Nature, Published online: 05 March 2025; doi:10.1038/s41586-025-08618-7A peripherally restricted CB1 agonist (VIP36) targeting a cryptic receptor pocket was developed, showing high efficacy in mouse pain models with minimal side effects and tolerance, potentially revolutionizing chronic pain treatment and GPCR drug design.

Nature, Published online: 05 March 2025; doi:10.1038/s41586-025-08637-4The analysis of pairs of identical SARS-CoV-2 genome sequences enables characterization of transmission patterns between geographies and age groups.

Predictions on the dawn of the AI singularity vary wildly but scientists generally say it will come before 2040, according to new analysis, slashing 20 years off previous predictions.

submitted by /u/ViscousRealm [link] [comments]

I made the blue version because the client asked to match the listing color. But i perfer the first one. What do you think ? submitted by /u/OkSubject2900 [link] [comments]

The horror gaming genre has evolved a great deal in the last few decades, and it's taken many different forms. Horror games have gone from simple text-based adventures to fixed-camera survival horror to third-person action games, and a whole lot in between. That constant evolution has meant that the definition of a horror game is rather loose, but it usually boils down to any game that puts a primary focus on scaring the player, through eerie environments, intense music, spooky monster design, or any combination of the three.

Attack on Titan's iconic and complex story came to an end with Eren's death. Eren's path from being the protagonist to becoming the antagonist changed the course of the anime completely. He chased freedom for as long as he could remember. Was he finally able to reach it? How did his death impact the world left behind?

I had no idea what I was getting into when I jumped into the world of Sorry Were Closed, a narrative-driven survival horror adventure that pairs the grime and decay of Silent Hill with the stylish, sexed-up demons of Persona games. But the artists behind Sorry Were Closed have managed to remix some of my favorite gaming memories into something unique and surprising.That even includes pairing Resident Evil-style tank controls and fixed camera angles with arcade light-gun shooters. Somehow all of these disparate gameplay influences come together in a nearly magical way.Sorry Were Closed focuses on Michelle, a struggling, heartbroken Londoner who has an unlucky encounter with a sleep-paralysis archdemon known as the Duchess. This experience sends Michelle on a journey of discovery, during which she becomes immersed in a world of angels and demons in conflict; this experience ultimately unlocks magical powers within her. Cursed with mystical vision through a third eye, Michelle can see through the veil of the real world into the demon world and converse with its residents.The Duchess has pursued Michelle as part of the archdemons mission to find love, and shell stop at nothing to convince her heartbroken prey to give in to these advances. Rebuffing her archdemon suitor, Michelle works with her friends (some of whom have secretly been demons this whole time) to break free of the Duchess curse and chase down the archdemons former flames/victims.Michelles Evil Eye vision comes into play both narratively and in gameplay. With the press of a button and a snap of her fingers, Michelle can see other layers of her world, uncovering secret doors, hidden objects, and the corporeal forms of ethereal figures. Sorry Were Closed uses this vision for environmental puzzles as well; a painting of eyes on a wall in the real world is revealed to be a smart-mouthed eye demon that blocks a pathway, and obstructions like an indestructible metal box can be revealed in the demon world as wooden boxes that can be smashed with an ax.These Evil Eye powers also factor into combat. In the real world, youll face monsters that can be killed with multiple swings of an ax or riddled with bullets. But if Michelle flicks on her Evil Eye, she can see into the hearts of her enemies, attacking their weak point to slay them quickly. Michelles otherworldly vision only extends so far, though. Theres a trade-off between fighting enemies inefficiently in the real world at distance and allowing them to get closer so Michelle can kill them quickly but incur more risk in the process.Combat and movement can be a bit clunky in Sorry Were Closed. While exploration is done in third-person view, combat switches to a sometimes disorienting first-person view. Here, the developers draw influence from light-gun games like Time Crisis or House of the Dead, pushing the player to attack rapidly and chain together combos. Pulling off a series of perfect attacks charges up a weapon called the Heartbreaker, a powerful rifle that deals massive damage to enemy demons.Combat encounters in Sorry Were Closed clicked with me, but I can see them being a sticking point for some players. Fortunately, failure in Sorry Were Closed is rarely frustrating. The game has a manual save system with frequent save points and generous autosaving. While rationing bullets and health items water bottles, because its important to stay hydrated is a concern, the game is less punishing than many other survival horror games. (Accessibility options can also make the game much, much easier.)Beyond combat and exploration of the games demonic worlds, Michelle spends a good deal of her time conversing with friends, frenemies, and the angels and demons she can see through her third eye. Theres a rich cast of characters, many of them relatably flawed people trying their best to find love or heal from trauma. These characters (and monsters) are all beautifully realized; Sorry Were Closed oozes style with its mix of horny, elegant, and wonderfully weird misfits. Its lovely to see a horror game with bright, flashy pops of color.Sorry Were Closed has been out on PC platforms since November 2024. Developer la mode games and publisher Akupara Games have since brought the game to consoles (Nintendo Switch, PlayStation 4, PlayStation 5, Xbox One, and Xbox Series X) and upgraded the original release with new features. For survival horror fans looking for a queer-romance-infused spin on retro Resident Evil-style gameplay, Sorry Were Closed comes highly recommended. You might just fall in love, which is exactly what the Duchess wants.Sorry Were Closedwas released Nov. 14, 2024, on Windows PC and March 6 on Nintendo Switch, PlayStation 4, PlayStation 5, Xbox One, and Xbox Series X. The game was reviewed on PC using a download code provided by Valve. Vox Media has affiliate partnerships. These do not influence editorial content, though Vox Media may earn commissions for products purchased via affiliate links. You can findadditional information about Polygons ethics policy here.

Spring is nearly here, and that means Netflix has mixed up its library with plenty of new movies for you to discover.Every month, we handpick a few of the best thrillers on Netflix that fit the current season. Sometimes they pair well with an upcoming release. Other titles might be new additions to the platform.This month we have an excellent Gene Hackman performance to celebrate the incredible career of the late acting legend, Bong Joon Hos Oscar-winning masterpiece to get you ready for his new movie Mickey 17, and a sleek and sexy thriller to catch up on because its getting a sequel in just a few months.Editors pick: Runaway JuryDirector: Gary FlederCast: Gene Hackman, John Cusack, Dustin HoffmanGene Hackman passed away in February at the age of 95. Its difficult to pick a favorite performance out of his more than four-decade-long career as an actor, boasting iconic roles in such classics as Crimson Tide, Unforgiven, and The French Connection, with the latter two earning him Academy Awards. For me, Ill always remember Hackman for his role as the amoral jury consultant Rankin Fitch in 2003s Runaway Jury. That alone would guarantee the films place on this weeks list, but top that off with a terrific trio of performances by Dustin Hoffman, John Cusack, and Rachel Weisz, and you have an absolute knockout of a legal thriller. Toussaint EganA Simple FavorDirector: Paul FeigCast: Anna Kendrick, Blake Lively, Henry GoldingA Simple Favor 2, technically called Another Simple Favor, is finally real. Theres a legit, non-fan-edited trailer, and a Prime Video release date of May 1. And that means its the perfect time for you to rewatch or catch up on Paul Feigs campy thriller romp. If you havent seen it yet, A Simple Favor follows Stephanie Smothers (Anna Kendrick), a mommy vlogger who meets Emily Nelson (Blake Lively), a rich, self-assured, and effortlessly cool mom whos exactly the kind of person Stephanie wishes she was. The two quickly strike up a friendship, but when tragedy strikes, Stephanie starts to wonder if her new friend was only using her this whole time. A Simple Favor is a delicious, airy thriller that relishes every opportunity to pull the rug out from under you and reverse your expectations, all without losing its wonderful sense of fun. Now lets hope the sequel can live up. Austen GoslinParasiteDirector: Bong Joon HoCast: Song Kang-ho, Lee Sun-kyun, Choi Woo-shikBong Joon Ho is back in theaters this weekend with his new sci-fi comedy Mickey 17, his first film since his 2019 black comedy thriller Parasite won the Academy Award for Best Picture. What better time than now to revisit the film that catapulted Bong to the meteoric heights of Hollywood history? Following the story of a poor family who infiltrate the home of a wealthy couple, Parasite feels as revelatory, hilarious, and deeply tragic as it did upon release. Song Kang-hos performance as Kim Ki-taek, the put-upon father who is hired as the personal chauffeur for the wealthy Park Dong-iks family, is exceptional per usual, but Park So-dams performance as Kims daughter Ki-jung and her Jessica from Chicago chant stand out in an ensemble of terrific performances. I strain to throw any more accolades at this movie that havent already been laid at the feet of its director and performers, but trust me when I say this: This film lives up to its reputation and then some. TE

Americans take billions of photos, yet only a small fraction make it into printed albums, risking future loss.