Supplementary materials

Table S1 The 168 BBR-related targets obtained from CTD database.

TNF PTEN DDIT3 AKT2 GPX1 H4C8 PRL HGF SIRT1 EDN1 ALB H2AC11 H4C9 PRMT1 PPARG SIRT3 EDNRA APP H2AC12 HAT1 PRMT2 BCL2 SOD2 FASLG AURKB H2AC14 HDAC2 PRMT5 CD36 SPP1 FOXO1 AURKC H2AC15 HDAC5 PRMT6 CYP3A4 TP53 FOXO3 BCHE H2AC17 HDAC8 PRMT7 BAX CYP1A2 GJA1 BCL2L1 H2AC18 HNF4 PRMT8 CASP3 CYP2B10 GSR CASP8 H2AC4 IDH3A PTGS2 MMP2 CYP2B9 HDAC9 CCND1 H2AC6 IFNG RBP4 NFE2L2 CYP4A10 HNF4A CCND2 H2AC8 IL2 RELA CEBPB CYP4A14 HSPA5 CCNE1 H2AW ITGA1 RPS6 CYP1A1 GPT HTR1A CDH2 H2BC11 KDM1A SETD1B IL1B GSK3B IGF1R CDKN1B H2BC12 KDM4A SETD2 IL6 HMOX1 IL23A CDKN1C H2BC13 KDM5B SETD3 LDLR IL10 IL4 CHEK1 H2BC14 KDM6A SETD5 ACHE KCNH2 JUN CHEK2 H2BC15 KDM6B SETD6 CEBPA NAMPT MAPK3 COL10A1 H2BC17 KMT5A SETD7 CTNNB1 PRKCE MMP14 COL1A1 H2BC4 LHB SETDB1 CXCL8 RLN1 MMP9 COL2A1 H2BC5 MAP3K5 SETDB2 CYP2E1 RUNX2 MYC CPT1A H2BC6 MAPK1 SIRT2 CYP3A11 SI NCF1 CREBBP H2BC7 MAPT SLC27A5 FABP4 TGFB1 NGF CYCS H2BC8 MCM2 SLC2A4 NOS2 TLR4 NOS3 CYP17A1 H2BC9 MIR19A SMYD3 SREBF1 ADIPOQ NR1I2 DNMT1 H2BW2 MIR92A1 SOX9 STAR AHR ODC1 DNMT3B H3-3A MMP13 SP7 ABCB1A BBC3 PARP1 DRD1 H3-4 MPO SPARC ABCB1B BCL2L11 PRKCA DRD2 H3C1 MTTP TERT AKT1 BIRC5 SHC1 DZIP3 H3C10 NFKBIA TOP1 BGLAP CCNT1 SLC6A19 EIF4EBP1 H3C12 NR1I3 TRAF1 CASP9 CDK2 SOD1 EP300 H3C2 NSD2 TSTD1 CAT CDK4 TOP2A ESR1 H3C4 OMD UBE2A CCL2 CDK6 TRAF2 ESRRA H3C7 P2RX7 UBE2B DKK1 CDK9 ACADM FN1 H3C8 PPARA UCP2 EIF2AK3 CDKN1A ACAN FOS H4C14 PPARGC1A VEGFC FAS CYBA ACOX1 FSHB H4C2 PRG4 H2AX CYBB ACTA2 GDF5 H4C3 PRKAA1

Table S2 The 207 HUA-related targets obtained from CTD and DiseGeNET databases.

ABCA1 CD36 FASN JUN RELA ADH1B P2RX3 ABCB1 CD68 FBP1 KLF5 RPS6 PNP TCTA ABCB11 CDH1 FGF21 LCAT SCD REN PSPH ABCC1 CDK2 FN1 LDHB SELE CST3 LCN2 ABCC2 CDK4 FOS LDLR SERPINE1 GH1 HNF4G ABCC3 CDKN1A GDF15 LEP SIRT1 HLA-B PRPSAP1 ABCG2 CDKN1B GLUL MAPK1 SLC22A1 APOE DECR1 ACACA CHUK GPAM MAPK3 SLC22A12 APOC3 HFE ACADL COL1A1 GPT MAPK8 SLC22A2 AFP ZPBP2 ACADM CP GPX1 MMP2 SLC22A4 SHBG SLC25A26 ACLY CPT1A GSK3B MMP7 SLC22A5 ALDOB ZNF365 ACTA2 CPT1B GSR MMP9 SLC22A6 ALDH2 SHLD2 ADIPOQ CREB3L3 GSTP1 MPO SLC27A2 SERPINA5 IFNL3 AGER CRP GSTT1 MYC SLC2A9 REG1A SLC22A8 AGT CSF2 HAVCR1 NFATC4 SLCO1A1 THBD TMEM171 AGTR1A CTNNB1 HMGCR NFE2L2 SLCO2B1 CAPN1 OIT3 AHR CTSD HMGCS1 NFKB1 SNAI1 MSMB P2RX5 AKT1 CXCL10 HMGCS2 NFKBIA SOD1 SAA1 BPIFA2 ALB CXCL8 HMOX1 NFKBIB SOD2 CSH1 SLC47A1 ALDH9A1 CYBA HSD17B4 NOS2 SREBF1 CSH2 LRIG1 ALPL CYP1A1 HSP90AA1 NOS3 STAT3 PC NLRP3 APOA1 CYP2B6 HSPA5 NPPA TGFB1 FABP2 P2RX4 ATF3 CYP2C19 HSPE1 NPPB TH ETFA P2RX7 ATF4 CYP2C29 ICAM1 NR0B2 TNF ADRB3 RARRES2 ATP2A2 CYP2C8 ID3 NR1H3 TP53 PHKG2 GORASP1 BAX CYP2C9 IFNG NR1I2 TXNIP MUC1 FUZ BCL2 CYP2E1 IGF1 NR3C1 UCP1 DPEP1 SARS2 BCL2L1 CYP3A23-3A1 IKBKB PCK1 UGT1A1 GNB3 SLC22A11 BGLAP CYP3A4 IL10 PCNA UGT2B7 ACAT1 EIF2AK3 BIRC5 CYP4A14 IL12B PDX1 UMOD PON1 RRBP1 CASP1 DDIT3 IL18 PIK3R1 VASN SLC5A2 P2RX2 CASP3 DDIT4 IL1A PLD1 VCAM1 GJA4 SLC2A6 CASP8 DNMT1 IL1B PLIN4 VEGFA G6PC SLC23A1 CASP9 EDN1 IL4 POR XBP1 HMGCL SLC17A4 CAT EGF IL5 PPARA XDH P2RY2 RIPK3 CBR1 EGFR IL6 PPARD STXBP3 MTHFR CLDN16 CCL2 EIF2S1 INS PPARG ABCC4 COMP TNFRSF11A CCL5 EIF4EBP1 INS1 PPARGC1A P2RX6 KHK CCN2 ERN1 INSR PRKAA1 SLC37A4 P2RX1 CCNA2 ESR1 IRS1 PRKAB1 PRPSAP2 KCNQ1 CCNB1 FABP4 JAK1 PRKCA PSPN RIDA CCND1 FAS JAK2 PTGS2 BCAS1 UCP2 Table S3 The 82 BBR-HUA intersecting through which BBR may exert anti-HUA effect.

TNF LDLR EIF2AK3 AHR MAPK3 CCND1 MPO PPARG CTNNB1 FAS BIRC5 MMP9 CDKN1B NFKBIA BCL2 CXCL8 SIRT1 CDK2 MYC COL1A1 P2RX7 CD36 CYP2E1 SOD2 CDK4 NOS3 CPT1A PPARA CYP3A4 FABP4 TP53 CDKN1A NR1I2 DNMT1 PPARGC1A BAX NOS2 CYP4A14 CYBA PRKCA EIF4EBP1 PRKAA1 CASP3 SREBF1 GPT DDIT3 SOD1 ESR1 PTGS2 MMP2 AKT1 GSK3B EDN1 ACADM FN1 RELA NFE2L2 BGLAP HMOX1 GSR ACTA2 FOS RPS6 CYP1A1 CASP9 IL10 HSPA5 ALB GPX1 UCP2 IL1B CAT TGFB1 IL4 BCL2L1 IFNG IL6 CCL2 ADIPOQ JUN CASP8 MAPK1

Table S4 The first screening of BBR-HUA intersecting genes.

Gene name Betweenness name Betweenness TP53 13877.360 EGFR 2016.532 INS 13464.200 LEP 2012.339 AKT1 10186.080 FOXO1 1938.191 IL6 5637.242 CTNNB1 1895.253 EP300 5120.026 PPARG 1879.024 MYC 4828.027 PTGS2 1845.352 CREBBP 4648.952 CASP3 1775.594 JUN 4464.272 MMP9 1756.629 HSP90AA1 4084.612 CDH1 1733.187 ALB 3991.096 FOS 1634.398 MAPK8 3688.512 IGF1 1548.530 APP 3561.875 FN1 1531.755 TNF 3462.743 ADIPOQ 1346.849 EGF 3304.192 CCND1 1325.318 STAT3 2788.958 CXCL8 1258.871 VEGFA 2778.171 EDN1 1214.360 RELA 2597.351 JAK2 1208.908 ESR1 2592.789 NFKB1 1076.066 MAPK3 2484.491 NOS3 1058.610 MAPK1 2434.432 IL1B 838.501 SIRT1 2305.370 FOXO3 704.135 PIK3R1 2237.259 ICAM1 657.707

Table S5 The second screening of BBR-HUA intersecting genes based on the first screening result (Top 15).

Gene name Betweenness AKT1 37.951 IL6 36.140 VEGFA 34.191 STAT3 32.894 TP53 27.900 INS 25.225 MAPK1 24.843 MAPK3 24.647 IGF1 24.501 TNF 23.759 JUN 23.010 MAPK8 22.803 MYC 20.262 IL1B 19.352 ESR1 18.991

Figure S1 Repeat 1 Repeat 2 Repeat 3 Caspase1

the second band (from top to bottom) the second band (from top to bottom)

Figure S2 Repeat 1 Repeat 2 Repeat 3 ASC

the first band (from top to bottom) the first band (from top to bottom)

Figure S3 Repeat 1 Repeat 2 Repeat 3 IL-1

Figure S4 Repeat 1 Repeat 2 Repeat 3 NLRP3 see repeat 2 the first band (from top to bottom)

the second band (from top to bottom) the second band (from top to bottom)

Figure S5 Repeat 1 Repeat 2 Repeat 3 ACTIN

Figure S6 Repeat 1 Repeat 2 Repeat 3 URAT1

Figure S7 Repeat 1 Repeat 2 Repeat 3 ACTIN

the second band (from top to bottom)

Figure S8 Q-Q plots for data (n > 5) The points in the QQ-normal plots lied on a straight diagonal line approximately, which means the data was normally distributed.

Day 10 weight-Normal QQ plot Serum UA-Normal QQ plot Serum BUN-Normal QQ plot Serum CRE-Normal QQ plot 30

30 60 28 100 40 20 26

Predicted Predicted 50 Predicted Predicted 20 24 10 0 0 24 26 28 30 0 50 100 10 20 30 0 20 40 60 Actual Actual Actual Actual

Kidney index-Normal QQ plot Histological score-Normal QQ plot Serum IL1β-Normal QQ plot Serum IL18-Normal QQ plot 120 90

2.0 15 100 80

10 1.5 80 70 Predicted Predicted Predicted Predicted 5 60 60 1.0 0 40 50 1.0 1.5 2.0 0 5 10 15 40 60 80 100 120 50 60 70 80 90 Actual Actual Actual Actual

Kidney IL1β-Normal QQ plot Kidney IL18-Normal QQ plot 120 Con HUA 110 160 HUA+BZB 5 100 140 HUA+BBR 50

Predicted 90 Predicted HUA+BBR 100 80 120

80 90 100 110 120 120 140 160 Actual Actual