Virtual reality gameplay classification illustrates the multidimensionality of visuospatial neglect.

Brain injuries can significantly impact mental processes and lead to hidden disabilities not easily detectable. Traditional methods for assessing these impacts are imprecise, leading to unreliable prevalence estimates and treatments with uncertain effectiveness. Immersive virtual reality has shown promise for assessment, but its use as a standalone tool is rare. Our research focused on developing and validating a standalone immersive virtual reality classification system for unilateral spatial neglect, a condition common following brain injury characterized by inattention to one side of space. Our study involved 51 brain injury inpatients and 30 controls, all engaging with 'The Attention Atlas', an immersive virtual reality game for testing visual search skills. Our classification system aimed to identify patients with neglect, 'minor atypicality' (indicative of inattention not consistent enough to be labelled as neglect) or non-neglect. This categorization was based on a simple mathematical definition, utilizing gameplay to describe spatial orientation (to the left or right side) and attentional challenge (indicative of search inefficiency). These metrics were benchmarked against a normative model to detect atypical visual search, which refers to gameplay beyond the usual bounds. The combination of neglected side, orientation and challenge factors was used to categorize neglect. We discovered a strong correlation between atypical visual search patterns and neglect risk factors, such as middle cerebral artery stroke, parietal injuries and existing neglect diagnoses (Poisson regression incidence rate ratio = 7.18, 95% confidence interval = 4.41-11.90). In our study, immersive virtual reality-identified neglect in one-fourth of the patients (n = 13, 25.5%), minor atypicality in 17.6% (n = 9) and non-neglect in the majority, 56.9% (n = 29). This contrasts with standard assessments, which detected neglect in 17.6% (n = 9) of cases and had no intermediate category. Our analysis determined six categories of neglect, the most common being left hemispace neglect with above-median orientation and challenge scores. Traditional assessments were not significantly more accurate (accuracy = 84.3%, P = 0.06) than a blanket assumption of non-neglect. Traditional assessments were also relatively insensitive in detecting immersive virtual reality-identified neglect (53.8%), particularly in less severe cases and those involving right-side inattention. Our findings underline the effectiveness of immersive virtual reality in revealing various dimensions of neglect, surpassing traditional methods in sensitivity and detail and operating independently from them. To integrate immersive virtual reality into real-world clinical settings, collaboration with healthcare professionals, patients and other stakeholders is crucial to ensure practical applicability and accessibility.

Olfactory Dysfunction as a Marker for Cognitive Impairment in General Paresis of the Insane: A Clinical Study.

BACKGROUND General paresis of the insane (GPI) is characterized by cognitive impairment, neuropsychiatric symptoms, and brain structural abnormalities, mimicking many neuropsychiatric diseases. Olfactory dysfunction has been linked to cognitive decline and neuropsychiatric symptoms in numerous neuropsychiatric diseases. Nevertheless, it remains unclear whether patients with GPI experience olfactory dysfunction and whether olfactory dysfunction is associated with their clinical manifestations. MATERIAL AND METHODS Forty patients with GPI and 37 healthy controls (HCs) underwent the "Sniffin Sticks" test battery, Mini-Mental State Examination, and Neuropsychiatric Inventory to measure olfactory function, cognitive function, and neuropsychiatric symptoms, respectively. Brain structural abnormalities were evaluated using visual assessment scales including the medial temporal lobe atrophy (MTA) visual rating scale and Fazekas scale. RESULTS Compared with HCs, patients with GPI exhibited significant olfactory dysfunction, as indicated by deficits in the odor threshold (OT) (P=0.001), odor discrimination (OD) (P<0.001), and odor identification (OI) (P<0.001). In patients with GPI, the OI was positively correlated with cognitive function (r=0.57, P<0.001), but no significant correlation was found between olfactory function and neuropsychiatric symptoms, blood, or cerebrospinal fluid biomarkers (rapid plasma reagin circle card test and Treponema pallidum particle agglutination test), or brain structural abnormalities (MTA and Fazekas scale scores). Mediation analysis indicated that the impaired OI in patients with GPI was mediated by cognitive impairment and impaired OT respectively. CONCLUSIONS Patients with GPI exhibited overall olfactory dysfunction. OI is correlated with cognitive function and the impaired OI is mediated by cognitive impairment in patients with GPI. Thus, OI may serve as a marker for reflecting cognitive function in patients with GPI.

Routine maternal ABO/Rhesus D blood typing can alert of massive foetomaternal haemorrhage.

BACKGROUND AND OBJECTIVES: Spontaneous massive foetomaternal haemorrhage (SM-FMH) is a rare yet critical condition that poses substantial risk to foetal health and survival. Existing data indicate that many cases may be undiagnosed. The current study aimed to investigate and validate the utility of identifying mixed field red blood cell (RBC) agglutination during maternal blood typing as a diagnostic aid for SM-FMH. MATERIALS AND METHODS: Retrospective analysis of medical records from neonates born at our tertiary, university-affiliated medical centre between 2016 and 2023 was performed. Diagnosis of SM-FMH was based on neonates born with severe anaemia (haematocrit [HCT] <15%) within the first 24 h post-delivery with positive maternal Kleihauer-Betke (KB) test. Maternal ABO/Rhesus D (RhD) blood typing results were scrutinized with the primary objective of assessing the ability to identify dual RBC populations in cases clinically diagnosed with SM-FMH. RESULTS: Among 29,192 neonates studied, a mere 0.02% (5 cases) exhibited severe SM-FMH. Notably, a mixed field RBC agglutination was discerned in 80% (4/5) of these cases. CONCLUSION: This study underscores the significance of detecting mixed field RBC agglutination during antepartum maternal ABO/RhD blood typing as a potential indicator for SM-FMH. Increased awareness among blood bank technology specialists and obstetricians regarding these laboratory findings could prove instrumental in saving foetal lives.

Oral alginate microspheres for the efficient site-specific delivery of epidermal growth factor attenuated murine ulcerative colitis via repairing the mucosal barrier.

Ulcerative colitis (UC) is a chronic bowel inflammatory disease affecting the colorectum. Epidermal growth factor (EGF) has been demonstrated to be effective to counteract UC. However, there exists the gastrointestinal challenges such as stomach acid, enzyme and bile salts for oral delivery of EGF. Herein, calcium alginate microsphere was prepared by the microfluidic technique to encapsulate EGF. The morphology of EGF-loaded microsphere (MS-EGF) was spherical and its average particle size was 80 ± 23 µm. The encapsulation efficiency of EGF was reaching to 93.8 % ± 1.6 %. In vitro release experiments showed that MS-EGF presented the good pH-sensitive properties, that was, it could effectively resist the gastric acid and small intestinal fluids, and undergone the rapid dissolution in the artificial colon fluid. In vitro cellular experiments demonstrated that the bioactivity of EGF was well preserved by microsphere. Moreover, in vivo murine colitis model showed that MS-EGF presented the obvious colitis alleviation. Furthermore, the colonic morphology of colitis mice was effectively recovered and the tight junction between the gut epithelium was obviously repaired. In conclusion, calcium alginate microsphere might be a promising vehicle of EGF for UC treatment.

No increase of soil wind erosion with the establishment of center pivot irrigation system in Mu-Us sandy land.

Center Pivot Irrigation system (CPIs) is widely used in newly exploited arable land in sandy lands. These sandy lands are currently stable because of climate change and ecological restoration efforts since the beginning of the 21st century in northern China. The exploitation of these fixed sandy lands to arable land with CPIs may affect the soil wind erosion, yet it remains unknown. The temporal changes of CPIs and its effect on wind erosion module were analyzed and modeled from 2000 to 2020 in Mu-Us sandy land using satellite images and Revised Wind Erosion Equation (RWEQ). The establishment of CPIs started from 2010, boomed in 2015 and peaked in 2020. They were mainly transformed from woodland, grassland, and barren land near rivers in east and southeast, and from cropland in inter-dunes in west and southwest of Mu-Us sandy land. The temporal and spatial pattern of CPIs well aligns with the land consolidation and requisition-compensation balance policies. In most of the Mu-Us sandy land, the annual erosion module is <25 t ha-1 a-1. Despite great variation, the annual, Winter and Spring erosion module of the Mu-Us sandy land or in Otog Qian and Yuyang, the CPIs concentrated counties, all decreased during 2000-2019. Although, wind erosion module in CPIs was lower than the surrounding area, it increased in 2019 given the same climate conditions as in 2010. Our results suggest 1) the establishment of CPIs in Mu-Us sandy land greatly depends on the local policy and natural endowment, and 2) although the set-up of CPIs showed no impact on the wind erosion with CPIs accounting for <1 % of Mu-Us sandy land, post-harvest of CPIs should be carefully concerned to prevent soil wind erosion.

Functional Role of DUSP6 in the EGFR-mediated Progression of Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) over-expression is commonly observed in advanced head and neck squamous cell carcinoma (HNSCC) and is correlated with poor patient outcomes. However, the role of dual-specificity phosphatase 6 (DUSP6) in EGFR-associated HNSCC progression remains poorly understood. This study aimed to investigate the correlation between DUSP6 expression and EGFR signaling in malignant HNSCC tissues. MATERIALS AND METHODS: Data mining and in vitro assays were employed to assess DUSP6 expression levels in HNSCC tissues compared to normal tissues. Additionally, the correlation between DUSP6 and EGFR expression was examined. Functional assays were conducted to investigate the modulation of DUSP6 expression by EGFR signaling and its involvement in EGF-induced cell migration and anoikis resistance. RESULTS: Our analysis revealed a significant elevation in DUSP6 expression in HNSCC tissues compared to normal tissues and a strong correlation between DUSP6 and EGFR expression. EGFR signaling modulated DUSP6 expression in a dose- and time-dependent manner, primarily through the extracellular signal-regulated kinase (ERK) pathway. Knockdown experiments demonstrated the functional role of DUSP6 in EGF-induced cell migration and anoikis resistance. CONCLUSION: The findings of this study elucidate the intricate signaling networks governing DUSP6 expression and its interplay with EGFR signaling in HNSCC. Moreover, the results provide insights into the potential role of DUSP6 as a therapeutic target and highlight the importance of personalized treatment strategies in HNSCC management.

Static and dynamic functional connectivity of the habenula in late-life depression patient with suicidal ideation.

BACKGROUND: Suicide is one of the most lethal complications of late-life depression (LLD), and habenular dysfunction may be involved in depression-related suicidality and may serve as a potential target for alleviating suicidal ideation. This study aimed to investigate abnormal functional connectivity of the habenula in LLD patients with suicidal ideation. METHODS: One hundred twenty-seven patients with LLD (51 with suicidal ideation (LLD-S) and 76 without suicidal ideation (LLD-NS)) and 75 healthy controls (HCs) were recruited. The static functional connectivity (sFC) and dynamic functional connectivity (dFC) between the habenula and the whole brain were compared among the three groups, and correlation and moderation analyses were applied to investigate whether suicidal ideation moderated the relationships of habenular FC with depressive symptoms and cognitive impairment. RESULTS: The dFC between the right habenula and the left orbitofrontal cortex (OFC) increased in the following order: LLD-S > LLD-NS > control. No significant difference in the habenular sFC was found among the LLD-S, LLD-NS and control groups. The dFC between the right habenula and the left OFC was positively associated with global cognitive function and visuospatial skills, and the association between this dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD. CONCLUSION: The increased variability in dFC between the right habenula and left OFC was more pronounced in the LLD-S group than in the LLD-NS group, and the association between habenular-OFC dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD.

Construction of 3,4-Dihydroquinolone Derivatives through Pd-Catalyzed [4+2] Cycloaddition of Vinyl Benzoxazinanones with α-Alkylidene Succinimides.

The construction of 3,4-dihydroquinolone derivatives has attracted a considerable amount of attention due to their extensive applications in medicinal chemistry. In this study, we present the Pd-catalyzed [4+2] cycloaddition of vinyl benzoxazinanones with α-alkylidene succinimides for the efficient synthesis of 3,4-dihydroquinolones. This approach presents numerous advantages, including the ready availability of starting materials, mild reaction conditions without the use of additional bases, and a wide range of substrates. In particular, all of the desired products can be easily afforded in high yields (≤99%) and excellent diastereoselectivities (>20:1). The practicality and reliability of this strategy were demonstrated by the successful scale-up synthesis and subsequent straightforward synthetic transformations.

Increasing variance of rich-club nodes distribution in early onset depression according to dynamic network.

Early onset depression (EOD) and late onset depression (LOD) are thought to have different pathogeneses, but lack of pathological evidence. In the current study we describe the dynamic rich-club properties of patients with EOD and LOD to address this question indirectly. We recruited 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. Memory, executive function and processing speed were measured, and resting-stage functional MRI was performed with all participants. We constructed a dynamic functional connectivity network and carried out rich-club and modularity analyses. Normalized mutual information (NMI) was applied to describe the variance in rich-club nodes distribution and partitioning. The NMI coefficient of rich club nodes distribution among the three groups was the lowest in the EOD patients (F = 4.298; P = 0.0151, FDR = 0.0231), which was positively correlated with rich-club connectivity (R = 0.886, P < 0.001) and negatively correlated with memory (R = -0.347, P = 0.038) in the EOD group. In the LOD patients, non-rich-club connectivity was positively correlated with memory (R = 0.353, P = 0.030 and R = 0.420, P = 0.009). Furthermore, local connectivity was positively correlated with processing speed in the LOD patients (R = 0.374, P = 0.021). The modular partition was different between the EOD patients and the HCs (P = 0.0013 < 0.05/3). The temporal instability of rich-club nodes was found in the EOD patients, but not the LOD patients, supporting the hypothesis that EOD and LOD result from different pathogenesis, and showing that the instability of the rich-club nodes across time might disrupt rich-club connectivity.

Growth Factors-Loaded Temperature-Sensitive Hydrogel as Biomimetic Mucus Attenuated Murine Ulcerative Colitis via Repairing the Mucosal Barriers.

The pathogenesis of ulcerative colitis (UC) is associated with the shedding of the gut mucus. Herein, inspired by the biological functions of mucus, growth factors-loaded in situ hydrogel (PHE-EK) was designed for UC treatment by integrating dihydrocaffeic acid-modified poloxamer as a thermosensitive material with hyaluronic acid (colitis-specific adhesive), epigallocatechin-3-gallate (antibacterial agent), and bioactive factors (KPV tripeptide and epidermal growth factor). PHE-EK presented good thermosensitive properties, as a flowable liquid at room temperature and gelled within 10 s when exposed to body temperature. PHE-EK hydrogel presented good mechanical strength with a strain of 77.8%. Moreover, PHE-EK hydrogel displayed antibacterial activity against Escherichia coli. Importantly, in vitro and in vivo adhesive tests showed that the PHE-EK hydrogel could specifically adhere to the inflamed colon via electrostatic interaction. When PHE-EK as a biomimetic mucus was rectally administrated to colitis rats, it effectively hindered the body weight loss, reduced the disease activity index and improved the colonic shorting. Moreover, the expression of pro-inflammatory cytokines (e.g., IL-1ß, IL-6, and TNF-α) at the laminae propria or epitheliums of the colon for colitis rats was substantially inhibited by PHE-EK. Besides, the colonic epitheliums were well rearranged, and the tight junction proteins (Zonula-1 and Claudin-5) between them were greatly upregulated after PHE-EK treatment. Collectively, PHE-EK might be a promising therapy for UC.

Accurate leukocyte detection based on deformable-DETR and multi-level feature fusion for aiding diagnosis of blood diseases.

In standard hospital blood tests, the traditional process requires doctors to manually isolate leukocytes from microscopic images of patients' blood using microscopes. These isolated leukocytes are then categorized via automatic leukocyte classifiers to determine the proportion and volume of different types of leukocytes present in the blood samples, aiding disease diagnosis. This methodology is not only time-consuming and labor-intensive, but it also has a high propensity for errors due to factors such as image quality and environmental conditions, which could potentially lead to incorrect subsequent classifications and misdiagnosis. Contemporary leukocyte detection methods exhibit limitations in dealing with images with fewer leukocyte features and the disparity in scale among different leukocytes, leading to unsatisfactory results in most instances. To address these issues, this paper proposes an innovative method of leukocyte detection: the Multi-level Feature Fusion and Deformable Self-attention DETR (MFDS-DETR). To tackle the issue of leukocyte scale disparity, we designed the High-level Screening-feature Fusion Pyramid (HS-FPN), enabling multi-level fusion. This model uses high-level features as weights to filter low-level feature information via a channel attention module and then merges the screened information with the high-level features, thus enhancing the model's feature expression capability. Further, we address the issue of leukocyte feature scarcity by incorporating a multi-scale deformable self-attention module in the encoder and using the self-attention and cross-deformable attention mechanisms in the decoder, which aids in the extraction of the global features of the leukocyte feature maps. The effectiveness, superiority, and generalizability of the proposed MFDS-DETR method are confirmed through comparisons with other cutting-edge leukocyte detection models using the private WBCDD, public LISC and BCCD datasets. Our source code and private WBCCD dataset are available at https://github.com/JustlfC03/MFDS-DETR.

Disrupted functional connectivity of the habenula links psychomotor retardation and deficit of verbal fluency and working memory in late-life depression.

BACKGROUND: Functional abnormalities of the habenula in patients with depression have been demonstrated in an increasing number of studies, and the habenula is involved in cognitive processing. However, whether patients with late-life depression (LLD) exhibit disrupted habenular functional connectivity (FC) and whether habenular FC mediates the relationship between depressive symptoms and cognitive impairment remain unclear. METHODS: Overall, 127 patients with LLD and 75 healthy controls were recruited. The static and dynamic FC between the habenula and the whole brain was compared between LLD patients and healthy controls, and the relationships of habenular FC with depressive symptoms and cognitive impairment were explored by correlation and mediation analyses. RESULTS: Compared with the controls, patients with LLD exhibited decreased static FC between the right habenula and bilateral inferior frontal gyrus (IFG); there was no significant difference in dynamic FC of the habenula between the two groups. Additionally, the decreased static FC between the right habenula and IFG was associated with more severe depressive symptoms (especially psychomotor retardation) and cognitive impairment (language, memory, and visuospatial skills). Last, static FC between the right habenula and left IFG partially mediated the relationship between depressive symptoms (especially psychomotor retardation) and cognitive impairment (verbal fluency and working memory). CONCLUSIONS: Patients with LLD exhibited decreased static FC between the habenula and IFG but intact dynamic FC of the habenula. This decreased static FC mediated the relationship between depressive symptoms and cognitive impairment.

High-Efficiency and Emission-Tunable Inorganic Blue Perovskite Light-Emitting Diodes Based on Vacuum Deposition.

The fabrication of perovskite light-emitting diodes (PeLEDs) with vacuum deposition shows great potential and commercial value in realizing large-area display panel manufacturing. However, the electroluminescence (EL) performance of vacuum-deposited PeLEDs still lags behind the counterparts fabricated by solution process, especially in the field of blue PeLEDs. Here, the fabrication of high-quality CsPbBr3- x Clx film through tri-source co-evaporation is reported to achieve high photoluminescence quantum yield (PLQY). Compared with the conventional traditional dual-source co-evaporation, the tri-source co-evaporation method allows for freely adjustable elemental ratios, enabling the introduction of the lattice-matched Cs4 Pb(Br/Cl)6 phase with the quantum-limited effect into the inorganic CsPb(Br/Cl)3 emitter. By adjusting the phase distribution, the surface defects of the emitter can be effectively reduced, leading to better blue emission and film quality. Further, the effects of Cs/Pb ratio and Br/Cl ratio on the PLQY and carrier recombination dynamics of perovskite films are investigated. By optimizing the deposition rate of each precursor source, spectrally stable blue PeLEDs are achieved with tunable emission ranging from 468 to 488 nm. Particularly, the PeLEDs with an EL peak at 488 nm show an external quantum efficiency (EQE) of 4.56%, which is the highest EQE value for mixed-halide PeLEDs fabricated by vacuum deposition.

Regulation of the pigment production by changing Cell morphology and gene expression of Monascus ruber in high-sugar synergistic high-salt stress fermentation.

AIMS: Extreme environment of microbial fermentation is the focus of research, which provides new thinking for the production and application of Monascus pigments (MPs). In this work, the high-sugar synergistic high-salt stress fermentation (HSSF) of MPs was investigated. METHODS AND RESULTS: The Monascus fungus grew well under HSSF conditions with 35 g L-1 NaCl and 150 g L-1 glucose, and the extracellular yellow pigment and intracellular orange pigment yield in HSSF was 98% and 43% higher than that in conventional fermentation, respectively. Moreover, the mycelial morphology was maintained in a better status with more branches and complete surface structure, indicating good biocatalytic activity for pigment synthesis. Four extracellular yellow pigments (Y1, Y2, Y3, and Y4) were transformed into each other, and ratio of the relative content of intracellular orange pigments to yellow pigments (O/Y) significantly (P < 0.05) changed. Moreover, the ratio of unsaturated fatty acids to saturated fatty acids (unsaturated/saturated) was significantly (P < 0.05) increased, indicating that the metabolism and secretion of intracellular and extracellular pigment might be regulated in HSSF. The pigment biosynthesis genes mppB, mppC, mppD, MpPKS5, and MpFasB2 were up-regulated, whereas the genes mppR1, mppR2, and mppE were down-regulated, suggesting that the gene expression to regulate pigment biosynthesis might be a dynamic change process in HSSF. CONCLUSIONS: The HSSF system of MPs is successfully performed to improve the pigment yields. Mycelial morphology is varied to enhanced pigment secretion, and gene expression is dynamically regulated to promote pigment accumulation in HSSF.

Continuous vs intermittent induction of labor with oxytocin in nulliparous patients: a randomized controlled trial.

BACKGROUND: Oxytocin is considered the drug of choice for the induction of labor, although the optimal protocol and infusion duration remain to be determined. OBJECTIVE: This study aimed to assess whether the duration of oxytocin infusion increases 24-hour delivery rates and affects the length of time-to-delivery and patient's experience. STUDY DESIGN: A randomized controlled trial was performed at a single tertiary medical center, between January 1, 2020 and June 30, 2022. Nulliparous patients with a singleton pregnancy at a vertex presentation and a Bishop score ≥6 were randomly assigned to receive either continuous (16 hours, with a 4 hours pause in between infusions) or intermittent (8 hours, with a 4 hours pause in between infusions) oxytocin infusion, until delivery. In both groups, infusion was halted when signs of maternal or fetal compromise were observed. Randomization was conducted with a computer randomization sequence generation program. The primary outcome was delivery within 24 hours from the first oxytocin infusion and the secondary outcome included time-to-delivery, mode of delivery, and additional maternal and neonatal outcomes. Seventy-two patients per group were randomized to reach 80% statistical power with a 20% difference in the primary outcome according to previous studies. RESULTS: A total of 153 patients were randomized, 72 to the continuous oxytocin infusion group and 81 to the intermittent infusion group. The total oxytocin infusion time was similar between the groups. Patients in the continuous arm were more likely to deliver within 24 hours from oxytocin initiation (79.73% vs 62.96%, P<.05), and had a shorter oxytocin-to-delivery time interval, compared with patients receiving intermittent treatment (9.3±3.7 hours vs 21±11.7 hours, P<.001). Furthermore, time from ruptured membranes to delivery was shorter (9.3±3.7 hours vs 21±11.7 hours; P<.0001) and chorioamnionitis was less frequent (9.46% vs 21%; P<.05) in the continuous compared with the intermittent arm. Cesarean delivery rate was 20% in both groups (P=.226). There was no difference in postpartum hemorrhage, or adverse neonatal outcomes between the groups. Patients receiving continuous oxytocin infusion were more satisfied with the birthing experience. CONCLUSION: Continuous infusion of oxytocin for labor induction in nulliparous patients with a favorable cervix may be superior to intermittent oxytocin infusion, because it shortens time-to-delivery, decreases chorioamnionitis rate, and improves maternal satisfaction, without affecting adverse maternal or neonatal outcomes.

RNA-binding protein-regulated fibronectin is essential for EGFR-activated metastasis of head and neck squamous cell carcinoma.

There is a higher expression level of epidermal growth factor receptor (EGFR) in up to 90% of advanced head and neck squamous cell carcinoma (HNSCC) tissue than in normal surrounding tissues. However, the role of RNA-binding proteins (RBPs) in EGFR-associated metastasis of HNSCC remains unclear. In this study, we reveal that RBPs, specifically nucleolin (NCL) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), correlated with the mesenchymal phenotype of HNSCC. The depletion of RBPs significantly attenuated EGF-induced HNSCC metastasis. Intriguingly, the EGF-induced EMT markers, such as fibronectin, were regulated by RBPs through the ERK and NF-κB pathway, followed by the enhancement of mRNA stability of fibronectin through the 5' untranslated region (5'-UTR) of the gene. The upregulation of fibronectin triggered the integrin signaling activation to enhance tumor cells' attachment to endothelial cells and increase endothelial permeability. In addition, the concurrence of EGFR and RBPs or EGFR and fibronectin was associated with overall survival and disease-free survival of HNSCC. The in vivo study showed that depletion of NCL, hnRNPA2B1, and fibronectin significantly inhibited EGF-promoted extravasation of tumor cells into lung tissues. The depletion of fibronectin or treatment with integrin inhibitors dramatically attenuated EGF-induced HNSCC metastatic nodules in the lung. Our data suggest that the RBPs/fibronectin axis is essential for EGF-induced tumor-endothelial cell interactions to enhance HNSCC cell metastasis.

Li+ mobility powered by a crystal compound for fast Li-S chemistry.

Placing blocking layers between electrodes has shown paramount prospects in suppressing the shuttle effect of Li-S batteries, but the associated ionic transport would be a concurrent obstacle. Herein, we present a Li-based crystal composited with carbon (LiPN2@C) by a one-step annealing of Li+ absorbed melamine polyphosphate, which simultaneously achieves alleviated polysulfide-shuttling and facilitated Li+ transport. As a homologous crystal, LiPN2 with abundant lithiophilic sites makes Li+ transport more efficient and sustainable. With a LiPN2@C-modified separator, the Li2S cathode exhibits a much-lower activation potential of 2.4 V and a high-rate capacity of 519 mA h g-1 at 2C. Impressively, the battery delivers a capacity of 726 mA h g-1 at 0.5C with a low decay rate of 0.25% per cycle during 100 continuous cycles.

Oleic acid-induced metastasis of KRAS/p53-mutant colorectal cancer relies on concurrent KRAS activation and IL-8 expression bypassing EGFR activation.

Background: Multigene mutations in colorectal cancer (CRC), including KRAS, BRAF, and p53, afford high metastatic ability and resistance to EGFR-targeting therapy. Understanding the molecular mechanisms regulating anti-EGFR-resistant CRC metastasis can improve CRC therapy. This study aimed to investigate the effects of IL-8 and the activation of KRAS on reactive oxygen species (ROS) production and metastasis of hyperlipidemia-associated CRC harboring mutations of KRAS and p53. Methods: The cytokine array analysis determined the up-expression of secreted factors, including IL-8. The clinical relevance of the relationship between IL-8 and angiopoietin-like 4 (ANGPTL4) was examined in CRC patients from National Cheng Kung University Hospital and TCGA dataset. Expressions of IL-8, ANGPTL4, NADPH oxidase 4 (NOX4), and epithelial-mesenchymal transition (EMT) markers in free fatty acids (FFAs)-treated KRAS/p53 mutant CRC cells were determined. The hyperlipidemia-triggered metastatic ability of CRC cells under treatments of antioxidants, statin, and cetuximab or knockdown of IL-8, KRAS, and EGFR was evaluated in vitro and in vivo. In addition, the effects of antioxidants and depletion of IL-8 and KRAS on the correlation between ROS production and hyperlipidemia-promoted CRC metastasis were also clarified. Results: In this study, we found that free fatty acids promoted KRAS/p53-mutant but not single-mutant or non-mutant CRC cell metastasis. IL-8, the most abundant secreted factor in KRAS/p53-mutant cells, was correlated with the upregulation of NOX4 expression and ROS production under oleic acid (OA)-treated conditions. In addition, the metastasis of KRAS/p53-mutant CRC relies on the ANGPTL4/IL-8/NOX4 axis and the activation of KRAS. The antioxidants and inactivation of KRAS also inhibited OA-induced EMT and metastasis. Although KRAS mediated EGF- and OA-promoted CRC cell invasion, the inhibition of EGFR did not affect OA-induced ANGPTL4/IL-8/NOX4 axis and CRC metastasis. The high-fat diet mice fed with vitamin E and statin or in IL-8-depleted cells significantly inhibited tumor extravasation and metastatic lung growth of CRC. Conclusion: The antioxidants, statins, and targeting IL-8 may provide better outcomes for treating metastatic CRC that harbors multigene mutations and anti-EGFR resistance.

3DVizSNP: a tool for rapidly visualizing missense mutations identified in high throughput experiments in iCn3D.

BACKGROUND: High throughput experiments in cancer and other areas of genomic research identify large numbers of sequence variants that need to be evaluated for phenotypic impact. While many tools exist to score the likely impact of single nucleotide polymorphisms (SNPs) based on sequence alone, the three-dimensional structural environment is essential for understanding the biological impact of a nonsynonymous mutation. RESULTS: We present a program, 3DVizSNP, that enables the rapid visualization of nonsynonymous missense mutations extracted from a variant caller format file using the web-based iCn3D visualization platform. The program, written in Python, leverages REST APIs and can be run locally without installing any other software or databases, or from a webserver hosted by the National Cancer Institute. It automatically selects the appropriate experimental structure from the Protein Data Bank, if available, or the predicted structure from the AlphaFold database, enabling users to rapidly screen SNPs based on their local structural environment. 3DVizSNP leverages iCn3D annotations and its structural analysis functions to assess changes in structural contacts associated with mutations. CONCLUSIONS: This tool enables researchers to efficiently make use of 3D structural information to prioritize mutations for further computational and experimental impact assessment. The program is available as a webserver at https://analysistools.cancer.gov/3dvizsnp or as a standalone python program at https://github.com/CBIIT-CGBB/3DVizSNP .