Trajectory of Urine Parameters by Adding Herbal Kampo Medicine Goreisan to Tolvaptan in Patients with Congestive Heart Failure.

Even in current guideline-directed medical therapy, including recently introduced vasopressin type 2 receptor antagonist tolvaptan, congestion has not been resolved in patients with heart failure. Kampo medicine goreisan has been receiving considerable attention as an additional therapy for patients who are refractory to conventional diuretics therapy, including tolvaptan. However, the impact of goreisan on urine electrolytes remains uncertain.

Skeletal muscle oxidative capacity related to intramyocellular lipid in young but not in older individuals.

Skeletal muscles contain lipids inside and outside cells, namely intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL), respectively; lipids have also been found to be interspersed between these muscles as adipose tissue, namely intermuscular adipose tissue (IMAT). Metabolized IMCL has been recognized as an important substrate for energy production and their metabolism is determined by the muscle oxidative capacity. Therefore, it has been speculated that muscle oxidative capacity is related to muscle lipid content.

Photocatalytic → isomerization of -bromofluoroalkenes: stereoselective synthesis of β-fluorostyrene derivatives.

Stereoselective synthesis of β-fluorostyrene derivatives has been achieved. Selective isomerization of -bromofluoroalkenyl benzenes bearing various -substituents is enabled by using Ir photocatalysts with high triplet energy. Subsequent one-pot transition-metal (TM)-catalyzed reactions enable pot-economical synthesis of monofluoroalkenes in a stereoselective manner.

Discovery of 2-(6-{[(1R,2R)-2-hydroxycyclohexyl]amino}-4,5-dimethylpyridazin-3-yl)-5-(trifluoromethyl)phenol (ASP0965): A potent, orally active and brain-penetrable NLRP3 inflammasome inhibitor with a novel scaffold for the treatment of α-synucleinopathy.

NLRP3 inflammasome inhibitor is a highly attractive drug target for the treatment of various inflammatory diseases. Here, we report the discovery of pyridazine derivatives as a new class of scaffold for NLRP3 inflammasome inhibitors. We optimized HTS hit 2a to improve both in vitro IL-1β inhibitory activity and the mean photo effect (MPE) value in the in vitro 3T3 neutral red uptake (NRU) phototoxicity test.

Environmental Conditions Modulate Warming Effects on Plant Litter Decomposition Globally.

Empirical studies worldwide show that warming has variable effects on plant litter decomposition, leaving the overall impact of climate change on decomposition uncertain. We conducted a meta-analysis of 109 experimental warming studies across seven continents, using natural and standardised plant material, to assess the overarching effect of warming on litter decomposition and identify potential moderating factors. We determined that at least 5.