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As the current calculation methods for wellbore separation factor have some deficiencies, we propose and analyze a new calculation approach for wellbore separation factor based on the relative position of adjacent wellbores, named as relative position method for short. Based on the trajectory error ellipsoid model of single wellbore, the error ellipsoids model of adjacent wellbore was derived considering the correlation of trajectory errors between adjacent wells. Furthermore, the calculation formula of the separation factor based on relative position of adjacent wellbore was derived and solved with the conjugate gradient algorithm. Case study shows that the new approach is more precise and higher in applicability than the ellipsoid scaling method and the minimum distance method, it can evaluate the state of well collision more reasonably. By doing batch calculation with the new method and following the criterion of well collision avoidance, the permissible ranges of key parameters in the well design can be worked out quickly. This method has good application in the design of cluster wells and directional wells. Key words: wellhole separation factor, wellhole collision avoidance, relative wellbores error, conjugate gradient algorithm, cluster wells

Additional file 1: Figure S1. Effect of PA on macrophage repolarization and synergistic effect with SV. (A–C) The mRNA levels of M1-associated pro-inflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) in PA-treated RAW264.7 macrophages, as measured by qPCR. (D, E) Western blot analysis of Akt/MAPK/NF-κB pathway-related biomarkers and M2-related MR expression after PA treatment. (F) The mRNA levels of the M1-related pro-inflammatory molecules (e.g., TNF-α, iNOS, and COX-2) and M2-related Arg1 in SV-treated RAW264.7 macrophages, as measured by qPCR. (G) IL-6 mRNA levels in LPS-induced peritoneal macrophages treated with PA (10 μM) and SV (0, 1, and 2 μM). Figure S2. Cytotoxicity study of PA and SV on (A) Caco-2 cells, (B) RAW264.7 cells, and (C) L929 cells. Cytotoxicity of the NPs in (D) L929 cells and (E) M2Φ. Figure S3. Anti-colitis treatment of synergistic drugs. (A) Schematic diagram of DSS-induced colitis and treatment. (B) Changes in daily bodyweight of each group during the trial period. (C) Statistical analysis and (D) images of colon lengths in each group (n = 4). Figure S4. Preliminary biosafety assessment of PA and SV. (A) Organ coefficients. (B) H&E staining of the major organs (Scale bar: 100 μm). Figure S5. Fluorescence images of (A) M1Φ and (B) L929 after incubation with the coumarin 6-labeled NPs (scale bar: 50 µm). (C, E) Histogram and (D, F) mean fluorescence intensity of the NPs-internalized M1Φ (LPS-induced RAW264.7 cells) and L929 cells were analyzed by flow cytometry (n = 3). Figure S6. Specific accumulation of CS-PLGA NPs in inflamed colons. Ex vivo imaging and radiant efficiency of (A, B) organs and (C) colons at 3 h. Ex vivo imaging and radiant efficiency of (D, E) organs and (F) colons at 5 h (n = 3). Figure S7. (A–E) Individual bodyweight curves and (F–J) DAI curves in CMC-Na, DSS, PA/SV, PLGA NPs, or CS-PLGA NPs groups (n = 6). Figure S8. Preliminary biosafety assessment. (A) Organ coefficients. (B) H&E staining of the major organs (Scale bar: 100 μm). Figure S9. The dot plots of M2Φ and DCs in the colon tissue. Figure S10. The dot plots of neutrophils, inflammatory monocytes, and G-MDSCs in the colon tissue. Figure S11. The dot plots of Tregs in the colon tissue. Table S1. The primer sequence used in qPCR. Table S2. Disease activity index (DAI) scoring. Table S3. Characterization of the NPs. Table S4. Drug encapsulation efficiency and drug loading efficacy.

Facile synthesis of zero-valent iron nanoparticles has been developed using Tie Guanyin tea extract as reducing and stabilizing agent. The characterization carried out by UV-Vis, SEM, TEM, XRD, and FTIR techniques has identified the successful synthesis of the zero-valent iron nanoparticles. It is evident from the TEM result that spherical zero-valent iron nanoparticles with average size of 6.58±0.76 nm have been obtained through biological method in this study. FTIR spectrum demonstrates that the polyphenols play an important role in the synthetic process. Diffraction peak at 2θ of 44.9° and 49.1° in XRD spectrum explains the existence of the iron nanoparticles. Additionally, effect of concentration of iron nanoparticles and concentration of bromothymol blue on the kinetic rate constants during the degradation process was studied.