Three-time champions Inter Milan face a battle to get through Europa League Group K after a second successive defeat.
A 3-1 setback against Sparta Prague followed up a 2-0 loss to Hapoel Be'er Sheva to leave Inter pointless and bottom of the group, four points behind Hapoel and Southampton, who drew 0-0 in Israel.
Vaclac Kadlec's first-half brace set Sparta on their way and though Inter captain Rodrigo Palacio pulled one back, Mario Holek quickly put the game to bed.
Krasnodar and Schalke took a stranglehold on Group I after each recording their second straight win.
The Russian side won 5-2 against Nice as Joaozinho's double added to Fedor Smolov's opener.
Nice twice pulled within one, through first Mario Balotelli and then Wylan Cyprien, but substitute Ari's late double secured victory.
Schalke beat Salzburg 3-1 with goals from Leon Goretzka and Naldo either side of Duje Caleta-Car's own goal. Jonatan Soriano pulled one back for the Austrians.
Fiorentina were also comfortable winners, beating 10-man Qarabag 5-1 to top Group J. Khouma Babacar and Mauro Zarate scored twice each, with Nikola Kalinic also on target. Dino Ndlovu scored in injury time for Qarabag, who had Elvin Yunuszada sent off after half an hour.
PAOK Salonika beat Slovan Liberec 2-1 in the same group, Stefanos Athanasiadis scoring twice to overcome Nikolay Komlichenko's first-minute opener.
Kasper Dolberg's goal was enough to keep Ajax top of Group G with a 1-0 win over Standard Liege, who hit a post late on through Isaac Mbenza. Celta Vigo are two points back after late goals from John Guidetti and Daniel Wass saw them beat Panathinaikos 2-0.
Shakhtar Donetsk beat Braga 2-0 with goals from Taras Stepanenko and Viktor Kovalenko to stay clear in Group H, despite Fred's red card early in the second half. Gent beat Konyaspor by the same score thanks to Kenneth Saief and Renato Neto.
FC Zurich beat Osmanlispor 2-1 with goals from Marco Schonbachler and Dzengis Cavusevic as Group L closed up.
Adam Maher scored for the previous group leaders, who were overhauled by Villarreal after the Yellow Submarine's 1-1 draw with Steaua Bucharest - Rafael Borre and Sulley Muniru with the goals.
Mainz beat Gabala 3-2 in Group C's early game, leading through Yoshinori Muto but falling behind to goals from Ruslan Gurbanov and Sergei Zenjov before Jhon Cordoba and Levin Oztunali swung the game decisively back their way.