Multi-Level Content-Aware Boundary Detection for Temporal Action Proposal Generation.

It is challenging to generate temporal action proposals from untrimmed videos. In general, boundary-based temporal action proposal generators are based on detecting temporal action boundaries, where a classifier is usually applied to evaluate the probability of each temporal action location. However, most existing approaches treat boundaries and contents separately, which neglect that the context of actions and the temporal locations complement each other, resulting in incomplete modeling of boundaries and contents. In addition, temporal boundaries are often located by exploiting either local clues or global information, without mining local temporal information and temporal-to-temporal relations sufficiently at different levels. Facing these challenges, a novel approach named multi-level content-aware boundary detection (MCBD) is proposed to generate temporal action proposals from videos, which jointly models the boundaries and contents of actions and captures multi-level (i.e., frame level and proposal level) temporal and context information. Specifically, the proposed MCBD preliminarily mines rich frame-level features to generate one-dimensional probability sequences, and further exploits temporal-to-temporal proposal-level relations to produce two-dimensional probability maps. The final temporal action proposals are obtained by a fusion of the multi-level boundary and content probabilities, achieving precise boundaries and reliable confidence of proposals. The extensive experiments on the three benchmark datasets of THUMOS14, ActivityNet v1.3 and HACS demonstrate the effectiveness of the proposed MCBD compared to state-of-the-art methods. The source code of this work can be found in https://mic.tongji.edu.cn.

Perceptually Weighted Rate Distortion Optimization for Video-Based Point Cloud Compression.

Dynamic point cloud is a volumetric visual data representing realistic 3D scenes for virtual reality and augmented reality applications. However, its large data volume has been the bottleneck of data processing, transmission, and storage, which requires effective compression. In this paper, we propose a Perceptually Weighted Rate-Distortion Optimization (PWRDO) scheme for Video-based Point Cloud Compression (V-PCC), which aims to minimize the perceptual distortion of reconstructed point cloud at the given bit rate. Firstly, we propose a general framework of perceptually optimized V-PCC to exploit visual redundancies in point clouds. Secondly, a multi-scale Projection based Point Cloud quality Metric (PPCM) is proposed to measure the perceptual quality of 3D point cloud. The PPCM model comprises 3D-to-2D patch projection, multi-scale structural distortion measurement, and fusion model. Approximations and simplifications of the proposed PPCM are also presented for both V-PCC integration and low complexity. Thirdly, based on the simplified PPCM model, we propose a PWRDO scheme with Lagrange multiplier adaptation, which is incorporated into the V-PCC to enhance the coding efficiency. Experimental results show that the proposed PPCM models can be used as standalone quality metrics, and they are able to achieve higher consistency with the human subjective scores than the state-of-the-art objective visual quality metrics. Also, compared with the latest V-PCC reference model, the proposed PWRDO-based V-PCC scheme achieves an average bit rate reduction of 13.52%, 8.16%, 10.56% and 9.54%, respectively, in terms of four objective visual quality metrics for point clouds. It is significantly superior to the state-of-the-art coding algorithms. The computational complexity of the proposed PWRDO increases by 1.71% and 0.05% on average to the V-PCC encoder and decoder, respectively, which is negligible. The source codes of the PPCM and PWRDO schemes are available at https://github.com/VVCodec/PPCM-PWRDO.

E3 ligase TRIM28 promotes anti-PD-1 resistance in non-small cell lung cancer by enhancing the recruitment of myeloid-derived suppressor cells.

BACKGROUND: Alterations in several tripartite motif-containing (TRIM) family proteins have been implicated in the pathogenesis of lung cancer. TRIM28, a member of the TRIM E3 ligase family, has been associated with tumorigenesis, cell proliferation, and inflammation. However, little is known about TRIM28 expression and its role in the immune microenvironment of non-small cell lung cancer (NSCLC). METHODS: We assessed the clinical significance of TRIM28 in tissue microarrays and TCGA cohorts. We investigated the function of TRIM28 in syngeneic mouse tumor models, the KrasLSL-G12D/+; Tp53fl/fl (KP) mouse model, and humanized mice. Immune cell composition was analyzed using flow cytometry and immunohistochemistry. RESULTS: Our findings revealed a positive correlation between TRIM28 expression and the infiltration of suppressive myeloid-derived suppressor cells (MDSCs) in NSCLC. Moreover, silencing TRIM28 enhanced the efficacy of anti-PD-1 immunotherapy by reshaping the inflamed tumor microenvironment. Mechanistically, we demonstrated that TRIM28 could physically interact with receptor-interacting protein kinase 1 (RIPK1) and promote K63-linked ubiquitination of RIPK1, which is crucial for sustaining activation of the NF-κB pathway. Mutagenesis of the E3 ligase domain corroborated the essential role of E3 ligase activity in TRIM28-mediated NF-κB activation. Further experiments revealed that TRIM28 could upregulate the expression of CXCL1 by activating NF-κB signaling. CXCL1 could bind to CXCR2 on MDSCs and promote their migration to the tumor microenvironment. TRIM28 knockdown increased responsiveness to anti-PD-1 therapy in immunocompetent mice, characterized by increased CD8+T tumor-infiltrating lymphocytes and decreased MDSCs. CONCLUSION: The present study identified TRIM28 as a promoter of chemokine-driven recruitment of MDSCs through RIPK1-mediated NF-κB activation, leading to the suppression of infiltrating activated CD8+T cells and the development of anti-PD-1 resistance. Understanding the regulation of MDSC recruitment and function by TRIM28 provides crucial insights into the association between TRIM28 signaling and the development of an immunosuppressive tumor microenvironment. These insights may inform the development of combination therapies to enhance the effectiveness of immune checkpoint blockade therapy in NSCLC.

Amidoxime Modified UiO-66@PIM-1 Mixed-Matrix Membranes to Enhance CO2 Separation and Anti-Aging Performance.

Mixed matrix membranes (MMMs) generally have some fatal defects, such as poor compatibility between the two phases leading to non-selective pores. In this work, PIM-1 was chosen as the polymer matrix, and UiO-66 modified with amidoxime (UiO-66-AO) was used as the filler to prepare the MMMs. In the MMMs, the amino and hydroxyl groups on UO-66-AO form a rich hydrogen bond network with the N and O atoms in the polymer PIM-1 chain to improve the compatibility between the polymer matrix and the filler. In addition, the selective adsorption of CO2 by the amidoxime group can promote the transport of CO2 in the membrane, which enhances the gas selectivity. The CO2 permeability and CO2/N2 selectivity of UiO-66-AO@PIM-1 MMMs are increased by 35.2% and 45.2% compared to pure PIM-1 membranes, reaching 7535.5 Barrer and 26.9, surpassing the Robeson Upper Bound (2008) and close to the 2019 Upper Bound. After 38 days of the aging experiment, the CO2 permeability is approximately 74% of the original. The results show that the addition of UiO-66-AO has an obvious effect on improving the aging properties of the membrane. The UiO-66-AO@PIM-1 MMMs have a bright prospect for CO2 separation in the future.

Design and Optimization of a Novel Hybrid Membrane-Electrochemical Hydrogen Pump Process for Recovering Helium from NRU off Gas.

Due to the low boiling point of helium, the nitrogen-rich off gas of the nitrogen rejection unit (NRU) in the liquefied natural gas (LNG) plant usually contains a small amount of CH4, approximately 1-4% He, and associated gases, such as H2. However, it is difficult to separate hydrogen and helium. Here, we propose two different integrated processes coupled with membrane separation, pressure swing adsorption (PSA), and the electrochemical hydrogen pump (EHP) based on different sequences of hydrogen gas removal. Both processes use membrane separation and PSA in order to recover and purify helium, and the EHP is used to remove hydrogen. The processes were strictly simulated using UniSim Design, and an economic assessment was conducted. The results of the economic assessment show that flowsheet #2 was more cost-effective due to the significant reduction in the capacity of the compressor and PSA because of the pre-removal of hydrogen. Additionally, using the response surface methodology (RSM), a Box-Behnken design experiment was conducted, and an accurate and reliable quadratic response surface regression model was fitted through variance analysis. The optimized operating parameters for the integrated process were determined as follows: the membrane area of M101 was 966.6 m2, the permeate pressure of M101 was 100 kPa, and the membrane area of M102 was 41.2 m2. The maximum recovery fraction was 90.66%, and the minimum cost of helium production was 2.21 $/kg. Thus, proposed flowsheet #2 has prospects and value for industrial application.

CSformer: Bridging Convolution and Transformer for Compressive Sensing.

Convolutional Neural Networks (CNNs) dominate image processing but suffer from local inductive bias, which is addressed by the transformer framework with its inherent ability to capture global context through self-attention mechanisms. However, how to inherit and integrate their advantages to improve compressed sensing is still an open issue. This paper proposes CSformer, a hybrid framework to explore the representation capacity of local and global features. The proposed approach is well-designed for end-to-end compressive image sensing, composed of adaptive sampling and recovery. In the sampling module, images are measured block-by-block by the learned sampling matrix. In the reconstruction stage, the measurements are projected into an initialization stem, a CNN stem, and a transformer stem. The initialization stem mimics the traditional reconstruction of compressive sensing but generates the initial reconstruction in a learnable and efficient manner. The CNN stem and transformer stem are concurrent, simultaneously calculating fine-grained and long-range features and efficiently aggregating them. Furthermore, we explore a progressive strategy and window-based transformer block to reduce the parameters and computational complexity. The experimental results demonstrate the effectiveness of the dedicated transformer-based architecture for compressive sensing, which achieves superior performance compared to state-of-the-art methods on different datasets. Our codes is available at: https://github.com/Lineves7/CSformer.

Knowledge-Enriched Attention Network With Group-Wise Semantic for Visual Storytelling.

As a technically challenging topic, visual storytelling aims at generating an imaginary and coherent story with narrative multi-sentences from a group of relevant images. Existing methods often generate direct and rigid descriptions of apparent image-based contents, because they are not capable of exploring implicit information beyond images. Hence, these schemes could not capture consistent dependencies from holistic representation, impairing the generation of reasonable and fluent stories. To address these problems, a novel knowledge-enriched attention network with group-wise semantic model is proposed. Three main novel components are designed and supported by substantial experiments to reveal practical advantages. First, a knowledge-enriched attention network is designed to extract implicit concepts from external knowledge system, and these concepts are followed by a cascade cross-modal attention mechanism to characterize imaginative and concrete representations. Second, a group-wise semantic module with second-order pooling is developed to explore the globally consistent guidance. Third, a unified one-stage story generation model with encoder-decoder structure is proposed to simultaneously train and infer the knowledge-enriched attention network, group-wise semantic module and multi-modal story generation decoder in an end-to-end fashion. Substantial experiments on the visual storytelling datasets with both objective and subjective evaluation metrics demonstrate the superior performance of the proposed scheme as compared with other state-of-the-art methods. The source code of this work can be found in https://mic.tongji.edu.cn.

Constructing Gas Transmission Pathways in Two-Dimensional Composite Material ZIF-8@BNNS Mixed-Matrix Membranes to Enhance CO2/N2 Separation Performance.

Two-dimensional (2D) nanomaterials, due to their high aspect ratio and high specific surface area, which provide a more tortuous pathway for larger gas molecules, are frequently used in membrane separation. However, in mixed-matrix membranes (MMMs), the high aspect ratio and high specific surface area of 2D fillers can increase transport resistance, thereby reducing the permeability of gas molecules. In this work, we combine boron nitride nanosheets (BNNS) with ZIF-8 nanoparticles to develop a novel material, ZIF-8@BNNS, to improve both CO2 permeability and CO2/N2 selectivity. Growth of ZIF-8 nanoparticles on the BNNS surface is achieved using an in-situ growth method where the amino groups of BNNS are complexed with Zn2+, creating gas transmission pathways that accelerate CO2 transmission. The 2D-BNNS material acts as a barrier in MMMs to improve CO2/N2 selectivity. The MMMs with a 20 wt.% ZIF-8@BNNS loading achieved a CO2 permeability of 106.5 Barrer and CO2/N2 selectivity of 83.2, surpassing the Robeson upper bound (2008) and demonstrating that MOF layers can efficiently reduce mass transfer resistance and enhance gas separation performance.

Efficacy and safety of curcumin in diabetic retinopathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common complications of diabetes and has become a major global cause of blindness. Curcumin, an extract of Curcuma longa (turmeric), is effective in preventing and treating diabetes. Recent studies have shown that curcumin can delay DR development. However, there has been no systematic review of its treatment of DR. This study will conduct a systematic review and meta-analysis of currently published randomized controlled trials (RCT) of curcumin for treating DR patients to evaluate its efficacy and safety. METHODS: We will search the relevant studies of curcumin in the treatment of DR in PubMed, Medline, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases from their respective inception dates to May 2022. A meta-analysis of the data extracted from qualified RCTs will be conducted, including the progression of DR, visual acuity, visual field, macular edema, quality of life, and adverse events. The meta-analysis will be performed using Review Manager 5.4.1 software, and the results will be based on either random-effects or fixed-effects models, depending on the heterogeneity. The Grading of Recommendations, Development, and Evaluation (GRADE) system will be used to evaluate the reliability and quality of evidence. RESULTS: The results of this study will provide sound and high-quality evidence for the efficacy and safety of curcumin in the treatment of DR. CONCLUSION: This study will be the first meta-analysis to comprehensively assess the efficacy and safety of curcumin in the treatment of DR and will provide helpful evidence for the clinical management of this disease. SYSTEMATIC REVIEW REGISTRATION: INPLASY202250002.

Molecular Design, Preparation, and Characterization of Fluoro-Containing Polyimide Ultrafine Fibrous Membranes with High Whiteness, High Thermal Stability, and Good Hydrophobicity.

Polymeric ultrafine fibrous membranes (UFMs) with high thermal stability and high whiteness are highly desired in modern optoelectronic applications. A series of fluoro-containing polyimide (FPI) UFMs with high whiteness, good thermal stability, and good hydrophobicity were prepared via a one-step electrospinning procedure from the organo-soluble FPI resins derived from a fluoro-containing dianhydride, 4,4'-(hexafluoroisopropylidene) diphthalic anhydride (6FDA), and various diamines containing either pendant trifluoromethyl (-CF3) groups or alicyclic units in the side chains. The obtained FPI UFMs, including FPI-1 from 6FDA and 3,5-diaminobenzotrifluoride (TFMDA), FPI-2 from 6FDA and 2'-trifluoromethyl-3,4'-oxydianiline (3FODA), FPI-3 from 6FDA and 1,4-bis[(4-amino-2-trifluoromethyl)phenoxy]benzene (6FAPB), FPI-4 from 4,4'-bis[(4-amino-2-trifluoromethyl)phenoxy]biphenyl (6FBAB), and FPI-5 from 6FDA and 4'-tert-butyl-cyclohexyl-3,5-diaminobenzoate (DABC) showed whiteness indices (WI) higher than 87.00 and optical reflectance values higher than 80% at the wavelength of 457 nm (R457), respectively. The FPI-5 UFM, especially, showed the highest WI of 92.88. Meanwhile, the prepared PI UFMs exhibited good hydrophobic features with water contact angles (WCA) higher than 105°. At last, the PI UFMs exhibited good thermal stability with glass transition temperatures (Tg) higher than 255 °C, and the 5% weight-loss temperatures (T5%) higher than 510 °C in nitrogen.

Synthesis and Properties of Optically Transparent Fluoro-Containing Polyimide Films with Reduced Linear Coefficients of Thermal Expansion from Organo-Soluble Resins Derived from Aromatic Diamine with Benzanilide Units.

Wholly aromatic polyimide (PI) films with good solution processability, light colors, good optical transparency, high storage modulus, and improved heat resistance were prepared and characterized. For this purpose, a multi-component copolymerization methodology was performed from a fluoro-containing dianhydride, 4,4'-(hexafluoroisopropylidene)diphthalic anhydride (6FDA), a rigid dianhydride, 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA), and a fluoro-containing diamine, 2,2'-bis(trifluoromethyl)-4,4'-bis [4-(4-amino-3-methyl)benzamide]biphenyl (MABTFMB). One homopolymer, FPI-1 (6FDA-MABTFMB), and five copolymers, FPI-2~FPI-6, containing the BPDA units from 10 mol% to 50 mol% in the dianhydride moieties, were prepared, respectively. The derived PI resins showed good solubility in the polar aprotic solvents, such as N-methyl-2-pyrrolidone (NMP) and N,N-dimethylacetamide (DMAc). The flexible PI films obtained by the solution casting procedure showed good optical properties with the transmittances higher than 74.0% at the wavelength of 450 nm. The PI films exhibited excellent thermal properties, including 5% weight loss temperatures (T5%) over 510 °C, together with glass transition temperatures (Tg) over 350.0 °C according to the peak temperatures of the loss modulus in dynamical mechanical analysis (DMA) measurements. The FPI-6 film also showed the lowest linear coefficient of thermal expansion (CTE) value of 23.4 × 10-6/K from 50 to 250 °C according to the thermomechanical analysis (TMA) measurements, which was obviously lower than that of FPI-1 (CTE = 30.6 × 10-6/K).

E3 ligase TRIM15 facilitates non-small cell lung cancer progression through mediating Keap1-Nrf2 signaling pathway.

BACKGROUND: Recent studies have indicated that some members of the tripartite motif (TRIM) proteins function as important regulators for non-small cell lung cancer (NSCLC), However, the regulatory mechanism underpinning aberrant expression of TRIM in NSCLC remains unclear. Here we report that TRIM15 plays important roles in NSCLC progression through modulating Keap1-Nrf2 signaling pathway. METHODS: TRIM15 expression was evaluated by western blot analysis, tissue microarray-based immunohistochemistry analysis. The interactions between TRIM15 and Keap1 were analyzed by co-immunoprecipitation (Co-IP) and immunofluorescence co-localization assay. The correlation between TRIM15 and Keap1 was measured by Co-IP and ubiquitination analysis in vitro. Gain- and lost-of-function experiments were used to detect TRIM15 promotes proliferation and invasion of NSCLC cells both in vitro and vivo. RESULTS: Here, we revealed that TRIM15 was frequently upregulated in NSCLC samples and associated with poor prognosis. Functionally, TRIM15 knockdown resulted in decreased cancer cell proliferation and metastasis, whereas ectopic TRIM15 expression facilitated tumor cancer cell proliferation and metastasis in vitro and in vivo. Moreover, TRIM15 promoted cell proliferation and metastasis depends on its E3 ubiquitin ligase. Mechanistically, TRIM15 directly targeted Keap1 by ubiquitination and degradation, the principal regulator of Nrf2 degradation, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant response and tumor progression. CONCLUSIONS: Therefore, our study characterizes the pivotal roles of TRIM15 promotes NSCLC progression via Nrf2 stability mediated by promoting Keap1 ubiquitination and degradation and could be a valuable prognostic biomarker and a potential therapeutic target in NSCLC. Video Abstract.

Procyanidins inhibit zearalenone-induced apoptosis and oxidative stress of porcine testis cells through activation of Nrf2 signaling pathway.

The mycotoxin zearalenone (ZEA) in food and feed seriously harms human and animal health. How to reduce its toxicity is an important direction of current research on food safety. This study aim to assess the effects of procyanidins (PC) on cell apoptosis caused by ZEA and to clarify the role of Nrf2 in the process. Swine testicle (ST) cells were treated with ZEA (57.5 µmol/L) and/or PC (10 mg/L) for 24 h. Cell viability was detected by CCK-8 assay. Cell apoptosis and the level of ROS were detected by flow cytometry. The expression levels of mRNA and protein was detected by qRT-PCR and western blotting. Our results showed that ZEA reduced the antioxidant capacity of the ST cells, induced the cell apoptosis and inhibited the gene and protein expression of Nrf2 and its downstream genes (ho-1,nqo1), while PC improved the cell antioxidant capacity, reduced the degree of ZEA-induced cell apoptosis and promoted the gene and protein expression of Nrf2 and its downstream genes. However, when the Nrf2 small molecule inhibitor ML385 was added, the ability of PC to inhibit ZEA-induced cell apoptosis and promote the expression of Nrf2 and its downstream genes were decreased. Our results demonstrated that ZEA induced oxidative stress and apoptosis of ST cells, which were alleviated by PC intervention via activating Nrf2 signaling pathway. This finding of this study provided a molecular basis for the clinical application of PC to prevent ZEN-caused reproductive toxicity.

Preparation and Characterization of Transparent Polyimide Nanocomposite Films with Potential Applications as Spacecraft Antenna Substrates with Low Dielectric Features and Good Sustainability in Atomic-Oxygen Environments.

Optically transparent polyimide (PI) films with good dielectric properties and long-term sustainability in atomic-oxygen (AO) environments have been highly desired as antenna substrates in low earth orbit (LEO) aerospace applications. However, PI substrates with low dielectric constant (low-Dk), low dielectric dissipation factor (low-Df) and high AO resistance have rarely been reported due to the difficulties in achieving both high AO survivability and good dielectric parameters simultaneously. In the present work, an intrinsically low-Dk and low-Df optically transparent PI film matrix, poly[4,4'-(hexafluoroisopropylidene)diphthalic anhydride-co-2,2-bis(4-(4-aminophenoxy)phenyl)hexafluoropropane] (6FPI) was combined with a nanocage trisilanolphenyl polyhedral oligomeric silsesquioxane (TSP-POSS) additive in order to afford novel organic-inorganic nanocomposite films with enhanced AO-resistant properties and reduced dielectric parameters. The derived 6FPI/POSS films exhibited the Dk and Df values as low as 2.52 and 0.006 at the frequency of 1 MHz, respectively. Meanwhile, the composite films showed good AO resistance with the erosion yield as low as 4.0 × 10-25 cm3/atom at the exposure flux of 4.02 × 1020 atom/cm2, which decreased by nearly one order of magnitude compared with the value of 3.0 × 10-24 cm3/atom of the standard PI-ref Kapton® film.

Zearalenone promotes apoptosis of mouse Leydig cells by targeting phosphatase and tensin homolog and thus inhibiting the PI3K/AKT signal pathway.

Zearalenone (ZEA) is a mycotoxin with estrogenic activity whose main effect is to impair the reproductive systems of animals. It leads to reproductive disorders in livestock and thus causes serious losses to agriculture and animal husbandry. This study aims to examine whether ZEA induces toxicity in Leydig cells through the PI3K/AKT signaling pathway and also to investigate the role played by the upstream phosphatase and tensin homolog (PTEN) gene. An adenovirus vector model was constructed to interfere with the PTEN gene to investigate whether ZEA promotes the apoptosis of TM3 cells through the PI3K/AKT pathway. Apoptosis was detected cytometrically and the protein expression levels of PTEN, AKT, p-AKT, Bax, and Bcl-2 were evaluated via western blot analysis. The results show that ZEA induces apoptosis of TM3 cells. PTEN expression is significantly increased (P < 0.01), Bax expression is increased (P < 0.05), AKT and p-AKT expression of anti-apoptotic protein is significantly decreased (P < 0.01), and Bcl-2 protein expression is decreased (P < 0.05) in the ZEA group compared with the control group. In the shRNA+ZEA group, the expression levels of PTEN and Bax proteins are significantly decreased (P < 0.01), AKT protein is significantly increased (P < 0.01), and p-AKT protein is increased (P < 0.05) compared with the ZEA group. This study thus demonstrates that ZEA promotes apoptosis of TM3 cells by targeting PTEN and thus inhibiting the PI3K/AKT signal pathway.

MABAN: Multi-Agent Boundary-Aware Network for Natural Language Moment Retrieval.

The amount of videos over the Internet and electronic surveillant cameras is growing dramatically, meanwhile paired sentence descriptions are significant clues to select attentional contents from videos. The task of natural language moment retrieval (NLMR) has drawn great interests from both academia and industry, which aims to associate specific video moments with the text descriptions figuring complex scenarios and multiple activities. In general, NLMR requires temporal context to be properly comprehended, and the existing studies suffer from two problems: (1) limited moment selection and (2) insufficient comprehension of structural context. To address these issues, a multi-agent boundary-aware network (MABAN) is proposed in this work. To guarantee flexible and goal-oriented moment selection, MABAN utilizes multi-agent reinforcement learning to decompose NLMR into localizing the two temporal boundary points for each moment. Specially, MABAN employs a two-phase cross-modal interaction to exploit the rich contextual semantic information. Moreover, temporal distance regression is considered to deduce the temporal boundaries, with which the agents can enhance the comprehension of structural context. Extensive experiments are carried out on two challenging benchmark datasets of ActivityNet Captions and Charades-STA, which demonstrate the effectiveness of the proposed approach as compared to state-of-the-art methods. The project page can be found in https://mic.tongji.edu.cn/e5/23/c9778a189731/page.htm.

Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression.

BACKGROUND: Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. The communication between tumor-derived exosomes and macrophages has a critical role in facilitating tumor progression. However, the mechanisms by which exosomes modulate tumor development in lung cancer are not fully understood. METHODS: Short hairpin RNA mediated knockdown or exogenous expression of TRIM59 combined with in vitro and in vivo assays were performed to prove the functional significance of TRIM59. Western blotting, real-time PCR, co-immunoprecipitation, immunofluorescence (IF) staining assays, proximity ligation assay (PLA), ubiquitination assays, lactate secretion and lipid droplets content measurement, and rescue experiments were used to evaluate the mechanism. Lewis lung carcinoma (LLC) cells were injected via subcutaneously or tail vein into C57BL/6 wild-type (WT) and transgenic mice to assess the role of TRIM59 in vivo. RESULTS: We demonstrated that tripartite motif-containing 59 (TRIM59) was expressed in lung cancer cells-derived exosomes, and can be transferred to macrophages through the exosomes. Activated macrophages by TRIM59 promote lung cancer progression in vitro and in vivo. Mechanistic investigations revealed that TRIM59 physically interacts with abhydrolase domain containing 5 (ABHD5) and directly induced the ubiquitination of ABHD5 and led to its proteasome-dependent degradation. ABHD5, an lipolytic co-activator, deficiency induced metabolic reprogramming and enabled NLRP3 inflammasome activation in macrophages. Further studies showed that the exacerbation of NLRP3 inflammasome activation by ABHD5 deficiency, provides a positive feedback loop to promote cancer progression by preferentially secrete the proinflammatory cytokine IL-1ß. CONCLUSIONS: Collectively, these data indicate that tumor-derived exosomal TRIM59 converts macrophages to tumor-promoting functions of macrophages via regulating ABHD5 proteasomal degradation, to activate NLRP3 inflammasome signaling pathway to promote lung cancer progression by IL-1ß secretion. Our findings also indicate that tumor-derived exosomal TRIM59 has an important role in intercellular communication for fostering an inflammatory microenvironment and promoting lung metastasis.

Curcumin inhibits zearalenone-induced apoptosis and oxidative stress in Leydig cells via modulation of the PTEN/Nrf2/Bip signaling pathway.

The toxic effect of zearalenone (ZEA) is not fully understood and there is an urgent need for the development of effective agents to protect against the toxic effects of ZEA. In this study, we detected whether curcumin (CUR) can reduce Leydig cells apoptosis induced by ZEA. The Effects of ZEA and CUR on cell viability was evaluated using a Cell Counting kit-8 assay (CCK-8). Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry. The protective effect of CUR on oxidative stress induced by ZEA was determined by ROS, MDA, T-SOD, GSH and GSH-Px levels. In addition, we also determined effects of key signaling pathways and proteins involved in the apoptotic, PI3K-AKT, Nrf2 and endoplasmic reticulum stress signaling pathways by Western blotting. The expressions of proteins (PTEN, AKT, p-AKT, Bax, Bcl-2, GRP78, CHOP, JNK, P-JNK, Caspase-12, Caspase-9, Caspase-3, Nrf2, Keap1 and HO-1) were measured. The experimental results showed that CUR can alleviate oxidative stress and apoptosis caused by ZEA through the PI3K-AKT, Nrf2 and endoplasmic reticulum stress signaling pathways. Our results provide a theoretical basis for molecular studies of ZEA toxicology and clinical application of CUR.

MOTS-c inhibits Osteolysis in the Mouse Calvaria by affecting osteocyte-osteoclast crosstalk and inhibiting inflammation.

The Mitochondrial-derived peptide MOTS-c has recently been reported as a 16-amino acid peptide regulating metabolism and homeostasis in different cells. However, its effects on immune cells and bone metabolism are rarely reported. Here we demonstrate that MOTS-c treatment in ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis mouse model alleviated bone erosion and inflammation. MOTS-c increased osteoprotegerin (OPG)/ receptor activator of nuclear factor kappa-B ligand (RANKL) ratio in osteocytes, leading to inhibition of osteoclastogenesis. In primary bone marrow macrophages (BMMs) MOTS-c alleviated STAT1 and NF-κB phosphorylation triggered by UHMWPE particles. Promoting ROS production or suppressing peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) by adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) repression blocked these anti-inflammatory effects of MOTS-c treatment. Taken together, these findings provide evidence that the small peptide inhibits osteoclastogenesis by regulating osteocyte OPG/RANKL secretion and suppressing inflammation via restraining NF-κB and STAT1 pathway. Moreover, its effects on NF-κB activation is dependent on the AMPK-PGC-1α-ROS axis, suggesting its potential use in osteolysis and other inflammation disorders.