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Objective Dexmedetomidine (DEX) has been shown to have anti-apoptotic effects in diabetes mellitus, but its role in mitigating diabetic cardiomyopathy (DCM) through ferroptosis regulation is unclear. Methods An in vitro DCM model was established using H9C2 cells induced with high glucose (HG) and treated with DEX at varying doses and a nuclear factor erythroid 2-realated factor 2 (Nrf2) specific inhibitor ML385. Cell viability was evaluated using the MTT method after treatment with DEX or mannitol (MAN), and the dosage of DEX used in subsequent experimentation was determined. The effects of HG-induced high osmotic pressure were assessed using MAN as a control. Cell apoptosis was evaluated using flow cytometry. Protein levels of Bcl2, Bax, nuclear Nrf2, and glutathione peroxidase 4 (GPX4) were measured using Western blot. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, Fe 2+ concentration and reactive oxygen species (ROS) levels were measured using corresponding kits and dichlorodihydrofluorescein diacetate, respectively. Results Treatment with DEX or MAN had no effect on H9C2 cell viability. HG induction reduced H9C2 cell viability, increased cell apoptosis, upregulated levels of Bax, Fe 2+ , MDA, and ROS, and downregulated Bcl2 protein levels, SOD activity, and protein levels of nuclear Nrf2 and GPX4. DEX inhibited HG-induced H9C2 cell apoptosis, promoted Nrf2 nuclear translocation, and activated the Nrf2/GPX4 pathway. Inhibition of Nrf2 partially reversed the protective effects of DEX against HG-evoked H9C2 cell injury. Conclusion Our findings demonstrate that DEX attenuates HG-induced cardiomyocyte injury by inhibiting ferroptosis through the Nrf2/GPX4 pathway, providing potential therapeutic targets for DCM treatment.

Genomic analysis of 5,303 Chinese women with recurrent major depressive disorder (MDD) enables the identification and replication of two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene; the other in an intron of the LHPP gene. Genetic risk factors for depression This genomic analysis of more than 5,000 Chinese women with recurrent major depressive disorder (MDD) has identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10. One is near the sirtuin1 ( SIRT1 ) gene, and the other is in an intron of the phospholysine phosphohistidine inorganic pyrophosphate phosphatase ( LHPP ) gene. The authors suggest that the association close to SIRT1 may implicate abnormalities in mitochondria as risk factors for the disease. Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide 1 , poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified 2 , despite analysis of more than 9,000 cases 3 . Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene ( P  = 2.53 × 10 −10 ), the other in an intron of the LHPP gene ( P = 6.45 × 10 −12 ). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

Postoperative cognitive dysfunction (POCD) is a frequent complication of cardiac surgery. The present study aimed to quantify changes in Mini-Mental State Examination (MMSE) scores following on-pump cardiac surgery and explore potential study-level moderators associated with variability in cognitive outcomes. A systematic review and random-effects meta-analysis was performed following PRISMA guidelines. MEDLINE, Embase, Cumulative Index to Nursing & Allied Health Literature, Cochrane, PsycINFO, Web of Science, and Scopus were searched up to May 2025; eight prospective single-center cohorts (867 patients) met predefined criteria, providing 14 independent pre/postoperative comparisons of cognitive function. The mean MMSE score was extracted at baseline and final reported follow-up (7 days to 6 months). Hedges' g was pooled using a random-effects model; heterogeneity was summarized with τ² and I², and a 95% prediction interval (PI) was calculated. Overall, cardiac surgery was associated with a moderate decline in MMSE scores (g=-0.60, 95% confidence interval, -0.85 to -0.35; P<0.001). Heterogeneity was high (τ²=0.178; I²=88.8%), yet leave-one-out and Hartung-Knapp adjustments produced similar estimates. The 95% PI (-1.56 to 0.36) spans both negative and slightly positive values, indicating that while most cohorts show cognitive decline, the inclusion of values above zero suggests that small improvements remain possible in some populations. Subgroup analysis showed a large decline among patients meeting POCD criteria (g=-0.893) compared with a small, non-significant change in non-POCD patients (g=-0.274; Q_between=9.08, P=0.003). Meta-regression identified cardiopulmonary-bypass time as the only statistically significant moderator (β=-0.014 MMSE SD units/min; P=0.023), explaining ~50% of between-study variance. Funnel-plot tests suggested possible small-study effects, but trim-and-fill imputed no missing studies and Rosenthal's fail-safe N was 431, supporting the robustness of the pooled estimate. These findings suggest that on-pump cardiac surgery is frequently associated with a moderate decline in global cognitive performance as measured by the MMSE, particularly among patients who develop clinical POCD. Awareness of this association may support perioperative cognitive monitoring and efforts to minimize modifiable intraoperative factors such as prolonged cardiopulmonary bypass duration.

Cell death plays an important role in host-pathogen interactions. Crystal proteins (toxins) are essential components of Bacillus thuringiensis (Bt) biological pesticides because of their specific toxicity against insects and nematodes. However, the mode of action by which crystal toxins to induce cell death is not completely understood. Here we show that crystal toxin triggers cell death by necrosis signaling pathway using crystal toxin Cry6Aa-Caenorhabditis elegans toxin-host interaction system, which involves an increase in concentrations of cytoplasmic calcium, lysosomal lyses, uptake of propidium iodide, and burst of death fluorescence. We find that a deficiency in the necrosis pathway confers tolerance to Cry6Aa toxin. Intriguingly, the necrosis pathway is specifically triggered by Cry6Aa, not by Cry5Ba, whose amino acid sequence is different from that of Cry6Aa. Furthermore, Cry6Aa-induced necrosis pathway requires aspartic protease (ASP-1). In addition, ASP-1 protects Cry6Aa from over-degradation in C. elegans. This is the first demonstration that deficiency in necrosis pathway confers tolerance to Bt crystal protein, and that Cry6A triggers necrosis represents a newly added necrosis paradigm in the C. elegans. Understanding this model could lead to new strategies for nematode control.

In situ X-ray diffraction indicates that the structural phase transition from h-MoOs to «-Mot h is a first-order transition with a phase transition temperature range of 378.5-443.1 °C. The linear coefficients of thermal expansion of h-MoO3 are strongly anisotropic, that is. aa=i, = 72.87 x 10-6 K_1 and 0^ = -19.44 x 10-6 K_1. In the h-MoO^ phase, water molecules are located at the (0 0 0.25) site inside the MoOg octahedra tunnel that is formed by six MoOg corner-sharing octahedron zigzag chains. With increasing temperature. the release of water molecules from the octahedra tunnel causes the octahedra chains to shrink and the octahedra tunnel to expand. When the phase transition occurs, the anomalous expansion of the MoOg octahedra tunnel ruptures the MO-O2 bonds, forming individual MoOg octahedron zigzag chains that then share corners to generate octahedron layers in the (100)a direction. The octahedron layers are bonded by van der Waals interactions in the (010)a direction, crystalizing into the a-MoO3 structure.

Plant-parasitic nematodes (PPNs) are piercing/sucking pests, which cause severe damage to crops worldwide, and are difficult to control. The cyst and root-knot nematodes (RKN) are sedentary endoparasites that develop specialized multinucleate feeding structures from the plant cells called syncytia or giant cells respectively. Within these structures the nematodes produce feeding tubes, which act as molecular sieves with exclusion limits. For example, Heterodera schachtii is reportedly unable to ingest proteins larger than 28 kDa. However, it is unknown yet what is the molecular exclusion limit of the Meloidogyne hapla. Several types of Bacillus thuringiensis crystal proteins showed toxicity to M. hapla. To monitor the entry pathway of crystal proteins into M. hapla, second-stage juveniles (J2) were treated with NHS-rhodamine labeled nematicidal crystal proteins (Cry55Aa, Cry6Aa, and Cry5Ba). Confocal microscopic observation showed that these crystal proteins were initially detected in the stylet and esophageal lumen, and subsequently in the gut. Western blot analysis revealed that these crystal proteins were modified to different molecular sizes after being ingested. The uptake efficiency of the crystal proteins by the M. hapla J2 decreased with increasing of protein molecular mass, based on enzyme-linked immunosorbent assay analysis. Our discovery revealed 140 kDa nematicidal crystal proteins entered M. hapla J2 via the stylet, and it has important implications in designing a transgenic resistance approach to control RKN.

Pedestrian attribute retrieval (PAR) aims at retrieving soft-biometric attributes of pedestrian images from video surveillance. Despite advancements, PAR grapples with challenges, notably the concern of attribute imbalanced distribution. Within this context, we highlight a critical observation: this challenge encompasses both inter-attribute and overlooked intra-attribute imbalanced data distribution. To address the overlooked intra-attribute imbalance problem, we introduce an attribute-wise reasoning reinforcement learning framework (AwRL). AwRL formulates PAR as a Markov decision process (MDP), orchestrating attribute retrieval individually within reinforcement learning episodes. By traversing the entire PAR dataset, each attribute retrieval is calibrated with distinct reward scales, thereby ameliorating the intra-attribute imbalance. Additionally, we develop a novel supervised reinforcement loss function (SR-Loss) to enhance the robustness of the retrieval model. SR-Loss mitigates reinforcement learning’s inherent training instability in the trial-and-error interactions with the environment. The experimental results on three benchmark datasets of PETA, RAP and PA100K demonstrate the effectiveness of our approach, underscoring its capacity to surmount the intra-attribute imbalanced problem.

In situ X-ray diffraction indicates that the structural phase transition from h-MoO 3 to α-MoO 3 is a first-order transition with a phase transition temperature range of 378.5–443.1 °C. The linear coefficients of thermal expansion of h-MoO 3 are strongly anisotropic, that is, α a = b = 72.87 × 10 −6 K −1 and α c = −19.44 × 10 −6 K −1 . In the h-MoO 3 phase, water molecules are located at the (0 0 0.25) site inside the MoO 6 octahedra tunnel that is formed by six MoO 6 corner-sharing octahedron zigzag chains. With increasing temperature, the release of water molecules from the octahedra tunnel causes the octahedra chains to shrink and the octahedra tunnel to expand. When the phase transition occurs, the anomalous expansion of the MoO 6 octahedra tunnel ruptures the Mo–O 2 bonds, forming individual MoO 6 octahedron zigzag chains that then share corners to generate octahedron layers in the ⟨100⟩ α direction. The octahedron layers are bonded by van der Waals interactions in the ⟨010⟩ α direction, crystalizing into the α-MoO 3 structure.

Cell death plays an important role in host-pathogen interactions. Crystal proteins (toxins) are essential components of Bacillus thuringiensis (Bt) biological pesticides because of their specific toxicity against insects and nematodes. However, the mode of action by which crystal toxins to induce cell death is not completely understood. Here we show that crystal toxin triggers cell death by necrosis signaling pathway using crystal toxin Cry6Aa-Caenorhabditis elegans toxin-host interaction system, which involves an increase in concentrations of cytoplasmic calcium, lysosomal lyses, uptake of propidium iodide, and burst of death fluorescence. We find that a deficiency in the necrosis pathway confers tolerance to Cry6Aa toxin. Intriguingly, the necrosis pathway is specifically triggered by Cry6Aa, not by Cry5Ba, whose amino acid sequence is different from that of Cry6Aa. Furthermore, Cry6Aa-induced necrosis pathway requires aspartic protease (ASP-1). In addition, ASP-1 protects Cry6Aa from over-degradation in C. elegans. This is the first demonstration that deficiency in necrosis pathway confers tolerance to Bt crystal protein, and that Cry6A triggers necrosis represents a newly added necrosis paradigm in the C. elegans. Understanding this model could lead to new strategies for nematode control.