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.

P3, N=1889, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial primary completion date: Jan 2028 --> Sep 2027

This study provides a first-in-class characterization of saruparib resistance and maps a clear therapeutic path forward. By identifying these specific PARP1 mutations and their collateral DDR vulnerabilities, we provide the molecular framework necessary to monitor and treat patients who progress on next-generation PARP1-selective inhibitors.

To delineate underlying mechanisms, we employed Network Perturbation Amplitude (NPA) analysis, which uncovered qualitatively distinct toxicity architectures: HTP-1 exhibited higher overall toxicity and elicited broad-spectrum network perturbations involving cell stress, proliferation, and immune regulation, correlating with greater apoptotic induction; HTP-2 triggered focused activation of damage-sensing pathways, consistent with its earlier membrane disruption and more pronounced genotoxicity. Multi-omics analysis further linked these mechanistic perturbations to human disease-relevant pathways, with HTP-1 showing stronger enrichment for COPD-associated expression patterns and HTP-2 for lung cancer-related signatures, suggesting the acute molecular response to each product exhibits similarity to specific pulmonary disease-associated molecular signatures. These findings establish human-derived airway organoids as a sensitive, human-relevant platform within the New Approach Methodologies‌ (NAMs) framework for qualitative comparison and mechanistic interrogation of product-specific toxicity.

E. fischeriana disrupts intestinal metabolic and circadian coordination, leading to epithelial barrier dysfunction. Milk processing partially mitigates intestinal metabolic disturbance and structural injury, but fails to fully restore circadian regulation. These findings provide mechanistic insight into the intestinal toxicity of E. fischeriana and the detoxification mechanism of traditional milk processing.

Pyramidal neurons in the auditory cortex of TNF-α KO mice had larger miniature excitatory postsynaptic current (mEPSC) amplitude and lower miniature inhibitory postsynaptic current (mIPSC) frequency, suggesting a shift in synaptic E/I balance...Here, we show that TNF-α-deficient mice have reduced parvalbumin-positive (PV) inhibitory interneuron density, an increased E/I ratio, impaired sensory restriction-induced homeostatic plasticity, and persistent critical period-like plasticity in adulthood. Together, these findings suggest a nonlinear, bell-shaped relationship between TNF-α signaling and cortical circuit function, in which both excessive and deficient TNF-α levels are associated with impaired PV interneuron function and increased E/I ratio.

This concept may be particularly relevant to in vivo CAR T platforms, which could extend temporal control beyond infusion timing through repeatable induction, tunable amplitude, and reversible shutdown...We further examine how viral vectors, lipid nanoparticles, and programmable control circuits might enable circadian-aware CAR installation and duty-cycling. Together, these observations support chrono-synthetic CAR T as a testable translational framework for precision immuno-oncology.