[Bioinformatics analysis of primary biliary cholangitis key genes and molecular mechanisms].

Objective: To extract the differentially expressed key genes of primary biliary cholangitis (PBC) using bioinformatics methods, so as to provide information for further study into the mechanism. Methods: The GSE119600 dataset was downloaded from the GEO database to obtain differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Protein-protein interaction (PPI) network reconstruction, Cytoscape software visualization, and core gene screening were performed. The area under the receiver operating characteristic curve (ROC AUC) was used to assess the diagnostic effectiveness of genes and plot the pROC software package. The x-Cell software was used to calculate the enrichment score of 34 immune cells in each sample. Finally, four key genes (PSMA4, PSMA1, PSMB1, and PSMA3) were selected. Blood samples were analyzed using the qPCR method. Results:: A total of 373 immune-related differentially expressed genes were identified. Eight genes (PSMC6, PSMB2, PSMB1, PSMA3, PSMA4, PSMA1, PSMD7, and PSMB5) were screened from the 178 nodes and 596 edges as hub genes of the PPI network, which were significantly related to amino acid metabolism, hematopoietic stem cell differentiation, cell cycle, and immune processes. PSMA4, PSMA1, PSMB1, and PSMA3 were defined as immunological biomarkers for PBC with an AUC value of the ROC curve > 0.7. Immunoinfiltrating cell analysis showed that the proportion of eosinophils was significantly higher in PBC patients compared to the control group, whereas the proportion of CD4+ memory T cells, plasma cells, Th2 cells, and cDC cells was significantly lower in PBC patients than the control group. Plasma cells were associated with all four immunological biomarkers. Seven PBC patients and seven healthy subjects were selected for peripheral blood qPCR validation, which demonstrates that PSMB1, PSMA3, PSMA1, and PSMA4 levels were significantly lower in PBC patients than healthy subjects, with a statistically significant difference. Conclusion:: Bioinformatics screened eight key genes, of which four were key immunological markers and may serve as a basis for clinical diagnosis and mechanism exploration.

Controllable valley filter in graphene topological line defect with magnetic field.

The extended line defect of graphene is an extraordinary candidate in valleytronics while the high valley polarization can only occur for electrons with high incidence angles which brings about tremendous challenges to experimental realization. In this paper, we propose a novel quantum mechanism to filter one conical valley state in the line defect of graphene by applying a local magnetic field. It is found that due to the movement of the Dirac points, the transmission profiles of the two valleys are shifted along the injection-angle axis at the same pace, resulting in the peak transmission of one valley state being reduced drastically while remaining unaffected for the other valley state, which induces nearly perfect valley polarization. The valley polarization effect can occur for all the incident angle and plays a key role in graphene valleytronics.

Assessing adaptation measures on agricultural water productivity under climate change: A case study of Huai River Basin, China.

This study explored an integrated framework to assess the effectiveness of adaptation measures on the water productivity (WP) of the agricultural water management (AWM) system in the Huai river basin of China considering climate change impact. The adaptation measures include optimization of cropping pattern (OCP) and upgradation of irrigation techniques (UIT). The delta change method was used to downscale the climate variables from RCP4.5 and RCP8.5 of general circulation models (GCMs) during 2021-2050, the water footprint theory was used to estimate the spatial distribution of blue water to calculate the WP, and the nonlinear optimization model was used to seek optimal cropping pattern aiming at maximizing the system's WP. The changes in WP due to climate change and adaptation measures (e.g. combinations of OCP and UIT) were compared. Results indicated that WP under RCP4.5 and RCP8.5 would be 4.56% and 6.51% lower than those under the benchmark scenario, respectively. The mitigation rates to the negative impact of climate change on WP under RCP4.5 and RCP8.5 would be (1) 3.05% and 3.37% for the combination of spay irrigation technique and OCP, and (2) 4.34% and 4.59% for the combination of drip irrigation technique and OCP, respectively. It was revealed that the combination of drip irrigation and cropping pattern optimization could largely offset the adverse effect from climate change on WP under RCP4.5. Under such a scenario, the total plant areas of wheat and maize would reduce over the basin and so would the net export of crops in the basin; this would lead to a decrease in the crop trade benefit of 7.07 × 109 $ and a relief of 7.50 × 109 m3 of blue water loss. This study results could offer strategic decision support for long-term sustainable AWM of Huai river basin in a changing environment.

The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration.

The integrity of the genome is maintained by a host of surveillance and repair mechanisms that are pivotal for cellular function. The tumour suppressor protein p53 is a major component of the DNA damage response pathway and plays a vital role in the maintenance of cell-cycle checkpoints. Here we show that a microRNA, miR-486, and its host gene ankyrin-1 (ANK1) are induced by p53 following DNA damage. Strikingly, the cytoskeleton adaptor protein ankyrin-1 was induced over 80-fold following DNA damage. ANK1 is upregulated in response to a variety of DNA damage agents in a range of cell types. We demonstrate that miR-486-5p is involved in controlling G1/S transition following DNA damage, whereas the induction of the ankyrin-1 protein alters the structure of the actin cytoskeleton and sustains limited cell migration during DNA damage. Importantly, we found that higher ANK1 expression correlates with decreased survival in cancer patients. Thus, these observations highlight ANK1 as an important effector downstream of the p53 pathway.

Translational repression and eIF4A2 activity are critical for microRNA-mediated gene regulation.

MicroRNAs (miRNAs) control gene expression through both translational repression and degradation of target messenger RNAs (mRNAs). However, the interplay between these processes and the precise molecular mechanisms involved remain unclear. Here, we show that translational inhibition is the primary event required for mRNA degradation. Translational inhibition depends on miRNAs impairing the function of the eIF4F initiation complex. We define the RNA helicase eIF4A2 as the key factor of eIF4F through which miRNAs function. We uncover a correlation between the presence of miRNA target sites in the 3' untranslated region (3'UTR) of mRNAs and secondary structure in the 5'UTR and show that mRNAs with unstructured 5'UTRs are refractory to miRNA repression. These data support a linear model for miRNA-mediated gene regulation in which translational repression via eIF4A2 is required first, followed by mRNA destabilization.

Imaging with subwavelength resolution by a generalized superlens at infrared wavelengths.

We demonstrate experimentally negative refraction by a photonic crystal prism and imaging of a point source by a photonic crystal slab at 1.5 microm wavelength. The photonic crystal structures were nanofabricated in a InGaAsP/InP heterostructure platform, and optical characterization was performed using a near-field scanning optical microscope. By designing a suitable lens surface termination, an image spot size of 0.12lambda2 was achieved, demonstrating superlens imaging with subwavelength resolution well below Abbe's diffraction limit (0.5lambda2).

A new mechanism for negative refraction and focusing using selective diffraction from surface corrugation.

Refraction at a smooth interface is accompanied by momentum transfer normal to the interface. We show that corrugating an initially smooth, totally reflecting, non-metallic interface provides a momentum kick parallel to the surface, which can be used to refract light negatively or positively. This new mechanism of negative refraction is demonstrated by visible light and microwave experiments on grisms (grating-prisms). Single-beam all-angle-negative-refraction is achieved by incorporating a surface grating on a flat multilayered material. This negative refraction mechanism is used to create a new optical device, a grating lens. A planoconcave grating lens is demonstrated to focus plane microwaves to a point image. These results show that customized surface engineering can be used to achieve negative refraction even though the bulk material has positive refractive index. The surface periodicity provides a tunable parameter to control beam propagation leading to novel optical and microwave devices.

Duality between quantum and classical dynamics for integrable billiards.

We establish a duality between the quantum wave vector spectrum and the eigenmodes of the classical Liouvillian dynamics for integrable billiards. Signatures of the classical eigenmodes appear as peaks in the correlation function of the quantum wave vector spectrum. A semiclassical derivation and numerical calculations are presented in support of the results. These classical eigenmodes can be observed in physical experiments through the autocorrelation of the transmission coefficient of waves in quantum billiards. Exact classical trace formulas of the resolvent are derived for the rectangle, equilateral triangle, and circle billiards. We also establish a correspondence between the classical periodic orbit length spectrum and the quantum spectrum for integrable polygonal billiards.

Effects of intrahepatic canine islet autotransplantation on the portal vein pressure and liver function.

Currently, the most common method used for human islet transplantation is intrahepatic implantation via the portal vein, which may affect portal vein pressure and liver function. The aim of this study was to investigate the effects of intrahepatic canine islet autotransplantation on portal vein pressure and liver function. After total pancreatectomy was performed in 30 mongrel dogs, islets were isolated and transplanted back into the portal vein of the same dog. In our series, 12 dogs achieved normoglycemia (fasting glucose <200 mg/dL) without exogenous insulin after transplantation. The portal vein pressure increased from 4.6 +/- 1.5 to 7.7 +/- 2.9 cm H(2)O after islet infusion (P < .05). Alanine transferase amino transferase (ALT) levels gradually increased after pancreatectomy with the peak at 4 weeks after islet infusion. But the changes of portal vein pressure and ALT were not significantly different between successful and failed islet transplantation. In summary, elevation of portal vein pressure and liver enzymes were noted after intrahepatic canine islet autotransplantation. However, they did not influence the transplant outcome.

Soluble kagome Ising model in a magnetic field.

An Ising model on the kagome lattice with super-exchange interactions is solved exactly under the presence of a nonzero external magnetic field. The model generalizes the super-exchange model introduced by Fisher in 1960 and is analyzed in light of a free-fermion model. We deduce the critical condition and present detailed analyses of its thermodynamic and magnetic properties. The system is found to exhibit a second-order transition with logarithmic singularities at criticality.

Negative refraction and left-handed electromagnetism in microwave photonic crystals.

We demonstrate the negative refraction of microwaves in a metallic photonic crystal prism. The spectral response of the photonic crystal prism, which manifests both positive and negative refraction, is in complete agreement with band-structure calculations and numerical simulations. The validity of Snell's law with a negative refractive index is confirmed experimentally and theoretically. The negative refraction observed corresponds to left-handed electromagnetism that arises due to the dispersion characteristics of waves in a periodic medium. This mechanism for negative refraction is different from that in metamaterials.

Refraction of electromagnetic energy for wave packets incident on a negative-index medium is always negative.

We analyze refraction of electromagnetic wave packets on passing from an isotropic positive to an isotropic negative-refractive-index medium. We definitively show that in all cases the energy is always refracted negatively. For localized wave packets, the group refraction is also always negative.

Fractal Weyl laws for chaotic open systems.

We present a conjecture relating the density of quantum resonances for an open chaotic system to the fractal dimension of the associated classical repeller. Mathematical arguments justifying this conjecture are discussed. Numerical evidence based on computation of resonances of systems of n disks on a plane are presented supporting this conjecture. The result generalizes the Weyl law for the density of states of a closed system to chaotic open systems.

Reduction in primary nonfunction of syngeneic islet transplants with nordihydroguaiaretic acid, a lipoxygenase inhibitor.

To study the effectiveness of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), in the reduction of primary nonfunction, an insufficient number of syngeneic islets were transplanted underneath the renal capsule with NDGA administered daily for 4 weeks. After transplantation of the 150 islets, the decrement of blood glucose levels was significantly faster in the mice that had received NDGA than in the mice that had received no drug at all or dimethyl sulfoxide (DMSO) (p < 0.005, p < 0.05). The mean duration of temporary posttransplant hyperglycemia was 22.3 +/- 3.2 (n = 10), 35.9 +/- 2.3 (n = 14), and 33.7 +/- 4.1 (n = 6) days for the respective groups. The diabetic mice that received 300 islets had their blood glucose levels decrease faster than those that received 150 islets (19.7 +/- 1.6 vs. 35.9 +/- 2.3 days, n = 14. p < 0.0001). There was no significant difference in the blood glucose reducing effect between the mice that received 150 islets with NDGA and the mice that received 300 islets [22.3 +/- 3.2 (n = 10) vs. 19.7 +/- 1.6 (n = 14) days, p > 0.05]. The insulin content of the graft from the mice treated with 150 islets and NDGA (3.02 +/- 0.24 microg, n = 4) was higher than that from the mice that received 150 islets but no treatment (1.10 +/- 0.26 microg, n = 15, p < 0.005) or that had been treated with DMSO (1.21 +/- 0.30 microg, n = 4, p <0.05). The insulin content of the pancreas remnant had no significant differences among the three groups. The net glucose-stimulated insulin secretion was 0.82 +/- 0.14 vs. 0.20 +/- 0.10 microIU/islet x 60 min (n = 8, p < 0.005) and 0.59 +/- 0.08 vs. 0.04 +/- 0.02 microIU/islet x 60 min (n = 8, p < 0.0001) for islets cultured without NDGA vs. with NDGA at 1 and 2 weeks, respectively. However, the insulin content of the cultured islets was similar between the two groups for up to 2 weeks of incubation (at 1 week: 0.71 +/- 0.01 vs. 0.67 +/- 0.04 ng/islet, n = 8, p > 0.05; at 2 weeks: 0.71 +/- 0.02 vs. 0.80 +/- 0.07 ng/islet, n = 8, p > 0.05). Serum leukotriene B4 (LTB4) concentrations before and between the fifth and seventh days after transplantation were determined. For diabetic mice that received 150 islets, serum LTB4 levels were 25,835 +/- 3,335 and 27,631 +/- 3,136 pg/ml (n = 4, p > 0.05). For diabetic mice that received 150 islets and NDGA, the corresponding figures were 22,401 +/- 2,706 pg/ml and 27,530 +/- 2,190 pg/ml (n = 8, p > 0.05). The graft histology revealed viable islet cells and networks of close vascular structures around the islets and did not reveal microscopic differences among the samples of all four groups. In conclusion, our data revealed that daily administration of NDGA for 4 weeks enhanced isoislet engraftment and preserved three times more mass of the islet beta cells in the isografts. This result indicates that NDGA reduces primary nonfunction of islet syngeneic grafts in diabetic mice.