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1st Appearances 2021
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- 1st appearance of Somnus
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- 1st full appearance of Catalina Chavez, the sister of America
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- Premiere issue of a 5-issue prelude to the War of the Bounty Hunters event
- 1st appearance of Doc Ragon
- First mention of Wyrmen Lictor
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- 1st full appearance of Miracle Molly, a member of the Unsanity Collective
- 1st appearance of Squeak, member of the Unsanity Collective
- 1st full appearance of Master Wyze, leader of the Unsanity Collective
- Origin of Peacemaker-01
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- 1st appearance of Lucy Nguyen, a protégé of Natasha who she names Marigold
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- 1st appearance of Jacks Chopra
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- 1st appearance of Kevin Schumer
- 1st cameo appearance of Threadneedle
- 1st cameo appearance of Zarala, a Wakandan
- 1st team appearance of the Avengers: Captain America, Aero, the Human Torch, Golden Age Vision, Black Cat, Iron Man, Storm, Kevin Schumer, Warbird
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- 1st team appearance of the Squadron Supreme of America
- 1st appearance of Daywalker Blade
- 1st appearance of Dr. Juggernaut
- 1st appearance of the Black Skull
- 1st appearance of the Silver Witch
- 1st appearance of the Unstoppable All-Gog
- Introduction of Thanos' Infinity Rings
- Previews sketches of multiple characters
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- 1st appearance of Captain America of Harrisburg named Nichelle Wright
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- 1st appearance of Vengeance, daughter of Bane
- 1st team appearance of the Sampson family, inspired by the family from Texas Chainsaw Massacre
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- 1st appearance of Ameyra Khalan, Thanagarian captain of the United Planets Brigade
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- 1st appearance of Saya Ishii
- Reintroduction of Kasha, a Japanese cat demon who first appeared in X-Force #221
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- 1st appearance of Alice, a possible sidekick in the making for Elektra as Daredevil
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- 1st full appearance of Marchion Ro
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- 1st appearance of the Gardener
- 1st appearance of The Instigator, a martial artist and terrorist
- 1st appearance of Madame Midas, the richest woman on Earth
- 1st appearance of Kid Kawaii, an robot mercenary
- 1st appearance of Brainstorm, a telekinetic
- 1st appearance of Razorline, a monster alien
- For the Ghost-Maker backup story's multiple first appearances, writer James Tynion drew inspiration from the Batman story that introduced Harley Quinn in print, 'Almost Got 'Im'
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- 1st appearance of Taegukgi, a Korean superhero
- 1st partial team appearance of Tiger Division
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