Demographics will reverse three multi-decade global trends

Between the 1980s and the 2000s, the largest ever positive labour supply shock occurred, resulting from demographic trends and from the inclusion of China and eastern Europe into the World Trade Organization. This led to a shift in manufacturing to Asia, especially China; a stagnation in real wages; a collapse in the power of private sector trade unions; increasing inequality within countries, but less inequality between countries; deflationary pressures; and falling interest rates. This shock is now reversing. As the world ages, real interest rates will rise, inflation and wage growth will pick up and inequality will fall. What is the biggest challenge to our thesis? The hardest prior trend to reverse will be that of low interest rates, which have resulted in a huge and persistent debt overhang, apart from some deleveraging in advanced economy banks. Future problems may now intensify as the demographic structure worsens, growth slows, and there is little stomach for major inflation. Are we in a trap where the debt overhang enforces continuing low interest rates, and those low interest rates encourage yet more debt finance? There is no silver bullet, but we recommend policy measures to switch from debt to equity finance

Additional file 8: of A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia

Figure S5. The anti-leukemia effects of miR-375 in vivo. (A) Volumes of all tumors were detected every 3 days after 2 weeks. *P < 0.05 versus MSCV-NC. (B) HE staining was taken to indicate the infiltration of THP1 leukemic cells in murine spleens. (TIFF 367 kb

Additional file 4: of A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia

Table S3. Multivariate analyses of overall survival (OS) and disease-free survival (DFS) of AML. (DOCX 19 kb

Additional file 1: of A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia

Table S1. AML patients’ characteristics. (DOCX 20 kb

Additional file 7: of A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia

Figure S4. HOXB3 enhances the expression of DNMT3B to bind in pre-miR-375 promoter. (A) A schematic representation of the promoter regions amplified by ChIP-PCR assay. (B) HL-60 and THP1 cells were transduced with sh-NC or sh-HOXB3. Soluble chromatin from these cells was immunoprecipitated with anti-DNMT3B antibody. Immunoprecipitated DNA was analyzed by qRT-PCR. *P < 0.01 versus sh-NC. (C) The expression of miR-375 was detected in HL-60 and THP1 cells transduced with sh-NC or sh-HOXB3. *P < 0.01 versus sh-NC. (TIFF 310 kb

Additional file 3: of A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia

Figure S1. The expression of miR-126 and miR-375 in normal controls, CpG islands around the region encoding miR-375, and expression of pre-miR-375. (A) The expressions of miR-126 and miR-375 were detected in all CD34+ cells from 20 normal controls (NC). Housekeeping gene U6 is used as a reference. The lowest expression of miR-375 in one NC was set to 1.0 and then the expressions of miR-375 and miR-126 in all other specimens were normalized by this lowest specimen. The fold change of miR-375 and miR-126 were calculated by Student’s t-test. (B) CpG islands around the region encoding pre-miR-375 were analyzed by MethPrimer software. (C) The expression of pre-miR-375 was detected by qRT-PCR in HL-60 and THP1 cells, which were transduced with MSCV-miR-375 or MSCV-NC. *P < 0.01 versus MSCV-NC. (TIFF 221 kb

Additional file 2: of A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia

Table S2. The sequences of primers. (DOCX 25 kb

Additional file 6: of A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia

Figure S3. Knockdown of HOXB3 and DNMT3B by another shRNA. (A) HL-60 and THP1 cells were transduced with another special shRNA for HOXB3 (sh-HOXB3#2) or a control shRNA (sh-NC). HOXB3 and CDCA3 expressions were detected by western blot. (B) Viable cell number by the trypan-blue exclusion assay was counted in HL-60 and THP1 cells, which were transduced with sh-HOXB3#2 or sh-NC for the indicated times. *P < 0.01 versus sh-NC. (C) HL-60 and THP1 cells were transduced with another special shRNA for DNMT3B (sh-DNMT3B#2) or a control shRNA (sh-NC). DNMT3B expression was detected by western blot. (D) MiR-375 expression was measured in HL-60 and THP1 cells transduced with sh-DNMT3B#2 or sh-NC. *P < 0.01 versus sh-NC. (TIFF 345 kb

Additional file 5: of A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia

Figure S2. Cell cycle in HL-60 and THP1 cells transduced with MSCV-NC or MSCV-miR-375. (A and B) Distribution of cells were recorded in different stage of cell cycle analyzed using flow cytometry in HL-60 and THP1 cells, which were transduced with MSCV-NC or MSCV-miR-375. Shown is a representative cell cycle (A) and summary of G0/G1, S, and G2/M phases (B). *P < 0.05 verse MSCV-NC. (TIFF 304 kb

Additional file 9: of A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia

Figure S6. An illustration of miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry. (A) In normal hematological cells or leukemic cells treated with AZA, miR-375 expression is increased because of DNA hypomethylation. Upregulation of miR-375 inhibits HOXB3 expression, resulting in the arrest of proliferation and reduction of colony formation via decreasing the expression of CDCA3. Moreover, the decreased expression of HOXB3 can not increase and recruit DNMT3B to bind in the pre-miR-375 promoter and maintains the hypomethylation of pre-miR-375, which finally leads to the upregulated expression of miR-375, in turn. (TIFF 592 kb