This study clarifies the clinical relevance of cytoplasmic AR-V7 in circulating tumor cells from men with metastatic castration-resistant prostate cancer. While nuclear-localized AR-V7 predicts extremely poor response, PFS, and overall survival with AR pathway inhibitors, cytoplasmic AR-V7 expands the definition of AR-V7-positive status and identifies patients with equally poor PFS and intermediate response and overall survival outcomes. Assessing both nuclear and cytoplasmic AR-V7 fractions may thus improve risk stratification heterogeneity and could better guide poor-risk ARPI treatment decisions by avoiding ineffective ARPI treatment, helping personalize therapy, and improving outcomes in men with mCRPC.

Finally, our in vitro and in vivo experiments indicate that the CREB1 phosphorylation inhibitor 666-15 significantly enhances the therapeutic efficacy of Abi-RT combination therapy. In summary, our study reveals that inhibition of the CREB1-CtIP axis effectively improves the therapeutic outcomes of Abi-RT combination therapy, which may offer a novel clinical strategy for the treatment of prostate cancer.

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.

P2, N=102, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

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.

In a castrated PC-3 xenograft model, PLP (400 mg/kg/day) suppressed tumor volume growth by 91.7% and tumor weight growth by 78.0% compared with the control group, showing efficacy comparable to abiraterone/prednisone without hepatorenal toxicity...Integrative transcriptomic and multi-omics analyses revealed coordinated downregulation of phosphatidylinositol 3-kinase-protein kinase B-mechanistic target of rapamycin signaling and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Functional validation showed that overexpression of phosphoinositide-3-kinase regulatory subunit 1 rescued PLP-induced tumor suppression, whereas knockdown of PGC-1α abolished its antioxidative and antiproliferative effects, indicating that both pathways are critically involved. These findings suggest that PLP combats CRPC by simultaneously inhibiting oncogenic signaling and mitigating oxidative stress, positioning it as a promising natural therapeutic candidate for CRPC.

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.

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.

P2, N=7, Terminated, M.D. Anderson Cancer Center | Trial completion date: Apr 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2027 --> Mar 2026; <75% participation

In addition, IRX6 expression showed associations with reduced sensitivity to abiraterone, suggesting a potential link with therapeutic resistance in these tumours. Collectively, these findings highlight the context-dependent expression patterns and clinical associations of IRX genes across hormone-driven cancers. While largely correlative, this study provides a framework for future functional investigations and suggests that selected IRXs may have potential utility as biomarkers for disease stratification and treatment response in hormone-sensitive cancers.