Facile Fabrication of Highly Efficient Chitosan-Based Multifunctional Coating for Cotton Fabrics with Excellent Flame-Retardant and Antibacterial Properties.

Interest in the development of eco-friendly, sustainable, and convenient bio-based coatings to enhance flame retardancy and antibacterial properties in cotton fabrics is growing. In this work, chitosan was protonated at its amino groups using a method with a high atom economy using an equimolar amount of amino trimethylene phosphonic acid (ATMP), resulting in the fabrication of a single-component chitosan-based multifunctional coating (ATMP-CS), thereby avoiding any additional neutralization or purification steps. Cotton fabrics coated with various loads of ATMP-CS were prepared through a padding-drying-curing process. The morphology, thermal stability, mechanical properties, antibacterial properties, flame-retardant behavior, and flame-retardant mechanism of these fabrics were investigated. The coating exhibited excellent film-forming properties, and it imparted a uniform protective layer onto the surfaces of the cotton fabrics. When the load capacity reached 11.5%, the coated fabrics achieved a limiting oxygen index of 29.7% and successfully passed the VFT test. Moreover, the ATMP-CS coating demonstrated antibacterial rates against Escherichia coli and Staphylococcus aureus reaching 95.1% and 99.9%, respectively. This work presents a straightforward and gentle approach to fabricating colorless, environmentally friendly, and highly efficient fabric coatings that have potential applications in promoting the use of bio-based materials.

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.

A real-time constellation image classification method of wireless communication signals based on the lightweight network MobileViT.

Automatic modulation classification (AMC) is a challenging topic in the development of cognitive radio, which can sense and learn surrounding electromagnetic environments and help to make corresponding decisions. In this paper, we propose to complete the real-time AMC through constructing a lightweight neural network MobileViT driven by the clustered constellation images. Firstly, the clustered constellation images are transformed from I/Q sequences to help extract robust and discriminative features. Then the lightweight neural network called MobileViT is developed for the real-time constellation image classification. Experimental results on the public dataset RadioML 2016.10a with edge computing platform demonstrate the superiority and efficiency of MobileViT. Furthermore, the extensive ablation tests prove the robustness of the proposed method to the learning rate and batch size. To the best of our knowledge, this is the first attempt to deploy the deep learning model to complete the real-time classification of modulation schemes of received signals at the edge.

Study on energy evolution and fractal characteristics of sandstone with different fracture dip angles under uniaxial compression.

In order to investigate the failure modes and instability mechanism of fractured rock. Uniaxial compression tests were conducted on sandstone specimens with different dip angles. Based on rock energy dissipation theory and fractal theory, the energy evolution characteristics and fragmentation fractal characteristics in the process of deformation and failure of specimens were analyzed. The results show that the peak strength and elastic modulus of fractured rock mass are lower than those of intact samples, and both show an exponential increase with the increase of fracture dip angle. The energy evolution laws of different fracture specimens are roughly similar and can be classified into four stages based on the stress-strain curve: pressure-tight, elastic, plastic, and post-destructive. The total strain energy, elastic strain energy, and dissipated strain energy of the specimen at the peak stress point increased exponentially with crack inclination, and the dissipated strain energy and compressive strength conformed to a power function growth relationship. The distribution of the fragments after the failure of the fracture sample has fractal characteristics, and the fractal dimension increases with the increase of the fracture dip angle. In addition, the higher the compressive strength of the specimen, the greater the energy dissipation, the more serious the degree of fragmentation, and the greater the fractal dimension. The data fitting further shows that there is a power function relationship between the dissipated strain energy and the fractal dimension. The research results can provide a theoretical basis for the stability of rock mass engineering and structural deformation control.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Influence of Cation-Size Effects of Alkaline Earth (Ae) Metals on Dimensionality and Optical Anisotropy Regulation in K4AeP2S8 Thiophosphates.

Cationic substitution demonstrates significant potential for regulating structural dimensionality and physicochemical performance owing to the cation-size effect. Leveraging this characteristic, this study synthesized a new family of K4AeP2S8 (Ae = alkaline earth elements: Mg, Ca, Sr, and Ba) thiophosphates, involving the substitution of Ae2+ cations. The synthesized compounds crystallized in distinct space groups, monoclinic P2/c (Ae = Mg) versus orthorhombic Ibam (Ae = Ca, Sr, and Ba), exhibiting intriguing dimensionality transformations from zero-dimensional (0D) [Mg2P4S16]8- clusters in K4MgP2S8 to 1D ∞[AeP2S8]4- chains in other K4AeP2S8 thiophosphates owing to the varying ionic radii of Ae2+ cations, Ae-S bond lengths, and coordination numbers of AeSn (Mg: n = 6 versus other: n = 8). Experimental investigations revealed that K4AeP2S8 thiophosphates featured wide optical bandgaps (3.37-3.64 eV), and their optical absorptions were predominantly influenced by the S 3p and P 3s orbitals, with negligible contributions from the K and Ae cations. Notably, within the K4AeP2S8 series, birefringence (Δn) increased from K4MgP2S8 (Δn = 0.034) to other K4AeP2S8 (Δn = 0.050-0.079) compounds, suggesting that infinite 1D chains more significantly influence Δn origins than 0D clusters, thus offering a feasible approach for enhancing optical anisotropy and exploring potential new birefringent materials.

Coin-sized, fully integrated, and minimally invasive continuous glucose monitoring system based on organic electrochemical transistors.

Continuous glucose monitoring systems (CGMs) are critical toward closed-loop diabetes management. The field's progress urges next-generation CGMs with enhanced antinoise ability, reliability, and wearability. Here, we propose a coin-sized, fully integrated, and wearable CGM, achieved by holistically synergizing state-of-the-art interdisciplinary technologies of biosensors, minimally invasive tools, and hydrogels. The proposed CGM consists of three major parts: (i) an emerging biochemical signal amplifier, the organic electrochemical transistor (OECT), improving the signal-to-noise ratio (SNR) beyond traditional electrochemical sensors; (ii) a microneedle array to facilitate subcutaneous glucose sampling with minimized pain; and (iii) a soft hydrogel to stabilize the skin-device interface. Compared to conventional CGMs, the OECT-CGM offers a high antinoise ability, tunable sensitivity and resolution, and comfort wearability, enabling personalized glucose sensing for future precision diabetes health care. Last, we discuss how OECT technology can help push the limit of detection of current wearable electrochemical biosensors, especially when operating in complicated conditions.

CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and Vimentin.

Circular RNAs (circRNAs) play a crucial role in regulating various tumors. However, their biological functions and mechanisms in gastric cancer (GC) have not been well understood. Here, we discovered a stable cytoplasmic circRNA named circUSP1 (hsa_circ_000613) in GC. CircUSP1 upregulation in GC tissues was correlated with tumor size and differentiation. We observed that circUSP1 promoted GC growth and metastasis. Mechanistically, circUSP1 mainly interacted with the RRM1 domain of an RNA-binding protein (RBP) called HuR, stabilizing its protein level by inhibiting ß-TrCP-mediated ubiquitination degradation. The oncogenic properties of HuR mediated promotive effects of circUSP1 in GC progression. Moreover, we identified USP1 and Vimentin as downstream targets of HuR in post-transcriptional regulation, mediating the effects of circUSP1. The parent gene USP1 also enhanced the viability and mobility of GC cells. Additionally, tissue-derived circUSP1 could serve as an independent prognostic factor for GC, while plasma-derived circUSP1 showed promise as a diagnostic biomarker, outperforming conventional markers including serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9). Our study highlights that circUSP1 promotes GC progression by binding to and stabilizing oncogenic HuR, thereby facilitating the upregulation of USP1 and Vimentin at the post-transcriptional level. These findings suggest that circUSP1 could be a potential therapeutic target and a diagnostic and prognostic biomarker for GC.

Optimizing image quality and minimizing radiation dose in pediatric abdominal multiphase contrast-enhanced computed tomography: a study on CARE kV and CARE Dose 4D.

Background: Multiphase contrast-enhanced computed tomography (CECT) is a commonly used modality in pediatric computed tomography (CT) scans. However, the purposes and focus of each phase, such as CT angiography (CTA), and parenchymal phase, are different. In routine practice, the same scanning parameters are used for all phases, resulting in unnecessary radiation exposure for children. Accurately and rapidly adjusting the scanning parameters for each phase of CECT is challenging in clinical settings. This retrospective cross-sectional study was designed to investigate the feasibility of using both CARE kV and CARE Dose 4D to reduce the radiation dose while maintaining diagnostic quality in multiphase CECT scans of children. Methods: Overall, 57 children (33 males and 24 females) who underwent multiphase abdominal CECT in Xinjiang Hospital of Beijing Children's Hospital with an average age of 6.52±4.30 years (range, 0.1-15 years), were enrolled. The tube voltage was automatically modulated using CARE kV. The tube current was automatically modulated using CARE Dose 4D. Different dose saving optimization indices (DI) were used for the three phases: a DI value of 3 was used for the unenhanced CT phase, a DI value of 12 was used for the CTA phase, and a DI value of 7 was used for the parenchymal phase. The tube voltage and volume CT dose index (CTDIvol) were recorded for each phase. Two reviewers subjectively evaluated the overall image quality and noise level of the three phases using a 5-point Likert scale (1-2 points: unqualified, 3 points: qualified, 4 points: better, 5 points: best). The CT and noise values of the descending aorta, liver, and back muscle were measured objectively. The voltage distribution and the image quality and CTDIvol in each phase were compared. Results: The most selected tube voltage in the unenhanced CT, CTA, and parenchymal phases was 100 kV (49/57, 85.96%), 70 kV (36/57, 63.16%), and 80 kV (32/57, 56.14%), respectively. The differences between the three phases were statistically significant (P<0.001). The CTDIvol values of the three phases were 3.99±1.99, 2.02±1.71, and 3.18±2.10 mGy, respectively, with a significant difference between the three phases (P<0.001). The CTDIvol decreased linearly as the DI value increased. All images met the diagnostic requirements. The overall quality scores for the three phases were 4.24±0.42, 4.41±0.49, and 4.50±0.45, respectively, with no significant linear relationship with the change in the DI. Conclusions: The combined use of CARE Dose 4D and CARE kV could effectively reduce the radiation dose in children during multiphase abdominal CECT without compromising the diagnostic image quality.

cGAS-STING pathway agonists are promising vaccine adjuvants.

Adjuvants are of critical value in vaccine development as they act on enhancing immunogenicity of antigen and inducing long-lasting immunity. However, there are only a few adjuvants that have been approved for clinical use, which highlights the need for exploring and developing new adjuvants to meet the growing demand for vaccination. Recently, emerging evidence demonstrates that the cGAS-STING pathway orchestrates innate and adaptive immunity by generating type I interferon responses. Many cGAS-STING pathway agonists have been developed and tested in preclinical research for the treatment of cancer or infectious diseases with promising results. As adjuvants, cGAS-STING agonists have demonstrated their potential to activate robust defense immunity in various diseases, including COVID-19 infection. This review summarized the current developments in the field of cGAS-STING agonists with a special focus on the latest applications of cGAS-STING agonists as adjuvants in vaccination. Potential challenges were also discussed in the hope of sparking future research interests to further the development of cGAS-STING as vaccine adjuvants.

Immunoglobulin superfamily 6 is a molecule involved in the anti-tumor activity of macrophages in lung adenocarcinoma.

BACKGROUND: Immunoglobulin superfamily 6 (IGSF6) is a novel member of the immunoglobulin superfamily and has been implicated in various diseases. However, the specific role of IGSF6 in the anti-tumor immunity within lung adenocarcinoma (LUAD) remains unclear. METHODS: We analyzed the IGSF6 expression in LUAD using data from TCGA, and we performed qRT-PCR and western blotting to validate these findings using tissue samples obtained from LUAD patients. Images of IHC staining were obtained from HPA. To assess the clinical relevance of IGSF6 expression, we utilized UALCAN and SPSS to analyze its association with major clinical features of LUAD. Additionally, we employed ROC curves and survival analysis to evaluate the potential diagnostic and prognostic value of IGSF6 in LUAD. To gain insights into the functional implications of IGSF6, we performed enrichment analysis using the R software clusterProfiler package. Moreover, we utilized TIMER2.0 and TISIDB to investigate the relationship between IGSF6 and immune infiltrates in LUAD. The proportion of tumor-infiltrating immune cells in LUAD was assessed using FCM, and their correlation with IGSF6 expression in tumor tissues was analyzed. The localization of IGSF6 protein on macrophages was confirmed using the HPA and FCM. To determine the regulatory role of IGSF6 on macrophage activity in LUAD, we employed ELISA, FCM, and tumor-bearing models. RESULTS: We discovered that both IGSF6 mRNA and protein levels were significantly decreased in LUAD. Additionally, we observed a negative correlation between IGSF6 expression and TNM stages as well as pathologic stages in LUAD. Notably, IGSF6 exhibited high sensitivity and specificity in diagnosing LUAD, and was positively associated with the survival rate of LUAD patients. Furthermore, IGSF6 expression was closely linked to gene sets involved in immune response. IGSF6 expression showed a positive correlation with immune infiltrates exhibiting anti-tumor activity, particularly M1 macrophages. We confirmed the predominant localization of the IGSF6 protein on the membrane of M1 macrophages. Importantly, the knockdown of IGSF6 resulted in a reduction in the anti-tumor activity of M1 macrophages, thereby promoting tumor progression. CONCLUSION: IGSF6 is a molecule that is essential for the anti-tumor activity of macrophages in LUAD.

Noncentrosymmetric Na6Pb3P4S16 and Centrosymmetric K2MIIP2S6 (MII = Mg and Zn) Displaying Multiple Membered-Ring Configurations and Strong Optical Anisotropy.

Three thiophosphates including noncentrosymmetric Na6Pb3P4S16 and centrosymmetric K2MIIP2S6 (MII = Mg and Zn) were successfully synthesized in vacuum-sealed silica tubes. Note that interesting multiple six membered-rings (6-MRs) including 6-NaS6-MRs and 6-KSn-MRs (n = 6 and 7) formed by A+-centered polyhedra were discovered in the structures of title thiophosphates and these MR-composed three-dimensional (3D) tunnels show great possibility to facilitate the filling of various structural blocks (such as zero-dimensional (0D) Pb3S10 trimers or one-dimensional (1D) (MIISn)n chains). Na6Pb3P4S16 exhibits the strongest nonlinear optical (NLO) response (5.4 × AgGaS2) with phase-matching (PM) behavior among the known Pb-based PM NLO sulfides, which is much larger than that of Pb3P2S8 (3.5 × AgGaS2); it was verified that such large second harmonic generation (SHG) response in Na6Pb3P4S16 can be attributed to the huge contribution of stereochemically active PbS4 units based on the SHG-density and dipole-moment calculations. Moreover, title thiophosphates show large birefringences (Δn = 0.102-0.21), which indicates that incorporation of [P2S6] dimers or polarized PbS4 units into structures provides positive benefits for the onset of strong optical anisotropy.

Repression of LSD1 potentiates homologous recombination-proficient ovarian cancer to PARP inhibitors through down-regulation of BRCA1/2 and RAD51.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are selectively active in ovarian cancer (OC) with homologous recombination (HR) deficiency (HRD) caused by mutations in BRCA1/2 and other DNA repair pathway members. We sought molecular targeted therapy that induce HRD in HR-proficient cells to induce synthetic lethality with PARPi and extend the utility of PARPi. Here, we demonstrate that lysine-specific demethylase 1 (LSD1) is an important regulator for OC. Importantly, genetic depletion or pharmacological inhibition of LSD1 induces HRD and sensitizes HR-proficient OC cells to PARPi in vitro and in multiple in vivo models. Mechanistically, LSD1 inhibition directly impairs transcription of BRCA1/2 and RAD51, three genes essential for HR, dependently of its canonical demethylase function. Collectively, our work indicates combination with LSD1 inhibitor could greatly expand the utility of PARPi to patients with HR-proficient tumor, warranting assessment in human clinical trials.

In Vitro Biological Activity and Primary Structure of Polysaccharide Extracted from Flower of Panax Ginseng C.A. Meyer.

This study investigates how three different extraction methods impact the biological activity and structure characteristics of polysaccharides from the flower of Panax ginseng C.A. Meyer. The three polysaccharides were named AHEP, DWEP and ANEP that extracted by acid solvent (HCL 0.01 mol/L), distilled water and alkali solvent (NaOH 0.01 mol/L) respectively. The results showed that the yield of ANEP was highest compared to the others, as well as the capacity of antioxidant, cholate-binding and inhibition to α-glucosidase were better than AHEP and DWEP (P<0.05). Moreover, the activity retention rate in vitro with simulated digestion demonstrated that ANEP were superior to AHEP and DWEP. The large components, nominated ANEP-1 and ANEP-2, were eluted from the ANEP by DEAE-52-cellulose. UV-Vis and FT-IR analysis demonstrated that ANEP-1 and ANEP-2 had typical characteristic absorption of proteoglycan, but SEM results showed that the surface shapes of ANEP-1 and ANEP-2 were quite different. It can be concluded that ANEP has great potential as an effective strategy for obtaining polysaccharides from ginseng flower.

Diradicaloid Boron-Doped Molecular Carbons Achieved by Pentagon-Fusion.

Molecular carbons (MCs) are molecular cutouts of carbon materials. Doping with heteroatoms and constructing open-shell structures are two powerful approaches to achieve unexpected and unique properties of MCs. Herein, we disclose a new strategy to design open-shell boron-doped MCs (BMCs), namely by pentagon-fusion of an organoborane π-system. We synthesized two diradicaloid BMC molecules that feature C24 B and C38 B π-skeletons containing a pentagonal ring. A thorough investigation reveals that such pentagon-fusion not only leads to their local antiaromaticity, but also incorporates an internal quinoidal substructure and thereby induces open-shell singlet diradical states. Moreover, their fully fused structures enable efficient π conjugation, which is expanded over the whole frameworks. Consequently, some intriguing physical properties are achieved, such as narrow energy gaps, very broad light absorptions, and superior photothermal capability, along with excellent photostability. Notably, the solid of the C38 B molecule exhibits absorption that covers the range of 300-1200 nm and an efficiency of 93.5 % for solar-driven water evaporation, thus demonstrating the potential of diradicaloid BMCs as high-performance organic photothermal materials.

Deep learning assisted sparse array ultrasound imaging.

This study aims to restore grating lobe artifacts and improve the image resolution of sparse array ultrasonography via a deep learning predictive model. A deep learning assisted sparse array was developed using only 64 or 16 channels out of the 128 channels in which the pitch is two or eight times the original array. The deep learning assisted sparse array imaging system was demonstrated on ex vivo porcine teeth. 64- and 16-channel sparse array images were used as the input and corresponding 128-channel dense array images were used as the ground truth. The structural similarity index measure, mean squared error, and peak signal-to-noise ratio of predicted images improved significantly (p < 0.0001). The resolution of predicted images presented close values to ground truth images (0.18 mm and 0.15 mm versus 0.15 mm). The gingival thickness measurement showed a high level of agreement between the predicted sparse array images and the ground truth images, as indicated with a bias of -0.01 mm and 0.02 mm for the 64- and 16-channel predicted images, respectively, and a Pearson's r = 0.99 (p < 0.0001) for both. The gingival thickness bias measured by deep learning assisted sparse array imaging and clinical probing needle was found to be <0.05 mm. Additionally, the deep learning model showed capability of generalization. To conclude, the deep learning assisted sparse array can reconstruct high-resolution ultrasound image using only 16 channels of 128 channels. The deep learning model performed generalization capability for the 64-channel array, while the 16-channel array generalization would require further optimization.

Effects of Lactiplantibacillus plantarum on oxidative stress, mitophagy, and NLRP3 inflammasome activation in broiler breast meat.

Poultry meat has a high polyunsaturated fatty acids content, making it vulnerable to oxidative stress. Mitophagy participates in the regulation of oxidative stress and the nucleotide-binding and oligomerization domain (NOD)-like receptor family as well as pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Lactiplantibacillus plantarum P8 (P8) is a probiotic strain with an antioxidant capacity. In the present study, we investigated the effects of P8 on oxidative stress, mitochondrial function, mitophagy, and NLRP3 inflammasome in the breast meat of oxidatively stressed broilers. Four hundred 1-day-old male broilers were assigned to a 2 × 2 factorial design with 2 P8 levels (0 or 1 × 108 cfu/g), either with or without dexamethasone (DEX) injection, for a 21-day experimental period. DEX was injected intraperitoneally once daily from d 16 to 21. The breast meat was collected on d 21. The results showed that P8 supplementation decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and activated the Keap1-Nrf2 pathway in DEX-injected broilers. Moreover, P8 supplementation downregulated mitochondrial DNA (mtDNA) copy number and increased the expressions of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), silent information regulator 1 (SIRT1), mitochondrial fusion protein 1 (Mfn1), and optic atrophy protein 1 (OPA1) in DEX-treated broilers. In addition, the decreased mitophagy level in DEX-treated broilers was elevated with P8 supplementation, as reflected by the increased gene expression of autophagy-related gene 5 (ATG5), Bcl-2-interacting protein (Becline-1), Parkin, PTEN-induced kinase 1 (PINK1), light chain 3 II (LC3II)/LC31, and the protein expression of Parkin as well as decreased p62 expression. In addition, P8 supplementation inhibited NLRP3 inflammasome activation by decreasing the transcription of NLRP3, IL-18, cysteinyl aspartate-specific proteinase-1 (Caspase-1), and the expression of NLRP3 and IL-18 in DEX-treated broilers. In conclusion, dietary P8 supplementation alleviates oxidative stress, improves mitophagy, and inhibits NLRP3 inflammasome activation in the breast meat of oxidatively stressed broilers.

KDM2B regulates inflammation and oxidative stress of sepsis via targeting NF-κB and AP-1 pathways.

BACKGROUNDS: The kidney is an easily affected organ with sepsis which is a main underlying cause of acute kidney injury (AKI). Histone-modifying lysine-specific demethylase 2B (KDM2B) is involved in numerous pathological processes, such as cell senescence and tumor development. However, the role of KDM2B in sepsis-induced AKI is unclear. OBJECTS: To investigate the role of KDM2B on cell viability, inflammation and oxidative stress of sepsis-associated AKI, and the involved signaling pathways. METHODS: An AKI model in vitro was established through lipopolysaccharide (LPS)-induction in HK-2 cells. Western blots were performed to evaluate the expression of KDM2B, cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), p65, c-Jun and c-Fos, as well as p65 phosphorylation. Cell viability was measured using CCK-8 kit. ELISA was performed to analyze the production of layered double hydroxide (LDH), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-18, vascular cell adhesion molecule-1 (VCAM-1), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and H2 O2 . The qPCR was used to evaluate the transcription level of TNF-α, IL-1ß, IL-18, and VCAM-1. RESULTS: KDM2B knockdown alleviated LPS-induced cytotoxicity, decreased LDH release, and improved cell viability. KDM2B knockdown reduced concentration of inflammation-related molecules including TNF-α, IL-1ß, IL-18, and VCAM-1, and inhibited their transcription. Moreover, KDM2B knockdown promoted the quantity of SOD and GSH, while declined the production of MDA, H2 O2 , COX2, and iNOS. Further, KDM2B played a role in LPS-induced HK-2 cell injury by activating nuclear factor κB (NF-κB) and activator protein 1 (AP-1) pathways. CONCLUSION: KDM2B knockdown reduced cytotoxicity, inflammation and oxidative stress in LPS-induced AKI via inhibiting NF-κB and AP-1 pathways, indicating KDM2B may be a promising therapeutic target for the treatment of sepsis-associated AKI.

Small molecule activators of TAK1 promotes its activity-dependent ubiquitination and TRAIL-mediated tumor cell death.

TAK1 is a key modulator of both NF-κB signaling and RIPK1. In TNF signaling pathway, activation of TAK1 directly mediates the phosphorylation of IKK complex and RIPK1. In a search for small molecule activators of RIPK1-mediated necroptosis, we found R406/R788, two small molecule analogs that could promote sustained activation of TAK1. Treatment with R406 sensitized cells to TNF-mediated necroptosis and RIPK1-dependent apoptosis by promoting sustained RIPK1 activation. Using click chemistry and multiple biochemical binding assays, we showed that treatment with R406 promotes the activation of TAK1 by directly binding to TAK1, independent of its original target Syk kinase. Treatment with R406 promoted the ubiquitination of TAK1 and the interaction of activated TAK1 with ubiquitinated RIPK1. Finally, we showed that R406/R788 could promote the cancer-killing activities of TRAIL in vitro and in mouse models. Our studies demonstrate the possibility of developing small molecule TAK1 activators to potentiate the effect of TRAIL as anticancer therapies.