Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202502000-00027/figure1/v/2024-05-28T214302Z/r/image-tiff Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury. Low-density lipoprotein receptor, a classic cholesterol regulatory receptor, has been found to inhibit NLR family pyrin domain containing protein 3 (NLRP3) inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer's disease. However, little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke. To address this issue in the present study, we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models. First, we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis. We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation. Second, we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus. Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype. Finally, we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin, an NLRP3 agonist, restored the neurotoxic astrocyte phenotype. These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

Long-term associations of PM1 versus PM2.5 and PM10 with asthma and asthma-related respiratory symptoms in the middle-aged and elderly population.

Background: Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5 and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults. Methods: We calculated the mean 722-day personal exposure estimates of PM1, PM2.5 and PM10 at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10 concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months. Results: We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5 and PM10 was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02-1.45); PM2.5: 1.24 (1.04-1.48); PM10: 1.30 (1.07-1.57)), wheeze (PM1: 1.27 (1.11-1.44); PM2.5: 1.30 (1.14-1.48); PM10: 1.34 (1.17-1.55)), persistent cough (PM1: 1.33 (1.06-1.66); PM2.5: 1.36 (1.09-1.71); PM10: 1.31 (1.02-1.68)) and dyspnoea (PM1: 2.10 (1.84-2.41); PM2.5: 2.17 (1.90-2.48); PM10: 2.29 (1.96-2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5 and PM10 with asthma and asthma-related respiratory symptoms were slightly stronger in males. Conclusion: Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.

Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment.

Precise measurement of the binding activity changes of therapeutic antibodies is important to determine the potential critical quality attributes (CQAs) in developability assessment at the early stage of antibody development. Here, we report a surface plasmon resonance (SPR)-based relative binding activity method, which incorporates both binding affinity and binding response and allows us to determine relative binding activity of antibodies with high accuracy and precision. We applied the SPR-based relative binding activity method in multiple forced degradation studies of antibody developability assessment. The current developability assessment strategy provided comprehensive, precise characterization of antibody binding activity in the stability studies, enabling us to perform correlation analysis and establish the structure-function relationship between relative binding activity and quality attributes. The impact of a given quality attribute on binding activity could be confidently determined without isolating antibody variants. We identified several potential CQAs, including Asp isomerization, Asn deamidation, and fragmentation. Some potential CQAs affected binding affinity of antibody and resulted in a reduction of binding activity. Certain potential CQAs impaired antibody binding to antigen and led to a loss of binding activity. A few potential CQAs could influence both binding affinity and binding response and cause a substantial decrease in antibody binding activity. Specifically, we identified low abundance Asn33 deamidation in the light chain complementarity-determining region as a potential CQA, in which all the stressed antibody samples showed Asn33 deamidation abundances ranging from 4.2% to 27.5% and a mild binding affinity change from 1.76 nM to 2.16 nM.

In vitro antifungal and physicochemical properties of polymerized acrylic resin containing strontium-modified phosphate-based glass.

Acrylic resins are widely used as the main components in removable orthodontic appliances. However, poor oral hygiene and maintenance of orthodontic appliances provide a suitable environment for the growth of pathogenic microorganisms. In this study, strontium-modified phosphate-based glass (Sr-PBG) was added to orthodontic acrylic resin at 0% (control), 3.75%, 7.5%, and 15% by weight to evaluate the surface and physicochemical properties of the novel material and its in vitro antifungal effect against Candida albicans (C. albicans). Surface microhardness and contact angle did not vary between the control and 3.75% Sr-PBG groups (p > 0.05), and the flexural strength was lower in the experimental groups than in the control group (p < 0.05), but no difference was found with Sr-PBG content (p > 0.05). All experimental groups showed an antifungal effect at 24 and 48 h compared to that in the control group (p < 0.05). This study demonstrated that 3.75% Sr-PBG exhibits antifungal effects against C. albicans along with suitable physicochemical properties, which may help to minimize the risk of adverse effects associated with harmful microbial living on removable orthodontic appliances and promote the use of various materials.

Successful treatment with efgartigimod as an add-on therapy in acute attack of anti-AQP4 antibody-positive NMOSD: a case report.

BACKGROUND: Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune demyelinating disease characterized by recurrent myelitis and optic neuritis. It is associated with high rates of relapse and disability. The main treatment strategies for acute attacks include intravenous methylprednisolone pulse (IVMP) treatment and rescue treatment with plasma exchange (PLEX). Recently, the blockade of neonatal Fc receptor (FcRn)-IgG interaction has gained momentum as a therapeutic strategy. Efgartigimod, the first approved FcRn inhibitor for treating generalized myasthenia gravis, has shown impressive safety, efficacy, and tolerability, and is being regarded as "PLEX in a bottle". CASE DESCRIPTION: We report a 65-year-old female patient who was diagnosed with anti-AQP4 antibody positive NMOSD. Add-on treatment with efgartigimod to IVMP and intravenous immunoglobulin (IVIG) at the second acute relapse showed favorable results. CONCLUSION: This case suggests that efgartigimod is a potentially effective add-on therapy in acute attacks of AQP4-IgG-positive NMOSD.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

Physiological and genetic responses of the benthic dinoflagellate Prorocentrum lima to polystyrene microplastics.

Microplastics are well known as contaminants in marine environments. With the development of biofilms, most microplastics will eventually sink and deposit in benthic environment. However, little research has been done on benthic toxic dinoflagellates, and the effects of microplastics on benthic dinoflagellates are unknown. Prorocentrum lima is a cosmopolitan toxic benthic dinoflagellate, which can produce a range of polyether metabolites, such as diarrhetic shellfish poisoning (DSP) toxins. In order to explore the impact of microplastics on marine benthic dinoflagellates, in this paper, we studied the effects of polystyrene (PS) on the growth and toxin production of P. lima. The molecular response of P. lima to microplastic stress was analyzed by transcriptomics. We selected 100 nm, 10 µm and 100 µm PS, and set three concentrations of 1 mg L-1, 10 mg L-1 and 100 mg L-1. The results showed that PS exposure had limited effects on cell growth, but increased the OA and extracellular polysaccharide content at high concentrations. After exposure to PS MPs, genes associated with DSP toxins synthesis, carbohydrate synthesis and energy metabolism, such as glycolysis, TCA cycle and pyruvate metabolism, were significantly up-regulated. We speculated that after exposure to microplastics, P. lima may increase the synthesis of DSP toxins and extracellular polysaccharides, improve the level of energy metabolism and gene expression of ABC transporter, thereby protecting algal cells from damage. Our findings provide new insights into the effects of microplastics on toxic benthic dinoflagellates.

Generation and transcriptomic characterization of MIR137 knockout miniature pig model for neurodevelopmental disorders.

BACKGROUND: Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions. Genetic factors are recognized as playing a major role in NDD, with a multitude of genes and genomic regions implicated. While the functional validation of NDD-associated genes has predominantly been carried out using mouse models, the significant differences in brain structure and gene function between mice and humans have limited the effectiveness of mouse models in exploring the underlying mechanisms of NDD. Therefore, it is important to establish alternative animal models that are more evolutionarily aligned with humans. RESULTS: In this study, we employed CRISPR/Cas9 and somatic cell nuclear transplantation technologies to successfully generate a knockout miniature pig model of the MIR137 gene, which encodes the neuropsychiatric disorder-associated microRNA miR-137. The homozygous knockout of MIR137 (MIR137-/-) effectively suppressed the expression of mature miR-137 and led to the birth of stillborn or short-lived piglets. Transcriptomic analysis revealed significant changes in genes associated with neurodevelopment and synaptic signaling in the brains of MIR137-/- miniature pig, mirroring findings from human ASD transcriptomic data. In comparison to miR-137-deficient mouse and human induced pluripotent stem cell (hiPSC)-derived neuron models, the miniature pig model exhibited more consistent changes in critical neuronal genes relevant to humans following the loss of miR-137. Furthermore, a comparative analysis identified differentially expressed genes associated with ASD and ID risk genes in both miniature pig and hiPSC-derived neurons. Notably, human-specific miR-137 targets, such as CAMK2A, known to be linked to cognitive impairments and NDD, exhibited dysregulation in MIR137-/- miniature pigs. These findings suggest that the loss of miR-137 in miniature pigs affects genes crucial for neurodevelopment, potentially contributing to the development of NDD. CONCLUSIONS: Our study highlights the impact of miR-137 loss on critical genes involved in neurodevelopment and related disorders in MIR137-/- miniature pigs. It establishes the miniature pig model as a valuable tool for investigating neurodevelopmental disorders, providing valuable insights for potential applications in human research.

Polystyrene microplastics exacerbated the toxicity of okadaic acid to the small intestine in mice.

Microplastics (MPs) and okadaic acid (OA) are known to coexist in marine organisms, potentially impacting humans through food chain. However, the combined toxicity of OA and MPs remains unknown. In this study, mice were orally administered OA at 200 µg/kg bw and MPs at 2 mg/kg bw. The co-exposure group showed a significant increase in malondialdehyde (MDA) content and significant decreases in superoxide dismutase (SOD) activity and glutathione (GSH) level compared to the control, MPs and OA groups (p < 0.05). Additionally, the co-exposure group exhibited significantly higher levels of IL-1ß and IL-18 compared to other groups (p < 0.05). These results demonstrated that co-exposure to MPs and OA induces oxidative stress and exacerbates inflammation. Histological and cellular ultrastructure analyses suggested that this combined exposure may enhance gut damage and compromise barrier integrity. Consequently, the concentration of OA in the small intestine of the co-exposure group was significantly higher than that in the OA group. Furthermore, MPs were observed in the lamina propria of the gut in the co-exposure group. Transcriptomic analysis revealed that the co-exposure led to increased expression of certain genes related to the NF-κB/NLRP3 pathway compared to the OA and MPs groups. Overall, this combined exposure may disrupt the intestinal barrier, and promote inflammation through the NF-κB/NLRP3 pathway. These findings provide precious information for the understanding of health risks associated with MPs and phycotoxins.

Impact of butylparaben on growth dynamics and microcystin-LR production in Microcystis aeruginosa.

The presence of butylparaben (BP), a prevalent pharmaceutical and personal care product, in surface waters has raised concerns regarding its impact on aquatic ecosystems. Despite its frequent detection, the toxicity of BP to the cyanobacterium Microcystis aeruginosa remains poorly understood. This study investigates the influence of BP on the growth and physiological responses of M. aeruginosa. Results indicate that low concentrations of BP (below 2.5 mg/L) have negligible effects on M. aeruginosa growth, whereas higher concentrations (5 mg/L and 10 mg/L) lead to significant growth inhibition. This inhibition is attributed to the severe disruption of photosynthesis, evidenced by decreased Fv/Fm values and chlorophyll a content. BP exposure also triggers the production of reactive oxygen species (ROS), resulting in elevated activity of antioxidant enzymes. Excessive ROS generation stimulates the production of microcystin-LR (MC-LR). Furthermore, lipid peroxidation and cell membrane damage indicate that high BP concentrations cause cell membrane rupture, facilitating the release of MC-LR into the environment. Transcriptome analysis reveals that BP disrupts energy metabolic processes, particularly affecting genes associated with photosynthesis, carbon fixation, electron transport, glycolysis, and the tricarboxylic acid cycle. These findings underscore the profound physiological impact of BP on M. aeruginosa and highlight its role in stimulating the production and release of MC-LR, thereby amplifying environmental risks in aquatic systems.

Synergistic and stepwise treatment of resveratrol and catechol in Haematococcus pluvialis for the overproduction of biomass and astaxanthin.

To increase the production of biomass and astaxanthin from Haematococcus pluvialis to meet the high market demand for astaxanthin, this study recruited two typical and negligible phytohormones (namely resveratrol and catechol) for the stepwise treatments of H. pluvialis. It was found that the hybrid and sequential treatments of resveratrol (200 µmol) and catechol (100 µmol) had achieved the maximum astaxanthin content at 33.96 mg/L and 42.99 mg/L, respectively. Compared with the hybrid treatment, the physiological data of H. pluvialis using the sequential strategy revealed that the enhanced photosynthetic performance via the Calvin cycle by RuBisCO improved the biomass accumulation during the macrozooid stage; meanwhile, the excessive ROS production had occurred to enhance astaxanthin production with the help of NADPH overproduction during the hematocyst stage. Overall, this study provides improved knowledge of the impacts of phytohormones in improving biomass and astaxanthin of H. pluvialis, which shed valuable insights for advancing microalgae-based biorefinery.

The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.

Jnk1 and downstream signalling hubs regulate anxiety-like behaviours in a zebrafish larvae phenotypic screen.

Current treatments for anxiety and depression show limited efficacy in many patients, indicating the need for further research into the underlying mechanisms. JNK1 has been shown to regulate anxiety- and depressive-like behaviours in mice, however the effectors downstream of JNK1 are not known. Here we compare the phosphoproteomes from wild-type and Jnk1-/- mouse brains and identify JNK1-regulated signalling hubs. We next employ a zebrafish (Danio rerio) larvae behavioural assay to identify an antidepressant- and anxiolytic-like (AA) phenotype based on 2759 measured stereotypic responses to clinically proven antidepressant and anxiolytic (AA) drugs. Employing machine learning, we classify an AA phenotype from extracted features measured during and after a startle battery in fish exposed to AA drugs. Using this classifier, we demonstrate that structurally independent JNK inhibitors replicate the AA phenotype with high accuracy, consistent with findings in mice. Furthermore, pharmacological targeting of JNK1-regulated signalling hubs identifies AKT, GSK-3, 14-3-3 ζ/ε and PKCε as downstream hubs that phenocopy clinically proven AA drugs. This study identifies AKT and related signalling molecules as mediators of JNK1-regulated antidepressant- and anxiolytic-like behaviours. Moreover, the assay shows promise for early phase screening of compounds with anti-stress-axis properties and for mode of action analysis.

Clinical study on treatment of cervical spondylotic radiculopathy (Qi stagnation and blood stasis syndrome) with Gao's nape needle and Shentong Zhuyu decoction.

BACKGROUND: Cervical spondylotic radiculopathy is currently one of the common orthopedic diseases, mainly characterized by neck pain, stiffness, limited mobility, and related symptoms of nerve root compression, which seriously troubles people's work and life. METHODS: Ninety cases of cervical spondylotic radiculopathy (Qi stagnation and blood stasis syndrome) were randomly divided into treatment group and control group, 45 cases in each group. The control group was treated with western medicine (nerve nutrition, pain relief, and circulation improvement drugs), and the treatment group was treated with Gao's nape needle combined with modified Shentong Zhuyu decoction on the basis of the control group. Before and after 2 weeks, TCM syndrome score, TCM curative effect, visual analogue scale score, numbness score, neck disability index score, related serum inflammatory factors (interleukin-10 [IL-10], interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α]), related hemorheological indexes (plasma viscosity, high shear whole blood viscosity, low shear whole blood viscosity level) were used as evaluation indexes to evaluate the effect. RESULTS: After treatment, the total effective rate of the treatment group was 91.11%, which was better than that of the control group (78.78%), and the TCM syndrome scores of the 2 groups were decreased, the treatment group was better than that of the control group, and the differences were statistically significant (P < .05). After treatment, the visual analogue scale score, numbness score, and neck disability index score were decreased in both groups, and the decrease in the treatment group was more significant than that in the control group, and the differences were statistically significant (P < .05). After treatment, the related serum inflammatory factors (IL-10, IL-6, TNF-α) and related hemorheological indexes (plasma viscosity, high-shear whole blood viscosity, low-shear whole blood viscosity) were decreased in both groups, and the decrease in the treatment group was more significant than that in the control group, and the differences were statistically significant (P < .05). CONCLUSION: The treatment of cervical spondylotic radiculopathy (Qi stagnation and blood stasis syndrome) with Gao's nape needle and modified Shentong Zhuyu decoction can improve the curative effect of traditional Chinese medicine, improve the related discomfort symptoms (neck tenderness, adverse activity, numbness, etc), improve the neck function, reduce IL-10, IL-6, TNF-α, and other related serum inflammatory factors, and improve hemorheological indicators.

A cost-effective and high efficient Janus membrane for the treatment of oily brine using membrane distillation.

Membrane distillation technology could utilize low-grade heat to desalinate brine, but the membrane material often suffers from disadvantages of low permeation flux and weak robustness to contaminants. To address these issues, the commercial polytetrafluoroethylene (PTFE) membrane was modified by cost-effective chemicals of tannic acid and (3-Aminopropyl)-triethoxysilane (APTES) to construct hydrophilic/underwater superoleophobic nano-rough structures on the surface to enhance its flux and oil-fouling resistance in direct contact membrane distillation. The results show that a high underwater oil contact angle of 180° is observed to the membrane surface due to the rough nanostructures functionalized by abundant hydroxyl groups. Despite the additional mass transfer resistance provided by the rough nanostructures, the flux was increased noticeably. This is mainly attributed to the strong interactions between the abundant hydroxyl groups of hydrophilic layer surface and water molecules, leading to a part of free water staying at intermediate transition state (IW). The mass transfer resistance of the hydrophilic layer itself is reduced as a consequence of decreased evaporation enthalpy of water, thereby increasing the flux. Moreover, while the flux of the pristine membrane is reduced by 84.18%, the flux of Janus membrane remains the same when treating mineral oil brine emulsions with oil concentration up to 1500 ppm in comparison with the result for 35 g l-1brine solution, indicating that the Janus membrane is safe from the oil contamination. Our work provides a fine guidance for membrane distillation to treat high oily brine.

Continuous selenite biotransformation and biofuel production by marine diatom in the presence of fulvic acid.

In this study, the biochemical response of Phaeodactylum tricornutum to varying concentrations of inorganic selenium (Se) was investigated. It was observed that, when combined with fulvic acid, P. tricornutum exhibited enhanced uptake and biotransformation of inorganic Se, as well as increased microalgal lipid biosynthesis. Notably, when subjected to moderate (5 and 10 mg/L) and high (20 and 40 mg/L) concentrations of selenite under fulvic acid treatment, there was a discernible redirection of carbon flux towards lipogenesis and protein biosynthesis from carbohydrates. In addition, the key parameters of microalgae-based biofuels aligned with the necessary criteria outlined in biofuel regulations. Furthermore, the Se removal capabilities of P. tricornutum, assisted by fulvic acid, were coupled with the accumulation of substantial amounts of organic Se, specifically SeCys. These findings present a viable and successful approach to establish a microalgae-based system for Se uptake and biotransformation.

Exposure to microplastics renders immunity of the thick-shell mussel more vulnerable to diarrhetic shellfish toxin-producing harmful algae.

Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Association of vitamin B1 intake with geriatric cognitive function: An analysis of the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014.

Background: The association between dietary vitamin B1 intake and cognitive performance in the noninstitutionalized older adult population of the United States remains unclear. Purpose: This study aimed to investigate the association between vitamin B1 intake and cognitive performance in older adults in the United States. Methods: Vitamin B1 intake was assessed through two 24-h dietary recalls. Weighted logistic regression was used to evaluate the association between vitamin B1 intake and three cognitive scores (immediate recall test [IRT], animal fluency test [AFT], and digit symbol substitution test [DSST]). Cognitive performance was measured by these three tests, and individuals scoring below the lowest quartile were categorized as cognitive impairment. Sensitivity analysis, including dose-response curves, subgroup analyses, interaction effects, per 1 SD, and quartiles, were performed to ensure the accuracy of the conclusion. Results: A total of 2896 participants over the age of 60 were included in this study. In the adjusted final model, the association between vitamin B1 intake and low cognitive performance in old age was statistically significant, with the following odds ratios (ORs) and 95% confidence intervals (CIs): IRT, 0.75 (0.57, 0.97), P = 0.018; AFT, 0.68 (0.50, 0.92), P = 0.007; DSST, 0.71 (0.54, 0.92), P = 0.005. Subgroup analyses showed that this association was statistically significant among males, white, low-education, and no memory impairment. The results of the sensitivity analyses confirmed the association between VB1 and cognitive function in old age and the absence of interactions in the final calibrated model. Conclusion: Dietary vitamin B1 intake is negatively associated with cognitive performance in older adults.