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Ba= ThisWorkbook=P N?8X@"1Calibri1[SO1[SO1[SO1[SO1Calibri1 Calibri1h8Cambria1,8Calibri18Calibri18Calibri1Calibri1Calibri1Calibri14Calibri1 Calibri1Calibri1 Calibri14Calibri1<Calibri1?Calibri1>Calibri1Times New Roman1Calibri"$"#,##0_);\("$"#,##0\)!"$"#,##0_);[Red]\("$"#,##0\)""$"#,##0.00_);\("$"#,##0.00\)'""$"#,##0.00_);[Red]\("$"#,##0.00\)7*2_("$"* #,##0_);_("$"* \(#,##0\);_("$"* "-"_);_(@_).))_(* #,##0_);_(* \(#,##0\);_(* "-"_);_(@_)?,:_("$"* #,##0.00_);_("$"* \(#,##0.00\);_("$"* "-"??_);_(@_)6+1_(* #,##0.00_);_(* \(#,##0.00\);_(* "-"??_);_(@_)""#,##0;""\-#,##0""#,##0;[Red]""\-#,##0""#,##0.00;""\-#,##0.00#""#,##0.00;[Red]""\-#,##0.0072_ ""* #,##0_ ;_ ""* \-#,##0_ ;_ ""* "-"_ ;_ @_ .)_ * #,##0_ ;_ * \-#,##0_ ;_ * "-"_ ;_ @_ ?:_ ""* #,##0.00_ ;_ ""* \-#,##0.00_ ;_ ""* "-"??_ ;_ @_ 61_ * #,##0.00_ ;_ * \-#,##0.00_ ;_ * "-"??_ ;_ @_ \$#,##0_);\(\$#,##0\)\$#,##0_);[Red]\(\$#,##0\) \$#,##0.00_);\(\$#,##0.00\)% \$#,##0.00_);[Red]\(\$#,##0.00\)"Yes";"Yes";"No""True";"True";"False""On";"On";"Off"],[$ -2]\ #,##0.00_);[Red]\([$ -2]\ #,##0.00\)                                            ff         P  P        `         a>     20% - Accent1 20% - Accent2 20% - Accent3 20% - Accent4 20% - Accent5 20% - Accent6 40% - Accent1 40% - Accent2 40% - Accent3 40% - Accent4 40% - Accent5 40% - Accent6 60% - Accent1 60% - Accent2 60% - Accent3 60% - Accent4 60% - Accent5! 60% - Accent6 "Accent1 #Accent2 $Accent3 %Accent4 &Accent5 'Accent6(Bad) Calculation* Check Cell+,-./Explanatory Text 0Good1 Heading 12 Heading 23 Heading 34 Heading 4 5Input6 Linked Cell 7Neutral 8Note 9Output: ;Title <Total= Warning Text8dq:F3ffff̙̙3f3fff3f3f33333f33333\`cSupplementary Table 34 rno05166HTLV-I infectionWnt3,Wnt2b,Adcy1rno05203Viral carcinogenesis Scin,Hdac11rno01200Carbon metabolismrno04142LysosomeMcpt8l2rno05205Proteoglycans in cancerrno04380Osteoclast differentiationrno05160 Hepatitis Crno04015Rap1 signaling pathway Fgfr2,Adcy1rno03040 SpliceosomeThoc2rno04120Ubiquitin mediated proteolysisrno04140Autophagy - animalPrkaa2rno03010RibosomeRpl35al1rno05206MicroRNAs in cancerWnt3rno04141+Protein processing in endoplasmic reticulum LOC103694875rno04360 Axon guidanceNtng1rno05016Huntington's diseasePpargc1arno05168Herpes simplex infectionPer3rno04740Olfactory transductionSlc8a1,Pde1c,Gng7Supplementary Table 3. The list of KEGG enrichment analysis of upregulated genes between HKL treated UC samples and water treated UC samples.rno05221Acute myeloid leukemiaZbtb16rno04611Platelet activationrno04370VEGF signaling pathwayrno04730Long-term depressionrno04137Mitophagy - animalMitfrno04068FoxO signaling pathway Fbxo32,Prkaa2rno04115p53 signaling pathwayIgfbp3rno05230#Central carbon metabolism in cancerFgfr2rno05034 Alcoholism Hdac11,Gng7rno04010MAPK signaling pathwayCacna1e,Fgfr2,Pla2g4c,Cacna2d1rno05218Melanomarno04630Jak-STAT signaling pathway Lifr,Ctf1rno04144 EndocytosisAdrb3,Fgfr2,Psd,Vps25rno05222Small cell lung cancerCol4a3rno04310Wnt signaling pathway Wnt3,Wnt2brno05224 Breast cancerrno04610#Complement and coagulation cascadesrno01230Biosynthesis of amino acidsrno04514Cell adhesion molecules (CAMs) Itgb8,Ntng1rno01521)EGFR tyrosine kinase inhibitor resistancerno04060&Cytokine-cytokine receptor interactionLifr,Cxcl14,Ctf1rno04014Ras signaling pathwayFgfr2,Gng7,Pla2g4crno03015mRNA surveillance pathwayGenetic Information ProcessingPpp2r2crno04350TGF-beta signaling pathwayBmp8arno03013 RNA transport Thoc2,Eef1a2rno04145 Phagosome Mpo,Sftpdrno04666 Fc gamma R-mediated phagocytosisScinrno00564Glycerophospholipid metabolismrno04540 Gap junctionAdcy1rno04530Tight junctionPrkaa2,Ppp2r2crno01522Endocrine resistancerno04915Estrogen signaling pathwayrno00240Pyrimidine metabolismrno04062Chemokine signaling pathwayrno049334AGE-RAGE signaling pathway in diabetic complicationsrno05145 ToxoplasmosisTlr11Starch and sucrose metabolismPygmrno04950$Maturity onset diabetes of the youngPklrrno04071Sphingolipid signaling pathwayFcer1a,Adora3,Ppp2r2crno00052Galactose metabolismGalmrno01524Platinum drug resistancerno00760&Nicotinate and nicotinamide metabolismNmnat2rno04728Dopaminergic synapseCaly,Gng7,Ppp2r2crno04925#Aldosterone synthesis and secretion Cyp21a1,Adcy1rno00350Tyrosine metabolismrno04215Apoptosis - multiple speciesBirc6rno04146 Peroxisome Ephx2,Ech1rno05020Prion diseasesC8grno04640Hematopoietic cell lineage Cd7,Itga1rno04080'Neuroactive ligand-receptor interaction'Adrb3,Htr1b,Chrnb4,Mcpt8l2,Tacr2,Adora3rno05215Prostate cancerAr,Fgfr2rno04912GnRH signaling pathway Pla2g4c,Adcy1rno05418&Fluid shear stress and atherosclerosisPrkaa2,Gsta4,Gsta3rno04727GABAergic synapse Gng7,Adcy1rno00620Pyruvate metabolismrno04973%Carbohydrate digestion and absorptionAtp1a2rno04072!Phospholipase D signaling pathwayFcer1a,Pla2g4c,Adcy1rno04975Fat digestion and absorptionFabp1rno04723$Retrograde endocannabinoid signalingRims1,Gng7,Adcy1rno04150mTOR signaling pathwayWnt3,Prkaa2,Wnt2brno04932)Non-alcoholic fatty liver disease (NAFLD)Adipoq,Prkaa2,Pklrrno00600Sphingolipid metabolismGal3st1rno05142)Chagas disease (American trypanosomiasis) Ppp2r2c,Adcy1rno00330Arginine and proline metabolismCkmrno05030Cocaine addictionrno00510N-Glycan biosynthesisMgat5rno00310Lysine degradationAsh1lrno05134 LegionellosisEef1a2Ppargc1a,Prkaa2,Pygmrno05231Choline metabolism in cancerSlc22a1,Slc22a3,Pla2g4crno04510Focal adhesionrno00480Glutathione metabolism Gsta4,Gsta3rno00770!Pantothenate and CoA biosynthesisDpydrno04923%Regulation of lipolysis in adipocytes Adrb3,Adcy1rno00360Phenylalanine metabolismAldh3a1rno00910Nitrogen metabolismCar3rno04390Hippo signaling pathwayWnt3,Wnt2b,Bmp8a,Ppp2r2crno00592alpha-Linolenic acid metabolismPla2g4crno05202'Transcriptional misregulation in cancerAff1,Mpo,Zbtb16,Igfbp3rno04721Synaptic vesicle cycle Syt1,Rims1rno04931Insulin resistancerno04213/Longevity regulating pathway - multiple species Prkaa2,Adcy1rno01100Metabolic pathwaysSt6galnac1,Cyp21a1,Aldh3a1,Ltc4s,Mgat5,Galm,Hsd17b2,Ces1d,Ckm,Dpyd,Cyp27a1,Ephx2,Aldh1a1,Hmgcs2,Cyp8b1,Pklr,Acadsb,Pygm,Pla2g4c,Nmnat2,Cyp2j4,Acsm5,LOC108348266,Gal3st1,Cyp2j10,Ak5rno00340Histidine metabolismrno00900Terpenoid backbone biosynthesisrno04810 Regulation of actin cytoskeletonScin,Itgb8,Itga7,Fgfr2,Itga1rno04664Fc epsilon RI signaling pathwayFcer1a,Pla2g4crno04720Long-term potentiation Ppp1r1a,Adcy1rno04724Glutamatergic synapseGng7,Pla2g4c,Adcy1rno04725Cholinergic synapseChrnb4,Gng7,Adcy1rno04392)Hippo signaling pathway -multiple speciesFat4rno00512 Mucin type O-glycan biosynthesis St6galnac1rno01040'Biosynthesis of unsaturated fatty acidsScdrno04744PhototransductionRgs9rno05310AsthmaFcer1arno04270"Vascular smooth muscle contractionPpp1r14a,Pla2g4c,Adcy1rno04918Thyroid hormone synthesis Atp1a2,Adcy1rno00500"Prkaa2,Ryr2,Pla2g4c,Cacna2d1,Adcy1rno00983Drug metabolism - other enzymes Ces1d,Dpydrno04924Renin secretionPde1c,Adrb3,Clca1rno047500Inflammatory mediator regulation of TRP channelsPla2g4c,Cyp2j4,Cyp2j10,Adcy1rno04971Gastric acid secretionSst,Atp1a2,Adcy1rno04114Oocyte meiosisCellular ProcessesAr,Cpeb1,Cpeb4,Adcy1rno00072*Synthesis and degradation of ketone bodiesHmgcs2rno04960)Aldosterone-regulated sodium reabsorption Atp1a2,Nr3c2rno04919!Thyroid hormone signaling pathwayAtp1a2,Ncoa2,Rcan2,Dio1rno02010ABC transporters Abca8a,Abcb1brno05322Systemic lupus erythematosusTrove2,C8g,Mcpt8l2rno05200Pathways in cancer6Wnt3,Ar,Mitf,Wnt2b,Col4a3,Fgfr2,Hhip,Gng7,Zbtb16,Adcy1rno04340Hedgehog signaling pathway Spopl,Hhiprno00565Ether lipid metabolismPla2g4c,Gal3st1rno00071Fatty acid degradation Eci1,Acadsbrno00230Purine metabolismPde1c,Pde5a,Pklr,Ak5,Adcy1rno04911Insulin secretionAtp1a2,Ryr2,Adcy1rno04914'Progesterone-mediated oocyte maturationCpeb1,Cpeb4,Adcy1rno04742Taste transductionPde1c,Htr1b,Trpm5rno00730Thiamine metabolismAk5rno00520+Amino sugar and nucleotide sugar metabolism Cmahp,Cyb5r2rno04910Insulin signaling pathwayPpargc1a,Prkaa2,Pklr,Pygmrno00280*Valine, leucine and isoleucine degradation Hmgcs2,Acadsbrno01212Fatty acid metabolism Scd,Acadsbrno05032Morphine addictionPde1c,Gng7,Adcy1rno045508Signaling pathways regulating pluripotency of stem cellsWnt3,Lifr,Wnt2b,Fgfr2rno05014#Amyotrophic lateral sclerosis (ALS) Nefl,Prphrno04922Glucagon signaling pathwaycGMP-PKG signaling pathway4Atp2b4,Atp1a2,Slc8a1,Adrb3,Pde5a,Adora3,Adcy1,Atp2b3rno04024cAMP signaling pathway5Sox9,Atp2b4,Atp1a2,Htr1b,Ryr2,Hhip,Fxyd1,Adcy1,Atp2b3rno04710Circadian rhythmPrkaa2,Nr1d1,Per3rno00591Linoleic acid metabolismPla2g4c,Cyp2j4,Cyp2j10rno04916 MelanogenesisWnt3,Mitf,Pomc,Wnt2b,Adcy1rno00120Primary bile acid biosynthesisCyp27a1,Cyp8b1rno04371Apelin signaling pathway&Ppargc1a,Prkaa2,Slc8a1,Ryr2,Gng7,Adcy1rno04920Adipocytokine signaling pathwayAdipoq,Ppargc1a,Prkaa2,Pomcrno04930<Q Type II diabetes mellitusAdipoq,Cacna1e,Pklrrno04260Cardiac muscle contractionAtp1a2,Slc8a1,Ryr2,Cacna2d1rno04974 Protein digestion and absorptionAtp1a2,Slc8a1,Cpa3,Col4a3rno049619Endocrine and other factor-regulated calcium reabsorptionAtp1a2,Calb1,Slc8a1rno04964'Proximal tubule bicarbonate reclamation Slc4a4,Atp1a2rno00982!Drug metabolism - cytochrome P450Aldh3a1,Gsta4,Gsta3rno04320Dorso-ventral axis formation Cpeb1,Cpeb4rno05217Basal cell carcinomaWnt3,Wnt2b,Hhiprno00650Butanoate metabolism Hmgcs2,Acsm5rno04152AMPK signaling pathway"Adipoq,Ppargc1a,Prkaa2,Scd,Ppp2r2crno05146 AmoebiasisCol4a3,C8g,Mcpt8l2,Adcy1rno04211Longevity regulating pathwayAdipoq,Ppargc1a,Prkaa2,Adcy1rno00410beta-Alanine metabolism Aldh3a1,Dpydrno04713Circadian entrainmentRyr2,Per3,Gng7,Adcy1rno00010Glycolysis / GluconeogenesisAldh3a1,Galm,Pklrrno00830Retinol metabolismRetsat,Aldh1a1,LOC108348266rno04151PI3K-Akt signaling pathway7Chad,Itgb8,Prkaa2,Itga7,Col4a3,Fgfr2,Gng7,Itga1,Ppp2r2crno04921Oxytocin signaling pathwayID DescriptionClass Enrich_factorPvalueFDR GeneCountGeneIDrno054126Arrhythmogenic right ventricular cardiomyopathy (ARVC)Human Diseases,Itgb8,Itga7,Slc8a1,Ryr2,Actn2,Cacna2d1,Itga1rno00980,Metabolism of xenobiotics by cytochrome P450 Metabolism'Aldh3a1,Ephx1,Akr7a2,Akr7a3,Gsta4,Gsta3rno04976Bile secretionOrganismal Systems-Slc4a4,Ephx1,Atp1a2,Abcb1b,Aqp8,Slc22a1,Adcy1rno04261&Adrenergic signaling in cardiomyocytesEAtp2b4,Atp1a2,Slc8a1,Ryr2,Scn7a,Cacna2d1,Ppp1r1a,Ppp2r2c,Adcy1,Atp2b3rno04972Pancreatic secretion1Atp2b4,Slc4a4,Atp1a2,Cpa3,Ryr2,Adcy1,Clca1,Atp2b3rno03320PPAR signaling pathway,Adipoq,Fabp1,Scd,Cyp27a1,Hmgcs2,Cyp8b1,Apoc3rno05410!Hypertrophic cardiomyopathy (HCM)-Itgb8,Prkaa2,Itga7,Slc8a1,Ryr2,Cacna2d1,Itga1rno05414Dilated cardiomyopathy,Itgb8,Itga7,Slc8a1,Ryr2,Cacna2d1,Itga1,Adcy1rno00140Steroid hormone biosynthesis1Cyp21a1,Cyp2d2,Hsd17b2,Srd5a1,Cyp2d5,LOC108348266rno04913Ovarian steroidogenesis$Hsd17b2,Pla2g4c,Cyp2j4,Cyp2j10,Adcy1rno04614Renin-angiotensin systemCpa3,Cma1,Mcpt8l2,LOC108348118rno05204Chemical carcinogenesis.Aldh3a1,Ephx1,Sult1a1,Gsta4,LOC108348266,Gsta3rno00590Arachidonic acid metabolism/Ltc4s,Ephx2,Pla2g4c,Cyp2j4,LOC108348266,Cyp2j10rno04970Salivary secretion&Atp2b4,Atp1a2,Adrb3,Trpv6,Adcy1,Atp2b3rno04726Serotonergic synapse/Cyp2d2,Htr1b,Gng7,Pla2g4c,Cyp2d5,Cyp2j4,Cyp2j10rno04512ECM-receptor interaction$Environmental Information ProcessingChad,Itgb8,Itga7,Col4a3,Itga1rno04020Calcium signaling pathway9Cacna1e,Atp2b4,Slc8a1,Pde1c,Adrb3,Ryr2,Tacr2,Adcy1,Atp2b3rno04978Mineral absorptionS100g,Atp1a2,Slc8a1,Trpv6rno04022\ JTp6n<g9ʧo?pGq~A.gO&U N  }-  0 * j O E !I<""\3#e#g-I$_$q%!&f-n'(-(b_))eer*"-*+qN,,-C1.-.}m/0011e]o2134D4$155fo67D7V8(-9Cu: [;,< C= -CpE-؃ D -X-T82X|CPp@,|C_EHEpE-EDXeC-xDpEDCCC DȄEEED*C-H-hh(&hCf -Hc}T- DT-Yd}T-]`8^,B-T-Type II diabetes mellitusAdipoq,Cacna1e,Pklrrno04260Cardiac muscle contractionAtp1a2,Slc8a1,Ryr2,Cacna2d1rno04974 Protein digestion and absorptionAtp1a2,Slc8a1,Cpa3,Col4a3rno049619Endocrine and other factor-regulated calcium reabsorptionAtp1a2,Calb1,Slc8a1rno04964'Proximal tubule bicarbonate reclamation Slc4a4,Atp1a2rno00982!Drug metabolism - 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