A flexible rotator-expanded molecular framework integrated strategy for improving microviscosity sensitivity of molecular rotor probes.

A novel approach was proposed to enhance the microviscosity sensitivity of molecular rotor probes by integrating flexible rotators and expanded molecular frameworks, addressing the crucial challenge of weakening microviscosity sensitivity in dilute solutions of macromolecules.

Intelligent extraction of reservoir dispatching information integrating large language model and structured prompts.

Reservoir dispatching regulations are a crucial basis for reservoir operation, and using information extraction technology to extract entities and relationships from heterogeneous texts to form triples can provide structured knowledge support for professionals in making dispatch decisions and intelligent recommendations. Current information extraction technologies require manual data labeling, consuming a significant amount of time. As the number of dispatch rules increases, this method cannot meet the need for timely generation of dispatch plans during emergency flood control periods. Furthermore, utilizing natural language prompts to guide large language models in completing reservoir dispatch extraction tasks also presents challenges of cognitive load and instability in model output. Therefore, this paper proposes an entity and relationship extraction method for reservoir dispatch based on structured prompt language. Initially, a variety of labels are refined according to the extraction tasks, then organized and defined using the Backus-Naur Form (BNF) to create a structured format, thus better guiding large language models in the extraction work. Moreover, an AI agent based on this method has been developed to facilitate operation by dispatch professionals, allowing for the quick acquisition of structured data. Experimental verification has shown that, in the task of extracting entities and relationships for reservoir dispatch, this AI agent not only effectively reduces cognitive burden and the impact of instability in model output but also demonstrates high extraction performance (with F1 scores for extracting entities and relationships both above 80%), offering a new solution approach for knowledge extraction tasks in other water resource fields.

Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

Lancao decoction alleviates cognitive dysfunction: A new therapeutic drug and its therapeutic mechanism.

BACKGROUND: Cognitive dysfunction (CD) is a neurodegenerative disease characterized primarily by the decline of learning and memory abilities. The physiological and pathological mechanisms of CD are very complex, which is mainly related to normal function of the hippocampus. Lancao decoction (LC) is a Chinese medicine formula, which has been used to treat neurodegenerative disorders. However, the potential of LC for the treatment of CD, as well as its underlying mechanisms, is unclear. PURPOSE: In the study, we aimed to reveal the functional and neuronal mechanisms of LC's treatments for CD in scopolamine-induced mice. METHODS: Gas chromatography (GC) was used to determine the stability of LC's extraction. CD model was established by the chronic induction of scopolamine (Scop, 1 mg/kg/day) for 1 week. Behavioral tests including morris water maze (MWM) and y-maze were used to evaluate learning and memory abilities of mice after LC's treatments. Immunofluorescence was used to detected the expressions of cFOS, Brdu and Ki67 after LC's treatments. Pharmacological blockade experiments explored the role of α-Amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in LC's treatments for CD and its relationships with regeneration, activities and differentiation of neurons. RESULTS: The results showed that LC was capable of improving spatial learning and memory and spontaneous alternating abilities in Scop-induced mice, which was similar to donepezil. LC could increase the number of cFOS positive cells, which was used as a marker of neuronal activity to upregulate by neuronal activities in hippocampus, but donepezil did not. Moreover, LC could strengthen neurogenesis and neuro-differentiation by increasing the number of Brdu and Ki67 positive cells in hippocampal dentate gyrus (DG), meanwhile, donepezil could only enhance the number of Ki67 positive cells. Transient inhibition of AMPAR by NBQX blunted the function of LC's treatment for CD and inhibited the enhanced effect of LC on Scop-induced hippocampal neuronal excitability and neurogenesis in mice. CONCLUSION: To sum up, our study demonstrated that LC had the function of treating CD by enhancing content of acetylcholine (ACh) to activate AMPAR, which further up-regulated neurogenesis and neuronal differentiation to strengthen neuroactivities in hippocampus.

Safety assessment of sand casting explosion accidents by testing cavity pressure of the sand mold to protect employee health.

Excessive cavity pressure may result in a sand casting explosion, and corresponding measures should be adopted to prevent these consequences. In this study, the pressure variations in the cavity were first investigated based upon on-site testing by taking the resin contents into consideration, and then the evolution characteristics of sand casting explosion accidents were analyzed in depth by system dynamics, chaos theory, and the bow-tie model. When the resin contents are 1.3 wt%, 1.4 wt%, and 1.5 wt%, the pressures of the gas vent increase by 27.0 Pa, 32.8 Pa, and 35.6 Pa, respectively. To reduce the pressure of the cavity, the resin content should be reduced. The evolutionary process of sand casting explosion accidents has a noticeable butterfly effect and randomness, whose occurrence is comprehensively affected by human, object, environment, management and emergency subsystems. The leading causes of sand casting explosion accidents mainly include the extensive gas evolution characteristics of foundry sand, cavity exhaust blockage, and inadequate safety monitoring. The leading consequences of sand casting explosion accidents mainly include casualties, secondary disasters, and social panic. The implications of these findings concerning sand casting explosion accidents can be regarded as the foundation for accident prevention in practice.

Nanocellulose based ultra-elastic and durable foams for smart packaging applications.

Foams with advanced sensing properties and excellent mechanical properties are promising candidates for smart packaging materials. However, the fabrication of ultra-elastic and durable foams is still challenging. Herein, we report a universal strategy to obtain ultra-elastic and durable foams by crosslinking cellulose nanofiber and MXene via strong covalent bonds and assembling the composites into anisotropic cellular structures. The obtained composite foam shows an excellent compressive strain of up to 90 % with height retention of 97.1 % and retains around 90.3 % of its original height even after 100,000 compressive cycles at 80 % strain. Their cushioning properties were systematically investigated, which are superior to that of wildly-used petroleum-based expanded polyethylene and expanded polystyrene. By employing the foam in a piezoelectric sensor, a smart cushioning packaging and pressure monitoring system is constructed to protect inner precision cargo and detect endured pressure during transportation for the first time.

Merazin hydrate produces rapid antidepressant effects by activating CaMKII to promote neuronal activities and proliferation in hippocampus.

In our previous studies, we demonstrated that merazin hydrate (MH) had rapid antidepressant effects, but the deep mechanism needed to be further investigated. In this study, we used depressive-like model, behavioral tests, molecular biology and pharmacological interventions to reveal the underlying mechanisms of MH's rapid antidepressants. We found that a single administration of MH was able to produce rapid antidepressant effects in chronic unpredictable mild stress (CUMS) exposed mice at 1 day later, similar to ketamine. Moreover, MH could not only significantly up-regulated the expressions of cFOS, but also obviously increased the number of Ki67 positive cells in hippocampal dentate gyrus (DG). Furthermore, we also found that the phosphorylated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) was significantly reduced by CUMS in hippocampus, which was also reversed by MH. In addition, pharmacological inhibition of CaMKII by using KN-93 (a CaMKII antagonist) blocked the MH's up-regulation of cFOS and Ki67 in hippocampal DG. To sum up, this study demonstrated that MH produced rapid antidepressant effects by activating CaMKII to promote neuronal activities and proliferation in hippocampus.

Acute lymphoblastic leukemia with central nervous system Aspergillus infection: A case report and literature review.

Ubiquitous in nature, Aspergillus rarely invades the brain to induce infection in general. However, in clinical practice, some patients with hematological malignancies or immunosuppression may suffer from Aspergillus infection of the central nervous system, which arises most commonly as a result of hematogenous dissemination from a pulmonary focus or direct extension from the paranasal sinus infection. Treatment is clinically challenging and the mortality rate is relatively high. Recently, a case diagnosed with acute lymphocytic leukemia was admitted to the Department of Neurosurgery, The First People's Hospital of Huzhou (First Affiliated Hospital of Huzhou University, Huzhou, China). During chemotherapy, space-occupying lesions were observed in the right occipital lobe of the patient, and lesion progression was captured. After treatment with surgery, an analysis of specimens collected from the patient was performed and was suggestive of Aspergillus infection. Following the symptomatic therapy with voriconazole, the patient's disease prognosis was favorable. The focus of infection due to pulmonary aspergillosis or Aspergillus sinusitis was not detected in the patient and the focus was not a common site of hematogenous infection. In addition, the patient exhibited no obvious clinical symptoms. In view of the above observations, the possibility of hospital-acquired infection was considered, to which clinicians should be alert.

Knowledge graph empowerment from knowledge learning to graduation requirements achievement.

A deep understanding of the relationship between the knowledge acquired and the graduation requirements is essential for students to precisely meet the graduation requirements and to become human resources with specific knowledge, skills and professionalism. In this paper, we define the ontology layer of the knowledge graph by deeply analyzing the relationship between graduation requirement, course and knowledge. Based on the implementation of the concept of Outcome Based Education, we use Knowledge extraction, fusion, reasoning techniques to construct a hierarchical knowledge graph with the main line of "knowledge-course-graduation requirements. In the process of knowledge extraction, in order to alleviate the huge labor overhead brought by traditional extraction methods, this paper adopts a transfer learning method to extract triadic knowledge using the multi-task framework EERJE, Finally, knowledge reasoning was also performed with the help of LLM to further expand the knowledge scope. The comprehensiveness, correctness and relatedness of the data were evaluated through the experiment, and the F1 value of the ternary group extraction was 87.76%, the accuracy rate of entity classification was 85.42%, the data coverage was more comprehensive, and the results showed that the data quality was better, and the knowledge graph constructed in this way can fully optimize the organization and management of teaching resources, help students intuitively and comprehensively grasp the correlation and difference between graduation requirements and various knowledge points, and let the Students can carry out personalized independent learning through the navigation mode of knowledge graph, strengthen their weak links, and complete the relevant graduation requirements, which effectively improves the degree of students' graduation requirements achievement. This new paradigm of knowledge graph enabled teaching is of reference significance for engineering education majors to improve the degree of graduation requirements achievement.

ACE2 Receptor: A Potential Pharmacological Target in COVID-19.

Studies have shown that injection of recombinant angiotensin-converting enzyme 2 (ACE2) significantly increased circulatory levels of ACE2 activity, reduced cardiac hypertrophy and fibrosis, and effectively lowered blood pressure. In addition, recombinant ACE2 ameliorated albuminuria and might contribute to renal protection. Meanwhile, potential pharmacological treatments based on ACE2 are attracting increasing attention from scientists following a growing understanding of the role of the ACE2 receptor in the pathogenesis of coronavirus disease 2019 (COVID-19). In this article, we comprehensively summarized the literature on the structure, distribution, and function of ACE2. More importantly, we draw a conclusion that ACE2 decoys such as sACE2, hrsACE2 and ACE2-derived peptides, drugs down-regulating the ACE2 or TMPRSS2 gene expression, and the application of epigenetic modifiers and Traditional Chinese Medicine might represent promising approaches for the future of COVID-19 treatment.

Multifunctional Hollow Porous Fe3O4@N-C Nanocomposites as Anodes of Lithium-Ion Battery, Adsorbents and Surface-Enhanced Raman Scattering Substrates.

At present, it is still a challenge to prepare multifunctional composite nanomaterials with simple composition and favorable structure. Here, multifunctional Fe3O4@nitrogen-doped carbon (N-C) nanocomposites with hollow porous core-shell structure and significant electrochemical, adsorption and sensing performances were successfully synthesized through the hydrothermal method, polymer coating, then thermal annealing process in nitrogen (N2) and lastly etching in hydrochloric acid (HCl). The morphologies and properties of the as-obtained Fe3O4@N-C nanocomposites were markedly affected by the etching time of HCl. When the Fe3O4@N-C nanocomposites after etching for 30 min (Fe3O4@N-C-3) were applied as the anodes for lithium-ion batteries (LIBs), the invertible capacity could reach 1772 mA h g-1 after 100 cycles at the current density of 0.2 A g-1, which is much better than that of Fe3O4@N-C nanocomposites etched, respectively, for 15 min and 45 min (948 mA h g-1 and 1127 mA h g-1). Additionally, the hollow porous Fe3O4@N-C-3 nanocomposites also exhibited superior rate capacity (950 mA h g-1 at 0.6 A g-1). The excellent electrochemical properties of Fe3O4@N-C nanocomposites are attributed to their distinctive hollow porous core-shell structure and appropriate N-doped carbon coating, which could provide high-efficiency transmission channels for ions/electrons, improve the structural stability and accommodate the volume variation in the repeated Li insertion/extraction procedure. In addition, the Fe3O4@N-C nanocomposites etched by HCl for different lengths of time, especially Fe3O4@N-C-3 nanocomposites, also show good performance as adsorbents for the removal of the organic dye (methyl orange, MO) and surface-enhanced Raman scattering (SERS) substrates for the determination of a pesticide (thiram). This work provides reference for the design and preparation of multifunctional materials with peculiar pore structure and uncomplicated composition.

A new Panax notoginseng Leaf Spot Caused by Boeremia linicola in Yunnan, China.

Panax notoginseng-also known as Tianqi and Sanqi-is one of the most highly valued medicinal perennial herbs in the world (Wang et al. 2016). In August 2021, leaf spot was observed on P. notoginseng leaves in Lincang sanqi base (23º43´10˝N, 100º7´32˝E, 13.33 hm2). Symptoms expanded from water soaked areas on the leaves to form irregular round or oval leaf spots with transparent or grayish-brown centers containing black granular matter, with an incidence of 10 to 20%. To identify the causal agent, ten symptomatic leaves were randomly selected from ten P. notoginseng plants. Symptomatic leaves were cut into small pieces (5 mm2) with asymptomatic tissue margins, disinfected in 75% ethanol for 30s and in 2% sodium hypochlorite for 3 min, and rinsed three times with sterile distilled water. The tissue portions were placed on potato dextrose agar (PDA) plates incubated at 20℃ with a 12 h light/dark photoperiod. Seven pure isolates were obtained with similar colony morphology, dark gray (top view) or taupe (back view) coloration, with flat and villous surfaces. Pycnidia were globose to subglobose, glabrous or with few mycelial outgrowths, dark brown to black, 22.46 to 155.94 (av. 69.57) µm × 18.20 to 130.5 (av. 57.65) µm (n=50) in size. Conidia were ellipsoidal to cylindrical, thinwalled, smooth, hyaline, aseptate, and measured 1.47 to 6.81 (av. 4.29) µm long and 1.01 to 2.97 (av. 1.98) µm thick (n=100). The isolated strains were preliminarily identified as Boeremia sp. based on the morphological characteristics of colonies and conidia. (Aveskamp et al. 2010; Schaffrath et al. 2021). To confirm pathogen identity, the total genomic DNA of two isolates (LYB-2 and LYB-3) was extracted using the T5 Direct PCR kit. The internal transcribed spacer (ITS), 28S large subunit nrRNA gene (LSU), and ß-tubulin (TUB2) gene regions were PCR-amplified using primers ITS1/ITS4, LR0Rf/LR5r, and BT2F/BT4R (Chen et al. 2015), respectively. Sequences have been deposited in GenBank (ON908942-ON908943 for ITS, ON908944-ON908945 for LSU, ON929285-ON929286 for TUB2). BLASTn searches of generated DNA sequences from 2 purified isolates (LYB-2 and LYB-3) against GenBank showed high similarity (>99%) with the sequences of Boeremia linicola. Moreover, a phylogenetic tree was constructed based on the neighbor-joining method in MEGA-X (Kumar et al. 2018) and revealed that the 2 isolates were closest to B. linicola (CBS 116.76). Pathogenicity tests were conducted with the 2 isolates (LYB-2 and LYB-3) as described by Cai et al. (2009) with slight modifications. Each isolate was inoculated with three healthy annual P. notoginseng plants, and each leaf was inoculated with three drops of conidia suspension (106 spores/mL). Three P. notoginseng plants inoculated with sterile water were used as controls. All plants were covered with plastic bags incubated in a greenhouse (20℃, 90%RH, 12 h light/dark photoperiod). Fifteen days post-inoculation, all inoculated leaves showed similar lesions, and the symptoms were identical to those in the field. The pathogen was reisolated from symptomatic leaf spots, and the colony characteristics were identical to the original isolates. Control plants remained healthy, and no fungus was re-isolated. Morphological characteristics, sequence alignment and pathogenicity tests confirmed that B. linicola was the cause of P. notoginseng leaf spot disease. This is the first report of B. linicola causing leaf spot on P. notoginseng in Yunnan, China. The identification of B. linicola as the causal agent of the observed leaf spot on P. notoginseng is critical to the prevention and control of this disease in the future.

Spatial-aware topic-driven-based image Chinese caption for disaster news.

Automatically generating descriptions for disaster news images could effectively accelerate the spread of disaster message and lighten the burden of news editors from tedious news materials. Image caption algorithms are remarkable for generating captions directly from the content of the image. However, current image caption algorithms trained on existing image caption datasets fail to describe the disaster images with fundamental news elements. In this paper, we developed a large-scale disaster news image Chinese caption dataset (DNICC19k), which collected and annotated enormous news images related to disaster. Furthermore, we proposed a spatial-aware topic driven caption network (STCNet) to encode the interrelationships between these news objects and generate descriptive sentences related to news topics. STCNet firstly constructs a graph representation based on objects feature similarity. The graph reasoning module uses the spatial information to infer the weights of aggregated adjacent nodes according to a learnable Gaussian kernel function. Finally, the generation of news sentences are driven by the spatial-aware graph representations and the news topics distribution. Experimental results demonstrate that STCNet trained on DNICC19k could not only automatically creates descriptive sentences related to news topics for disaster news images, but also outperforms benchmark models such as Bottom-up, NIC, Show attend and AoANet on multiple evaluation metrics, achieving CIDEr/BLEU-4 scores of 60.26 and 17.01, respectively.

Quantitative Measurement of Drug Release Dynamics within Targeted Organelles Using Förster Resonance Energy Transfer.

Measuring the release dynamics of drug molecules after their delivery to the target organelle is critical to improve therapeutic efficacy and reduce side effects. However, it remains challenging to quantitatively monitor subcellular drug release in real time. To address the knowledge gap, a novel gemini fluorescent surfactant capable of forming mitochondria-targeted and redox-responsive nanocarriers is designed. A quantitative Förster resonance energy transfer (FRET) platform is fabricated using this mitochondria-anchored fluorescent nanocarrier as a FRET donor and fluorescent drugs as a FRET acceptor. The FRET platform enables real-time measurement of drug release from organelle-targeted nanocarriers. Moreover, the obtained drug release dynamics can evaluate the duration of drug release at the subcellular level, which established a new quantitative method for organelle-targeted drug release. This quantitative FRET platform can compensate for the absent assessment of the targeted release performances of nanocarriers, offering in-depth understanding of the drug release behaviors at the subcellular targets.

Metabolic adaptation to high-starch diet in largemouth bass (Micropterus salmoides) was associated with the restoration of metabolic functions via inflammation, bile acid synthesis and energy metabolism.

A short-term 2-week (2w) and long-term 8-week (8w) feeding trial was conducted to investigate the effects of low-starch (LS) and high-starch (HS) diets on the growth performance, metabolism and liver health of largemouth bass (Micropterus salmoides). Two isonitrogenous and isolipidic diets containing two levels of starch (LS, 9·06 %; HS, 13·56 %) were fed to largemouth bass. The results indicated that HS diet had no significant effects on specific growth rate during 2w, whereas significantly lowered specific growth rate at 8w. HS diet significantly increased hepatic glycolysis and gluconeogenesis at postprandial 24 h in 2w. The hepatosomatic index, plasma alkaline phosphatase, total bile acid (TBA) levels, and hepatic glycogen, TAG, total cholesterol, TBA, and NEFA contents were significantly increased in the HS group at 2w. Moreover, HS diet up-regulated fatty acid and TAG synthesis-related genes and down-regulated TAG hydrolysis and ß-oxidation-related genes. Therefore, the glucolipid metabolism disorders resulted in metabolic liver disease induced by HS diet at 2w. However, the up-regulation of bile acid synthesis, inflammation and energy metabolism-related genes in 2w indicated that largemouth bass was still in a state of 'self-repair' response. Interestingly, all the metabolic parameters were returned to homoeostasis, with up-regulation of intestinal glucose uptake and transport-related genes, even hepatic histopathological analysis showed no obvious abnormality in the HS group in 8w. In conclusion, HS feed induced short-term acute metabolic disorder, but long-term metabolic adaptation to HS diet was related to repairing metabolism disorders via improving inflammatory responses, bile acid synthesis and energy metabolism. These results strongly indicated that the largemouth bass owned certain adaptability to HS diet.

Qishen Yiqi Dripping Pills for Cardiovascular Diseases: Effects and Mechanisms.

Qishen Yiqi Dripping Pills (QSYQ) is a compound of Chinese medicine, which has been used to treat coronary heart disease and cardiac dysfunction. Its natural components include astragaloside IV, flavonoids, danshensu, protocatechualdehyde, salvianolic acid B, salvianolic acid A, ginsenosides Rg1, ginsenosides Rb1, and essential oils, etc. It exerts effects of nourishing qi and promoting blood circulation to relieve pain. In this review, the bioactive components of QSYQ and its effects for treating cardiovascular diseases and possible mechanism were summarized, providing references for further study and clinical application of QSYQ.

Fabrication of SiCN(O) Aerogel Composites with Low Thermal Conductivity by Wrapping Mesoporous Aerogel Structures over Mullite Fibers.

Silicon-based ceramic aerogels obtained by the polymer pyrolysis route possess excellent thermophysical properties, but their poor mechanical properties limit their broader applicability in thermal insulation materials. Herein, SiCN(O) ceramic aerogels were prepared under the toughening effect of a crosslinker (hexamethylene diisocyanate, HDI), which maintains the structural integrity of the aerogel during the wet gel-to-aerogel conversion. The aerogel maintained a high surface area (88.6 m2 g-1) and large pore volume (0.21 cm3 g-1) after pyrolysis. Based on this, mullite-fiber-reinforced SiCN(O) aerogels composites with outstanding thermal insulation properties and better mechanical performance were synthesized via ambient pressure impregnation. Furthermore, the effect of the impregnation concentration on the mechanical and insulation properties of the composites was investigated. The results revealed that the composite prepared with a solution ratio of 95 wt.% exhibited a low density (0.11 g cm-3) and a low thermal conductivity (0.035 W m-1 K-1), indicating an ~30% enhancement in its thermal insulation performance compared to the mullite fiber; the mesoporous aerogel structures wrapped on the mullite fibers inhibited the gas thermal conduction inside the composites.

ANGPTL4 functions as an oncogene through regulation of the ETV5/CDH5/AKT/MMP9 axis to promote angiogenesis in ovarian cancer.

BACKGROUND: Angiopoietin-like 4 (ANGPTL4) is highly expressed in a variety of neoplasms and promotes cancer progression. Nevertheless, the mechanism of ANGPTL4 in ovarian cancer (OC) metastasis remains unclear. This study aimeds to explore whether ANGPTL4 regulates OC progression and elucidate the underlying mechanism. METHODS: ANGPTL4 expression in clinical patient tumor samples was determined by immunohistochemistry (IHC) and high-throughput sequencing. ANGPTL4 knockdown (KD) and the addition of exogeneous cANGPTL4 protein were used to investigate its function. An in vivo xenograft tumor experiment was performed by intraperitoneal injection of SKOV3 cells transfected with short hairpin RNAs (shRNAs) targeting ANGPTL4 in nude mice. Western blotting and qRT-PCR were used to detect the levels of ANGPTL4, CDH5, p-AKT, AKT, ETV5, MMP2 and MMP9 in SKOV3 and HO8910 cells transfected with sh-ANGPTL4 or shRNAs targeting ETV5. RESULTS: Increased levels of ANGPTL4 were associated with poor prognosis and metastasis in OC and induced the angiogenesis and metastasis of OC cells both in vivo and in vitro. This tumorigenic effect was dependent on CDH5, and the expression levels of ANGPTL4 and CDH5 in human OC werepositively correlated. In addition, CDH5 activated p-AKT, and upregulated the expression of MMP2 and MMP9. We also found that the expression of ETV5 was upregulated by ANGPTL4, which could bind the promoter region of CDH5, leading to increased CDH5 expression. CONCLUSION: Our data indicated that an increase in the ANGPTL4 level results in increased ETV5 expression in OC, leading to metastasis via activation of the CDH5/AKT/MMP9 signaling pathway.