Correlation between epicardial adipose tissue and myocardial injury in patients with COVID-19.

Background: Many people infected with COVID-19 develop myocardial injury. Epicardial adipose tissue (EAT) is among the various risk factors contributing to coronary artery disease. However, its correlation with myocardial injury in patients diagnosed with COVID-19 remains uncertain. Methods: We examined myocardial biomarkers in population affected by COVID-19 during the period from December 2022 to January 2023. The patients without myocardial injury were referred to as group A (n = 152) and those with myocardial injury were referred to as group B (n = 212). Results: 1) The A group and the B group exhibitedstatistically significant differences in terms of age, TC, CRP, Cr, BUN, LDL-C, IL-6, BNP, LVEF and EAT (p < 0.05). 2) EAT volumehad a close relationship with IL-6, LDL-C, cTnI, and CRP (p < 0.05); the corresponding correlation coefficient values were 0.24, 0.21, 0.24, and 0.16. In contrast to those with lower EAT volume, more subjects with a higher volume of EAT had myocardial injury (p < 0.05). Regression analysis showed that EAT, LDL-C, Age and Cr were established as independent risk variables for myocardial injury in subjects affected by COVID-19. 3) In COVID-19 patients, the likelihood of myocardial injury rised notably as EAT levels increase (p < 0.001). Addition of EAT to the basic risk model for myocardial injury resulted in improved reclassification. (Net reclassification index: 58.17%, 95% CI: 38.35%, 77.99%, p < 0.001). Conclusion: Patients suffering from COVID-19 with higher volume EAT was prone to follow myocardial injury and EAT was an independent predictor of heart damage in these individuals.

Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology.

Objective: Recombinase-aided polymerase chain reaction (RAP) is a sensitive, single-tube, two-stage nucleic acid amplification method. This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Acinetobacter baumannii (AB) in the bloodstream based on recombinant human mannan-binding lectin protein (M1 protein)-conjugated magnetic bead (M1 bead) enrichment of pathogens combined with RAP. Methods: Recombinant plasmids were used to evaluate the assay sensitivity. Common blood influenza bacteria were used for the specific detection. Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR (M-RAP) and quantitative PCR (qPCR) assays. Kappa analysis was used to evaluate the consistency between the two assays. Results: The M-RAP method had sensitivity rates of 1, 10, and 1 copies/µL for the detection of SA, PA, and AB plasmids, respectively, without cross-reaction to other bacterial species. The M-RAP assay obtained results for < 10 CFU/mL pathogens in the blood within 4 h, with higher sensitivity than qPCR. M-RAP and qPCR for SA, PA, and AB yielded Kappa values of 0.839, 0.815, and 0.856, respectively ( P < 0.05). Conclusion: An M-RAP assay for SA, PA, and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

Actomyosin-II protects axons from degeneration induced by mild mechanical stress.

Whether, to what extent, and how the axons in the central nervous system (CNS) can withstand sudden mechanical impacts remain unclear. By using a microfluidic device to apply controlled transverse mechanical stress to axons, we determined the stress levels that most axons can withstand and explored their instant responses at nanoscale resolution. We found mild stress triggers a highly reversible, rapid axon beading response, driven by actomyosin-II-dependent dynamic diameter modulations. This mechanism contributes to hindering the long-range spread of stress-induced Ca2+ elevations into non-stressed neuronal regions. Through pharmacological and molecular manipulations in vitro, we found that actomyosin-II inactivation diminishes the reversible beading process, fostering progressive Ca2+ spreading and thereby increasing acute axonal degeneration in stressed axons. Conversely, upregulating actomyosin-II activity prevents the progression of initial injury, protecting stressed axons from acute degeneration both in vitro and in vivo. Our study unveils the periodic actomyosin-II in axon shafts cortex as a novel protective mechanism, shielding neurons from detrimental effects caused by mechanical stress.

Jingfang granules protects against intracerebral hemorrhage by inhibiting neuroinflammation and protecting blood-brain barrier damage.

Intracerebral hemorrhage (ICH) can induce intensive oxidative stress, neuroinflammation, and brain cell apoptosis. However, conventional methods for ICH treatment have many disadvantages. There is an urgent need for alternative, effective therapies with minimal side effects. Pharmacodynamics experiment, molecular docking, network pharmacology, and metabolomics were adopted to investigate the treatment and its mechanism of Jingfang Granules (JFG) in ICH. In this study, we investigated the therapeutic effects of JFG on ICH using behavioral, brain water content and Magnetic resonance imaging experiments. However, the key active component and targets of JFG remain unknown. Here we verified that JFG was beneficial to improve brain injury after ICH. A network pharmacology analysis revealed that the anti-inflammatory effect of JFG is predominantly mediated by its activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway through Luteolin, (+)-Anomalin and Phaseol and their targeting of AKT1, tumor necrosis factorα (TNF-α), and interleukin-1ß (IL-1ß). Molecular docking analyses revealed an average affinity of -8.633 kcal/mol, indicating a binding strength of less than -5 kcal/mol. Metabolomic analysis showed that JFG exerted its therapeutic effect on ICH by regulating metabolic pathways, such as the metabolism of taurine and hypotaurine, biosynthesis of valine, leucine, and isoleucine. In conclusion, we demonstrated that JFG attenuated neuroinflammation and BBB injury subsequent to ICH by activating the PI3K/Akt signaling pathway.

Intermittent theta-burst stimulation alleviates hypoxia-ischemia-caused myelin damage and neurologic disability.

Neonatal hypoxia-ischemia (HI) results in behavioral deficits, characterized by neuronal injury and retarded myelin formation. To date, limited treatment methods are available to prevent or alleviate neurologic sequelae of HI. Intermittent theta-burst stimulation (iTBS), a non-invasive therapeutic procedure, is considered a promising therapeutic tool for treating some neurocognitive disorders and neuropsychiatric diseases. Hence, this study aims to investigate whether iTBS can prevent the negative behavioral manifestations of HI and explore the mechanisms for associations. We exposed postnatal day 10 Sprague-Dawley male and female rats to 2 h of hypoxia (6% O2) following right common carotid artery ligation, resulting in oligodendrocyte (OL) dysfunction, including reduced proliferation and differentiation of oligodendrocyte precursor cells (OPCs), decreased OL survival, and compromised myelin in the corpus callosum (CC) and hippocampal dentate gyrus (DG). These alterations were concomitant with cognitive dysfunction and depression-like behaviors. Crucially, early iTBS treatment (15 G, 190 s, seven days, initiated one day post-HI) significantly alleviated HI-caused myelin damage and mitigated the neurologic sequelae both in male and female rats. However, the late iTBS treatment (initiated 18 days after HI insult) could not significantly impact these behavioral deficits. In summary, our findings support that early iTBS treatment may be a promising strategy to improve HI-induced neurologic disability. The underlying mechanisms of iTBS treatment are associated with promoting the differentiation of OPCs and alleviating myelin damage.

Structurally Tunable Donor-Bridge-Fluorophore Architecture Enables Highly Efficient and Concentration-Independent Narrowband Electroluminescence.

Luminescent materials with narrowband emission have extraordinary significance for developing ultrahigh-definition display. B-N-containing multiple resonance thermally activated delayed fluorescence (MR-TADF) materials are strong contenders. However, their device performances pervasively encounter detrimental aggregation-caused quenching effect that is highly vulnerable to doping concentration, complicating device fabrication. Therefore, constructing highly efficient and concentration-independent MR-TADF emitters is of pragmatic importance for improving device controllability and reproducibility, simplifying manufacturing procedures, and conserving production costs. Here, by systematic arrangement of donor triphenylamine and fluorophore BNCz on distinct bridges, we have developed a spatial confinement strategy with a donor-bridge-fluorophore (D-B-F) architecture. Structurally fine modulation and progressive evolution to construct molecular entities with congested steric hindrance effect that can suppress intermolecular interactions without substantially affecting the luminescence tone of fluorophore BNCz, resulting in highly efficient and concentration-independent narrowband emitters; through isomer engineering, two isomers BN-PCz-TPA and TPA-PCz-BN with different crystal stacking patterns are synthesized by altering the connection mode between triphenylamine and BNCz. As a result, BN-PCz-TPA-based device showcases maximum external quantum efficiency (EQE) of 36.3% with narrow full-width at half-maximum (FWHM) of 27 nm at 10 wt% doping concentration. Even at 20 wt% doping concentration, the maximum EQE remains at 32.5% and the emission spectrum is almost unchanged. This article is protected by copyright. All rights reserved.

Gastrointestinal Incomplete Degradation Exacerbates Neurotoxic Effects of PLA Microplastics via Oligomer Nanoplastics Formation.

Biodegradable plastics, hailed for their environmental friendliness, may pose unforeseen risks as they undergo gastrointestinal degradation, forming oligomer nanoplastics. Despite this, the influence of gastrointestinal degradation on the potential human toxicity of biodegradable plastics remains poorly understood. To this end, the impact of the murine in vivo digestive system is investigated on the biotransformation, biodistribution, and toxicity of PLA polymer and PLA oligomer MPs. Through a 28-day repeated oral gavage study in mice, it is revealed that PLA polymer and oligomer microplastics undergo incomplete and complete degradation, respectively, in the gastrointestinal tract. Incompletely degraded PLA polymer microplastics transform into oligomer nanoplastics, heightening bioavailability and toxicity, thereby exacerbating overall toxic effects. Conversely, complete degradation of PLA oligomer microplastics reduces bioavailability and mitigates toxicity, offering a potential avenue for toxicity reduction. Additionally, the study illuminates shared targets and toxicity mechanisms in Parkinson's disease-like neurotoxicity induced by both PLA polymer and PLA oligomer microplastics. This involves the upregulation of MICU3 in midbrains, leading to neuronal mitochondrial calcium overload. Notably, neurotoxicity is mitigated by inhibiting mitochondrial calcium influx with MCU-i4 or facilitating mitochondrial calcium efflux with DBcAMP in mice. These findings enhance the understanding of the toxicological implications of biodegradable microplastics on human health.

Gender-specific effects of polystyrene nanoplastic exposure on triclosan-induced reproductive toxicity in zebrafish (Danio rerio).

Nanoplastics (NPs) and triclosan (TCS) are ubiquitous emerging environmental contaminants detected in human samples. While the reproductive toxicity of TCS alone has been studied, its combined effects with NPs remain unclear. Herein, we employed Fourier transform infrared spectroscopy and dynamic light scattering to characterize the coexposure of polystyrene nanoplastics (PS-NPs, 50 nm) with TCS. Then, adult zebrafish were exposed to TCS at environmentally relevant concentrations (0.361-48.2 µg/L), with or without PS-NPs (1.0 mg/L) for 21 days. TCS biodistribution in zebrafish tissues was investigated using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Reproductive toxicity was assessed through gonadal histopathology, fertility tests, changes in steroid hormone synthesis and gene expression within the hypothalamus-pituitary-gonad-liver (HPGL) axis. Transcriptomics and proteomics were applied to explore the underlying mechanisms. The results showed that PS-NPs could adsorb TCS, thus altering the PS-NPs' physical characteristics. Our observations revealed that coexposure with PS-NPs reduced TCS levels in the ovaries, livers, and brains of female zebrafish. Conversely, in males, coexposure with PS-NPs increased TCS levels in the testes and livers, while decreasing them in the brain. We found that co-exposure mitigated TCS-induced ovary development inhibition while exacerbated TCS-induced spermatogenesis suppression, resulting in increased embryonic mortality and larval malformations. This co-exposure influenced the expression of genes linked to steroid hormone synthesis (cyp11a1, hsd17ß, cyp19a1) and attenuated the TCS-decreased estradiol (E2) in females. Conversely, testosterone levels were suppressed, and E2 levels were elevated due to the upregulation of specific genes (cyp11a1, hsd3ß, cyp19a1) in males. Finally, the integrated analysis of transcriptomics and proteomics suggested that the aqp12-dctn2 pathway was involved in PS-NPs' attenuation of TCS-induced reproductive toxicity in females, while the pck2-katnal1 pathway played a role in PS-NPs' exacerbation of TCS-induced reproductive toxicity in males. Collectively, PS-NPs altered TCS-induced reproductive toxicity by disrupting the HPGL axis, with gender-specific effects.

Model Prediction and Experimental Validation of Transverse Permeability of Large-Tow Carbon Fiber Composites.

Large-tow carbon fiber (LCF) meets the low-cost requirements of modern industry. However, due to the large and dense number of monofilaments, there are problems with uneven and insufficient infiltration during material preparation. The permeability of large-tow carbon fibers can be used as a two-scale expression of resin flow during infiltration, making it an important factor to consider. This paper provides support for the study of pore formation. A two-dimensional model of randomly bundled large-filament carbon fibers is generated based on scanning electron microscope (SEM) maps. Microstructure size parameters are obtained, and a semi-analytical model of the transverse permeability of large-filament-bundled carbon fibers is established. Permeability values are then obtained. The analysis shows that the monofilaments in the tow are arranged randomly, and their periodic arrangement cannot be used to calculate permeability. Additionally, the number of monofilaments in a carbon fiber tow of the same volume fraction affects the permeability of the tow. Therefore, the permeability model of large-tow carbon fibers is reliable.

Structural and functional insights into transcription activation of the essential LysR-type transcriptional regulators.

The enormous LysR-type transcriptional regulators (LTTRs), which are diversely distributed amongst prokaryotes, play crucial roles in transcription regulation of genes involved in basic metabolic pathways, virulence and stress resistance. However, the precise transcription activation mechanism of these genes by LTTRs remains to be explored. Here, we determine the cryo-EM structure of a LTTR-dependent transcription activation complex comprising of Escherichia coli RNA polymerase (RNAP), an essential LTTR protein GcvA and its cognate promoter DNA. Structural analysis shows two N-terminal DNA binding domains of GcvA (GcvA_DBD) dimerize and engage the GcvA activation binding sites, presenting the -35 element for specific recognition with the conserved σ70R4. In particular, the versatile C-terminal domain of α subunit of RNAP directly interconnects with GcvA_DBD, σ70R4 and promoter DNA, providing more interfaces for stabilizing the complex. Moreover, molecular docking supports glycine as one potential inducer of GcvA, and single molecule photobleaching experiments kinetically visualize the occurrence of tetrameric GcvA-engaged transcription activation complex as suggested for the other LTTR homologs. Thus, a general model for tetrameric LTTR-dependent transcription activation is proposed. These findings will provide new structural and functional insights into transcription activation of the essential LTTRs.

Green Manuring Enhances Soil Multifunctionality in Tobacco Field in Southwest China.

The use of green manure can substantially increase the microbial diversity and multifunctionality of soil. Green manuring practices are becoming popular for tobacco production in China. However, the influence of different green manures in tobacco fields has not yet been clarified. Here, smooth vetch (SV), hairy vetch (HV), broad bean (BB), common vetch (CV), rapeseed (RS), and radish (RD) were selected as green manures to investigate their impact on soil multifunctionality and evaluate their effects on enhancing soil quality for tobacco cultivation in southwest China. The biomass of tobacco was highest in the SV treatment. Soil pH declined, and soil organic matter (SOM), total nitrogen (TN), and dissolved organic carbon (DOC) content in CV and BB and activity of extracellular enzymes in SV and CV treatments were higher than those in other treatments. Fungal diversity declined in SV and CV but did not affect soil multifunctionality, indicating that bacterial communities contributed more to soil multifunctionality than fungal communities. The abundance of Firmicutes, Rhizobiales, and Micrococcales in SV and CV treatments increased and was negatively correlated with soil pH but positively correlated with soil multifunctionality, suggesting that the decrease in soil pH contributed to increases in the abundance of functional bacteria. In the bacteria-fungi co-occurrence network, the relative abundance of key ecological modules negatively correlated with soil multifunctionality and was low in SV, CV, BB, and RS treatments, and this was associated with reductions in soil pH and increases in the content of SOM and nitrate nitrogen (NO3--N). Overall, we found that SV and CV are more beneficial for soil multifunctionality, and this was driven by the decrease in soil pH and the increase in SOM, TN, NO3--N, and C- and N-cycling functional bacteria.

Association of the retinol to all-trans retinoic acid pathway with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research. METHODS: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels. CONCLUSION: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes.

Simultaneous Detection of Adenosine-to-Inosine Editing and N6-Methyladenosine at Identical RNA Sites through Deamination-Assisted Reverse Transcription Stalling.

Adenosine-to-inosine (A-to-I) editing and N6-methyladenosine (m6A) modifications are pivotal RNA modifications with widespread functional significance in physiological and pathological processes. Although significant effort has been dedicated to developing methodologies for identifying and quantifying these modifications, traditional approaches have often focused on each modification independently, neglecting the potential co-occurrence of A-to-I editing and m6A modifications at the same adenosine residues. This limitation has constrained our understanding of the intricate regulatory mechanisms governing RNA function and the interplay between different types of RNA modifications. To address this gap, we introduced an innovative technique called deamination-assisted reverse transcription stalling (DARTS), specifically designed for the simultaneous quantification of A-to-I editing and m6A at the same RNA sites. DARTS leverages the selective deamination activity of the engineered TadA-TadA8e protein, which converts adenosine residues to inosine, in combination with the unique property of Bst 2.0 DNA polymerase, which stalls when encountering inosine during reverse transcription. This approach enables the accurate quantification of A-to-I editing, m6A, and unmodified adenosine at identical RNA sites. The DARTS method is remarkable for its ability to directly quantify two distinct types of RNA modifications simultaneously, a capability that has remained largely unexplored in the field of RNA biology. By facilitating a comprehensive analysis of the co-occurrence and interaction between A-to-I editing and m6A modifications, DARTS opens new avenues for exploring the complex regulatory networks modulated by different RNA modifications.

Rapid and Definitive Identification of Cyclic Peptide Soft Spots by Isotope-Labeled Reductive Dimethylation and Mass Spectrometry Fragmentation.

Cyclic peptides are an emerging therapeutic modality over the past few decades. To identify drug candidates with sufficient proteolytic stability for oral administration, it is critical to pinpoint the amide bond hydrolysis sites, or soft spots, to better understand their metabolism and provide guidance on further structure optimization. However, the unambiguous characterization of cyclic peptide soft spots remains a significant challenge during early stage discovery studies, as amide bond hydrolysis forms a linearized isobaric sequence with the addition of a water molecule, regardless of the amide hydrolysis location. In this study, an innovative strategy was developed to enable the rapid and definitive identification of cyclic peptide soft spots by isotope-labeled reductive dimethylation and mass spectrometry fragmentation. The dimethylated immonium ion with enhanced MS signal at a distinctive m/z in MS/MS fragmentation spectra reveals the N-terminal amino acid on a linearized peptide sequence definitively and, thus, significantly simplifies the soft spot identification workflow. This approach has been evaluated to demonstrate the potential of isotope-labeled dimethylation to be a powerful analytical tool in cyclic peptide drug discovery and development.

One-step high efficiency separation of prolyl endopeptidase from Aspergillus niger and its application.

Prolyl endopeptidase from Aspergillus niger (An-PEP) is an enzyme that recognizes C-terminal peptide bonds of amino acid chains and cleaves them by hydrolysis. An aqueous two-phase system (ATPS) was used to separate An-PEP from fermentation broth. Through single factor experiments, the ATPS containing 16 % (w/w) PEG2000 and 15 % (w/w) (NH4)2SO4 at pH 6.0 obtained the recovery of 79.74 ±â€¯0.16 % and the purification coefficient of 7.64 ±â€¯0.08. It was then used to produce soy protein isolate peptide (SPIP) by hydrolysis of soy protein isolate (SPI), and SPIP-Ferrous chelate (SPIP-Fe) was prepared with SPIP and Fe2+. The chelation conditions were optimized by RSM, as the chelation time was 30 min, chelation temperature was 25 °C, SPIP mass to VC mass was two to one and pH was 6.0. The obtained chelation rate was 82.56 ±â€¯2.30 %. The change in the structures and functional features of SPIP before and after chelation were investigated. The FTIR and UV-Vis results indicated that the chelation of Fe2+ and SPIP depended mainly on the formation of amide bonds. The fluorescence, SEM and amino acid composition analysis results indicated that Fe2+ could induce and stabilize the surface conformation and change the amino acid distribution on the surfaces of SPIP. The chelation of SPIP and Fe2+ resulted in the enhancement of radical scavenging activities and ACE inhibitory activities. This work provided a new perspective for the further development of peptide-Fe chelates for iron supplement.

Clinical Observations on the Combined Use of Hyperbaric Oxygenation and Conventional Medications in the Management of Type 2 Diabetes Mellitus Concurrent With Sudden Deafness.

Objective: The aim of this study is to investigate the effectiveness of combining hyperbaric oxygen therapy (HBOT) with conventional pharmacological interventions in the management of type 2 diabetes mellitus concurrent with sudden deafness. Methods: A cohort of 96 patients diagnosed with sudden deafness was enrolled and subsequently randomized into 2 groups: a treatment group (n = 50) and a control group (n = 46). The control group received standard conventional treatment aimed at enhancing microcirculation and nutritional support for nerves, while the treatment group underwent conventional symptomatic treatment coupled with HBOT. The evaluation encompassed the monitoring of blood glucose and blood lipid levels, clinical efficacy, and absolute hearing threshold improvement in both groups. Results: Following the intervention, noteworthy reductions in blood glucose and blood lipid levels were observed in both groups compared to their respective pretreatment values. Furthermore, posttreatment values in the treatment group exhibited a statistically significant decrease in comparison to those in the control group (P < .05). On assessing clinical efficacy posttreatment, the treatment group demonstrated a significantly higher efficacy than the control group (P < .05). In addition, the absolute hearing thresholds in both groups exhibited a significant decrease posttreatment compared to baseline values. Notably, the treatment group displayed a statistically significant reduction in absolute hearing thresholds compared to the control group posttreatment (P < .05). Conclusion: The combined therapeutic approach utilizing hyperbaric oxygen exhibits effectiveness in mitigating auditory impairment among individuals manifesting sudden deafness concomitant with type 2 diabetes mellitus. Furthermore, this treatment approach is associated with a concurrent reduction in blood glucose and blood lipid levels.

From cradle to grave: Deciphering sex-specific disruptions of the nervous and reproductive systems through interactions of 4-methylbenzylidene camphor and nanoplastics in adult zebrafish.

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4832 µg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish.

Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy.

Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous in vivo electrophysiology in hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits. In contrast, abnormal synchronization within MEC and between HPC-MEC emerged later, by 8 weeks after Pilo-SE, when spatial memory impairment was more severe. Furthermore, a distinct subpopulation of MEC layer 3 excitatory neurons (active at theta troughs) was specifically impaired in epileptic mice. Together, these findings suggest that hippocampal-entorhinal circuit dysfunction accumulates and shifts as cognitive impairment progresses in TLE.

[Serum folate and vitamin B12 levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder]. / å­¦é¾„å‰å­¤ç‹¬ç—‡è°±ç³»éšœç¢å„¿ç«¥è¡€æ¸ å¶é ¸ã€ç»´ç”Ÿç´ B12æ°´å¹³åŠå ¶ä¸Žç¥žç»å‘è‚²ç‰¹å¾çš„å ³è”.

OBJECTIVES: To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.

Decreased RNA-binding protein heterogeneous nuclear ribonucleoprotein U improves multiple myeloma sensitivity to lenalidomide.

Multiple myeloma (MM) is an incurable plasma cell cancer in the bone marrow. Immunomodulatory drugs, such as lenalidomide (LEN) and pomalidomide, are backbone agents in MM treatment, and LEN resistance is commonly seen in the MM clinic. In this study, we presented that heterogeneous nuclear ribonucleoprotein U (hnRNPU) affected MM resistance to LEN via the regulation of target mRNA translation. hnRNPULow MM cells exhibited upregulated CRBN and IKZF1 proteins, stringent IKZF1/3 protein degradation upon LEN addition and increased sensitivity to LEN. RNA pulldown assays and RNA electrophoretic mobility shift assays revealed that hnRNPU bound to the 3'-untranslated region of CRBN and IKZF1 mRNA. A sucrose gradient assay suggested that hnRNPU specifically regulated CRBN and IKZF1 mRNA translation. The competition of hnRNPU binding to its target mRNAs by small RNAs with hnRNPU-binding sites restored MM sensitivity to LEN. hnRNPU function in vivo was confirmed in an immunocompetent MM mouse model constructed by the inoculation of Crbn-humanized murine 5TGM1 cells into CrbnI391V/+ mice. Overall, this study suggests a novel mechanism of LEN sensitivity in which hnRNPU represses CRBN and IKZF1 mRNA translation.