Comparative efficacy and safety of sodium–glucose cotransporter 2 inhibitors for renal outcomes in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis

In this study, the summarized WMDs and RRs were calculated using a pairwise analysis and a network meta-analysis with a random effects model, to compare and rank the efficacy and safety of SGLT-2i for renal outcomes in patients with T2DM. Among 1894 identified articles, 30 trials including 50,244 patients with T2DM were evaluated. Network analysis revealed that the administration of canagliflozin was associated with a reduced risk of renal impairment (surface under the cumulative ranking: 90.8%). Further, although the administration of SGLT-2i was not associated with the risk of renal impairment (RR = 0.88, 95%CI = 0.68–1.15, p = 0.354), the administration of empagliflozin was associated with a reduced risk of renal impairment compared to that with the administration of placebo (RR = 0.74, 95%CI = 0.62–0.90, p = 0.002). Moreover, compared with the administration of a placebo, the administration of 50, 100, and 200 mg of canagliflozin was associated with lower serum creatinine levels. Furthermore, compared with the administration of a placebo, the administration of 100 mg canagliflozin, 2.5 mg dapagliflozin, and 25 mg empagliflozin was associated with a lower reduction in the estimated glomerular filtration rate. Except for 300 mg canagliflozin, all SGLT-2i were associated with greater increases in blood urea nitrogen levels (WMD = 1.39, 95%CI = 1.20–1.59, p p < 0.001). Briefly, canagliflozin exerts the greatest therapeutic effect in terms of reducing the risk of renal impairment. Empagliflozin and canagliflozin may be more effective than other SGLT-2i in preventing renal impairment.</p

Additional file 3: of Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets

Table S3. The list of antibodies used in western blotting. (DOCX 26 kb

Additional file 8: of Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets

Figure S5. FAK inhibitor inhibited IPEC-J2 cells migration and FAK phosphorylation. A. The IPEC-J2 cells were seeded in 6 well plates, and pretreated for 48 h with or without 200 μmol/L putrescine, followed by the addition of 2 μg/mL Mitomycin C for 24 h. The cells were then treated with or without 100 μg/mL defactinib for 4 h before scratching. Images were taken immediately after scratching (0 h) and at 8 h post scratching to calculate the area covered by cell migration, the scratched borders were enhanced with black lines. B. Western blotting of phospho-FAK. C. Western blotting of total-FAK. Values are means ± SE, n = 4. Means with different letters are different (P < 0.05). Ctrl, control; Def, defactinib; IPEC-J2, porcine intestinal epithelial cells; P-FAK, phospho-FAK; Put, putrescine. (PDF 93 kb

Additional file 4: of Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets

Figure S1. Effects of putrescine supplementation on tight junction gene expression in the jejunal mucosa of piglets. A. The mRNA level of ZO-1. B. The mRNA level of claudin-1. C. The mRNA level of occludin. Values are means ± SE, n = 6. Means with different letters are different (P < 0.05). Ctrl, control; Put, putrescine dihydrochloride; ZO-1: zona occludens 1. (PDF 26 kb

Additional file 5: of Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets

Figure S2. Effect of adding different level putrescine in the medium on the growth of IPEC-J2. The IPEC-J2 cells were seeded in 2% FBS containing DMEM/F12 supplemented with 0, 12.5, 25, 50, 100, or 200 μmol/L putrescine, cell numbers were determined at 0 h, 24 h, 48 h, 72 h, 96 h and 120 h with the CCK-8 kit. Cell growth was presented with plotting diagram (A), and was presented with histogram (B) to show the detail of difference among groups. Growth differences were presented with bar chart. Values are means ± SE, n = 4. Means with different letters are different (P < 0.05) in the histogram. IPEC-J2, porcine intestinal epithelial cells. (PDF 175 kb

Additional file 7 of Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets

Figure S4. ERK inhibitor inhibited IPEC-J2 cells growth and ERK1/2 phosphorylation. A. The IPEC-J2 cells were seeded in 2% FBS containing DMEM/F12 supplemented with or without 200 μmol/L putrescine in the presence or absence of ulixertinib, a specific inhibitor for ERK. Cell numbers were determined at 0 h, 24 h, 48 h, 72 h, 96 h and 120 h with the CCK-8 kit. Ulixertinib inhibited the growth of IPEC-J2 cells from 48 h to 120 h with or without putrescine. B. Western blotting of Phospho-ERK1/2 for different treatment. C. Western blotting of total-ERK1/2. Values are means ± SE, n = 4. Means with different letters are different (P < 0.05). CCK-8, cell counting kit-8; Ctrl, control; IPEC-J2, porcine intestinal epithelial cells; P-ERK1/2, phospho-ERK1/2; Put, putrescine; Uli, ulixertinib. (PDF 143 kb

Additional file 1: of Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets

Table S1. The body weight of slaughtered piglets on day 14 of the trial. (DOCX 25 kb

Additional file 2: of Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets

Table S2. The list of primers used for qPCR. (DOCX 30 kb

Application of Biuret, Dicyandiamide, or Urea as a Cathode Buffer Layer toward the Efficiency Enhancement of Polymer Solar Cells

Three amino-containing small-molecule organic materialsbiuret, dicyandiamide (DCDA), and ureawere successfully applied as novel cathode buffer layers (CBLs) in P3HT:PCBM bulk heterojunction polymer solar cells (BHJ-PSCs) for the first time, resulting in obvious efficiency enhancement. Under the optimized condition, the power conversion efficiencies (PCEs) of the CBL-incorporated BHJ-PSC devices are 3.84%, 4.25%, and 4.39% for biuret, DCDA, and urea, which are enhanced by ∼15%, ∼27%, and ∼31%, respectively, compared to the reference poly­(3-hexylthiophene-2,5-diyl) : [6,6]-phenyl-C₆₁-butyric acid methyl ester (P3HT:PCBM) BHJ-PSC device without any CBL. The efficiency enhancement is primarily attributed to the increases of both short-circuit current density (<i>J</i>_sc) and fill factor (FF), for which the enhancement ratio is found to be sensitively dependent on the molecular structure of small-molecule organic materials. The surface morphologies and surface potential changes of the CBL-incorporated P3HT:PCBM photoactive layers were studied by atomic force microscopy and scanning Kelvin probe microscopy, respectively, suggesting the formation of an interfacial dipole layer between the photoactive layer and Al cathode, which may decrease the energy level offset between the work function of Al and the lowest unoccipoed molecular orbital level (LUMO) of the PCBM acceptor and consequently facilitate electron extraction by the Al cathode. The difference in the enhancement effect of biuret, DCDA, and urea is due to their difference on the work function matching with P3HT:PCBM. Besides, the coordination interaction between the lone-pair electrons on the N atoms of the amino (−NH₂) group and the Al atoms may prohibit interaction between Al and the thiophene rings of P3HT, contributing to the efficiency enhancement of the CBL-incorporated devices as well. In this sense, the different CBL performance of biuret, DCDA, and urea is also proposed to partially originate from the differences on their chemical structure, specifically the number of amino groups

Additional file 6: of Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets

Figure S3. Mitomycin C suppressed completely cell growth at 24 h of treatment. 0.25 × 105 cell/mL IPEC-J2 cells were seeded in 24-well plates and treated with or without 2 μg/mL mitomycin C for 24 h. Cell number was measured with the CCK-8 kit. Values are means ± SE; n = 4. Means with different letters are different (P < 0.05). Ctrl, control; IPEC-J2, porcine intestinal epithelial cells. (PDF 93 kb