known endogenous anti-inflammatory mediator,plays a critical role in a variety of pathological processes.Fibrosis is described by a failure of tissue regeneration and contributes to the development of many diseases.Accumulating evidence supports that Annexin A1 participates in the progression of tissue fibrosis.However,the fundamental mechanisms by which Annexin A1 regulates fibrosis remain elusive,and even the functions of Annexin A1 in fibrotic diseases are still paradoxical.This review focuses on the roles of Annexin A1 in the development of fibrosis of lung,liver,heart,and other tissues,with emphasis on the therapy potential of Annexin A1 in fibrosis,and presents future research interests and directions in fibrotic diseases.

Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor(GLP-1 R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl_(4), a-naphthyl-isothiocyanate(ANIT), bile duct ligation(BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix(ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl_(4)-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of proinflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha(NFκB/IKBa) pathways as well as cJun N-terminal kinase(JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1 R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl_(4)-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.