In this single-center retrospective cohort study, we compared extracorporeal membrane oxygenation (ECMO) cannulation and early management performed in the emergency resuscitation room (ERR) versus the intensive care unit (ICU). A total of 105 patients undergoing venoarterial ECMO were analyzed using inverse probability of treatment weighting to reduce baseline imbalance. Patients in the ERR group presented with greater physiological instability, including higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, severe metabolic acidosis, and a predominance of extracorporeal cardiopulmonary resuscitation cases. Although ERR cannulation was associated with significantly higher unadjusted 3 day mortality, this association was attenuated after adjustment for confounders. Baseline physiological variables, particularly arterial pH and the need for precannulation mechanical ventilation, independently predicted mortality, whereas procedural timing and cannulation setting were not significant determinants of outcome. Importantly, rates of bleeding, thrombosis, and infection were comparable between the ERR and ICU groups, suggesting that ECMO cannulation in the ERR can be performed safely by a dedicated experienced team using standardized protocols. These findings indicate that early mortality after ECMO is primarily driven by the severity of precannulation physiological collapse rather than the procedural environment itself, supporting the feasibility and safety of ERR-initiated ECMO in critically unstable patients.

Post-tuberculous spinal deformity remains an important cause of chronic morbidity following healed spinal tuberculosis, particularly in low- and middle-income countries. Residual kyphosis may result in persistent pain, sagittal imbalance, cosmetic deformity and late neurological deterioration. Surgical correction is technically demanding because of rigid deformity and compromised bone quality, yet it may offer meaningful functional recovery when appropriately indicated. We report a case series of three adult patients with post-tuberculous spinal deformity managed surgically at a Nigerian tertiary orthopaedic centre. All patients underwent single-stage posterior-only decompression, deformity correction and pedicle screw-rod instrumentation. Anterior column reconstruction was performed in all cases using either an expandable titanium cage or a fibular strut graft. Clinical, radiological and neurological outcomes were assessed during follow-up. The patients were aged 24-33 years (median 32 years), with follow-up ranging from 26 to 60 months (median 36 months). Two patients presented with thoracic kyphotic deformity (90° and 92°), while one had lumbar involvement (20°). Postoperatively, thoracic kyphosis improved to 25° and 45°, and lumbar alignment was restored to physiological lordosis. The median angular correction achieved was 47° (range 40°-65°). One patient presented with paraparesis (ASIA D) and achieved complete neurological recovery, while the remaining two maintained intact neurology (ASIA E). All patients demonstrated radiological fusion and maintained deformity correction at the latest follow-up, with no implant-related complications. Single-stage posterior-only surgical correction of post-tuberculous spinal deformity in adults can achieve satisfactory deformity correction, solid fusion and neurological recovery in carefully selected patients.

The Earth's energy imbalance (EEI) that develops at the top of the atmosphere is accommodated by gains or losses of energy in Earth's heat reservoirs, leading to temperature and sea level change. The global ocean has stored about 90% of the EEI from anthropogenic forcing, but the attribution of past changes of EEI remains largely unknown, thus obscuring our understanding of past climate change. Here, we reconstruct changes in mean ocean temperature over the past 150,000 years that, with a reconstruction of ice sheet-volume changes, allow us to isolate the contributions of the dominant ocean and ice sheet heat reservoirs to the global energy inventory as well as to derive their associated contributions to EEI. We attribute orbital-scale EEI variability to joint precessional and CO2 forcing that caused changes in rates of ice sheet energy storage. In contrast, millennial-scale EEI variability can be attributed to radiative responses to decreases in the Atlantic meridional overturning circulation and increasing CO2 during Heinrich stadials that caused changes in rates of ocean energy storage.

Spinal cord injury (SCI) causes myelin breakdown and membrane disruption, leading to the release and redistribution of cholesterol, fatty acids, and other lipids within the lesion. The resulting disruption of lipid homeostasis can promote sustained lipid peroxidation, neuroinflammation, and repair failure. In recent years, lipid droplets (LDs) have been recognized as highly dynamic organelles that coordinate lipid storage, mobilization, energy metabolism, and stress responses. However, the stage- and cell-specific roles of LDs in lipid-redox dysregulation after SCI remain poorly understood.

Vulvovaginal candidiasis (VVC) is a common fungal infection that significantly affects women's health worldwide. Antifungal agent therapies are not particularly effective for VVC and can further promote an imbalance in the vaginal microbiota, increasing recurrence. Nanozymes are currently being evaluated as an alternative therapy owing to their broad-spectrum antibacterial activity and negligible biological toxicity. However, their inherently low catalytic activity limits their antibacterial properties. In this study, an Mn,Fe-doped polyoxometalate (Mn,Fe-POM) nanozyme was successfully constructed as a potential treatment for VVC through the synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT). The developed approach was based on Lactobacillus in the vagina, which provides a suitable microenvironment for promoting the peroxidase (POD)-like activity of Mn,Fe-POM. Mn,Fe-POM-bound Lactobacillus exhibited excellent near-infrared-triggered POD-like activity for CDT and noteworthy photothermal performance for PTT. Electron transfer between Fe2+/Fe3+ and Mn3+/Mn4+ provided abundant active sites, increasing POD-like catalytic activity based on Fenton-like mechanisms and amplifying the CDT potential. In vitro, Mn,Fe-POM demonstrated a remarkable synergistic effect in killing Candida albicans (C. albicans) and disrupting the biofilm, while also preserving the Lactobacillus species. This outstanding anti-C. albicans activity was achieved without significant damage to the vaginal mucosa cells, reducing vaginal inflammation in an in vivo VVC mouse model. The increased Lactobacillus proportions and reduced C. albicans numbers allowed the reconstruction of healthy vaginal microbiota to decrease infection recurrence. This study presents an innovative and promising therapeutic approach for VVC.

Neonicotinoid insecticides raise concerns about neurotoxicity in nontarget organisms, motivating evaluation of alternatives such as flupyradifurone (FPF). We compared the neurotoxicity of imidacloprid (IMI) and FPF in Caenorhabditis elegans after 72 h exposure to 0.1-100 μg/L. Behavioral, neuronal, neurochemical, transcriptional, and oxidative-stress end points were assessed. IMI impaired locomotion more potently, with lowest observed effect concentrations of 0.1 μg/L for head thrashes and body bends, whereas corresponding FPF values were 100 and 1 μg/L, respectively. At 100 μg/L, FPF caused neurodegeneration comparable to or greater than that induced by IMI across several neuronal subtypes. IMI preferentially reduced dopamine, whereas FPF increased GABA and glutamate. Transcriptional and molecular docking analyses suggested potential disruptions in neurotransmitter synthesis, transport, signaling, and reuptake. Both insecticides increased reactive oxygen species, while transcriptional patterns suggested a comparatively weaker antioxidant response to FPF. These findings reveal distinct neurotoxic profiles and support cautious safety evaluation of replacement insecticides.

Natural polysaccharides derived from Zingiber officinale (ZO) can alleviate ulcerative colitis (UC). In this study, a homogeneous glucan, ZOP-1a (250.39 kDa), was isolated from ZO and structurally characterized. ZOP-1a possessed an α-1,4-d-Glcp backbone, with branches substituted at H-6 by α-d-Glcp-(1 → 6)-α-d-Glcp-(1→ and at H-3 by α-d-Glcp-(1 → 3)-β-d-Glcp-(1→ and α-d-Glcpp-(1→ residues. In DSS-induced colitis mice, ZOP-1a markedly ameliorated colon injury, as reflected by improved body weight, colon length, and histopathological damage, inhibited NF-κB/MAPK signaling and reshaped gut microbiota dysbiosis, thereby restoring intestinal homeostasis. Moreover, ZOP-1a increased the abundance of short-chain fatty acid (SCFA)-producing bacteria, and in vitro Lactobacillus fermentation supported its potential contribution to SCFA generation. Fecal microbiota transplantation from ZOP-1a-treated colitis mice effectively alleviated UC symptoms in recipient mice. Overall, ZOP-1a may serve as a promising prebiotic candidate for maintaining intestinal homeostasis and preventing UC.

Glutathione (GSH), as an important class of antioxidants, exhibits a close correlation with cellular oxidative stress. Usually, GSH serves as an essential biomarker for evaluating redox homeostasis in plants. In this work, we developed a GSH-specific fluorescent probe by employing the aza-IR780 cyanine scaffold as the near-infrared fluorophore, the naphthalimide block as the visible light fluorophore, and sulfonamide as the GSH-responsive unit. The optical performance showed that this probe could highly selectively detect GSH in both visible light (emission at 498 nm) and near-infrared (emission at 780 nm) channels and was not interfered by other amino acid species. The results of the plant imaging experiment showed that this probe could visualize the root tip tissues of plants, as well as GSH in the entire plant. When plants are subjected to abiotic stress, they upregulate GSH expression to combat the redox imbalance induced by oxidative stress. The results of plant imaging studies under abiotic stress show that this probe can monitor the GSH dynamics in the root tip tissues and the entire plant of Arabidopsis thaliana under high-temperature stress, drought stress, and salt stress with a high signal-to-noise ratio, which were exactly similar to its response behavior under oxidative stress conditions. These findings indicate that this probe can serve as an effective and visual molecular tool for analyzing the dynamics of plant oxidative stress.

To evaluate whether an integrated classification combining the CHAARTED and LATITUDE criteria improves prognostic stratification and to explore treatment effects across risk groups, including further stratification by metastasis timing, in metastatic castration-sensitive prostate cancer (mCSPC). This post hoc analysis included 1,052 patients from the TITAN trial (NCT02489318) randomized to receive apalutamide plus androgen deprivation therapy (ADT) or placebo plus ADT. Patients were classified into double low, intermediate, and double high groups based on the CHAARTED and LATITUDE criteria and further stratified by metastasis timing. Model discrimination was assessed using Harrell's concordance index (C-index). Overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards models, with baseline imbalances adjusted by inverse probability of treatment weighting. The integrated classification based on the CHAARTED and LATITUDE criteria significantly improved prognostic stratification, yielding a higher C-index for OS (0.645) than the CHAARTED (0.628; p = 0.011) or LATITUDE (0.621; p = 0.003) criteria alone. When further stratified by metastasis timing, apalutamide was associated with improved OS across most subgroups; however, no clear benefit was observed in the double low group with synchronous metastasis (hazard ratio: 0.93; 95% confidence interval [CI]: 0.48-1.79; p = 0.8). Integrating the CHAARTED and LATITUDE criteria significantly improves prognostic stratification in patients with mCSPC. While further stratification by metastasis timing suggested no clear survival benefit in the double low synchronous subgroup, wide CIs indicate substantial uncertainty. These exploratory findings require prospective validation.Clinical Trial Registration: NCT02489318.

Hyperexcitability of lateral (La) and basolateral (BL) amygdalar nuclei (BLA) is a hallmark of anxiety-related disorders in humans. Excitation of BLA projection neurons (PN) is fine-tuned by inhibitory interneurons (INs), and monoaminergic afferents to the BLA modulate PN and IN activity. In the present study, BLA-neurons immunoreactive(ir) for parvalbumin (PV) or neuropeptide Y (NPY) and their interrelations with serotonergic and catecholaminergic afferents were analyzed in wildtype (WT) and in serotonin (5-HT) transporter knockout (5-HTT KO) mice, a mouse model for anxiety- and stress-related disorders. In both genotypes, PV- and NPY-ir neurons possess perisomatic appositions by serotonergic and tyrosine hydroxylase-ir afferents. Dual immunolabeling shows no colocalization of PV and NPY. Qualitative analysis of NPY/somatostatin(SOM) dual labeling in WT and 5-HTT KO mice documents colocalization of the peptides in neurons with predominantly fusiform somata, and single labeling for NPY in neurons with predominantly round somata. Quantification of PV- and NPY-ir neurons documents a reduction in numbers and densities of NPY-ir neurons of the BLA in 5-HTT KO mice while PV-ir neuron numbers and densities remain unchanged. Quantitative PCR shows increased expression of Npy receptor 2, Som receptor 4, and corticotropin releasing factor receptor 1 in the BLA of 5-HTT KO mice. mRNA for the peptides is unchanged, indicating that it may be NPY propeptide translation which is reduced in 5-HTT KO mice. Taken together, the results document an effect of life-long serotonin imbalance on the BLA NPY-system, which may contribute to increased anxiety-like behavior in 5-HTT KO mice.