In vivo, compound C16a demonstrated excellent tumor growth inhibition (TGI) in the AZD5305-sensitive/-insensitive xenograft model with TGI values of 133.6% and 71.9%, respectively. Collectively, compound C16a may be a powerful therapeutic agent not only for treating PARPi-sensitive tumors but also PARPi-resistant tumors, even HR-proficient tumors.

Curcumin offers protective effects on the retinas of diabetic mice, likely through the modulation of the Hippo-YAP signaling pathway and the inhibition of EndMT. These findings provide support for the use of curcumin as a promising adjunctive therapy for diabetic retinopathy.

In contrast, Mode 3 exhibited comparatively more stable and physically interpretable interaction energy profiles with sustained negative interaction energies and reduced fluctuation amplitudes...Among the evaluated docking modes, Modes one and 3 exhibited the most favorable balance between structural persistence and energetic stability. These findings provide computational support for the potential of the quinazoline-based scaffold C9 as a candidate KRAS-targeting compound and establish a mechanistic framework for future structure-guided optimization and experimental validation in KRAS-driven lung cancer systems.

P1, N=113, Completed, AstraZeneca | Recruiting --> Completed

P1/2, N=152, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

D-box binding protein (DBP) is a high-amplitude proline- and acidic amino acid-rich basic leucine zipper (PAR bZIP) transcription factor that functions as a key circadian output regulator downstream of the core molecular clock...We also highlight the current limits of human translational evidence and propose that DBP-centered signatures may be useful for interpreting circadian output failure in disease. Overall, DBP provides a mechanistically informative framework for understanding how circadian time is transformed into organ-specific physiological function and pathological vulnerability.

Blunted nocturnal melatonin amplitude is linked to tumour-promoting inflammation in oesophageal-cancer survivors, but it is unclear whether restoring endogenous rhythms improves clinical outcomes...Behavioural realignment of endogenous melatonin rhythms was associated with sustained reductions in systemic inflammation and fewer adverse events in oesophageal-cancer survivors. Routine circadian-hygiene counselling combined with simple salivary monitoring may help support long-term oncologic and cardiometabolic health.

Autophagy inhibition downstream of the mTOR pathway is a mechanism of PARPi sensitivity in SCLC. This suggests that a therapeutic combination of autophagy inhibition and PARPi is a promising treatment strategy in SCLC, paving the way for the adoption of novel treatments in this disease context.

P1, N=60, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | N=141 --> 60

Current data support a circadian influence on NK biology, but the direction and magnitude of reported effects vary across species, sampling schedules, circadian phase definitions, tissue compartments, and NK-cell readouts. This heterogeneity underscores the need for longitudinal, high-frequency sampling with complementary continuous monitoring to define phase, amplitude, and stability across physiological and clinical contexts.

The tonic current was only partially reverted by the GluN2B subunit specific NMDA receptor (NMDAR) antagonist ifenprodil, whereas SICs were almost fully eliminated. The amplitude of the current was inversely proportional with the age of the patient and disappeared in elderly over the age of 70...In summary, NMDAR-dependent tonic inward currents are overlapping but partially separable phenomena from SICs. One might hypothesize that the tonic current is only present under excitotoxic conditions and do not determine physiological neuronal excitability in human.

This newly established model of mechanical stress injury effectively recapitulates the pathophysiology of CST damage following ICH. It also provides a simple and reproducible tool for conducting preclinical studies on mechanical stress-induced WMI in ICH.