Dapeng Yin

Clinical pathogen diagnostics detect targets by qPCR (but with low sensitivity) or blood culturing (but time-consuming). Here we leverage a dual-stem-loop DNA amplifier to enhance non-specific collateral enzymatic cleavage of an oligonucleotide linker between a fluophore and its quencher by CRISPR-CasΦ, achieving ultrasensitive target detection. Specifically, the target pathogens are lysed to release DNA, which binds its complementary gRNA in CRISPR-CasΦ to activate the collateral DNA-cleavage capability of CasΦ, enabling CasΦ to cleave the stem-loops in the amplifier. The cleavage product binds its complementary gRNA in another CRISPR-CasΦ to activate more CasΦ. The activated CasΦ collaterally cleaves the linker, releasing the fluophore to recover its fluorescent signal. The cycle of stem-loop-cleavage/CasΦ-activation/fluorescence-recovery amplifies the detection signal. Our target amplification-free collateral-cleavage-enhancing CRISPR-CasΦ method (TCC), with a detection limit of 0.11 copies/μL, demonstrates enhanced sensitivity compared to qPCR. It can detect pathogenic bacteria as low as 1.2 CFU/mL in serum within 40 min.

Background: In China, varicella is the third most frequently reported vaccine-preventable infectious disease after tuberculosis and influenza, and imposes a heavy burden on families and society. To inform future immunization policy, we investigated disease burden of varicella in China and explored cost-effectiveness of different varicella vaccination strategies at national and provincial levels. Methods: A dynamic transmission model was developed to assess disease burden of varicella and the impact of varicella vaccination in China. A cost-effectiveness analysis of three alternative vaccination strategies in China's National Immunization Program (NIP) compared with no vaccination was conducted. Scenario analyses and sensitivity analyses were performed to check the robustness of the results. Findings: It was estimated that 3.35 million new varicella cases occurred in 2019, more than three times of 982 thousand cases officially reported from National Notifiable Infectious Disease Surveillance System (NNIDSS). The under-reported rate was approximately 71%. The economic analysis revealed that from the societal perspective, the incremental cost-effectiveness ratio (ICER) for one dose of varicella vaccination in NIP was US$ 2357 per QALY at the national level and it was cost-effective in 22 of 31 provinces. The ICER for one dose varicella vaccination plus a mass catch-up for unvaccinated children aged 2-11 years old would be US$ -5260 per QALY, cost-saving at the national level. The one dose plus mass catch-up NIP strategy was also cost-saving in 24 of the 31 provinces. Interpretation: Varicella incident cases were substantially under-reported in China. Varicella vaccination in the NIP could significantly contribute to reducing the burden of varicella disease. From the societal perspective, including varicella vaccination into China's NIP was highly cost-effective at the national level and in most provinces. Funding: Bill & Melinda Gates Foundation.

The transition of trapped-particle orbit topologies has been investigated in quasi-axisymmetric (QA) configurations, such as the Chinese First Quasi-axisymmetric Stellarator (CFQS). It is found that the axisymmetry-breaking phenomenon in QA configurations is of great significance at some specific locations, which could easily induce blocked particles to transit into localized particles. A novel aspect is presented to interpret the transition mechanism of trapped-particle orbit topologies in this paper, i.e., as the amplitudes of non-axisymmetric field increase along the radius direction, the region of large toroidal inhomogeneity is gradually generated, which makes the length of the trapped-particle trajectory substantially short, and hence, may restrict particles to a single helical field period. Meanwhile, at such locations the "pseudo-axisymmetric" field results in coupling of the maximum radial drift and the minimum poloidal drift, which enables the transition of trapped-particle orbit topologies considerably and forms specific loss channels, degrading plasma confinement. These results may shed light on the optimization of QA configurations via avoidance of such coupling with respect to energetic particle confinement. Moreover, this work is also relevant to the generation of inhomogeneity of particle flux deposition on the devertor plates.

A central solenoid model coil (CSMC) is to verify the large-scalar superconducting coil manufacture technology for China Fusion Engineering Test Reactor (CFETR) in Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP). The CSMC composed of Nb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> Sn and NbTi hybrid superconducting magnet can reach to 12 T maximum magnetic field. The main manufacturing processes of the coil are developed and verified by R&Ds and mockup coil fabrication. For now, all the five coils winding and 2/3 of terminals fabricating are finished, and the heat treatment for the Nb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> Sn inner coil is completed. The turn releasing and insulation wrapping process and station for the heat treated Nb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> Sn coil has been developed. The major remaining processes for the five coils are ground insulation wrapping and vacuum pressure impregnation (VPI). The mockup coil VPI will be performed firstly to validate the process. This article introduces the main manufacturing progress of the CFETR CSMC.

Objective: To explore biomarkers of diabetic nephropathy (DN) and predict upstream miRNAs. Methods: The data sets GSE142025 and GSE96804 were obtained from Gene Expression Omnibus database. Subsequently, common differentially expressed genes (DEGs) of renal tissue in DN and control group were identified and protein-protein interaction network (PPI) was constructed. Hub genes were screened from in DEGs and made an investigation on functional enrichment and pathway research. Finally, the target gene was selected for further study. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of target gene and predicted its upstream miRNAs. Results: 130 common DEGs were obtained through analysis, and 10 Hub genes were further identified. The function of Hub genes was mainly related to extracellular matrix (ECM), collagen fibrous tissue, transforming growth factor (TGF) -β, advanced glycosylation end product (AGE) -receptor (RAGE) and so on. Research showed that the expression level of Hub genes in DN group was significantly higher than that in control group. (all P<0.05). The target gene matrix metalloproteinase 2 (MMP2) was selected for further study, and it was found to be related to the fibrosis process and the genes regulating fibrosis. Meanwhile, ROC curve analysis showed that MMP2 had a good predictive value for DN. miRNA prediction suggested that miR-106b-5p and miR-93-5p could regulate the expression of MMP2. Conclusion: MMP2 can be used as a biomarker for DN to participate in the pathogenesis of fibrosis, and miR-106b-5p and miR-93-5p may regulate the expression of MMP2 as upstream signals.