Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species

The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.

Pharmacokinetic Study of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Objective To study the pharmacokinetics of a novel recombinant human granulocyte colonystimulating factor (rhG-CSFa) in rats and to determine the proteolytic rates of rhG-CSFa in the whole blood and serum of rats in vitro. Methods The pharmacokinetics of rhG-CSFa and conventional (wild type,WT) granulocyte colonystimulating factor (G-CSF) were investigated in Sprague-Dawley rats which received either intravenous or subcutaneous injection of rhG-CSFa or WT G-CSF at three different doses (20,50,or 100 μg/kg). The blood samples of rats were collected at multiple time points (from 0.08 to 12 h) and the concentrations of rhG-CSFa and WT G-CSF in serum were determined with a sandwich enzyme-linked immunosorbent assay (ELISA). For the study of proteolytic rates in vitro,the concentrations of rhG-CSFa or WT G-CSF were determined at 3-minute intervals after addition of the respective drug to rat’s whole blood or serum. Results Pharmacokinetic analysis of serum rhG-CSFa or WT G-CSF levels indicated that,at each dose tested,for either route of drug administration,the area under concentration-time curve values and the maximum serum concentration of rhG-CSFa were higher than those of WT G-CSF,and the serum half life of rhG-CSFa was longer than that of WT G-CSF. Subsequent in vitro whole blood and serum stability study showed that the rates of drug degradation in WT G-CSF were 1.8 folds and 1.5 folds higher than those in rhG-CSFa,respectively. Conclusion rhG-CSFa has better serum and whole blood stability in vitro and higher bioavailability in vivo as compared to WT G-CSF.

Cyclic Pulsating Pressure Enhanced Segregating Structuration of Ultra-High Molecular Weight Polyethylene/Graphene Composites as High-performance Light-Weight EMI Shields

Currently,the enhancement in electromagnetic interference(EMI)performance of polymeric composite generally relies on either improving electrical conductivity(σ)for stronger electromagnetic(EM)reflections or tailoring structure for higher EM resonances.Herein,we proposed a novel technique called cyclic pulsating pressure enhanced segregating structuration(CPP-SS),which can reinforce these two factors simultaneously.The structural information was supplied by optical microscopy(OM)and scanning electron microscopy(SEM),both of which confirmed the formation and evolution of segregate structured ultra-high molecular weight polyethylene(UHMWPE)/graphene composites.Then,the result showed that CPP-SS can significantly improve theσof samples.Ultimately,advanced specific EMI shielding efficiency of 31.1 d B/mm was achieved for UHMWPE/graphene composite at 1-mm thickness and a low graphene loading of 5 wt%.Meanwhile,it also confirmed that the intrinsic disadvantage of poor mechanical properties of conventional segregated structure composites can be surpassed.This work is believed to provide a fundamental understanding of the structural and performance evolutions of segregated structured composites prepared under CPPSS,and to bring us a simple and efficient approach for fabricating high-performance,strong and light-weight polymeric EMI shields.

A Transformer-Assisted Cascade Learning Network for Choroidal Vessel Segmentation

As a highly vascular eye part,the choroid is crucial in various eye disease diagnoses.However,limited research has focused on the inner structure of the choroid due to the challenges in obtaining sufficient accurate label data,particularly for the choroidal vessels.Meanwhile,the existing direct choroidal vessel segmentation methods for the intelligent diagnosis of vascular assisted ophthalmic diseases are still unsatisfactory due to noise data,while the synergistic segmentation methods compromise vessel segmentation performance for the choroid layer segmentation tasks.Common cascaded structures grapple with error propagation during training.To address these challenges,we propose a cascade learning segmentation method for the inner vessel structures of the choroid in this paper.Specifically,we propose TransformerAssisted Cascade Learning Network(TACLNet)for choroidal vessel segmentation,which comprises a two-stage training strategy:pre-training for choroid layer segmentation and joint training for choroid layer and choroidal vessel segmentation.We also enhance the skip connection structures by introducing a multi-scale subtraction connection module designated as MSC,capturing differential and detailed information simultaneously.Additionally,we implement an auxiliary Transformer branch named ATB to integrate global features into the segmentation process.Experimental results exhibit that our method achieves the state-of-the-art performance for choroidal vessel segmentation.Besides,we further validate the significant superiority of the proposed method for retinal fluid segmentation in optical coherence tomography(OCT)scans on a publicly available dataset.All these fully prove that our TACLNet contributes to the advancement of choroidal vessel segmentation and is of great significance for ophthalmic research and clinical application.

Enhanced strength and toughness in 40CrNiMo steels by austempering below martensite start temperature

The austempering above and below martensite transition temperature(M_(s))was employed in a medium-carbon low-alloy 40CrNiMo steel,and the bainite and martensite multiphase microstructures with different volume fractions were obtained.Here,the effect of pre-existing martensite on subsequent transformation of bainite microstructure and mechanical properties is focused and researched.The microstructure with a volume fraction of pre-existing martensite(V_(PM)),bainite(V_(B)),and martensite/austenite(V_(M/A))constituents of approximately 28%,46%,and 26%,respectively could be obtained by austenitizing below M_(s)(280℃)for 1 h,and an optimum combination of strength,ductility,and impact toughness(yield strength of 1420 MPa,ultimate tensile strength of 1795 MPa,total elongation of 7.9%,and V-notch impact value of 37 J)was achieved.The considerable enhancement of mechanical properties in the sample austenitized below M_(s)is mainly ascribed to the formation of the pre-existing martensite,resulting in an effective reduction in the size of the bainite plates and martensite/austenite constituents.

Embedment of red phosphorus in anthracite matrix for stable battery anode

Red phosphorus(red P)is a promising anode material for lithium-ion batteries(LIBs)due to its high theoretical capacity of 2596 mAh·g^(-1),abundant resource and low cost.However,the application of P-based anode suffers from several crucial issues,including limited electronic conductivity and drastic volume variation during its electrochemical lithiation/delithiation processes.Here,we reported a red P/anthracite composite featuring red P embedded into micrometer-sc ale porous anthracite framework fabricated through a one-pot ball milling synthesis process.

Heterometallic zinc uranium oxyfluorides incorporating imidazole ligands

Two heterometallic uranium oxyfluorides with hybrid networks were hydrothermally synthesized by incorporating two imidazoles, 1-（biphenyl-4-yl）-lH-imidazole （bpi） and 1,4-di（1H-imidazol-l-yl）ben- zene （dib）, formulated as Zn（bpi）2（UO2）2（H2O）F6 （1） and Zn（dib）（UO2）F4-0.5H20 （2）. Compound 1 consists of chains of edge-sharing UO2F5 and UO2F4（H20） pentagonal bipyramids, which are linked by Zn（bpi）2 moieties to form the sheet structure with decorated bpi. While in compound 2, sheets of edge- sharing dimers of UO2F5 pentagonal bipyramids and ZnF3N2 polyhedra are linked by dib, creating a pillared three-dimensional framework. The two compounds represent the few examples of heterometallic uranium oxyfluorides incorporating organic ligands. The syntheses, structure as well as the IR spectra, UV-vis spectra and luminescent properties of the bimetallic uranium oxyfluorides are studied.