/* RPL-CYTOKINE - Main Styles */
/* iPhone 17e Style - Dark Theme */

/* ================================
   CSS Variables
   ================================ */
:root {
  /* Background Colors */
  --bg-primary: #0a0a0f;
  --bg-secondary: #12121a;
  --bg-card: #1a1a25;
  --bg-hover: #252535;
  
  /* Accent Colors */
  --accent-primary: #00d4ff;
  --accent-secondary: #00d9a3;
  --accent-warm: #f59e0b;
  --accent-purple: #7c3aed;
  --accent-pink: #ec4899;
  
  /* Cytokine Colors - Th1 Pro-inflammatory */
  --th1-tnf: #ef4444;
  --th1-ifn: #f97316;
  --th1-il1: #f59e0b;
  
  /* Cytokine Colors - Th2 Anti-inflammatory */
  --th2-il4: #00d4ff;
  --th2-il5: #00d9a3;
  --th2-il10: #7c3aed;
  --th2-il13: #ec4899;
  
  /* Cytokine Colors - Th17/Treg */
  --th17-il17: #dc2626;
  --treg-blue: #3b82f6;
  
  /* Text Colors */
  --text-primary: #ffffff;
  --text-secondary: #a0a0b0;
  --text-muted: #6b7280;
  
  /* Fonts */
  --font-primary: -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, sans-serif;
  --font-mono: "SF Mono", Monaco, "Cascadia Code", monospace;
  
  /* Spacing */
  --space-xs: 0.5rem;
  --space-sm: 1rem;
  --space-md: 2rem;
  --space-lg: 4rem;
  --space-xl: 6rem;
  --space-2xl: 8rem;
  
  /* Transitions */
  --transition-fast: 0.2s ease;
  --transition-normal: 0.3s ease;
  --transition-slow: 0.5s ease;
}

/* ================================
   Reset & Base
   ================================ */
*, *::before, *::after {
  box-sizing: border-box;
  margin: 0;
  padding: 0;
}

html {
  scroll-behavior: smooth;
}

body {
  font-family: var(--font-primary);
  background: var(--bg-primary);
  color: var(--text-primary);
  line-height: 1.6;
  overflow-x: hidden;
}

a {
  color: var(--accent-primary);
  text-decoration: none;
  transition: color var(--transition-fast);
}

a:hover {
  color: var(--accent-secondary);
}

img {
  max-width: 100%;
  height: auto;
}

/* ================================
   Layout
   ================================ */
.container {
  max-width: 1200px;
  margin: 0 auto;
  padding: 0 1.5rem;
}

.section {
  padding: var(--space-xl) 0;
}

.section-header {
  text-align: center;
  margin-bottom: var(--space-lg);
}

.section-title {
  font-size: clamp(2rem, 5vw, 3rem);
  font-weight: 700;
  margin-bottom: var(--space-sm);
  background: linear-gradient(135deg, var(--text-primary) 0%, var(--text-secondary) 100%);
  -webkit-background-clip: text;
  -webkit-text-fill-color: transparent;
  background-clip: text;
}

.section-description {
  font-size: 1.125rem;
  color: var(--text-secondary);
  max-width: 600px;
  margin: 0 auto;
}

/* ================================
   Hero Section
   ================================ */
.hero {
  min-height: 100vh;
  display: flex;
  align-items: center;
  justify-content: center;
  position: relative;
  padding: var(--space-lg) 0;
  overflow: hidden;
}

.hero::before {
  content: '';
  position: absolute;
  top: 0;
  left: 0;
  right: 0;
  bottom: 0;
  background: 
    radial-gradient(ellipse at 20% 50%, rgba(0, 212, 255, 0.15) 0%, transparent 50%),
    radial-gradient(ellipse at 80% 50%, rgba(0, 217, 163, 0.1) 0%, transparent 50%),
    radial-gradient(ellipse at 50% 100%, rgba(239, 68, 68, 0.1) 0%, transparent 50%);
  pointer-events: none;
}

.hero-content {
  text-align: center;
  position: relative;
  z-index: 1;
}

.hero-badge {
  display: inline-flex;
  align-items: center;
  gap: 0.5rem;
  padding: 0.5rem 1rem;
  background: rgba(0, 212, 255, 0.1);
  border: 1px solid rgba(0, 212, 255, 0.3);
  border-radius: 9999px;
  font-size: 0.875rem;
  color: var(--accent-primary);
  margin-bottom: var(--space-md);
}

.hero-title {
  font-size: clamp(2.5rem, 8vw, 5rem);
  font-weight: 800;
  line-height: 1.1;
  margin-bottom: var(--space-sm);
  background: linear-gradient(135deg, #fff 0%, var(--accent-primary) 50%, var(--accent-secondary) 100%);
  -webkit-background-clip: text;
  -webkit-text-fill-color: transparent;
  background-clip: text;
}

.hero-subtitle {
  font-size: clamp(1.2rem, 3vw, 1.8rem);
  color: var(--text-secondary);
  margin-bottom: var(--space-sm);
  font-weight: 300;
}

.hero-description {
  font-size: 1.125rem;
  color: var(--text-muted);
  max-width: 600px;
  margin: 0 auto var(--space-md);
}

.hero-cta {
  display: flex;
  gap: var(--space-sm);
  justify-content: center;
  flex-wrap: wrap;
}

/* ================================
   Buttons
   ================================ */
.btn {
  display: inline-flex;
  align-items: center;
  gap: 0.5rem;
  padding: 0.875rem 1.75rem;
  border-radius: 9999px;
  font-weight: 500;
  font-size: 1rem;
  transition: all var(--transition-normal);
  cursor: pointer;
  border: none;
}

.btn-primary {
  background: var(--accent-primary);
  color: #000;
}

.btn-primary:hover {
  background: #33ddff;
  transform: translateY(-2px);
  box-shadow: 0 10px 30px rgba(0, 212, 255, 0.3);
}

.btn-secondary {
  background: rgba(255, 255, 255, 0.1);
  color: var(--text-primary);
  border: 1px solid rgba(255, 255, 255, 0.2);
}

.btn-secondary:hover {
  background: rgba(255, 255, 255, 0.15);
  border-color: rgba(255, 255, 255, 0.3);
}

/* ================================
   Cards
   ================================ */
.card {
  background: var(--bg-card);
  border-radius: 1.5rem;
  padding: 2rem;
  border: 1px solid rgba(255, 255, 255, 0.05);
  transition: all var(--transition-normal);
  height: 100%;
}

.card:hover {
  background: var(--bg-hover);
  transform: translateY(-4px);
  border-color: rgba(255, 255, 255, 0.1);
}

.card-icon {
  width: 3rem;
  height: 3rem;
  border-radius: 1rem;
  display: flex;
  align-items: center;
  justify-content: center;
  font-size: 1.5rem;
  margin-bottom: var(--space-sm);
}

.card-title {
  font-size: 1.25rem;
  font-weight: 600;
  margin-bottom: 0.5rem;
}

.card-content {
  color: var(--text-secondary);
  font-size: 0.95rem;
  line-height: 1.7;
}

.card-stat {
  font-size: 2.5rem;
  font-weight: 700;
  margin-top: var(--space-sm);
  background: linear-gradient(135deg, var(--accent-primary), var(--accent-secondary));
  -webkit-background-clip: text;
  -webkit-text-fill-color: transparent;
  background-clip: text;
}

.card-stat-label {
  font-size: 0.875rem;
  color: var(--text-muted);
}

/* ================================
   Grid
   ================================ */
.grid {
  display: grid;
  gap: var(--space-md);
}

.grid-2 {
  grid-template-columns: repeat(2, 1fr);
}

.grid-3 {
  grid-template-columns: repeat(3, 1fr);
}

.grid-4 {
  grid-template-columns: repeat(4, 1fr);
}

@media (max-width: 1024px) {
  .grid-4 {
    grid-template-columns: repeat(2, 1fr);
  }
}

@media (max-width: 768px) {
  .grid-2, .grid-3, .grid-4 {
    grid-template-columns: 1fr;
  }
}

/* ================================
   Background Section
   ================================ */
.background-section {
  background: var(--bg-secondary);
}

/* ================================
   Cytokine Section
   ================================ */
.cytokine-section {
  background: var(--bg-primary);
}

.cytokine-tabs {
  display: flex;
  gap: var(--space-xs);
  justify-content: center;
  flex-wrap: wrap;
  margin-bottom: var(--space-lg);
}

.tab-btn {
  padding: 0.75rem 1.5rem;
  border-radius: 9999px;
  background: transparent;
  color: var(--text-secondary);
  border: 1px solid rgba(255, 255, 255, 0.1);
  cursor: pointer;
  transition: all var(--transition-normal);
  font-size: 0.95rem;
  font-weight: 500;
}

.tab-btn:hover {
  background: rgba(255, 255, 255, 0.05);
  color: var(--text-primary);
}

.tab-btn.active {
  background: var(--accent-primary);
  color: #000;
  border-color: var(--accent-primary);
}

.tab-btn.th1.active {
  background: var(--th1-tnf);
  border-color: var(--th1-tnf);
}

.tab-btn.th2.active {
  background: var(--th2-il4);
  border-color: var(--th2-il4);
}

.tab-btn.th17.active {
  background: var(--th17-il17);
  border-color: var(--th17-il17);
}

.tab-btn.treg.active {
  background: var(--treg-blue);
  border-color: var(--treg-blue);
}

.tab-content {
  display: none;
}

.tab-content.active {
  display: block;
  animation: fadeIn 0.5s ease;
}

@keyframes fadeIn {
  from { opacity: 0; transform: translateY(10px); }
  to { opacity: 1; transform: translateY(0); }
}

.cytokine-category {
  background: var(--bg-card);
  border-radius: 2rem;
  padding: var(--space-lg);
  border: 1px solid rgba(255, 255, 255, 0.05);
}

.category-header {
  text-align: center;
  margin-bottom: var(--space-md);
}

.category-title {
  font-size: 1.75rem;
  font-weight: 700;
  margin-bottom: 0.5rem;
}

.category-description {
  color: var(--text-secondary);
  max-width: 600px;
  margin: 0 auto;
}

.cytokine-grid {
  display: grid;
  grid-template-columns: repeat(auto-fit, minmax(280px, 1fr));
  gap: var(--space-md);
}

.cytokine-card {
  background: var(--bg-secondary);
  border-radius: 1.5rem;
  padding: 1.5rem;
  border: 2px solid transparent;
  transition: all var(--transition-normal);
}

.cytokine-card:hover {
  transform: translateY(-4px);
}

.cytokine-card.th1 {
  border-color: rgba(239, 68, 68, 0.2);
}

.cytokine-card.th1:hover {
  border-color: rgba(239, 68, 68, 0.5);
  box-shadow: 0 10px 40px rgba(239, 68, 68, 0.15);
}

.cytokine-card.th2 {
  border-color: rgba(0, 212, 255, 0.2);
}

.cytokine-card.th2:hover {
  border-color: rgba(0, 212, 255, 0.5);
  box-shadow: 0 10px 40px rgba(0, 212, 255, 0.15);
}

.cytokine-card.th17 {
  border-color: rgba(220, 38, 38, 0.2);
}

.cytokine-card.th17:hover {
  border-color: rgba(220, 38, 38, 0.5);
  box-shadow: 0 10px 40px rgba(220, 38, 38, 0.15);
}

.cytokine-card.treg {
  border-color: rgba(59, 130, 246, 0.2);
}

.cytokine-card.treg:hover {
  border-color: rgba(59, 130, 246, 0.5);
  box-shadow: 0 10px 40px rgba(59, 130, 246, 0.15);
}

.cytokine-name {
  font-size: 1.5rem;
  font-weight: 700;
  margin-bottom: 0.25rem;
}

.cytokine-fullname {
  font-size: 0.875rem;
  color: var(--text-muted);
  margin-bottom: 1rem;
}

.cytokine-info {
  display: flex;
  flex-direction: column;
  gap: 0.75rem;
}

.cytokine-info-item {
  display: flex;
  flex-direction: column;
  gap: 0.25rem;
}

.cytokine-info-label {
  font-size: 0.75rem;
  text-transform: uppercase;
  letter-spacing: 0.05em;
  color: var(--text-muted);
}

.cytokine-info-value {
  font-size: 0.95rem;
  color: var(--text-secondary);
  line-height: 1.5;
}

/* ================================
   Mechanisms Section
   ================================ */
.mechanisms-section {
  background: var(--bg-secondary);
}

.mechanism-card {
  background: var(--bg-card);
  border-radius: 1.5rem;
  padding: 2rem;
  border: 1px solid rgba(255, 255, 255, 0.05);
  transition: all var(--transition-normal);
}

.mechanism-card:hover {
  background: var(--bg-hover);
  transform: translateY(-4px);
}

.mechanism-header {
  display: flex;
  align-items: center;
  gap: 1rem;
  margin-bottom: 1rem;
}

.mechanism-icon {
  width: 3.5rem;
  height: 3.5rem;
  border-radius: 1rem;
  background: linear-gradient(135deg, var(--accent-primary), var(--accent-secondary));
  display: flex;
  align-items: center;
  justify-content: center;
  font-size: 1.5rem;
}

.mechanism-title {
  font-size: 1.25rem;
  font-weight: 600;
}

.mechanism-phenotype {
  font-size: 0.875rem;
  color: var(--accent-primary);
  font-family: var(--font-mono);
}

.mechanism-content {
  color: var(--text-secondary);
  margin-bottom: 1rem;
  line-height: 1.7;
}

.mechanism-cytokines {
  display: flex;
  flex-wrap: wrap;
  gap: 0.5rem;
}

.cytokine-tag {
  padding: 0.375rem 0.75rem;
  background: rgba(0, 212, 255, 0.1);
  border: 1px solid rgba(0, 212, 255, 0.2);
  border-radius: 9999px;
  font-size: 0.875rem;
  color: var(--accent-primary);
  font-family: var(--font-mono);
}

.mechanism-rpl {
  margin-top: 1rem;
  padding-top: 1rem;
  border-top: 1px solid rgba(255, 255, 255, 0.1);
  font-size: 0.9rem;
  color: var(--text-secondary);
}

.mechanism-rpl strong {
  color: var(--th1-tnf);
}

/* ================================
   Clinical Section
   ================================ */
.clinical-section {
  background: var(--bg-primary);
}

.clinical-card {
  text-align: center;
}

.clinical-icon {
  width: 4rem;
  height: 4rem;
  border-radius: 1.25rem;
  background: linear-gradient(135deg, var(--accent-primary), var(--accent-secondary));
  display: flex;
  align-items: center;
  justify-content: center;
  font-size: 2rem;
  margin: 0 auto 1.5rem;
}

/* ================================
   Figures Section
   ================================ */
.figures-section {
  background: var(--bg-secondary);
}

.figures-section .grid-3 {
  grid-template-columns: 1fr;
  gap: var(--space-lg);
}

.figure-card {
  background: var(--bg-card);
  border-radius: 1.5rem;
  overflow: hidden;
  border: 1px solid rgba(255, 255, 255, 0.05);
  transition: all var(--transition-normal);
  max-width: 1000px;
  margin: 0 auto;
}

.figure-card:hover {
  transform: translateY(-4px);
  border-color: rgba(255, 255, 255, 0.1);
  box-shadow: 0 20px 60px rgba(0, 0, 0, 0.3);
}

.figure-image {
  width: 100%;
  max-height: 600px;
  object-fit: contain;
  background: #ffffff;
  padding: 2rem;
  display: block;
}

.figure-info {
  padding: 2rem;
  text-align: center;
}

.figure-title {
  font-size: 1.5rem;
  font-weight: 700;
  margin-bottom: 0.75rem;
  color: var(--text-primary);
}

.figure-description {
  font-size: 1rem;
  color: var(--text-secondary);
}

/* ================================
   Footer
   ================================ */
.footer {
  background: var(--bg-primary);
  border-top: 1px solid rgba(255, 255, 255, 0.05);
  padding: var(--space-lg) 0;
}

.footer-content {
  text-align: center;
}

.footer-citation {
  font-size: 0.9rem;
  color: var(--text-secondary);
  margin-bottom: 1rem;
  font-style: italic;
  line-height: 1.7;
}

.footer-doi {
  display: inline-flex;
  align-items: center;
  gap: 0.5rem;
  padding: 0.5rem 1rem;
  background: rgba(0, 212, 255, 0.1);
  border: 1px solid rgba(0, 212, 255, 0.2);
  border-radius: 9999px;
  font-size: 0.875rem;
  color: var(--accent-primary);
  font-family: var(--font-mono);
}

.footer-doi:hover {
  background: rgba(0, 212, 255, 0.2);
}

/* ================================
   Animations
   ================================ */
@keyframes fadeInUp {
  from {
    opacity: 0;
    transform: translateY(30px);
  }
  to {
    opacity: 1;
    transform: translateY(0);
  }
}

.animate-in {
  opacity: 0;
  animation: fadeInUp 0.6s ease forwards;
}

.animate-delay-1 { animation-delay: 0.1s; }
.animate-delay-2 { animation-delay: 0.2s; }
.animate-delay-3 { animation-delay: 0.3s; }
.animate-delay-4 { animation-delay: 0.4s; }

/* ================================
   Scrollbar
   ================================ */
::-webkit-scrollbar {
  width: 8px;
  height: 8px;
}

::-webkit-scrollbar-track {
  background: var(--bg-secondary);
}

::-webkit-scrollbar-thumb {
  background: var(--bg-hover);
  border-radius: 4px;
}

::-webkit-scrollbar-thumb:hover {
  background: var(--text-muted);
}

/* ================================
   Responsive
   ================================ */
@media (max-width: 768px) {
  .hero-cta {
    flex-direction: column;
    align-items: center;
  }
  
  .btn {
    width: 100%;
    max-width: 280px;
    justify-content: center;
  }
  
  .cytokine-tabs {
    flex-direction: column;
    align-items: center;
  }
  
  .tab-btn {
    width: 100%;
    max-width: 280px;
  }
}