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char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
result sql = Yin yang 1 is a novel regulator of pulmonary fibrosis.
Yin yang 1 is a novel regulator of pulmonary fibrosis.
char = <;code = 60
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char = R;code = 82
char = A;code = 65
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char = I;code = 73
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char = c;code = 99
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char = m;code = 109
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char = f;code = 102
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char = (;code = 40
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char = P;code = 80
char = F;code = 70
char = );code = 41
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = t;code = 116
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char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
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char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
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char = Y;code = 89
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char = ;code = 32
char = Y;code = 89
char = a;code = 97
char = n;code = 110
char = g;code = 103
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char = 1;code = 49
char = ;code = 32
char = (;code = 40
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
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char = l;code = 108
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char = i;code = 105
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char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = f;code = 102
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char = a;code = 97
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char = d;code = 100
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char = f;code = 102
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char = o;code = 111
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char = g;code = 103
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char = a;code = 97
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char = e;code = 101
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char = s;code = 115
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char = r;code = 114
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char = <;code = 60
char = b;code = 98
char = >;code = 62
char = O;code = 79
char = B;code = 66
char = J;code = 74
char = E;code = 69
char = C;code = 67
char = T;code = 84
char = I;code = 73
char = V;code = 86
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
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char = b;code = 98
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char = T;code = 84
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char = e;code = 101
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char = c;code = 99
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char = t;code = 116
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char = h;code = 104
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char = Y;code = 89
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char = r;code = 114
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char = g;code = 103
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char = e;code = 101
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char = f;code = 102
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char = r;code = 114
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char = n;code = 110
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char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = d;code = 100
char = ;code = 32
char = l;code = 108
char = u;code = 117
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char = g;code = 103
char = ;code = 32
char = f;code = 102
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char = b;code = 98
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char = .;code = 46
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char = <;code = 60
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char = >;code = 62
char = <;code = 60
char = b;code = 98
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char = E;code = 69
char = T;code = 84
char = H;code = 72
char = O;code = 79
char = D;code = 68
char = S;code = 83
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char = :;code = 58
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char = <;code = 60
char = /;code = 47
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char = L;code = 76
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char = n;code = 110
char = g;code = 103
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char = f;code = 102
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char = b;code = 98
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char = o;code = 111
char = b;code = 98
char = l;code = 108
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char = (;code = 40
char = N;code = 78
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char = #;code = 35
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char = A;code = 65
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char = .;code = 46
char = <;code = 60
char = b;code = 98
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = M;code = 77
char = E;code = 69
char = A;code = 65
char = S;code = 83
char = U;code = 85
char = R;code = 82
char = E;code = 69
char = M;code = 77
char = E;code = 69
char = N;code = 78
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = A;code = 65
char = N;code = 78
char = D;code = 68
char = ;code = 32
char = M;code = 77
char = A;code = 65
char = I;code = 73
char = N;code = 78
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 6;code = 54
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
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char = n;code = 110
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = -;code = 45
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 5;code = 53
char = ;;code = 59
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = u;code = 117
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 6;code = 54
char = ;;code = 59
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 5;code = 53
char = 4;code = 52
char = ;;code = 59
char = B;code = 66
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = I;code = 73
char = -;code = 45
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 5;code = 53
char = 4;code = 52
char = ;;code = 59
char = B;code = 66
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = P;code = 80
char = F;code = 70
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = u;code = 117
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = u;code = 117
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
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char = i;code = 105
char = s;code = 115
char = m;code = 109
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
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char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
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char = i;code = 105
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 5;code = 53
char = ;;code = 59
char = -;code = 45
char = S;code = 83
char = M;code = 77
char = A;code = 65
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = u;code = 117
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = e;code = 101
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char = t;code = 116
char = ;code = 32
char = (;code = 40
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
char = (;code = 40
char = +;code = 43
char = /;code = 47
char = -;code = 45
char = );code = 41
char = );code = 41
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = l;code = 108
char = u;code = 117
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
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char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 5;code = 53
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char = -;code = 45
char = S;code = 83
char = M;code = 77
char = A;code = 65
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = c;code = 99
char = o;code = 111
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char = l;code = 108
char = a;code = 97
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char = e;code = 101
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char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = .;code = 46
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char = F;code = 70
char = i;code = 105
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char = a;code = 97
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char = l;code = 108
char = y;code = 121
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char = a;code = 97
char = s;code = 115
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
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char = o;code = 111
char = n;code = 110
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char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
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char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = l;code = 108
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = e;code = 101
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char = o;code = 111
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = u;code = 117
char = s;code = 115
char = -;code = 45
char = c;code = 99
char = r;code = 114
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = o;code = 111
char = x;code = 120
char = e;code = 101
char = d;code = 100
char = -;code = 45
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
char = (;code = 40
char = f;code = 102
char = /;code = 47
char = f;code = 102
char = );code = 41
char = ;code = 32
char = m;code = 109
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char = c;code = 99
char = e;code = 101
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char = r;code = 114
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char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
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char = n;code = 110
char = g;code = 103
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char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
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char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = Y;code = 89
char = Y;code = 89
char = 1;code = 49
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char = i;code = 105
char = s;code = 115
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char = o;code = 111
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char = e;code = 101
char = r;code = 114
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
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char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = P;code = 80
char = F;code = 70
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = m;code = 109
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
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result sql = RATIONALE : The differentiation of fibroblasts into myofibroblasts is a cardinal feature of idiopathic pulmonary fibrosis (IPF). The transcription factor Yin Yang 1 (YY1) plays a role in the proliferation and differentiation of diverse cell types, but its role in fibrotic lung diseases is not known.

OBJECTIVES : To elucidate the mechanism by which YY1 regulates fibroblast differentiation and lung fibrosis.

METHODS : Lung fibroblasts were cultured with transforming growth factor (TGF)-β or tumor necrosis factor-α. Nuclear factor (NF)-κB, YY1, and α-smooth muscle actin (SMA) were determined in protein, mRNA, and promoter reporter level. Lung fibroblasts and lung fibrosis were assessed in a partial YY1-deficient mouse and a YY1(f/f) conditional knockout mouse after being exposed to silica or bleomycin.

MEASUREMENTS AND MAIN RESULTS : TGF-β and tumor necrosis factor-α up-regulated YY1 expression in lung fibroblasts. TGF-β-induced YY1 expression was dramatically decreased by an inhibitor of NF-κB, which blocked I-κB degradation. YY1 is significantly overexpressed in both human IPF and murine models of lung fibrosis, including in the aggregated pulmonary fibroblasts of fibrotic foci. Furthermore, the mechanism of fibrogenesis is that YY1 can up-regulate α-SMA expression in pulmonary fibroblasts. YY1-deficient (YY1(+/-)) mice were significantly protected from lung fibrosis, which was associated with attenuated α-SMA and collagen expression. Finally, decreasing YY1 expression through instilled adenovirus-cre in floxed-YY1(f/f) mice reduced lung fibrosis.

CONCLUSIONS : YY1 is overexpressed in fibroblasts in both human IPF and murine models in a NF-κB-dependent manner, and YY1 regulates fibrogenesis at least in part by increasing α-SMA and collagen expression. Decreasing YY1 expression may provide a new therapeutic strategy for pulmonary fibrosis.

Publication: Am. J. Respir. Crit. Care Med. 2011 Jun 15 ;183(12)::1689-97. :doi: 10.1164/rccm.201002-0232OC.
Publication Date: 2011 Jun 15
Study Author(s): Lin, Xin;Sime, Patricia J;Xu, Haodong;Williams, Marc A;LaRussa, Larry;Georas, Steve N;Guo, Jia;
Institution: Department of Medicine, University of Rochester Medical School, Rochester, New York 14642, USA.
Shortcut link to this study:
RATIONALE : The differentiation of fibroblasts into myofibroblasts is a cardinal feature of idiopathic pulmonary fibrosis (IPF). The transcription factor Yin Yang 1 (YY1) plays a role in the proliferation and differentiation of diverse cell types, but its role in fibrotic lung diseases is not known.

OBJECTIVES : To elucidate the mechanism by which YY1 regulates fibroblast differentiation and lung fibrosis.

METHODS : Lung fibroblasts were cultured with transforming growth factor (TGF)-β or tumor necrosis factor-α. Nuclear factor (NF)-κB, YY1, and α-smooth muscle actin (SMA) were determined in protein, mRNA, and promoter reporter level. Lung fibroblasts and lung fibrosis were assessed in a partial YY1-deficient mouse and a YY1(f/f) conditional knockout mouse after being exposed to silica or bleomycin.

MEASUREMENTS AND MAIN RESULTS : TGF-β and tumor necrosis factor-α up-regulated YY1 expression in lung fibroblasts. TGF-β-induced YY1 expression was dramatically decreased by an inhibitor of NF-κB, which blocked I-κB degradation. YY1 is significantly overexpressed in both human IPF and murine models of lung fibrosis, including in the aggregated pulmonary fibroblasts of fibrotic foci. Furthermore, the mechanism of fibrogenesis is that YY1 can up-regulate α-SMA expression in pulmonary fibroblasts. YY1-deficient (YY1(+/-)) mice were significantly protected from lung fibrosis, which was associated with attenuated α-SMA and collagen expression. Finally, decreasing YY1 expression through instilled adenovirus-cre in floxed-YY1(f/f) mice reduced lung fibrosis.

CONCLUSIONS : YY1 is overexpressed in fibroblasts in both human IPF and murine models in a NF-κB-dependent manner, and YY1 regulates fibrogenesis at least in part by increasing α-SMA and collagen expression. Decreasing YY1 expression may provide a new therapeutic strategy for pulmonary fibrosis.
PMID: 21169469

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