The effects of different nitrogen sources on camptothecin content and related gene expression in Camptotheca acuminata seedlings

Camptotheac acuminata Decne is a unique tree species in China with an important secondary metabolite,camptothecin(CPT),used in the treatment of cancer.Nitrogen(N)is an important element that affects plant growth and the accumulation of CPT.Reports on the effect of N on CPT synthesis from a genetic perspective are scarce.To explore the effects of different N sources and levels on CPT synthesis in C.acuminata,two-year-old seedlings were fertilized with different concentrations of pure ammonium sulphate,source of ammonium N(NH4+-N),and potassium nitrate for nitrate N(NO3--N).Concentrations of 2.5,5,7.5,and10 g pot-1 NH4+-N and NO3--N were used.The results showed that 7.5 g NH4+-N and NO3--N treatments were best for growth and fresh weight of leaves.Compared with the other treatments,the CPT content,tryptophan synthase and tryptophan decarboxylase activities,and expression of the CaTSB and CaTDCl genes under the 2.5 g NH4+-N and NO3--N treatments peaked significantly at 30 days.However,the expression of CaTDC2 surpassed that of the other two genes at 60 days.Therefore,compared with NH4+-N source,the NO3--N source was more beneficial for growth,and NO3--N was better for CPT yield.Consequently,leaves of C.acuminata treated with 2.5 g NO3--N could be harvested after 30 days to obtain maximum CPT content.CaTDC1 is more closely linked to CPT synthesis.The results of this study improved the production of CPT in C.acuminata via fertilization.

Microstructure and mechanical properties of railway wheels manufactured with low-medium carbon Si-Mn-Mo-V steel

The suitability of carbide-free bainite steel as railway wheel materials was investigated. The low-medium carbon Si-Mn- Mo-V steel was designed to make railway wheels by forging and rolling. The slack quenching with water was conducted on the tread of rim section by programmed control to simulate isothermal heat treatment after being austenitized. Microstructures and mechanical properties have been studied. The results indicate that the microstructure of the rim is mainly carbide-free bainite, and the mixed microstructure of bainitic ferrite and granular bainite is observed in web and hub. The mechanical properties are superior to both the standard requirements and the commercial production, such as CL60 plain carbon. The Charpy impact energy is relatively high at room and/or subzero temperatures. The force-displacement curves and fractographies reveal the excellent ability of resistance to crack initiation and propagation.

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication.Meplazumab is a humanized anti-CD147 IgG_(2) monoclonal antibody,which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019(COVID-19)patients.Here,we conducted a randomized,double-blinded,placebo-controlled phase 1 trial to evaluate the safety,tolerability,and pharmacokinetics of meplazumab in healthy subjects,and an open-labeled,concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients.In phase 1 study,59 subjects were enrolled and assigned to eight cohorts,and no serious treatment-emergent adverse event(TEAE)or TEAE grade≥3 was observed.The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics.No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort.The biodistribution study indicated that meplazumab reached lung tissue and maintained>14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32.In the exploratory phase 2 study,17 COVID-19 patients were enrolled,and 11 hospitalized patients were involved as concurrent control.The meplazumab treatment significantly improved the discharged(P=0.005)and case severity(P=0.021),and reduced the time to virus negative(P=0.045)in comparison to the control group.These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Effects of Polygonum hydropiper on the expressions of inflammatory cytokines and cytochrome P450 enzymes in mice with E.coli-induced diarrhea

In the present study,we aimed to investigate the effects of Polygonum hydropiper aqueous extract(PHE)on the expression levels of inflammatory cytokines and cytochrome P450(CYPs)in mice with E.coli-induced diarrhea.BALB/c mice were randomly divided into the control group,model group,enrofloxacin-treated group,and two PHE-treated groups with different doses.The diarrhea model was established by intraperitoneal injection of enteropathogenic E.coli(EPEC)in mice.The enrofloxacin-treated group was given enrofloxacin at 5 mg/kg by intragastric gavage(i.g.)for 11 d.PHE-treated groups were given PHE at 5 g/kg and 10 g/kg by i.g.for 11 d.The histopathological characteristics of the duodenum and liver were observed by HE staining.The levels of inflammatory cytokines and CYPs in the duodenum and liver of mice were determined by ELISA.The m RNA and protein expressions of CYPs were determined by q RT-PCR and Western blotting analysis,respectively.The results showed that PHE could significantly alleviate the injury of the duodenum and liver induced by EPEC infection,reduce the contents and m RNA expressions of inflammatory cytokines,and regulate the m RNA and protein expressions of the major subtypes of CYPs.These findings indicated that PHE had an apparent therapeutic effect on EPEC-induced diarrhea,and its mechanism might be related to inhibition of inflammatory cytokines and regulation of CYPs.