Objectives This study aimed to investigate the associations of parental SA recorded within 3 years before childbirth and parental SA recorded during pregnancy with the odds of autism in offspring. Methods We conducted a nationwide nested case-control study using Taiwan’s 2006–2015 national birth cohort linked to multigenerational health records from 2003 to 2017. The study included 14,961 children with autism and 59,844 controls individually matched by birth year and sex. Conditional logistic regression with inverse probability of treatment weighting (IPTW) was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results Paternal SA recorded within 3 years before childbirth was associated with higher odds of offspring autism in the IPTW model (aOR of 2.208, 95% CI = 1.542–3.163). SA recorded during pregnancy was also associated with higher odds of offspring autism, with an aOR of 2.055 (95% CI = 1.021–4.136) for maternal SA and 1.653 (95% CI = 1.311–2.084) for paternal SA. Conclusion Paternal SA recorded within 3 years before childbirth and parental SA recorded during pregnancy were associated with higher odds of autism in offspring. Further studies are needed to clarify the underlying mechanisms.
Major depressive disorder (MDD) is a leading cause of global morbidity and mortality. Although pharmacological treatments are widely used, their effects are often limited, and nearly half of patients show resistance to current antidepressants, including those unresponsive to all available therapies. These challenges highlight the need to better understand the neurobiological mechanisms driving MDD and to develop novel therapeutic strategies, especially those involving natural compounds with multitarget actions. Baicalin, a bioactive flavonoid from Scutellaria baicalensis, exhibits antioxidant, anti-inflammatory, and neuroprotective properties and has recently gained attention for its potential to improve cognitive deficits and mood disorders. In this study, we investigated baicalin's antidepressant potential and its underlying mechanisms across multiple experimental levels. We found that oral administration of baicalin produced antidepressant-like effects in both naïve mice and those subjected to chronic restraint stress (CRS). CRS impaired hippocampal long-term potentiation (LTP), whereas baicalin restored these synaptic deficits. Importantly, intra-dorsal hippocampal microinjection of the TrkB receptor antagonist ANA-12 abolished baicalin's antidepressant effects, indicating the involvement of BDNF-TrkB signaling. Baicalin also reduced reactive oxygen species (ROS)/H2O2 production in a BDNF-associated manner, demonstrating clear antioxidant activity. Molecular docking further suggested that baicalin binds more effectively to the TrkB receptor than ANA-12, supporting its capacity to activate TrkB-mediated signaling. By integrating in vivo, ex vivo, in vitro, and in silico approaches, our study shows that baicalin exerts robust antioxidant in vitro and antidepressant effects in vivo. These benefits are primarily mediated through activation of BDNF-TrkB signaling, leading to reduced ROS/H2O2 accumulation and alleviation of CRS-induced depression-like behaviors.
This study presents a high-performance flexible dual-layer sensor integrating piezoelectric and piezoresistive functionalities within a monolithic graphene/Polyvinylidene fluoride (PVDF) structure. Fabricated using near-field electrospinning (NFES), fibers were fabricated with controlled graphene concentrations to spatially separate sensing mechanisms. The piezoelectric layer (5 wt% graphene/PVDF) achieved high voltage output, while the 11 wt% layer delivered a piezoresistive response of 602 mV under 80 kPa pressure. Electrical conductivity increased from 18.8 mu S/cm (pure PVDF) to 115 mu S/cm (11 wt% graphene). The structural and morphological analyses using OM, XRD, and FTIR confirmed excellent fiber uniformity and crystallinity. Unlike conventional single-layer composite sensors, this work introduces a novel NFES-fabricated dual-layer sensor that spatially separates and independently optimizes each sensing mechanism. Uniform Design (UD) and Kriging optimization were employed to fine-tune fabrication parameters, ensuring fiber uniformity and phase enhancement. The sensor demonstrates high sensitivity, flexibility, and dual-mode capability, making it suitable for wearable electronics and IoT applications.
This study investigates the ethanolic extract of the sea urchin Temnopleurus toreumaticus (test and spine) for its larvicidal efficacy against Aedes aegypti, cytotoxicity, and in silico interactions supporting potential antimalarial and antiviral activities. Zoochemical profiling by Fourier-transform infrared spectroscopy (FT-IR) showed the presence of functional groups, while gas chromatography-mass spectrometry (GC-MS) analysis identified 24 bioactive compounds with insecticidal and enzyme-inhibitory properties. The extract exhibited strong larvicidal (LC₅₀ = 164.18 µg/mL) and pupicidal (LC₅₀ = 209.91 µg/mL) effects on A. aegypti in a concentration‑dependent manner, supported by significant acetylcholinesterase inhibition (IC₅₀ = 151.49 µg/mL). Morphological examinations showed epithelial disorganization and structural damage in treated larvae and pupae. In silico docking confirmed that the identified zoochemicals exhibited binding affinities ranging from -7 to -8 kcal/mol for juvenile hormone binding protein (PDB 5V13), -5 to -6 kcal/mol for acetylcholinesterase (PDB 1DX4), -4 to -5 kcal/mol for Plasmodium falciparum lactate dehydrogenase (PDB 1CEQ), and -4 to -5 kcal/mol for chikungunya nsP2 protease (PDB 3TRK), indicating their multitarget larvicidal, antimalarial, and antiviral potential. Yeast cell-based assays indicated cytotoxic activity (EC₅₀ = 159.27 µg/mL) with a strong dose-response relationship. Overall, the ethanolic extract of T. toreumaticus is a promising lead for next‑generation, environmentally safe biocontrol agents targeting vector‑borne diseases such as malaria and chikungunya, while clearly emphasizing that the antiviral and antimalarial properties are currently supported only by in silico evidence and require further in vitro and in vivo validation.
BACKGROUND:Manganese (Mn) is an essential trace element involved in multiple physiological processes. However, excessive Mn exposure is well known to induce neurotoxicity and has been extensively studied in neuronal and glial models. In contrast, the effects of manganese nitrate (Mn(NO₃)₂) on innate immune cells, particularly macrophages, remain poorly understood. Given the critical role of macrophages in immune regulation and inflammation, this study investigated the cytotoxic, genotoxic, and apoptotic effects of Mn(NO₃)₂ in RAW264.7 macrophages, with emphasis on oxidative stress, mitochondrial injury, and apoptotic signalling pathways. METHODS:Macrophages were treated with various concentrations of Mn(NO₃)₂. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and genotoxic effects were analysed using micronucleus and comet assays. Apoptosis was quantified using sub-G1 DNA analysis, Annexin V/PI staining, and the TUNEL assay. Furthermore, intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential, caspase activities, and apoptosis-related protein (BCL2, BAD, Fas, and TNFR1) expression were evaluated. FINDINGS:Mn(NO₃)₂ exposure was associated with concentration-dependent reductions in cell viability, along with increases in micronucleus formation, DNA strand breaks, and nuclear fragmentation. Elevated ROS generation and mitochondrial depolarisation levels were also observed. Moreover, BCL2 downregulation, BAD upregulation, and caspase-3, caspase-8, and caspase-9 activation were observed. Fas and TNFR1 upregulation confirmed the involvement of both intrinsic and extrinsic apoptotic pathways. CONCLUSION:In conclusion, the findings demonstrate that Mn(NO₃)₂ induces cytotoxicity, genotoxicity, and apoptosis in RAW264.7 macrophages through ROS-mediated mitochondrial dysfunction. Mn(NO₃)₂ activates both intrinsic and extrinsic apoptotic pathways, as evidenced by caspase-3/caspase-9 and caspase-8 activation along with BCL2 downregulation, BAD upregulation, and Fas and TNFR1 expression alterations. These findings provide new mechanistic insights into Mn-induced immunotoxicity.
