The industrial Rhodobacter sphaeroides HY01 accumulates an exceptionally high level of coenzyme Q10 (Q10), but the underlying mechanisms remain incompletely understood. Given the central role of Q10 in respiratory electron transport, previous observation of reduced expression of cbb 3 -type cytochrome c oxidase genes in HY01 suggested a potential mechanistic link. In this study, we found that cbb 3 oxidase activity in HY01 was only 21.8-32.8 % of that in the wild-type 2.4.1, and restoring this activity led to a 64.4 % decrease in Q10 accumulation, demonstrating a strong inverse correlation. This correlation was found to be mediated by the activation of the PrrAB two-component regulatory system, which is negatively regulated by cbb 3 oxidase. However, disruption of cbb 3 oxidase in 2.4.1 alone was insufficient to reproduce the high Q10 accumulation phenotype, indicating that additional factors may be required. Previous research also revealed restricted synthesis of geranylgeranyl diphosphate (GGPP) in HY01, which likely reduces the diversion of the Q10 precursor farnesyl diphosphate (FPP). Reconstituting this metabolic constraint in wild-type strain, combined with fine-tuning of PrrAB system activation, resulted in up to a 218.0 % increase in Q10 accumulation, achieving a level nearly identical to HY01. Combining mechanistic investigation and inverse metabolic engineering, this study demonstrates that the high Q10 accumulation in HY01 results from the synergistic effects of enhanced PrrAB activation and restricted FPP diversion, providing new insights into the key factors underlying high-level Q10 accumulation in R. sphaeroides.
Results of the KEYNOTE-590 trial showed that first-line pembrolizumab plus chemotherapy significantly improved overall and progression-free survival versus chemotherapy alone, and the safety profile was manageable for participants with previously untreated advanced or metastatic esophageal cancer. Using the quality-adjusted time without symptoms or toxicity (Q-TWiST) method of analysis, we assessed the benefit/risk profile of pembrolizumab plus chemotherapy. Using data from the KEYNOTE-590 study, we partitioned participant survival time into three health states: time living with all-cause grade ≥ 3 adverse events (AEs) before disease progression (PD; TOX), time before start of PD or death without grade ≥ 3 AEs (TWiST), and time from the start of PD to death or the censoring date (REL). We calculated Q-TWiST by summing the restricted mean time spent in each health state weighted by health state utilities estimated using the EuroQol 5-Dimension, 5-Level quality-of-life questionnaire (EQ-5D-5L). The relative gain in quality-adjusted survival time was defined as the Q-TWiST difference divided by the survival time from chemotherapy alone. A relative gain of > 10% is considered “clinically important,” and a relative gain of > 15% is considered “clearly clinically important.” This analysis was primarily focused on clinical significance rather than statistical significance due to the nature of the Q-TWiST analyses. No prespecified formal hypothesis testing was performed, and hence, there was no adjustment for multiplicity. At a maximum follow-up of 30 months, Q-TWiST was 2.23 months longer with pembrolizumab plus chemotherapy versus chemotherapy alone for all randomly assigned participants and was clearly clinically important, with a relative Q-TWiST gain of 17.86%. In all three subpopulations, including participants with esophageal squamous cell carcinoma (ESCC), programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 10, and ESCC PD-L1 CPS ≥ 10, Q-TWiST gain with pembrolizumab plus chemotherapy versus chemotherapy was 2.29 to 3.87 months, equivalent to a relative Q-TWiST gain of 18.12% to 33.47%, which are all clearly clinically important. Although this analysis is limited by missing data and short follow-up time, pembrolizumab plus chemotherapy provided clinically meaningful and substantial benefit in quality-adjusted survival by Q-TWiST analysis versus chemotherapy alone in participants with advanced esophageal cancer. Trial registration for KEYNOTE-590 ClinicalTrials.gov, NCT03189719 (date of registration: June 14, 2017). The online version contains supplementary material available at 10.1007/s11136-025-04109-4.
To examine whether maternal red blood cell (RBC) folate concentrations (biomarker of folate status) and documented periconceptional folic acid supplementation (FAS) are associated with neonatal brain maturation at term-equivalent age (TEA), using standardized MRI and EEG scoring. We retrospectively analyzed 144 mother-infant pairs (March 2022-March 2024). Analyses used a two-factor design denoted GA × Folate, combining gestational age group (Preterm < 37 weeks; Term ≥ 37 weeks) and RBC folate status (Deficient < 906 nmol/L; Sufficient ≥ 906 nmol/L). All MRI/EEG was performed at term-equivalent age (TEA) 40 ± 1 weeks postmenstrual age (PMA). MRI was scored using a modified Kidokoro system; EEG used standard neonatal metrics including Burdjalov aEEG background continuity and cycling, and conventional EEG delta-brush frequency. Readers were blinded to group. Analyses used two-way ANOVA (GA × Folate) with Benjamini-Hochberg FDR control, effect sizes, and ANCOVA adjusting for sex and birthweight. Maternal RBC folate sufficiency was associated with higher MRI myelination scores (Δ = 0.6 points, 95% CI 0.3-0.9, η2p = 0.08, q = 0.012) and greater EEG maturation (delta-brush frequency ↑ and aEEG continuity ↑; η2p = 0.07-0.10, q ≤ 0.02). Term infants outperformed preterm infants (main GA effect, q < 0.01). No GA × Folate interaction survived FDR. Maternal RBC folate correlated with MRI myelination (r = 0.42, 95% CI 0.27-0.55) and delta-brush frequency (r = 0.37, 95% CI 0.21-0.51), both q < 0.01. Inter-rater reliability: MRI ICC = 0.86; EEG ICC = 0.83. Higher maternal RBC folate at delivery is associated with more advanced structural and functional brain maturation at TEA. Documented periconceptional folic acid supplementation was more common among mothers with RBC folate sufficiency, suggesting supplementation may contribute to achieving adequate folate status.
Cocaine self-administration induces neurobiological adaptations in brain circuits involved in encoding reward-associated context. The dorsal hippocampus, particularly the dorsal dentate gyrus, plays a critical role in the precise encoding of spatial and contextual information. We hypothesized that the dentate gyrus is uniquely positioned to undergo epigenomic and transcriptomic changes because of the convergence of the contextual features of reward and cocaine-enhanced dopamine and norepinephrine signals during volitional drug-taking. We report that cocaine self-administration produces significant DNA methylation changes at an unusually large number of ~30,000 genomic regions (>10%, q<0.01) in dentate granule cells (DGCs) of male mice. Cocaine preferentially hypomethylated regions with heterogenous methylation, switching the methylation state in ~16% of DGCs on average. The cocaine-sensitive/responsive epigenomic regions were overrepresented in enhancers and were associated with 9,833 genes, many of which were involved in diverse functions relevant to neuronal functioning. However, among the differentially methylated genes only two regulatory genes, c-fos and cartpt (known to be activated by cocaine), and a cluster of genes encoding components of the extracellular matrix (implicated in neuroplasticity) were differentially expressed (mostly upregulated) following cocaine self-administration, suggesting a gene regulatory network that is transcriptionally robust to perturbations but still specific for context-driven and reward associated neuroplasticity in DGCs. Overall, our data demonstrates that cocaine self-administration induces epigenomic and transcriptomic changes in the dorsal dentate gyrus that may contribute to dorsal hippocampal plasticity and contextual memory associated with cocaine self-administration.
The European Union's Clinical Trial Regulation 536/2014 (EU-CTR) sought to harmonize clinical trial rules, ensure high standards of safety, and streamline processes through its new Clinical Trials Information System (CTIS). However, confusion remains regarding submission requirements for "patient-facing documents" in Parts I and II of clinical trial applications (CTAs). Misinterpretations-particularly around what qualifies as written information-have led to unnecessary submissions of materials like eCOA or ePRO "screenshots," which are not legally required. The EU's EUDRALEX Volume 10 Q&A (notably Question 1.24) clarified that only patient-facing documents linked to trial endpoints, such as questionnaires, diaries, or patient cards, need inclusion in Part I alongside the protocol. There is no legal basis to demand all patient materials or their translations in Part II. Despite this clarification, member states retain autonomy under Article 26 to set national translation and document requirements, leading to inconsistent practices and continued administrative burden. Recent initiatives, including CTR Collaborate (under the Accelerating Clinical Trials in the EU program) and MedEthics EU, seek to promote harmonization and efficient assessment. Empirical studies show that Ethics Committees (ECs) generally do not expect ePRO screenshots-most require only translated questionnaires. EU-CTR's success depends on collective awareness and streamlined processes. With ICH E6 Revision 3 and global efforts by organizations like the WHO, there is an opportunity to balance regulatory rigor with practical efficiency-reducing redundant submissions and emphasizing participant protection as the core ethical priority.
Xue-Fu-Zhu-Yu (XFZY) formulas are well-known traditional Chinese medicine extensively utilized to treat various blood stasis syndromes (BSS) by promoting blood circulation and eliminating blood stasis. However, their quality control remains incomplete, probably leading to fluctuations in product quality and thus causing unsatisfactory therapeutic effects. To establish a multidimensional strategy that integrates chemical analysis, intestinal absorption, and pharmacodynamic effects for exploring Q-markers of XFZY formulations. The fingerprint spectrum analysis of four XFZY formulation intermediates and their component identification were conducted to provide chemical dimensions. The intestinal absorption experiment with everted gut sac model was used to obtain absorbable prototype components, establishing a link between chemical and absorptive dimensions. Blood-activating effects of four XFZY formulation intermediates in BSS models were evaluated, with candidate Q-markers acquired via Pearson's correlation analysis with the pharmacodynamic and absorption outcomes, completing the chemical-absorptive-pharmacological framework. The molecular docking, plasma recalcification time assays, and platelet aggregation experiments were performed to further confirm the final Q-markers for XFZY formulations. The fingerprints of XFZY formulation intermediates were established, resulting in 30 common peaks with identified chemical structures. 23 of these common compounds were found to be absorbed through the predominant absorption site of the jejunum. Subsequently, the ameliorative effects of XFZY formulas on body weight, hemorheology, NO level, and lipid levels in BSS model rats were confirmed, and then 14 potential Q-markers were obtained via Pearson's correlation analysis with pharmacodynamic data and absorbable components. Finally, gallic acid, neochlorogenic acid, hydroxysafflor yellow A, albiflorin, ferulic acid, 20-hydroxyecdysone, neohesperidin, meranzin, glycyrrhizic acid, and nobiletin were verified as the Q-markers of XFZY formulations by molecular docking and anticoagulant assays. This study successfully constructed a chemical-absorptive-pharmacological three-dimensional strategy, identifying 10 Q-markers for XFZY formulations, which provides an important basis for constructing a comprehensive quality control system for XFZY formulations.
This study aimed to explore the utility of these biomarkers for evaluating glymphatic dysfunction in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and establish their effectiveness in differentiating patients from healthy controls (HCs). In this study, we enrolled 20 patients with anti-NMDAR encephalitis and 17 HCs. Glymphatic function was assessed using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, free water in white matter (FW-WM), and perivascular space volume fraction (PVSVF). Among the patient cohort, 13 completed follow-up MRI examinations at 3 months post-discharge. We performed correlation analyses between these glymphatic MRI indices and clinical parameters, and compared glymphatic function between patients with normal structural MRI findings and HCs. Patients exhibited impaired glymphatic function compared to HCs, evidenced by a lower DTI-ALPS (1.44 ± 0.16 vs. 1.62 ± 0.10, q < 0.001) and elevated FW-WM (0.21 ± 0.02 vs. 0.18 ± 0.01, q < 0.001) and PVSVF (all q < 0.05). Notably, these differences persisted even in patients with normal structural MRI (DTI-ALPS: 1.43 ± 0.22 vs. 1.62 ± 0.10, q = 0.014; FW-WM: 0.20 ± 0.02 vs. 0.18 ± 0.01, q = 0.005). Glymphatic dysfunction correlated with disease severity, showing a negative association between DTI-ALPS and CASE scores. Longitudinal analysis of the participants available for follow-up revealed improved glymphatic function (DTI-ALPS index: from 1.41 ± 0.17 to 1.50 ± 0.12; q = 0.042), alongside clinical recovery (CASE score: from 16 to 2, q = 0.005; mRS: from 5 to 1, q = 0.039). The glymphatic system could be impaired in patients with anti-NMDAR encephalitis. MRI indices of the glymphatic system may serve as biomarkers to differentiate these patients from HCs and evaluate disease severity.
Respiratory complex I is a multi-subunit energy-transducing membrane enzyme essential for mitochondrial and cellular energy metabolism. It couples NADH oxidation and ubiquinone-10 (Q10) reduction to the concomitant pumping of four protons to generate the proton-motive force that powers oxidative phosphorylation. Despite recent advances in structural knowledge of complex I, many mechanistic aspects including the reactive binding poses of Q10, how Q10 reduction initiates the proton transfer cascade, and how protons move through the membrane domain, remain unclear. Here, we use electron cryomicroscopy to determine structures of mammalian complex I, reconstituted into phospholipid nanodiscs containing exogenous Q10 and reduced by NADH, to global resolutions of 2.0 to 2.6 Å. Two conformations of a reduced Q10H2 molecule are observed, fully inserted into the Q-binding channel in the turnover-relevant closed state. By comparing the quinone species bound in oxidised and reduced complex I structures, paired with molecular dynamics simulations to investigate the charge states of key surrounding residues, we propose a series of substrate binding poses that Q10 transits through for reduction. Our highly hydrated structures exhibit near-continuous proton-transfer connections along the length of the membrane domain, enabling comparisons between them to assist in identifying the proton-transfer control points that are essential to catalysis.
Achieving angstrom-level control over porosity is a long-standing challenge in translating molecular design into selective membranes. We present the supramolecular assembly of crown-type [P8W48O184]40- polyoxometalate (POM) by alkylammonium functionalization using [CnH2n+1]4N+, where n = 4 (Q4P8), 7 (Q7P8), and 10 (Q10P8), into continuous POM thin films (POMbranes) featuring periodically aligned ∼1 nm intrinsic pores (Ip) of P8 (visualized with electron microscopy). Alkyl chain length modulations direct supramolecular packing and tune the extrinsic porosity (Ep) in POMbranes across large lateral dimensions (∼50 cm2) while preserving IP. Q7P8 and Q10P8 POMbranes with restricted Ep enforce precise sieving via Ip, whereas Q4P8 permits dual-path transport through Ip and Ep, as confirmed by cross-flow separations and molecular dynamics simulations. Q7P8 and Q10P8 POMbranes deliver single-digit pore selectivity (Isoporosity) and ∼10× higher separation efficiency for narrow molecular weight differences (100-200 Da) than state-of-the-art benchmark membranes, establishing a scalable strategy to embed crystalline nanopores for selective separation.
A novel bacterial strain, designated MF1-12-2T, was isolated from tidal mud collected at the Gochang coast, Republic of Korea. Cells of strain MF1-12-2T were non-motile, Gram-stain-negative short rods and formed pale white, circular colonies on marine agar after 6 days of incubation at 25 °C. The strain grew optimally at 25 °C, pH 7.0, and in the presence of 2% (w/v) NaCl. Phylogenetic analysis based on the 16 S rRNA gene sequence showed that strain MF1-12-2T belongs to the genus Silicimonas within the family Roseobacteraceae, with the highest sequence similarity (97.0%) to Silicimonas algicola DSM 103,371T. The genome of strain MF1-12-2T is 4.3 Mbp, with a DNA G + C content of 60.8%. The ANI (72.6%), AAI (72.6%), and digital DNA-DNA hybridization (dDDH; 19.3%) values between strain MF1-12-2ᵀ and Silicimonas algicola DSM 103371ᵀ, further support its status as a novel species. The major fatty acids were C18:0, C18:1 ω7c, and C18:1 ω7c 11-methyl. The predominant polar lipids were phosphatidylcholine (PC), phosphatidylglycerol (PG), and diphosphatidylglycerol (DPG). The respiratory quinone was ubiquinone-10 (Q-10). Based on its polyphasic taxonomic characteristics, strain MF1-12-2ᵀ represents a novel species within the genus Silicimonas, for which the name Silicimonas lutimaris sp. nov. is proposed. The type strain is MF1-12-2T (= KEMB 24353T =KCTC 8886T =TBRC 21243T).
Water scarcity necessitates a paradigm shift in maize production from maximizing yields to optimizing water productivity. Deficit irrigation (DI) offers significant water savings, but its effectiveness is often compromised by non-productive soil evaporation. This two-year field study quantified the synergistic effects of mulch type and DI on the physiology and yield of spring maize (Zea mays L.) in a semi-arid environment. A factorial experiment tested three mulch types (black plastic mulch-BPM, paddy straw mulch-PSM, no mulch-NM) and three drip irrigation levels (80%, 100%, 120% of crop evapotranspiration-ETc) and a conventional flood irrigation control. The combination of PSM with 100% ETc sustained superior photosynthetic physiology maintaining high photosynthetic rates, stomatal conductance, and photosystem II efficiency and achieved a grain yield of 84.04 q ha⁻1, statistically equivalent to the surplus-water treatment (120% ETc) and significantly greater than conventional flood irrigation (75.44 q ha-1). Crucially, PSM with 80% ETc achieved a grain yield (71.10 q ha-1) comparable to both NM with 100% ETc and the conventional control, thereby saving 20% of irrigation water with no significant yield penalty. In contrast, BPM resulted in the lowest physiological performance and yields under the high-temperature spring conditions, likely due to root zone overheating and restricted gas exchange. This study demonstrates that PSM with 100% ETc is optimal for yield maximization, while PSM with 80% ETc establishes a resilient, water-smart ‘more crop per drop’ strategy for sustainable maize intensification. The online version contains supplementary material available at 10.1038/s41598-026-40843-6.
Efficient hydrogen production from water is a key requirement for a successful hydrogen economy. The dodecaborate anion [B12H12]2- and its derivatives [B12X12]2- (X = F, Cl, Br, I, CN), known for their enhanced stability, have catalytic potential for activating small molecules, such as NH3, CO2, and N2, once a ligand is removed. In this work, we computationally explored the electronic structures of [B12Xn]q (X = Br, I, CN; n = 11, 10; q = 2-, 1-, 0) and the thermodynamics of their interaction with water. We show that, among these, [B12X10]-˙ (X = Br, I) are the most suitable for spontaneous hydrogen generation. A detailed description of the catalytic mechanism is presented.
The aim of this study was to evaluate the effect of natural antioxidant activity obtained from Q. cerris (Quercus cerris) extract and fluoride-releasing sealant on the shear bond strength (SBS) of orthodontic brackets in teeth after bleaching with hydrogen peroxide (HP). In this research, 200 teeth were divided into two groups, the TT (n = 100) and the OT (n = 100). Each group was further divided into five subgroups (n = 20): TT1 and OT1 = no bleaching; TT2 and OT2 = bleaching; TT3 and OT3 = bleaching+two weeks delayed bonding; TT4 and OT4 = bleaching+10% sodium ascorbate (SA) TT5 and OT5 = bleaching+10% Q. cerris extract. The TT groups were bonded with Transbond sealent + Transbond XT (TT; 3M/Unitek), and the OT groups were bonded with Opal Seal primer (Reliance Orthodontic Products Itasca, IL, USA)+ Transbond XT. Samples were assessed by SBS testing and adhesive remnant index (ARI) scoring. Two-way ANOVA variance analysis, Tukey multiple comparison test and the Chi-square test were used for statistical evaluation. The highest SBS values were obtained in the TT1 (3.17 ± 1.1 MPa) and OT1 (12.58 ± 1.47 MPa) groups, and the lowest SBS values were obtained in the TT2 (4.40 ± 1.11 MPa) and OT2 groups (4.19 ± 1.02 MPa) (p = 0.0001). The mean value of SBS of TT5 was statistically significantly lower than the mean SBS value of TT3 and TT4 (p = 0.042, p = 0.047). No statistically significant difference was observed in the ARI score distribution in the OT groups (p = 0.062), while a significant difference was noticed in the TT groups (p = 0.006). The results indicated that Q. cerris can be safely used to enhance SBS in bleached teeth, based on the dose, duration, and application procedure parameters utilized in this study. In addition, the fluoride-releasing sealant provides clinically sufficient SBS.
Determine the association of inflammatory biomarkers with clinical measures and recovery in participants with concussion. Multicenter study in National Collegiate Athletic Association member institutions including military service academies. Four hundred twenty-two participants with acute concussion. Clinical visits and blood draws were completed preinjury and at multiple visits postconcussion (0-12 hours, 12-36 hours, and 36-60 hours postinjury). Clinical measures included Sport Concussion Assessment Tool (SCAT) symptom severity, Balance Error Scoring System, Standardized Assessment of Concussion (SAC), Brief Symptom Inventory-18 (BSI-18) scores, time to initiation of graduated return-to-play (RTP) protocol, and time to RTP. Interleukin (IL)-6, IL-10, IL-8, IL-1 receptor antagonist (RA), tumor necrosis factor (TNF), c-reactive protein, and vascular endothelial growth factor (VEGF) were measured in serum. Prespecified analyses focused on IL-6 and IL-1RA at 0 to 12 hours; exploratory analyses were conducted with false discovery rate correction. For prespecified analyses, IL-1RA at 0 to 12 hours in female participants was positively associated with more errors on the SAC (B(standard error, SE) = 0.58(0.27), P < .05) and worse SCAT symptom severity (B(SE) = 0.96(0.44), P < .05). For exploratory analyses, higher levels of IL-1RA at 12 to 36 hours were associated with higher global (B(SE) = 0.55(0.14), q < 0.01), depression (B(SE) = 0.45(0.10), q < 0.005), and somatization scores on the BSI (B(SE) = 0.46(0.12), q < 0.01) in participants with concussion; Higher TNF at 12 to 36 hours was associated with fewer errors on the SAC (B(SE) = - 0.46(0.14), q < 0.05). Subanalyses showed similar results for male participants and participants who were athletes. No associations were discovered in nonathlete cadets. Higher IL-8 at 0 to 12 hours was associated with slower RTP in female participants (OR = 14.47; 95% confidence interval, 2.96-70.66, q < 0.05); no other associations with recovery were observed. Peripheral inflammatory markers are associated with clinical symptoms following concussion and potentially represent one mechanism for psychological symptoms observed postinjury. Current results do not provide strong support for a potential prognostic role for these markers.
Photosynthetic organisms have developed various light-harvesting antenna systems to capture light and transfer energy to reaction centers (RCs). Simultaneous utilization of the integral membrane light-harvesting antenna (LH complex) and the extrinsic antenna (chlorosomes) makes the phototrophic bacterium Chloroflexus (Cfx.) aurantiacus an ideal model for studying filamentous anoxygenic phototrophs (FAPs). Here, we determined the structure of a minimal RC-LH photocomplex from Cfx. aurantiacus J-10-fl (CaRC-LH) at 3.05-Å resolution. The CaRC-LH binds only to seven LH subunits, which form a crescent-shaped antenna surrounding the movable menaquinone-10 (QB) binding site of CaRC. In this complex with minimal LH units, an extra antenna is required to ensure sufficient light-gathering, providing a clear explanation for the presence of chlorosomes in Cfx. aurantiacus. More importantly, the semicircle of the antenna represents a novel RC-LH assembly pattern. Our structure provides a basis for understanding the existence of chlorosomes in Cfx. aurantiacus and the possible assembly pattern of RC-LH.
Determine whether mirror intracranial aneurysms (MIAs) confer risk beyond aneurysm multiplicity and describe their distribution and longitudinal change. Retrospective two-centre UK cohort of unruptured intracranial aneurysms (UIAs) diagnosed 2006-2020; outcomes to 2022. first rupture, SAH-specific/all-cause mortality, time to treatment, and lesion-level growth/morphology change. Rates used Poisson models with person-time offsets; lesion-level risks used GEE (modified Poisson). Rupture-free survival used inverse-probability-weighted Kaplan-Meier. Models adjusted for baseline aneurysm count. 1,985 UIAs were identified; 289 (14.6%) were MIAs. MIAs clustered at the MCA bifurcation (57.8%) and ICA terminus (34.6%). First-rupture incidence was higher in MIAs (1.74/100 person-years (PY)) than aMIAs (0.76/100 PY) or SIAs (0.39/100 PY); MIA > SIA IRR 4.46 (q = 0.0003), MIA > aMIA IRR 2.29 (q = 0.0044). SAH-specific mortality incidence was higher in MIAs (1.21/100 PY) than SIAs (0.36/100 PY; IRR 3.36, q = 0.0057) and aMIAs (0.19/100 PY; IRR 6.37, q = 0.0002). IPW survival was poorer for MIAs vs aMIAs (weighted log-rank χ2 = 9.95, p = 0.0016) and vs SIAs (χ2 = 18.09, p = 2.11 × 10⁻5). Lesion-level GEE showed no symmetry-specific increase in rupture risk (omnibus p = 0.72). Lesion-level growth ≥ 1 mm (RR 1.67, q = 0.0380) and morphology change (RR 2.10, q = 0.0121) were higher in MIAs. With aneurysm count adjustment, effects attenuated with wide CIs, consistent with limited power. MIAs were associated with higher patient-time rupture and SAH-specific mortality and greater lesion-level instability, but not with an independent per-aneurysm rupture hazard. The excess patient-level risk is largely explained by exposure (multiplicity); a symmetry-related effect remains plausible but unconfirmed. Larger, prospectively harmonised datasets are needed.
To investigate the relationship between hypo/hyperglycemia and EEG measures in term neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). Ninety-six neonates underwent concurrent continuous glucose monitoring (CGM) and EEG for 48 h within the first 72 h of life. Five-minute epochs of hypoglycemia (≤2.6 mmol/L; ≤47 mg/dL) and hyperglycemia (>10.1 mmol/L; >182 mg/dL) were identified. Continuous EEG data was segmented into 5-min epochs corresponding to 5-min CGM data. Visual EEG background score and 22 computational EEG measures were estimated and their relationship to dysglycemia was assessed after adjusting for hypoxia-ischemia severity and multiple testing. Among the 96 neonates, 12 had hypoglycemia, 16 had hyperglycemia, including 1 with both during the recording period. In the adjusted analyses, hyperglycemic epochs were associated with worse visual background scores (1.2, 95 %CI 0.51-1.89, q = 0.003) and 11 computational EEG measures. In contrast, hypoglycemic epochs were not associated with a significant change in visual background scores (-0.28, 95 %CI -0.66 - -0.10, q = 0.549), and were only associated with one computational EEG measure. Hyperglycemia is temporally associated with changes in brain function in term neonates with NE treated with TH. This temporal relationship suggests high glucose levels may contribute directly to brain injury after NE.
Childhood trauma is a well-established risk factor for psychosis, paranoia, and substance use, with cannabis being a modifiable environmental factor that exacerbates these vulnerabilities. This study examines the interplay between childhood trauma, cannabis use, and paranoia using standard tetrahydrocannabinol (THC) units as a comprehensive measure of cannabis exposure. Data were derived from the Cannabis&Me study, an observational, cross-sectional, online survey of 4,736 participants. Childhood trauma was assessed using a modified Childhood Trauma Screen Questionnaire, while paranoia was measured via the Green Paranoid Thoughts Scale. Cannabis use was quantified using weekly standard THC units. Structural equation modeling (SEM) was employed to evaluate direct and indirect pathways between trauma, cannabis use, and paranoia. Childhood trauma was strongly associated with paranoia, particularly emotional, and physical abuse (β = 16.10, q < 0.001; β = 16.40, q < 0.001). Cannabis use significantly predicted paranoia (β = 0.009, q < 0.001). Interactions emerged between standard THC units and both emotional abuse (β = 0.011, q < 0.001) and household discord (β = 0.011, q < 0.001). SEM revealed a small but significant indirect effect of trauma on paranoia via cannabis use (β = 0.004, p = 0.017). These findings highlight childhood trauma as a primary driver of paranoia, with cannabis use amplifying its effects. While trauma had a strong direct impact, cannabis played a significant mediating role. Integrating standard THC units into psychiatric research and clinical assessments may enhance risk detection and refine intervention strategies, particularly for childhood trauma-exposed individuals.
Four aerobic, Gram-stain-negative, rod-shaped, and non-motile bacterial strains, designated SYSU HZ0097ᵀ, SYSU HZ0136, SYSU LHT278ᵀ, and SYSU LHT272, were isolated from tidal flat sediment collected in Zhuhai, China. Phylogenetic analysis based on 16S rRNA gene sequences assigned all four strains to the family Erythrobacteraceae. Strains SYSU HZ0097ᵀ and SYSU HZ0136 showed the highest 16S rRNA gene sequence similarity (98.6 %) to Altererythrobacter epoxidivorans CGMCC 1.7731ᵀ, while SYSU LHT278ᵀ and SYSU LHT272 were most closely related (98.5 %) to Tsuneonella litorea KCTC 82812ᵀ. Whole-genome comparisons, including average nucleotide identity (ANI < 85.0 %) and digital DNA-DNA hybridization (dDDH <30.0 %), supported their assignment to two distinct species. All isolates contained ubiquinone-10 (Q-10) as the predominant respiratory quinone, and the major fatty acids (>10 %) were C18:1ω7c and C18:1ω6c. The polar lipid profiles included phosphatidylglycerol, phosphatidylethanolamine, and an unidentified glycolipid. The colonies exhibited yellow pigmentation, and genes associated with carotenoid biosynthesis (crtB, crtI) were identified in their genomes. Based on phylogenetic, genomic, phenotypic, and chemotaxonomic characteristics, strains SYSU HZ0097ᵀ and SYSU HZ0136 represent a new species of the genus Altererythrobacter, for which the name Altererythrobacter guangdongensis sp. nov. is proposed (type strain SYSU HZ0097ᵀ = MCCC 1K09423ᵀ = KCTC 8714ᵀ). Strains SYSU LHT278ᵀ and SYSU LHT272 represent a new species of the genus Tsuneonella, for which the name Tsuneonella sediminis sp. nov. is proposed (type strain SYSU LHT278ᵀ = MCCC 1K09543ᵀ = KCTC 8862ᵀ).
Coenzyme Q10 (Q10) is a mitochondrial coenzyme that facilitates ATP production via oxidative phosphorylation. This study hypothesized that Q10 enhances mitochondrial efficiency and lactate threshold, while high-intensity interval training (HIIT) promotes metabolic adaptations, improving glucose utilization and buffering capacity for faster recovery after high-intensity exercise. A randomized controlled trial was conducted using 24 male Sprague-Dawley rats (250.4 ± 6.1 g, 8 weeks old). The rats were allocated into four groups: control (C), coenzyme Q10 (CoQ10), HIIT, and HIIT + Q10. The Q10 administration involved a dosage of 10 mg/kg/day, given 30 min prior to the HIIT protocol. Lactate threshold, blood gas parameters, oximetry values, metabolite levels, and electrolyte status were analyzed utilizing the Radiometer 900 device. The blood samples were collected at the fifth and tenth minutes following the HIIT training trials. The HIIT + Q10 group exhibited a significant reduction in lactate threshold (p < 0.01), maintaining values below average. Significant improvements in blood gas parameters, including pH, pO2, and pCO2, were observed in this group. Enhanced oxygen transport capacity was indicated by improved oximetry parameters (Hb, HCT, sO2) and reduced COHb levels. Additionally, positive changes in HCO3- and base values indicated reduced metabolic stress. Q10 supplementation also stabilized electrolytes, particularly K+ and Na+. The Q10 supplementation supported metabolic balance, improved oxygen transport, and stabilized acid-base levels during HIIT. It reduced lactate accumulation, enhanced glucose availability, and alleviated metabolic stress, thereby improving recovery efficiency and physiological adaptation.