FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19.In the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.Using hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβcells.This upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 infection.Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the islets.Furthermore,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms.Finally,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in situ.Taken together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Spatially resolved expression landscape and generegulatory network of human gastric corpus epithelium

Molecular knowledge of human gastric corpus epithelium remains incomplete.Here,by integrated analyses using single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and single-cell assay for transposase accessible chromatin sequencing(scATAC-seq)techniques,we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.Specifically,we identified a stem/progenitor cell population in the isthmus of human gastric corpus,where EGF and WNT signaling pathways were activated.Meanwhile,LGR4,but not LGR5,was responsible for the activation of WNT signaling pathway.Importantly,FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells.Finally,we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level,and identified several important cell-type-specific transcription factors.In summary,our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.

Microstructures and high-temperature self-lubricating wearresistance mechanisms of graphene-modified WC–12Co coatings

To reduce the friction coefficient of cobalt-cemented tungsten carbide(WC–12Co)wear-resistant coatings,graphene was compounded into WC–12Co powder via wet ball milling and spray granulation.Selflubricating and wear-resistant graphene coatings were prepared via detonation gun spraying.The presence,morphologies,and phase compositions of graphene in the powders and coatings that are obtained through different powder preparation processes were analyzed.The analysis was performed using the following technologies:energy-dispersive X-ray-spectroscopy(EDXS),scanning electron microscopy(SEM),transmission electron microscopy(TEM),and Raman spectroscopy.The mechanical properties of the coatings were studied using a microhardness tester and a universal drawing machine.The friction and wear properties of the coatings were studied using an SRV-4 friction and wear tester.The results showed that the graphene content in the WC–12Co coating modified with graphene was higher than that without modification;graphene was embedded in the structure in a transparent and thin-layer state.The adhesive strength of this coating at approximately 25°C was approximately 60.33 MPa,and the hardness was approximately 984 HV0.3.After high-temperature treatment,the adhesive strength and hardness of the graphene oxide(GO)/WC–12Co coating decreased slightly(the lowest adhesive strength of 53.16 MPa was observed after treatment at 400°C,and the lowest hardness of approximately 837 HV0.3 was observed after treatment at 300°C).Compared to the friction coefficient(0.6)of the WC–12Co coating obtained at room temperature,the friction coefficient of the GO/WC–12Co coating was decreased by approximately 50%of that value.The graphene-modified coating was continuously exposed to the wear tracks on the surface of the contacting materials during friction,and a lubricating film was formed in the microareas in which the wear tracks were present.The coating exhibited improved self-lubricating and wear-resistant effects compared to the unmodified WC–12Co coating.The results of this study demonstrated that graphene could be effective in self-lubrication and wear-reduction in a temperature range of 100–200°C,as a friction coefficient of 0.3 was maintained.