NFL Predictions: Week 6 Picks and Hot Takes From Around the NFL

Oct 9, 2016; Oakland, CA, USA; Oakland Raiders quarterback Derek Carr (4) waves to the crowd after the game against the San Diego Chargers at Oakland Coliseum. The Raiders defeated the Chargers 34-31. Mandatory Credit: Cary Edmondson-USA TODAY Sports
Oct 9, 2016; Oakland, CA, USA; Oakland Raiders quarterback Derek Carr (4) waves to the crowd after the game against the San Diego Chargers at Oakland Coliseum. The Raiders defeated the Chargers 34-31. Mandatory Credit: Cary Edmondson-USA TODAY Sports /
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Oct 9, 2016; Los Angeles, CA, USA; Buffalo Bills head coach Rex Ryan reacts during a NFL game against the Los Angeles Rams at Los Angeles Memorial Coliseum. Mandatory Credit: Kirby Lee-USA TODAY Sports
Oct 9, 2016; Los Angeles, CA, USA; Buffalo Bills head coach Rex Ryan reacts during a NFL game against the Los Angeles Rams at Los Angeles Memorial Coliseum. Mandatory Credit: Kirby Lee-USA TODAY Sports /

San Francisco 49ers at Buffalo Bills, 1:00 p.m. ET on Sunday, FOX

Colin Kaepernick is set to make his 2016 debut, which will make this arguably the storyline of the weekend in the national media cycles. Unfortunately for the 49ers, the plot might just thicken even further after colliding with Buffalo in San Francisco’s cross-country trip.

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There’s a reason the Bills are 7.5-point favorites here. Riding a high and at home against a team with little momentum to speak of (four straight losses, three by double-digits), it’s hard to not like Rex Ryan’s squad in this one.

Though Tyrod Taylor hasn’t been brilliant, he’ll match up against a 49ers defense that has allowed 33+ points in three of their last four games after a week one shutout against L.A. As long as the offensive line wins in one-on-one battles in the trenches, this one shouldn’t be close.

On offense for the 49ers, it’s difficult to expect any profits after the switch to Kaepernick. Politics aside (as they should be), Kaepernick isn’t the fit in San Francisco. Chip Kelly’s decision to start Blaine Gabbert over Kaep says everything we need to know. With a lack of weapons available, in start number one of the season, and against a stout Buffalo defense, it surely doesn’t appear a win is in the cards for the visiting 49ers.

Bills win fourth straight against 49ers, 23-13.