Evaluation of inflammatory hyperreflective foci and plasma EPA as diagnostic and predictive markers for age-related macular degeneration.

Objectives: To detect the plasma polyunsaturated fatty acids (PUFAs) concentrations in age-related macular degeneration (AMD) patients and healthy controls. Additionally, advanced studies were conducted to investigate the relationship between PUFAs concentrations and ophthalmological characteristics, including hyperreflective foci (HRF), visual acuity, and anti-vascular endothelial growth factor (anti-VEGF) response in patients with AMD. Methods: This prospective, single-site study recruited a total of 315 participants, consisting of 105 individuals with dry AMD (early-stage AMD group), 105 individuals with neovascular AMD (late-stage AMD group), and 105 elderly individuals without any fundus diseases (healthy controls). The levels of omega-3 and omega-6 PUFAs in plasma were detected using gas chromatography. Retinal thickness, choroidal thickness, and macular volume were quantified using optical coherence tomography angiography (OCTA) scan with a 6 × 6 mm macular area, and the amounts of HRF were analyzed with OCTA scanning data. Results: Compared to the control group, AMD patients exhibited significantly lower plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha linolenic acid. HRF were observed in various retinal layers of AMD patients, particularly those with late-stage AMD. The correlation coefficient matrix and multiple linear regression models demonstrated that HRF played a crucial role in best corrected visual acuity for both early (p < 0.001) and late-stage AMD patients (p = 0.006), while EPA had an inverse effect on the logarithm of the minimum angle of resolution (logMAR) value in patients with early-stage AMD (p < 0.001). As compared to patients with good responses to anti-VEGF therapy, those with poor responses had significantly lower baseline logMAR (p < 0.001), central retina thickness (p = 0.002), macular volume (p = 0.027), HRF (p = 0.024), and plasma EPA (p < 0.001). This study used a ROC curve analysis to identify the combination of HRF and EPA as a potential biomarker for predicting the response to anti-VEGF treatment in late-stage AMD patients, with an area under the curve (AUC) value of 0.775. Conclusions: Reduced plasma EPA was detected in AMD cases and the lower EPA concentration was related to poorer visual acuity. Additionally, the quantity of HRF combined with concentration of plasma EPA may serve as the prognostic indicator for predicting the effect of anti-VEGF treatment in late-stage AMD patients.

SMLS-YOLO: an extremely lightweight pathological myopia instance segmentation method.

Pathological myopia is a major cause of blindness among people under 50 years old and can result in severe vision loss in extreme cases. Currently, its detection primarily relies on manual methods, which are slow and heavily dependent on the expertise of physicians, making them impractical for large-scale screening. To tackle these challenges, we propose SMLS-YOLO, an instance segmentation method based on YOLOv8n-seg. Designed for efficiency in large-scale screenings, SMLS-YOLO employs an extremely lightweight model. First, StarNet is introduced as the backbone of SMLS-YOLO to extract image features. Subsequently, the StarBlock from StarNet is utilized to enhance the C2f, resulting in the creation of the C2f-Star feature extraction module. Furthermore, shared convolution and scale reduction strategies are employed to optimize the segmentation head for a more lightweight design. Lastly, the model incorporates the Multi-Head Self-Attention (MHSA) mechanism following the backbone to further refine the feature extraction process. Experimental results on the pathological myopia dataset demonstrate that SMLS-YOLO outperforms the baseline YOLOv8n-seg by reducing model parameters by 46.9%, increasing Box mAP@0.5 by 2.4%, and enhancing Mask mAP@0.5 by 4%. Furthermore, when compared to other advanced instance segmentation and semantic segmentation algorithms, SMLS-YOLO also maintains a leading position, suggesting that SMLS-YOLO has promising applications in the segmentation of pathological myopia images.

A molecular mechanism underlies grass carp (Ctenopharyngodon idella) TARBP2 regulating PKR-mediated cell apoptosis.

Interferon-inducible double-stranded RNA-dependent protein kinase (PKR) is one of the key antiviral arms in the innate immune system. The activated PKR performs its antiviral function by inhibiting protein translation and inducing apoptosis. In our previous study, we identified grass carp TARBP2 as an inhibitor of PKR activity, thereby suppressing cell apoptosis. This study aimed to explore the effects of grass carp TARBP2 on PKR activity and cell apoptosis. Grass carp TARBP2 comprises two N-terminal dsRBDs and a C-terminal C4 domain. Subcellular localization analysis conducted in CIK cells revealed that TARBP2-FL (full-length TARBP2), TARBP2-Δ1 (lack of the first dsRBD), and TARBP2-Δ2 (lack of the second dsRBD) are predominantly located in the cytoplasm, while TARBP2-Δ3 (lack of the two dsRBDs) is distributed both in the nucleus and cytoplasm. Colocalization and immunoprecipitation assays confirmed the interaction of TARBP2-FL, TARBP2-Δ1, and TARBP2-Δ2 with PKR, while TARBP2-Δ3 showed no binding. Furthermore, our findings suggested that the inhibitory effect of TARBP2-Δ1 or TARBP2-Δ2 on the PKR-eIF2α pathway is depressed compared to TARBP2-FL. In cell apoptosis assays, it was observed that TARBP2-FL inhibits PKR-mediated cell apoptosis. TARBP2-Δ1 or TARBP2-Δ2 exhibits decreased inhibition to PKR-mediated cell apoptosis, whereas TARBP2-Δ3 nearly completely loses this inhibitory effect. These findings highlight the critical importance of two dsRBDs of TARBP2 in interaction with PKR, as well as in the inhibition of PKR activity, resulting in the suppression of cell apoptosis triggered by prolonged PKR activation.

Melatonin protects RPE cells from necroptosis and NLRP3 activation via promoting SERCA2-related intracellular Ca2+ homeostasis.

BACKGROUND: Melatonin is an antioxidant that also has anti-inflammatory effects. It has been reported to delay the progression of age-related macular degeneration (AMD), however, the mechanism has not been fully recognized. PURPOSE: The aim of the present study was to investigate the effects of melatonin on sodium iodate (SI)-induced retinal degeneration and elucidate the specific mechanisms, then, provide novel targets in AMD treatment. METHODS: Retinal degeneration mouse model and in vitro retinal pigment epithelium (RPE) death model were established by SI treatment. Melatonin was administrated intraperitoneally at a concentration of 20, 40 or 80 mg/kg for in vivo study or treated at 48 h before SI treatment. To confirm the therapeutic effects of melatonin on mouse, the retinal structure and visual function were evaluated. The specific cell death rates were determined by CCK-8 assay, PI staining and protein level of RIPK3. The cytosolic or mitochondrial calcium levels were determined by Fluo-4AM or Rhod-2AM staining. Mitochondrial functions including mitochondrial dynamics, mitochondrial membrane potential, or mitochondrial permeability pore opening were evaluated. The proteins involved in endoplasmic reticulum (ER) stress were measured by western blot assay while the genes expression in calcium signaling pathway were measured by RT-qPCR. RESULTS: We show that melatonin protects RPE cells from necroptosis and NLRP3 inflammasome activation induced by SI. Mechanistically, melatonin suppresses ER stress and intracellular calcium overload triggered by SI through restoring the function of SERCA2. Silencing of SERCA2 or blocking of melatonin receptors inhibit the protective effects of melatonin. Melatonin reduces mitochondrial Ca2+ levels and restores mitochondrial membrane potential. Constant mitochondrial Ca2+ overload directly promote cell necroptosis through mitochondrial fission. Inhibition of mitochondrial fission by Mdivi-1 prevent necroptosis induced by SI without altering the level of mitochondrial Ca2+. CONCLUSIONS: The results confirmed that melatonin protects RPE cells from SI-induced injury by regulates MT2/SERCA2/Ca2+ axis. This study highlighted the potential of melatonin in the treatment of AMD and elucidated the mechanism and signaling pathway that mediate the protective effects.

Subgraph-level federated graph neural network for privacy-preserving recommendation with meta-learning.

Graph neural networks (GNN) are widely used in recommendation systems, but traditional centralized methods raise privacy concerns. To address this, we introduce a federated framework for privacy-preserving GNN-based recommendations. This framework allows distributed training of GNN models using local user data. Each client trains a GNN using its own user-item graph and uploads gradients to a central server for aggregation. To overcome limited data, we propose expanding local graphs using Software Guard Extension (SGX) and Local Differential Privacy (LDP). SGX computes node intersections for subgraph exchange and expansion, while local differential privacy ensures privacy. Additionally, we introduce a personalized approach with Prototype Networks (PN) and Model-Agnostic Meta-Learning (MAML) to handle data heterogeneity. This enhances the encoding abilities of the federated meta-learner, enabling precise fine-tuning and quick adaptation to diverse client graph data. We leverage SGX and local differential privacy for secure parameter sharing and defense against malicious servers. Comprehensive experiments across six datasets demonstrate our method's superiority over centralized GNN-based recommendations, while preserving user privacy.

OCIAD2 promotes pancreatic cancer progression through the AKT signaling pathway.

BACKGROUND: OCIAD2（Ovarian carcinoma immunoreactive antigen-like protein 2） is a protein reported in various cancers. However, the role of OCIAD2 has not been explored in pan-cancer datasets. The purpose of this research lies in analyzing the expression level and prognostic-related value of OCIAD2 in different human cancers, as well as revealing the underlying mechanism in specific cancer type (pancreatic adenocarcinoma, PAAD). METHODS: The correlation between OCIAD2 expression level and clinical relevance in different human cancers was investigated from bioinformatical perspective (GTEx and TCGA). The OCIAD2 expression level and clinical significance in PAAD were explored in GEO datasets and tissue microarray. Functional experiments were used to determine the OCIAD2 cell functions in vitro and in vivo. GSEA, western blot and immunohistochemistry were used to uncover the potential mechanism. RESULTS: OCIAD2 expression level was closely correlated with clinical relevance in many cancer types through pan-cancer analysis, and we found OCIAD2 was highly expressed in PAAD and associated with poorer prognosis. OCIAD2 acted as the promotor of Warburg effect and influenced PAAD cells proliferation, migration and apoptosis. Mechanistically, OCIAD2 upregulation may boost glycolysis in PAAD via activating the AKT signaling pathway in PAAD. CONCLUSIONS: In PAAD, OCIAD2 promotes Warburg effect via AKT signaling pathway and targeting cancer cells metabolic reprogramming could be a potential treatment.

Grass carp (Ctenopharyngodon idella) NIK up-regulates the expression of IL-8 by activating the NF-κB canonical pathway.

NIK (NF-κB inducing kinase) belongs to the mitogen-activated protein kinase family, which activates NF-κB and plays a vital role in immunology, inflammation, apoptosis, and a series of pathological responses. In NF-κB noncanonical pathway, NIK and IKKα have been often studied in mammals and zebrafish. However, few have explored the relationship between NIK and other subunits of the IKK complex. As a classic kinase in the NF-κB canonical pathway, IKKß has never been researched with NIK in fish. In this paper, the full-length cDNA sequence of grass carp (Ctenopharyngodon idella) NIK (CiNIK) was first cloned and identified. The expression level of CiNIK in grass carp cells was increased under GCRV stimuli. Under the stimulation of GCRV, poly (I:C), and LPS, the expression of NIK in various tissues of grass carp was also increased. This suggests that CiNIK responds to viral stimuli. To study the relationship between CiNIK and CiIKKß, we co-transfected CiNIK-FLAG and CiIKKB-GFP into grass carp cells in coimmunoprecipitation and immunofluorescence experiments. The results revealed that CiNIK interacts with CiIKKß. Besides, the degree of autophosphorylation of CiNIK was enhanced under poly (I:C) stimulation. CiIKKß was phosphorylated by CiNIK and then activated the activity of p65. The activity change of p65 indicates that NF-κB downstream inflammatory genes will be functioning. CiNIK or CiIKKß up-regulated the expression of IL-8. It got higher when CiNIK and CiIKKß coexisted. This paper revealed that NF-κB canonical pathway and noncanonical pathway are not completely separated in generating benefits.

Gastric paraganglioma: a case report and review of literature.

Paragangliomas (PGLs) are rare neuroendocrine tumors which overproduce catecholamines (CAs). They are extra-adrenal, catecholamine-secreting tumors occurring outside the adrenal glands. Gastric PGLs originating from extra-adrenal paraganglia are exceptionally rare, and their presentation in geriatric patients further adds to the complexity of diagnosis and management. A 72-year-old male patient presented with enduring left upper abdominal pain and anemia persisting for over a year, and hypertension for six months. Physical examination revealed epigastric discomfort and pallor. Computed tomography scans revealed enlarged lymph nodes in the lesser curvature of the stomach and thickening of the gastric antrum wall with concavity. The patient underwent three cycles of neoadjuvant therapy before radical gastrectomy for gastric cancer. These imaging findings were confirmed during surgery and intraoperative blood pressure was in fluctuation. After the successful resection of the tumor, postoperative pathology confirmed paraganglioma. During postoperative examination, it was observed that the patient's CAs and their metabolites had returned to within the normal range. Combined with the existing ten literatures, we retrospective report the clinical and pathological characteristics and treatment strategies of the rare gastric paraganglioma.

Spatiotemporal dynamics of forest fires in the context of climate change: a review.

Forest fires are sudden, destructive, hazardous, and challenging to manage and rescue, earning them a place on UNESCO's list of the world's eight major natural disasters. Currently, amid global warming, all countries worldwide have entered a period of high forest fire incidence. Due to global warming, the frequency of forest fires has accelerated, the likelihood of large fires has increased, and the spatial and temporal dynamics of forest fires have shown different trends. Therefore, the impact of climate change on the spatiotemporal dynamics of forest fires has become a hot issue in the field of forest fire research in recent years. Therefore, it is of great significance and necessity to conduct a review of the research in this area. This review delves into the interactions and impacts between climate change and the spatiotemporal dynamics of forest fires. To address this issue, scholars have mainly adopted the following research methods: first, statistical analysis methods, second, the establishment of spatiotemporal prediction models for meteorology and forest fires, and third, the coupling of climate models with forest fire risk forecasting models. The statistical analysis method relies on the analysis of historical meteorological and fire-related data to study the effects of climate change and meteorological factors on fire occurrence. Meanwhile, forest fire prediction models utilize technical tools such as remote sensing. These models synthesize historical meteorological and fire-related data, incorporating key meteorological factors such as temperature, rainfall, relative humidity, and wind. The models revealed the spatial and temporal distribution patterns of fires, identified key drivers, and explored the interactions between climate change and forest fire dynamics, culminating in the construction of predictive models. With the deepening of the study, the coupling of climate models and fire risk ranking systems became a trend in the prediction of forest fire risk trends. Moreover, as the climate warms, the increased frequency of extreme weather events like heatwaves, droughts, snow and ice storms, and El Niño-Southern Oscillation (ENSO) has accelerated forest fire occurrences and raised the risk of major fires. This review offers valuable technical insights by comprehensively analyzing the spatial and temporal characteristics of forest fires, elucidating key meteorological drivers, and exploring potential mechanisms. These insights serve as a scientific foundation for preventive measures and effective forest fire management. In the face of a changing climate, this synthesis contributes to the development of informed strategies to mitigate the escalating threat of forest fires.

Organoids and organoids-on-a-chip as the new testing strategies for environmental toxicology-applications & advantages.

An increasing number of harmful environmental factors are causing serious impacts on human health, and there is an urgent need to accurately identify the toxic effects and mechanisms of these harmful environmental factors. However, traditional toxicity test methods (e.g., animal models and cell lines) often fail to provide accurate results. Fortunately, organoids differentiated from stem cells can more accurately, sensitively and specifically reflect the effects of harmful environmental factors on the human body. They are also suitable for specific studies and are frequently used in environmental toxicology nowadays. As a combination of organoids and organ-on-a-chip technology, organoids-on-a-chip has great potential in environmental toxicology. It is more controllable to the physicochemical microenvironment and is not easy to be contaminated. It has higher homogeneity in the size and shape of organoids. In addition, it can achieve vascularization and exchange the nutrients and metabolic wastes in time. Multi-organoids-chip can also simulate the interactions of different organs. These advantages can facilitate better function and maturity of organoids, which can also make up for the shortcomings of common organoids to a certain extent. This review firstly discussed the limitations of traditional toxicology testing platforms, leading to the introduction of new platforms: organoids and organoids-on-a-chip. Next, the applications of different organoids and organoids-on-a-chip in environmental toxicology were summarized and prospected. Since the advantages of the new platforms have not been sufficiently considered in previous literature, we particularly emphasized them. Finally, this review also summarized the opportunities and challenges faced by organoids and organoids-on-a-chip, with the expectation that readers will gain a deeper understanding of their value in the field of environmental toxicology.

Ferroptosis participated in inhaled polystyrene nanoplastics-induced liver injury and fibrosis.

The emerging contaminant nanoplastics (NPs) have received considerable attention. Due to their tiny size and unique colloidal properties, NPs could more easily enter the body and cross biological barriers with inhalation exposure. While NPs-induced hepatotoxicity has been reported, the hepatic impact of inhaled NPs was still unknown. To close this gap, a 40 nm polystyrene NPs (PS-NPs) inhalation exposure mice model was developed to explore the hepatotoxicity during acute (1 week), subacute (4 weeks), and subchronic period (12 weeks), with four exposure doses (0, 16, 40, and 100 µg/day). Results showed that inhaled PS-NPs caused a remarkable increase of ALT, AST, and ALP with a decrease of CHE, indicating liver dysfunction. Various histological abnormalities and significantly higher levels of inflammation in a dose- and time-dependent manner were observed. Moreover, after 4 weeks and 12 weeks of exposure, Masson staining and upregulated expression of TGF-ß, α-SMA, and Col1a1 identified that inhaled PS-NPs exposure triggered the progression of liver fibrosis with the exposure time prolonged. From the mechanistic perspective, transcriptome analysis revealed that ferroptosis was involved in PS-NPs-induced liver hepatotoxicity, and key features of ferroptosis were detected, including persistent oxidative stress, iron overload, increased LPO, mitochondria damage, and the expression changes of GPX4, TFRC, and Ferritin. And in vitro and in vivo recovery tests showed that ferroptosis inhibitor Fer-1 treatment alleviated liver injury and fibrosis. The above results confirmed the critical role of ferroptosis in PS-NPs-induced hepatotoxicity. Furthermore, to better conclude our findings and understand the mechanistic causality within it, an adverse outcome pathway (AOP) framework was established. In total, this present study conducted the first experimental assessment of inhalation exposure to PS-NPs on the liver, identified that continuous inhaled PS-NPs could cause liver injury and fibrosis, and PS-NPs- ferroptosis provided a novel mechanistic explanation.

Grass carp (Ctenopharyngodon idella) deacetylase SIRT1 targets p53 to suppress apoptosis in a KAT8 dependent or independent manner.

Sirtuin1 (SIRT1) is known as a deacetylase to control various physiological processes. In mammals, SIRT1 inhibits apoptotic process, but the detailed mechanism is not very clear. Here, our study revealed that grass carp (Ctenopharyngodon idella) SIRT1 (CiSIRT1, MN125614.1) inhibits apoptosis through targeting p53 in a KAT8-dependent or a KAT8-independent manner. In CIK cells, CiSIRT1 over-expression results in significant decrease of some apoptotic gene expressions, including Bax/Bcl2, caspase3 and caspase9, whereas CiKAT8 or Cip53 facilitates the induction of apoptosis. Because CiSIRT1 separately interacted with CiKAT8 and Cip53, we speculated that CiSIRT1 blocked apoptosis may be by virtue of KAT8-p53 axis or directly by p53. In a KAT8-dependent manner, CiSIRT1 interacted with CiKAT8, then reduced the acetylation of CiKAT8 and subsequently promoted its degradation. Then, CiKAT8 acetylated p53 and induced p53-mediated apoptosis. MYST domain of CiKAT8 was critical in this pathway. In a KAT8-independent manner, CiSIRT1 also inhibited p53-induced apoptosis by directly deacetylating p53 and promoting the degradation of p53. Generally, these findings uncovered two pathways in which CiSIRT1 decreases the acetylation of p53 via a KAT8-dependent or a KAT8-independent manner.

Upside-down stomach in paraesophageal hernia: A case report.

RATIONALE: Paraesophageal hernias, accounting for a mere 5% to 10% of all hiatal hernias, occasionally present an exceedingly uncommon yet gravely consequential complication characterized by the inversion of the stomach. Delving into the clinical manifestations and optimal therapeutic approaches for patients afflicted by this condition merits substantial exploration. PATIENT CONCERNS: A 60-year-old man was referred to our hospital with acute onset of severe epigastric pain, abdominal distension, and vomiting. A chest radiograph unveiled an elevated left diaphragmatic dome accompanied by a pronounced rightward shift of the mediastinum. Subsequent abdominal computed tomography imaging delineated the migration of the stomach, spleen, and colon into the left hemithorax, facilitated by a significant diaphragmatic defect. DIAGNOSES: The diagnosis of a giant paraesophageal hernia with complete gastric inversion was established through a comprehensive evaluation of the patient's clinical manifestations and imaging findings. INTERVENTIONS: Surgical intervention was performed on the patient. During the procedure, a left diaphragmatic defect measuring approximately 10 × 8 cm was identified and meticulously repositioned, followed by the repair of the diaphragmatic hernia. The herniated contents comprised the pancreas, stomach, spleen, a segment of the colon, and a portion of the greater omentum. OUTCOMES: The patient experienced a smooth postoperative recuperation and was discharged 12 days following the surgical procedure. Subsequently, during a 7-month follow-up period, the patient continued to exhibit favorable progress and recovery. LESSONS: Paraesophageal hernias are rare, and the presence of an inverted stomach in a giant paraesophageal hernia is exceptionally uncommon. Clinical presentation lacks distinct features and can lead to misdiagnosis. This case emphasizes the importance of timely surgical intervention guided by imaging, offering valuable clinical insights.

Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization.

Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization.

Multi-dimensional evaluation of cardiotoxicity in mice following respiratory exposure to polystyrene nanoplastics.

BACKGROUND: Nanoplastics (NPs) could be released into environment through the degradation of plastic products, and their content in the air cannot be ignored. To date, no studies have focused on the cardiac injury effects and underlying mechanisms induced by respiratory exposure to NPs. RESULTS: Here, we systematically investigated the cardiotoxicity of 40 nm polystyrene nanoplastics (PS-NPs) in mice exposed via inhalation. Four exposure concentrations (0 µg/day, 16 µg/day, 40 µg/day and 100 µg/day) and three exposure durations (1 week, 4 weeks, 12 weeks) were set for more comprehensive information and RNA-seq was performed to reveal the potential mechanisms of cardiotoxicity after acute, subacute and subchronic exposure. PS-NPs induced cardiac injury in a dose-dependent and time-dependent manner. Acute, subacute and subchronic exposure increased the levels of injury biomarkers and inflammation and disturbed the equilibrium between oxidase and antioxidase activity. Subacute and subchronic exposure dampened the cardiac systolic function and contributed to structural and ultrastructural damage in heart. Mechanistically, violent inflammatory and immune responses were evoked after acute exposure. Moreover, disturbed energy metabolism, especially the TCA cycle, in the myocardium caused by mitochondria damage may be the latent mechanism of PS-NPs-induced cardiac injury after subacute and subchronic exposure. CONCLUSION: The present study evaluated the cardiotoxicity induced by respiratory exposure to PS-NPs from multiple dimensions, including the accumulation of PS-NPs, cardiac functional assessment, histology observation, biomarkers detection and transcriptomic study. PS-NPs resulted in cardiac injury structurally and functionally in a dose-dependent and time-dependent manner, and mitochondria damage of myocardium induced by PS-NPs may be the potential mechanism for its cardiotoxicity.

Influence of Butter Layer Thickness on Microstructure and Mechanical Properties of Underwater Wet 16Mn/304L Dissimilar Welded Joint.

Butter layers of different thicknesses were successfully deposited on ferritic steel by using the tungsten arc welding (TIG) process. The effects of butter layer thickness on the microstructural characteristics, elemental distribution, and mechanical properties of underwater wet 16Mn/304L dissimilar welded joints were investigated. The results showed that the butter layer significantly changed the microstructure and elemental distribution of 16Mn/304L joints. As the thickness of butter increased, the heat-affected zone (HAZ) at the ferritic steel side changed from the original 16Mn steel to the ERNiCrMo-3 butter layer. The martensite content in HAZ also exhibited a downward trend. When the thickness of the butter layer exceeded 6 mm, the microstructure of HAZ at the ferritic steel side was composed of ferrite and pearlite, instead of quenched martensite. The microhardness of underwater dissimilar steel welded joints significantly reduced due to the absence of martensite. The addition of the butter layer increased the ultimate tensile strength from 515 MPa to 565 MPa. The results of this work could provide a robust basis for future applications of dissimilar steel structures.

Grass carp (Ctenopharyngodon idella) Mex3B positively regulates innate immunity by promoting the K63-linked ubiquitination of TLR3.

As a member of Mex3 (muscle excess protein-3) family, Mex3B (Mex-3 RNA binding family member B) is crucial in cell proliferation and migration in mammals. In this study, an ortholog of mammalian Mex3B (denominated CiMex3B, MT276802.1) was cloned and identified in grass carp (Ctenopharyngodon idella). CiMex3B is 1578 bp in length and encodes a polypeptide of 525 amino acids. Consistent with its mammalian counterpart, CiMex3B also contains one C-terminal RING domain and two N-terminal conserved tandem KH domains. CiMex3B up-regulates the expressions of IFN1, ISG15, MX2, as well as the expressions of inflammatory cytokines such as IL6, IL8 and TNFα in response to poly(I:C). A screening test for identifying potential targets indicated that CiMex3B is associated with TLR3 and TRIF. CiMex3B co-localizes with TLR3 in the late endosome, mitochondria and endoplasmic reticulum after poly(I:C) stimulation, whereas they are rarely discovered in the lysosomes. CiMex3B serves as a positive regulator in the phosphorylation of IRF3 and induces IFN1 expression. In addition, two truncation mutants of CiMex3B (1-220 and 221-525) were constructed to better understand the molecular mechanism of CiMex3B-mediated ubiquitination of TLR3. In line with wild-type protein, CiMex3B mutant (1-220) was found mainly in the cytoplasm; however, CiMex3B mutant (221-525) resided in the cytoplasm and the nucleus as well, and it was further confirmed that CiMex3B mutant (221-525) still interacts with TLR3. We also observed that CiMex3B promotes the K63-linked ubiquitination of TLR3, while neither of the truncation mutants (1-220 or 221-525) retains this activity. To sum up, this study revealed that CiMex3B potentiates the K63-linked ubiquitination of TLR3, and then elicits the IRF3-mediated antiviral innate immune responses.

A layer-stacked NiO nanowire/nanosheet homostructure for electrochromic smart windows with ultra-large optical modulation.

The structural engineering of active materials at the nanoscale level is crucial to improving the performance of electrochromic devices. However, an insufficient structural design inevitably results in limited electron/ion transportation and inadequate electrochromic performance. Herein, a new type of layer-stacked nanowire/nanosheet homostructure is proposed for enhancing the electrochromic properties of transition metal oxide films. Benefiting from the one-pot feature integration of nanowire and nanosheet structures, the NiO film with a unique homostructure delivers ultra-large optical modulation up to 93.4% at 550 nm and a high coloration efficiency of 72.1 cm2 C-1 in comparison with NiO-based materials. In addition, the film maintains 91% of its optical modulation over 1000 cycles of coloration and bleaching processes. Furthermore, the high performance of the device was verified by integrating the NiO film with the TiO2 ion storage layer in assembled smart windows with a dual function of electrochromic and energy storage. As a proof of concept, the integration of solar cells with electrochromic devices demonstrates the great significance of self-powered smart windows for energy-saving. To this end, such a strategy of structural design for electrochromic films would offer a distinctive pathway toward studying high-performance electrochromic systems.

Selective Electrochromic Regulation for Near-Infrared and Visible Light via Porous Tungsten Oxide Films with Core/Shell Architecture.

Dual-band electrochromic smart windows have become a research hotspot owing to their unique ability to selectively control near-infrared (NIR) and visible (VIS) light. However, the design and exploitation of dual-band electrochromic films are still an extreme challenge due to the scarcity of relevant high-performance materials. To solve this issue, we here proposed a type of porous WO3 film with nanowires/nanoparticles core/shell architecture as a promising candidate, endowing smart windows with a dual-band electrochromic feature. Moreover, the mechanism of the dual-band electrochromism is illustrated by the response of the transmittance spectra in Li+-based or TBA+-based electrolytes to distinguish the electrochemical behavior and the cyclic voltammetry to determine the degree of diffusion-limited kinetics. Our results indicate that the dual-band electrochromic performance is credited to the progressive electrochemical reduction procedure, in which the capacitive charging process gives rise to NIR regulation and the following ion intercalation contributes to VIS light modulation. Furthermore, we develop a dual-band electrochromic energy storage prototype device utilizing the porous WO3 film. This work describes a judicious strategy for designing dual-band electrochromic films, promoting the evolution of dual-band electrochromic technology.