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.

Multi-exponential analysis of time-domain fluorescence data was used to derive four amplitude-based metrics of PD-L1 expression...Among the evaluated metrics, a normalized parameter that accounts for inter-lifetime crosstalk demonstrated the strongest correlation with ex vivo PD-L1 expression (r 2  = 0.77). These findings establish a foundation for a noninvasive, nonionizing imaging approach to quantify and monitor receptor expression and support a future path for the longitudinal assessment of immune biomarkers in both preclinical studies and clinical settings.

Older participants showed dampened amplitudes, phase shifts, and inflammatory dominance...These findings establish sweat as a valid, real-time medium for capturing endocrine and immune cycles, with analytical tools capable of uncovering early physiological strain. This work lays a foundation for personalized chronobiological monitoring and stress-risk screening in naturalistic settings.

VNS was applied with varying frequencies, pulse widths, and amplitudes...VNS modulates distal colon transit and rectal tone through coordinated nitrergic and cholinergic signaling and central vagal-to-sacral circuits. These findings reveal functional crosstalk between vagal and sacral parasympathetic pathways and provide mechanistic insight into potential VNS therapy for lower GI disorders.

We found that suvorexant improved visual acuity and retinal vascular insufficiency by reducing retinal inflammation and improving glucose homeostasis in db/db mice. Our findings suggest that orexin receptor inhibition, with suvorexant, may be a potential treatment for ocular complications associated with T2D.

BMAL1 functional downregulation, REV-ERBα oscillatory output attenuation, NAD+ oscillatory amplitude reduction, and gut-liver axis circadian desynchronization together constitute an inferential framework for hepatic circadian failure...This evidence gap limits the clinical actionability of current mechanistic findings across all disease categories. Circadian phase inference algorithms and prospective temporally designed cohort studies offer a methodologically grounded path toward clinically actionable circadian hepatology.