Explore the vast range of titles available.

Metastasis is a multistep process that accounts for the majority of cancer-related death. By the end of metastasize dissemination, circulating tumor cells (CTC) need to extravasate the blood vessels at metastatic sites to form new colonization. Although cancer cell extravasation is a crucial step in cancer metastasis, it has not been successfully targeted by current anti-metastasis strategies due to the lack of a thorough understanding of the molecular mechanisms that regulate this process. This review focuses on recent progress in cancer extravasation visualization techniques, including the development of both in vitro and in vivo cancer extravasation models, that shed light on the underlying mechanisms. Specifically, multiple cancer extravasation stages, such as the adhesion to the endothelium and transendothelial migration, are successfully probed using these technologies. Moreover, the roles of different cell adhesive molecules, chemokines, and growth factors, as well as the mechanical factors in these stages are well illustrated. Deeper understandings of cancer extravasation mechanisms offer us new opportunities to escalate the discovery of anti-extravasation drugs and therapies and improve the prognosis of cancer patients.

Cardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the pericardial cavity as a natural “mold” for in situ cardiac patch formation after intrapericardial injection of therapeutics in biocompatible hydrogels. In rodent models of myocardial infarction, we demonstrate that intrapericardial injection is an effective and safe method to deliver hydrogels containing induced pluripotent stem cells-derived cardiac progenitor cells or mesenchymal stem cells-derived exosomes. After injection, the hydrogels form a cardiac patch-like structure in the pericardial cavity, mitigating immune response and increasing the cardiac retention of the therapeutics. With robust cardiovascular repair and stimulation of epicardium-derived cells, the delivered therapeutics mitigate cardiac remodeling and improve cardiac functions post myocardial infarction. Furthermore, we demonstrate the feasibility of minimally-invasive intrapericardial injection in a clinically-relevant porcine model. Collectively, our study establishes intrapericardial injection as a safe and effective method to deliver therapeutic-bearing hydrogels to the heart for cardiac repair. Current routes to deliver therapeutics to the heart are normally invasive or difficult to perform. Here the authors develop intrapericardial injection as an efficient, easy-to-perform and minimally invasive method to deliver therapeutics for cardiac repair.

Injection molding has been widely used in the mass production of high-precision products. The finished products obtained through injection molding must have a high quality. Machine parameters do not accurately reflect the molding conditions of the polymer melt; thus, the use of machine parameters leads to erroneous quality judgments. Moreover, the cost of mass inspections of finished products has led to strict restrictions on comprehensive quality testing. Therefore, an automatic quality inspection that provides effective and accurate quality judgment for each injection-molded part is required. This study proposes a multilayer perceptron (MLP) neural network model combined with quality indices for performing fast and automatic prediction of the geometry of finished products. The pressure curves detected by the in-mold pressure sensor, which reflect the flow state of the melt, changes in various indicators and molding quality, were considered in this study. Furthermore, the quality indices extracted from pressure curves with a strong correlation with the part quality were input into the MLP model for learning and prediction. The results indicate that the training and testing of the first-stage holding pressure index, pressure integral index, residual pressure drop index and peak pressure index with respect to the geometric widths were accurate (accuracy rate exceeded 92%), which demonstrates the feasibility of the proposed method.

Background Parkinson’s disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota. Results The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice. Conclusions Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. CoKvBsES-WQ_2hkhyhEj9X Video abstract

A series of undrained cyclic triaxial tests were carried out to study the nonplastic fines on the cyclic behaviour of saturated sand-fines mixtures. The influences of the fines content (FC), global void ratio (e), and relative density (Dr) were considered. The results show that the cyclic resistance ratio (CRR) of the mixtures firstly decreases and then increases, finally stabilizing with increasing FC when the samples are prepared at a constant Dr. The CRR reaches its minimum when the FC is 20%. However, the CRR decreases and then increases with increasing FC when the samples are prepared at a constant e. The CRR reaches its minimum when the FC is at 30%. The CRR of the mixtures increases with increasing Dr when the FC is given. A single Dr or e cannot describe the dense state of the mixture effectively. A new index, Dr/e, is proposed in this study to describe the dense state of the mixtures. A semiempirical model is proposed to evaluate the CRR of the mixtures using the parameters of Dr/e and FC of the mixture based on the back analysis method. The applicability of the model is verified by the test data from this study and other scholars. In addition, the parameters of Dr/e and FC of the mixture can be obtained from basic geotechnical tests, which is convenient for the application of the model.

The Taiwan Strait contains a vast potential for wind energy. However, the power grid balance is challenging due to wind energy’s uncertainty and intermittent nature. Wind speed forecasting reduces this risk, increasing the penetration rate. Machine learning (ML) models are adopted in this study for the short-term prediction of wind speed based on the complex nonlinear relationships among wind speed, terrain, air pressure, air temperature, and other weather conditions. Feature selection is crucial for ML modeling. Finding more valuable features in observations is the key to improving the accuracy of prediction models. The random forest method was selected because of its stability, interpretability, low computational cost, and immunity to noise, which helps maintain focus on investigating the essential features from vast data. In this study, several new exogenous features were found on the basis of physics and the spatiotemporal correlation of surrounding data. Apart from the conventional input features used for wind speed prediction, such as wind speed, wind direction, air pressure, and air temperature, new features were identified through the feature importance of the random forest method, including wave height, air pressure difference, air-sea temperature difference, and hours and months, representing the periodic components of time series analysis. The air–sea temperature difference is proposed to replace the wind speed difference to represent atmosphere stability due to the availability and adequate accuracy of the data. A random forest and an artificial neural network model were created to investigate the effectiveness and generality of these new features. Both models are superior to persistence models and models using only conventional features. The random forest model outperformed all models. We believe that time-consuming and tune-required sophisticated models may also benefit from these new features.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 ‘don’t eat me’ signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery. Early-stage liver metastasis of pancreatic ductal adenocarcinoma (PDAC) makes radical surgery not efficacious. Here, the authors show that MLKL-driven necroptosis contributes to PDAC early-stage metastasis by inducing tumour CD47 upregulation and macrophage extracellular traps formation.

This study aimed to investigate the ameliorative effect of the polysaccharides of Panax quinquefolius (WQP) on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice and to explore its mechanism. Male C57BL/6J mice were randomly divided into the control group (C), model group (DSS), positive control mesalazine (100 mg/kg, Y) group, and low (50 mg/kg, L), medium (100 mg/kg, M) and high dose (200 mg/kg, H) of WQP groups. The UC model was induced by free drinking water with 2.5% DSS for 7 days. During the experiment, the general condition of the mice was observed, and the disease activity index (DAI) was scored. The conventional HE staining was used to observe pathological changes in mice’s colon, and the ELISA method was used to detect the levels of interleukin-6 (IL-6), IL-4, IL-8, IL-10, IL-1β and tumor necrosis factor-α (TNF-α) in mice’s colon. The changes in gut microbiota in mice were detected by high-throughput sequencing; the concentration of short-chain fatty acids (SCFAs) was determined by gas chromatography; the expression of related proteins was detected by Western blot. Compared with the DSS group, the WQP group showed a significantly lower DAI score of mice and an alleviated colon tissue injury. In the middle- and high-dose polysaccharides groups, the levels of pro-inflammatory cytokines IL-6, IL-8, IL-1β and TNF-α in the colonic tissue were significantly decreased ( P <0.05), while the levels of IL-4 and IL-10 were significantly increased ( P <0.05). The 16S rRNA gene sequencing results showed that different doses of WQP could regulate the composition and diversity of gut microbiota and improve its structure. Specifically, at the phylum level, group H showed an increased relative abundance of Bacteroidetes and a decreased relative abundance of Firmicutes compared with the DSS group, which was closer to the case in group C. At the family level, the relative abundance of Rikenellaceae in L, M and H groups increased significantly, close to that in group C. At the genus level, the relative abundance of Bacteroides , Shigella and Oscillospira in the H group increased significantly, while that of Lactobacillus and Prevotella decreased significantly. The high-dose WQP group could significantly increase the contents of acetic acid, propionic acid, butyric acid, and total SCFAs. Different doses of WQP also increased the expression levels of tight junction proteins ZO-1, Occludin and Claudin-1. To sum up, WQP can regulate the gut microbiota structure of UC mice, accelerate the recovery of gut microbiota, and increase the content of Faecal SCFAs and the expression level of tight junction proteins in UC mice. This study can provide new ideas for the treatment and prevention of UC and theoretical references for the application of WQP.

Pleural empyema is an inflammatory condition characterized by accumulation of pus inside the pleural cavity, which is usually followed by bacterial pneumonia. During the disease process, the pro-inflammatory and pro-fibrotic cytokines in the purulent pleural effusion cause proliferation of fibroblasts and deposition of extracellular matrix, which lead to fibrin deposition and fibrothorax. Urokinase instillation therapy through a chest drainage tube is frequently used for fibrinolysis in patients with empyema. However, urokinase treatment requires multiple instillation (2-3 times per day, for 4-8 days) and easily flows out from the chest drainage tube due to its high water solubility. In this in vitro study, we developed a thermo-responsive hydrogel based on poloxamer 407 (P407) combined with hyaluronic acid (HA) for optimal loading and release of urokinase. Our results show that the addition of HA to poloxamer gels provides a significantly more compact microstructure, with smaller pore sizes (**p < 0.001). The differential scanning calorimetry (DSC) profile revealed no influence on the micellization intensity of poloxamer gel by HA. The 25% poloxamer-based gel was significantly superior to the 23% poloxamer-based gel, with slower gel erosion when comparing the 16th hour residual gel weight of both gels (*p < 0.05; **p < 0.001). The 25% poloxamer-HA gel also exhibited a superior urokinase release profile and longer release time. A Fourier-transform infrared spectroscopy (FT-IR) study of the P407/HA hydrogel showed no chemical interactions between P407 and HA in the hydrogel system. The thermoresponsive P407/HA hydrogel may have a promising potential in the loading and delivery of hydrophilic drugs. On top of that, in vitro toxicity test of this combination demonstrates a lower toxicity.

Developing heterogeneous photocatalysts for the applications in harsh conditions is of high importance but challenging. Herein, by converting the imine linkages into quinoline groups of triphenylamine incorporated covalent organic frameworks (COFs), two photosensitive COFs, namely TFPA-TAPT-COF-Q and TFPA-TPB-COF-Q, are successfully constructed. The obtained quinoline-linked COFs display improved stability and photocatalytic activity, making them suitable photocatalysts for photocatalytic reactions under harsh conditions, as verified by the recyclable photocatalytic reactions of organic acid involving oxidative decarboxylation and organic base involving benzylamine coupling. Under strong oxidative condition, the quinoline-linked COFs show a high efficiency up to 11831.6 μmol·g −1 ·h −1 and a long-term recyclable usability for photocatalytic production of H 2 O 2 , while the pristine imine-linked COFs are less catalytically active and easily decomposed in these harsh conditions. The results demonstrate that enhancing the linkage robustness of photoactive COFs is a promising strategy to construct heterogeneous catalysts for photocatalytic reactions under harsh conditions. The development of heterogeneous photocatalysts applicable under harsh conditions is challenging. Here the authors report the conversion of imine linkages into quinoline groups in triphenylamine incorporated photosensitive covalent organic frameworks to develop robust heterogeneous photocatalysts for photocatalytic applications in harsh conditions.