Saponins from Paris forrestii(Takht.) H. Li displays potent activity against acute myeloid leukemia by suppressing RNF6/AKT/mTOR signaling pathway

Acute myeloid leukemia(AML) is a heterogeneous disease characterized by the accu.mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi.esis and ultimately resulting in bone marrow failure.Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years(5.3%) and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML.Saponins are amphipathic glycosides found in traditional Chinese medicines.In the present study,we isolated a panel of saponins from Paris forrestii(Takht.) H.Li,a unique plant found in Tibet and Yunnan provinces,China.By examining their activities in suppressing acute myeloid leukemia cell proliferation,total saponins from Paris forrestii(TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines.TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg.ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa.tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con.firmed by the inactivation of 4 EBP-1 and p70 S6 K,two typical downstream signal molecules in the AKT/mTOR pathway.More specifically,TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6,a recently identified oncogene in AML.RNF6 activated AKT/mTOR,and consistently,knockdown of RNF6 led to inactivation of the AKT/mTOR pathway.Furthermore,TSPf suppressed the growth of AML xenografts in nude mice models.Oral administration of 100 mg · kg^(-1) body weight almost fully suppressed tumor growth within 14 d,without gross toxicity.This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway.Given its low toxicity,TSPf could be developed for the treatment of AML.

Multi-index analysis of the melting process of laterite metallized pellet

Herein, a multi-index analysis of the nickel content of an alloy, output rate of the alloy, nickel recovery rate, and iron recovery rate during the melting of laterite metallized pellets was performed. The thermodynamic reduction behavior of oxides such as NiO, FeO, Fe_3 O_4, and Cr_2 O_3 was studied using the FactSage software, which revealed that SiO_2 is not conducive to the reduction of iron oxides, whereas the addition of basic oxides such as CaO and MgO is beneficial for the reduction of iron oxides. On the basis of a comprehensive analysis to achieve greater nickel recovery and lower iron recovery rates, the optimum experimental parameters in the orthogonal experiment were A3 B1 C3(t = 30 min, C/O = 0.4, R = 1.2); the indicators wNi, φalloy, ηNi, and ηFe had values of 15.0 wt%, 12.1%, 44.9%, and 96.4%, respectively. In single-factor experiments, increasing basicity(R) substantially improved the separation effect in the low-basicity range 0.5 ≤ R ≤ 0.8 but not in the high-basicity range 0.8 ≤ R ≤ 1.2. Similar results were obtained for the effect of the C/O ratio. Moreover, the recovery rate of nickel increased with increasing recovery rate of iron.

Child with Wiskott–Aldrich syndrome underwent atypical immune reconstruction after umbilical cord blood transplantation: A case report

BACKGROUND Timely reconstitution of a donor-derived immune system is important for recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation(HSCT).We describe a case of Wiskott–Aldrich syndrome(WAS)treated by umbilical cord blood transplantation(UCBT)with atypical immune reconstruction.CASE SUMMARY A 1-year-old Chinese male infant was diagnosed with WAS.WAS gene sequencing identified the mutation c.777+1G>A(IVS8).On August 8,2017,he was admitted to our hospital for HSCT.We selected an unrelated Human leukocyte antigen 6/10-matched donor for UCBT.After HSCT,the immune reconstitution process was atypical,the lymphocytes reached 0.5×109/L on day 23,and the neutrophils reached 0.5×109/L on day 34.The patient’s recovery throughout the year was good.CONCLUSION An increase in lymphocytes(especially T cells)earlier than granulocytes may be a marker of a good prognosis in UCBT.

Cytogenetic Characteristics of Childhood Acute Lymphoblastic Leukemia:A Study of 1541 Chinese Patients Newly Diagnosed between 2001 and 2014

Objective:Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia(ALL).However,studies on the prevalence of cytogenetic abnormalities and their correlation to clinical features in Chinese pediatric patients are limited,especially large-scale studies.Methods:We collected the cytogenetics and clinical data of 1541 children newly diagnosed with ALL between 2001 and 2014 in four Chinese hospitals,and retrospectively analyzed their clinical features,prognosis and risk factors associated with pediatric ALL.

Interface characteristics between TiN and matrix and their effect on solidification structure

Heterogeneous nucleation is an effective way to promote the dispersion and precipitation of second-phase particles in steel and refine the grain size of the solidification structure.Not only refining as-cast structure grain size,but TiN in ferritic stainless steel can also pin grain boundaries and restrain the overgrowth of grains during rolling.The interface characteristics between TiN and heterogeneous phases(high-melting inclusions and ferrite phase)were studied based on the wetting angles between molten steel with different compositions and TiN substrate,and on the matching degree between TiN and ferrite lattice.It was found that,for the molten steel with the same composition,the wetting angle with the TiN substrate was significantly smaller than the contact angles with the other three substrates,while the wetting angle between ferrite phase and TiN was the smallest.The lattice matching was compared among MgAl_(2)O_(4),TiN andδmatrix by means of a high-resolution transmission electron microscope,which revealed that a coherent or semi-coherent interface was formed between the crystal plane(400)of MgAl_(2)O_(4)and the crystal plane(200)of TiN,as well as between the crystal plane(200)of TiN and the crystal plane(110)ofδmatrix,with a lattice misfit of 5.1%and 3.4%,respectively.Finally,these two characteristics between TiN and ferrite phase were both explained from the perspective of interfacial energy.The microstructure refinement mechanism from high temperature to room temperature can be better reflected by the proposed wetting–lattice misfit theory.

Numerical simulation and experimental measurement of transport phenomena for coherent jet with CH4 ＋ N2 mixed fuel gas

Coherent jet technology has been widely used in EAF steelmaking process because of the longer potential core length and stronger impacting power of the supersonic oxygen jet. However, more oxygen and fuel gas are consumed to achieve excel- lent characteristics of coherent jets, which causes the increase in steelmaking cost. Computational fluid dynamics simulation and experimental measurement of the coherent jets with CH4 ＋ N2 mixed fuel gas were carried out aiming at reducing the consumption of fuel gas. The numerical simulation results showed good agreement with the experimental data. As a result, high proportion of N2 negatively affects the combustion of CH4, which is not good for the protection of oxygen jets. While the gas composition is 75% CH4 ＋ 25% N2, the N2 addition to the CH4 leads to an expanding of CH4 combustion zone, and the energy generated by the combustion reaction could be delivered to the molten bath more efficiently, which is one control scheme with high performance-price ratio.