A microbial natural product fractionation library screen with HRMS/MS dereplication identifies new lipopeptaibiotics against Candida auris.

The rise of drug-resistant fungal pathogens, including , highlights the urgent need for novel antifungal therapies. We developed a cost-effective platform combining microbial extract prefractionation with rapid MS/MS-bioinformatics-based dereplication to efficiently prioritize new antifungal scaffolds. Screening and revealed novel lipopeptaibiotics, coniotins, from WAC11161, which were undetectable in crude extracts.

Description of STRIVE-ON Study Protocol: Safety and Tolerability of GTX-104 (Nimodipine Injection for IV Infusion) Compared with Oral Nimodipine in Patients Hospitalized for Aneurysmal Subarachnoid Hemorrhage (aSAH): A Prospective, Randomized, Phase III Trial (STRIVE-ON).

Oral nimodipine is the only drug approved in North America for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, bioavailability is variable and frequently poor, leading to fluctuations in peak plasma concentrations that cause dose-limiting hypotension. Furthermore, administration is problematic in patients who cannot swallow.

Mechanistic Insights into Melatonin's Antiarrhythmic Effects in Acute Ischemia-Reperfusion-Injured Rabbit Hearts Undergoing Therapeutic Hypothermia.

The electrophysiological mechanisms underlying melatonin's actions and the electrophysiological consequences of superimposed therapeutic hypothermia (TH) in preventing cardiac ischemia-reperfusion (IR) injury-induced arrhythmias remain largely unknown. This study aimed to unveil these issues using acute IR-injured hearts. Rabbits were divided into heart failure (HF), HF+melatonin, control, and control+melatonin groups.

Insufficient pretransplant induction therapy is associated with diffuse intrahepatic cholangiopathy in ABO-incompatible living donor liver transplantation for acute liver failure.

Background: ABO-incompatible liver transplantation (ABOi LT) can now be successfully performed with standard pretransplant induction therapy. For patients with chronic end-stage liver disease (ESLD), ABOi LT can achieve long-term outcomes comparable to those of blood type-compatible (ABOc) LT. Outcomes of patients with acute liver failure (ALF) who undergo urgent transplantation surgery with a limited induction period should be further investigated.

Butyrolactol A is a phospholipid flippase inhibitor that potentiates the bioactivity of caspofungin against resistant fungi.

Fungal infections cause millions of deaths annually and are challenging to treat due to limited antifungal options and increasing drug resistance. Cryptococci are intrinsically resistant to the latest generation of antifungals, echinocandins, while , a notorious global threat, is also increasingly resistant. We performed a natural product extract screen for rescue of the activity of the echinocandin caspofungin against H99, identifying butyrolactol A, which restores echinocandin efficacy against resistant fungal pathogens, including .