P1, N=120, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

Retinas in the LIM group showed thinning, disorganized layers, and reduced FERG amplitudes (Cone-b/Rod-b/OPs)...4-PBA mitigates retinal damage in myopia by inhibiting ATF6-mediated ERS, reducing calcium overload, restoring mitochondrial function, and suppressing the ATF6-CHOP-Bax apoptotic cascade. This study identifies the ATF6 pathway as a therapeutic target for myopic retinopathy and supports 4-PBA's potential as a retinal protective agent.

Model A predictors were age, sex, body mass index, HbA1c, mean glucose, mean amplitude of glycaemic excursions (MAGE) from the first 72 h of capillary glucose, 2-hour C-peptide, apolipoprotein A-I (ApoA-I), albumin, and sodium-glucose cotransporter 2 (SGLT2) inhibitor use...Adding tumour markers, particularly CYFRA21-1, improved discrimination. Prospective multicentre validation and assessment of clinical and economic impact are warranted before implementation.

For EC pyramidal neurons, the chemotherapeutic agent doxorubicin caused increases in the amplitudes of both spontaneous excitatory and inhibitory post-synaptic currents, with significant responses (***p < 0.001; **p < 0.01 respectively) in APOE3 brains. Doxorubicin doubled the percentage of PV cells that showed inactivation block in APOE3 brains (25% to 52%) but had no effect on APOE4 brains (50% to 54%). This ex vivo study suggests that APOE4 impairs homeostatic synaptic transmission in pyramidal cells under control conditions and causes a lack of responsiveness to a stressor (doxorubicin treatment) in PV cells.

Circadian oscillators act as temporal gatekeepers of stem-cell function. Mapping the molecular interfaces between clock genes and developmental signaling pathways reveals new opportunities to refine regenerative therapies. Chronotherapeutic strategies, i.e. timing interventions to intrinsic circadian phases may enhance the efficacy, precision, and safety of stem-cell-based treatments.

P1/2, N=156, Recruiting, Eikon Therapeutics | N=70 --> 156 | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Feb 2026 --> Jun 2027

Patch-clamp recordings revealed that zeta inhibitory peptide inhibited the amplitude of evoked excitatory postsynaptic currents (EPSCs) and the frequency of miniature EPSCs in CPTP and KIBRA overexpression groups. These results demonstrate that KIBRA in ACC neurons significantly contributes to CPTP by p-PKMζ/GluR1 and neuroinflammation, offering novel mechanistic insights. However, as the study was conducted exclusively in male animals, and studies in clinical settings have shown that the CPTP prevalence is higher among females, the findings primarily apply to males, underscoring the need for future sex-specific investigations.

Electromyography (EMG) was used to assess latency and amplitude ratios (affected/healthy side) of the frontal, orbicularis oculi, and orbicularis oris muscles...The total effective rate in the observation group was 93.1% (27/29), higher than that in the control group (82.1%, 23/28, P<0.05). Acupotomy combined with acupuncture could promote recovery of facial nerve function and shorten the duration of mastoid region pain in patients with acute peripheral facial paralysis with mastoid region pain.

Vasomotor pulsations may arise from amplitude modulations of respiratory (RPE) and cardiovascular (CHE) pulsations while cardiovascular fluctuations may be modulated by respiration through cardiorespiratory amplitude modulation (CREM)...While elevations in all pulsations were present within (peri)tumoral regions, AFRPE elevations extended into extra-tumoral white matter and grey matter. Thus, altered cardiorespiratory fluctuations give rise to dysfunctional vasomotor and CSF pulsations in PCNSL, predicting impaired glymphatic function.

Using patch-clamp recordings in cultured cortical neurons we found that lactate enhances NMDA receptor currents (INMDAR), increasing their amplitude and decay time constant...Lactate strengthens the interaction between CaMKII and GluN2B through redox-sensitive cysteine residues in GluN2B, facilitating synaptic localization of this complex and enhancing synaptic responses. These findings reveal a molecular pathway by which lactate, produced by astrocytes, can significantly influence neuronal activity and synaptic function, linking brain metabolism with learning and memory processes.

Herein, we report the rational design and synthesis of a series of second-generation selective PARP1/CDK6 dual inhibitors, based on the structural features of the latest selective PARP1 inhibitor AZD5305...Furthermore, compared with first-generation inhibitors, PC8 displays improved metabolic stability in liver microsomes. As a novel selective PARP1/CDK6 dual inhibitor with improved pharmacological properties, PC8 represents a promising lead structure for further optimization of second-generation PARP1/CDK6 dual inhibitors for the treatment of TNBC.

P1, N=41, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial completion date: Nov 2026 --> Apr 2026 | Trial primary completion date: Jul 2026 --> Feb 2026