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1.
Hematol Oncol Clin North Am ; 33(6): 1071-1093, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31668207

RESUMO

Nanotechnology has made remarkable contributions to clinical oncology. Nanotherapeutics and diagnostic tools have distinctive characteristics which allow them superior abilities to deliver therapeutics and imaging agents for radiation oncology. Compared to solid biopsies and imaging, the analysis of circulating tumor cells (CTCs) offers a more rapid, real-time, and less invasive method to monitor the dynamic molecular profiles of tumors. The potential of CTCs to be translated as a novel cancer biomarker has been demonstrated in numerous clinical studies. This review will discuss clinical applications of nanomaterials in radiation oncology and the implication of CTCs in cancer detection and monitoring.

3.
Physiol Behav ; : 112709, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655082

RESUMO

Maternal high-fat (HF) diet affects offspring's metabolic phenotype. Sweet taste is an important factor in promoting appetite. In order to determine the effects of maternal HF diet throughout gestation and lactation on taste sensitivity to sucrose in rat offspring, we measured conditioned aversion threshold for sucrose by conditioned taste aversion (CTA) associated with two-bottle choice tests, and measured mRNA expression of sweet taste receptors in taste buds. In male offspring, conditioned aversion threshold for sucrose lay between 0.007M and 0.009M in control group, while in those with HF dams, the threshold significantly increased to be between 0.011M and 0.02M. In female offspring, conditioned aversion threshold for sucrose lay between 0.003M and 0.005M in control group, whereas maternal HF diet increased it to be between 0.007M and 0.009M. Maternal HF diet increased T1R2 and T1R3 mRNA expression in taste buds of male offspring, while only increased T1R2 mRNA expression in female offspring. Both male and female offspring with HF dams had lower α-gustducin mRNA expression, whereas only male offspring with HF dams had lower OB-Rb mRNA expression in taste buds. Our data suggest that maternal HF diet decreased taste sensitivity to sucrose in both male and female offspring, which may be partly due to altered expression of sweet taste receptors and related downstream pathways in taste buds.

4.
FEBS J ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31618529

RESUMO

Crystallography has made a notable contribution to our knowledge of structural biology. For traditional crystallography experiments, the growth of crystals with large size and high quality is crucial, and it remains one of the bottlenecks. In recent years, the successful application of serial femtosecond crystallography (SFX) provides a new choice when only numerous microcrystals can be obtained. The intense pulsed radiation of X-ray free electron lasers (XFELs) enables the data collection of small-sized crystals, making the size of crystals no longer a limiting factor. The ultra-fast pulses of XFELs can achieve "diffraction before destruction" which effectively avoids radiation damage and realizes diffraction near physiological temperatures. More recently, the SFX has been expanded to serial crystallography (SX) that can additionally employ synchrotron radiation as the light source. In addition to the traditional ones, these techniques provide complementary opportunities for structural determination. The development of SX experiments strongly relies on the advancement of hardware including the sample delivery system, the X-ray source and the X-ray detector. Here, in this review, we categorize the existing sample delivery systems, summarize their progress, and propose their future prospectives.

5.
Theriogenology ; 142: 26-33, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31574397

RESUMO

Asiatic acid is a pentacyclic triterpene enriched in the medicinal herb Centella asiatica, and it has been suggested to possess free radical scavenging and anti-apoptotic properties. The purpose of the current study was to explore the effects of asiatic acid on porcine early-stage embryonic development and the potential mechanisms for any observed effects. The results showed that 10 µM asiatic acid supplementation during the in vitro culture period dramatically improved developmental competence in porcine embryos derived from parthenogenetic activation (PA), somatic cell nuclear transfer (SCNT) and in vitro fertilization (IVF). Further analysis revealed that asiatic acid attenuated H2O2-induced intracellular reactive oxygen species (ROS) generation. Notably, asiatic acid not only enhanced intracellular GSH levels but also attenuated mitochondrial dysfunction. Gene expression analysis revealed that asiatic acid upregulated expression of the antioxidant-related gene Sod-1 and the blastocyst formation related gene Cox-2, while downregulating expression of the apoptosis-related gene Caspase-9 in SCNT blastocysts. These results suggest that asiatic acid exerts beneficial effects on early embryonic development in porcine embryos and that asiatic acid may be useful for improving the in vitro production of porcine embryos.

6.
Dig Dis Sci ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562610

RESUMO

BACKGROUND: Endoscopic ablation of duodenal ampullary malignancy has not been fully assessed. AIMS: The study aimed to evaluate the efficacy and safety of Endoscopic retrograde cholangiopancreatograpy (ERCP)-guided radiofrequency ablation (RFA) for inoperable ampullary cancer. METHODS: Patients with inoperable ampullary cancer underwent ERCP-guided RFA from January 2012 to August 2017. RF energy (7-10 W) was delivered using bipolar RFA electrodes under endoscopic guidance. RFAs were repeated every 1-3 months until visible tumor was eliminated. All patients were followed up till June 2018, during which any biliary event was noted and managed endoscopically. RESULTS: Twenty-three patients underwent a median of two RFA sessions (range 1-6) at a median interval of 56 (range 35-90) days. Among 18 (78.3%) patients who received endoscopic re-evaluations, nine patients showed no remaining lesion and nine showed more than 50% tumor size reduction. During a median follow-up duration of 517 days (range 60-1836 days), eight (34.8%) patients required endoscopic re-interventions. The re-intervention rate at 6 months after RFA was 36.8%. Twelve patients were alive, among whom six required no biliary stenting. The accumulative mean survival was 1081 (95% CI 757.8-1404.0) days. RFA-related adverse events occurred in four cases (7.7%) including mild pancreatitis (1), bleeding (1), and late distal biliary stenosis (2). CONCLUSION: This pilot study shows that ERCP-guided RFA is safe to use and able to reduce tumor volume and re-interventions in patients with inoperable ampullary cancer.

7.
Biomed Environ Sci ; 32(8): 602-613, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31488236

RESUMO

OBJECTIVE: To comparatively study the toxicity of four metal-containing nanoparticles (MNPs) and their chemical counterparts to the air-blood barrier (ABB) permeability using an in vitro model. METHODS: ABB model, which was developed via the co-culturing of A549 and pulmonary capillary endothelium, was exposed to spherical CuO-NPs (divided into CuO-40, CuO-80, and CuO-100 based on particle size), nano-Al2O3 (sheet and short-rod-shaped), nano-ZnO, nano-PbS, CuSO4, Al2(SO4)3, Zn(CH3COO)2, and Pb(NO3)2 for 60 min. Every 10 min following exposure, the cumulative cleared volume (ΔTCL) of Lucifer yellow by the model was calculated. A clearance curve was established using linear regression analysis of ΔTCL versus time. Permeability coefficient (P) was calculated based on the slope of the curve to represent the degree of change in the ABB permeability. RESULTS: The results found the increased P values of CuO-40, CuO-80, sheet, and short-rod-shaped nano-Al2O3, Al2(SO4)3, and Pb(NO3)2. Among them, small CuO-40 and CuO-80 were stronger than CuO-100 and CuSO4; no difference was observed between Al2(SO4)3 and sheet and short-rod-shaped nano-Al2O3; and nano-PbS was slightly weaker than Pb(NO3)2. So clearly the MNPs possess diverse toxicity. CONCLUSION: ABB permeability abnormality means pulmonary toxicity potential. More studies are warranted to understand MNPs toxicity and ultimately control the health hazards.

8.
Surg Radiol Anat ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486863

RESUMO

BACKGROUND: Transverse ligament tubercles are unique structures that maintain the stability of the upper cervical spine. However, the density variations of tubercles in different clinical contexts or populations have not been carefully studied through multidetector computed tomography (MDCT). PURPOSE: This study aimed to evaluate the relationship between density variations in the transverse ligament tubercles, as measured through multidetector computed tomography (MDCT), with age, gender, or laterality. METHODS: A cohort of 339 Chinese patients that underwent MDCT in the head or neck were recruited. The patients were divided into eight age groups. The densities of the bilateral transverse ligament tubercles were classified through MDCT, and the potential relationship between the density of the tubercles and the age, gender, or laterality was analyzed. RESULTS: Based on MDCT findings, four different density types of tubercles were identified (type 0-III). Our data suggest that the density of tubercles increased with age (χ2 = 637.7, p < 0.05). However, the density of tubercles did not correlate with laterality (male: t = 0.217, p > 0.05, female: t = 1.448, p > 0.05) or gender (χ2 = 5.706, p > 0.05). CONCLUSIONS: The density of the transverse ligament tubercles, as measured through MDCT, shows a stereotyped dynamic pattern, i.e., it apparently increases with age, but neither gender nor laterality significantly contribute to these changes.

9.
JAMA Neurol ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31545352

RESUMO

Importance: Identifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices. Objective: To characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation and during follow-up in an inception cohort of prospectively monitored children with acquired demyelination. Design, Setting, and Participants: In this prospective cohort study, study participants were recruited from July 2004 to February 2017 through the multicenter Canadian Pediatric Demyelinating Disease Study. Inclusion criteria included (1) incident central nervous system demyelination, (2) at least 1 serum sample obtained within 45 days from onset, and (3) complete clinical information. Of 430 participants with acquired demyelinating syndrome recruited, 274 were included in analyses. Of 156 excluded participants, 154 were excluded owing to missing baseline samples and 2 owing to incomplete clinical information. Data were analyzed from May to October 2018. Main Outcomes and Measures: Presence of anti-MOG antibodies was blindly assessed in serial samples collected over a median of 4 years. Clinical, magnetic resonance imaging, and cerebrospinal fluid features were characterized at presentation, and subsequent disease course was assessed by development of new brain magnetic resonance imaging lesions, total lesion volume at last evaluation, annualized relapse rates, Expanded Disability Status Scale score and visual functional score at 4 years, and any disease-modifying treatment exposure. Results: Of the 274 included participants, 140 (51.1%) were female, and the median (interquartile range) age of all participants was 10.8 (6.2-13.9) years. One-third of children were positive for anti-MOG antibodies at the time of incident demyelination. Clinical presentations included a combination of optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis for 81 of 84 anti-MOG antibody-positive children (96%). Brain lesions were present in 51 of 76 anti-MOG antibody-positive participants (67%), but magnetic resonance imaging characteristics differed with age at presentation. Complete resolution of baseline lesions was observed in 26 of 49 anti-MOG antibody-positive participants (53%). On serial serum analysis, 38 of 67 participants (57%) who were seropositive at onset became seronegative (median time to conversion, 1 year). Among all participants who were positive for anti-MOG antibodies at presentation, clinical relapses occurred in 9 of 24 children (38%) who remained persistently seropositive and in 5 of 38 children (13%) who converted to seronegative status. Conclusions and Relevance: Myelin oligodendrocyte glycoprotein antibodies are common in children with acquired demyelinating syndrome and are transient in approximatively half of cases. Even when persistently positive, most anti-MOG antibody-positive children experience a monophasic disease. The presence of anti-MOG antibodies at the time of incident demyelination should not immediately prompt the initiation of long-term immunomodulatory therapy.

10.
Eur J Immunol ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31411745

RESUMO

MicroRNA 182 is important for the clonal expansion of CD4+ T cells (Th) following IL-2 stimulation and is a potential therapeutic target for autoimmune diseases. In the present study, we investigated the role of microRNA 182 in the differentiation of pro-inflammatory CD4+ T helper cell by overexpressing or silencing microRNA 182 expression both in in vivo and in vitro settings. We report that in the studied Chinese cohort, microRNA 182 is upregulated in patients with relapse and remitting multiple sclerosis (RRMS) and this upregulation is associated with increased IFN-γ producing CD4+ Th1 cells in the circulation. In the murine experimental autoimmune encephalomyelitis (EAE) model, global microRNA 182 overexpression exacerbates clinical symptoms and results in augmented CD4+ IFN-γ+ Th1 and CD4+ IL-17+ Th17 differentiation in vivo. Addition of microRNA 182 mimics in vitro represses both the protein expression and transcriptional activity of hypoxia induced factor 1α (HIF-1α) but increases the level of IFN-γ transcripts in sorted murine CD4+ T cells. Together, our results provide evidence that microRNA 182 may be one of the transitional hubs contribution to regulate Th cells expansion in response to self-antigens and differentiation of antigen specific Th cells during the progression of autoimmune inflammations.

11.
J Vis Exp ; (149)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31380834

RESUMO

Protein-nucleic acid interactions play important roles in biological processes such as transcription, recombination, and RNA metabolism. Experimental methods to study protein-nucleic acid interactions require the use of fluorescent tags, radioactive isotopes, or other labels to detect and analyze specific target molecules. Biotin, a non-radioactive nucleic acid label, is commonly used in electrophoretic mobility shift assays (EMSA) but has not been regularly employed to monitor protein activity during nucleic acid processes. This protocol illustrates the utility of biotin labeling during in vitro enzymatic reactions, demonstrating that this label works well with a range of different biochemical assays. Specifically, in alignment with previous findings using radioisotope 32P-labeled substrates, it is confirmed via biotin-labeled EMSA that MEIOB (a protein specifically involved in the meiotic recombination) is a DNA-binding protein, that MOV10 (an RNA helicase) resolves biotin-labeled RNA duplex structures, and that MEIOB cleaves biotin-labeled single-stranded DNA. This study demonstrates that biotin is capable of substituting 32P in various nucleic acid-related biochemical assays in vitro.

12.
Environ Sci Technol ; 53(17): 10227-10235, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31408326

RESUMO

The detection of soluble Mn(III) is typically accomplished using strong complexing agents to trap Mn(III), but the generation of soluble Mn(III) induced by strong complexing agents has seldom been considered. In this study, pyrophosphate (PP), a nonredox active ligand, was chosen as a typical Mn(III) chelating reagent to study the influence of ligands on soluble Mn(III) formation in reactions involving Mn oxides and Mn(VII). The presence of excess PP induced the generation of soluble Mn(III)-PP from α- and δ-MnO2 and led to the conproportionation reaction of α-, ß-, δ-, or colloidal MnO2 with Mn(II) at pH 7.0. Compared to MnO2 minerals, colloidal MnO2 showed much higher reactivity toward Mn(II) in the presence of PP and the conproportionation rate of colloidal MnO2 with Mn(II) elevated with increasing PP dosage and decreasing pH. The generation of Mn(III) was not observed in MnO4-/S2O32- or MnO4-/NH3OH+ system without PP while the introduction of excess PP induced the generation of Mn(III)-PP. Thermodynamic calculation results were consistent with the experimental observations. These findings not only provide evidence for the unsuitability of using strong ligands in quantification of soluble Mn(III) in manganese-involved redox reactions, but also advance the understanding of soluble Mn(III) generation in aquatic environment.

13.
Biomaterials ; 221: 119413, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31419650

RESUMO

Natural particles ranging from various cell membranes to nascent proteins are highly optimized for their specific functions in vivo and possess features that are desired in drug delivery carriers. However, the current endeavor in research on bioparticles is still seeking the appropriate strategy to shield multiple agents and circumvent biological hurdles. These issues have propelled the advancement of lipid-polymer hybrid nanocarriers, which could be employed as drug reservoirs and strive to meet these expectations. We thereby proposed functionalized biopeptide-lipid hybrid particles, which were applied to encapsulating a PLGA polymeric core together with indocyanine green (ICG) and packaged by a lipoprotein-inspired structural shell. To initiate precision tumor-penetrating performance, tLyP-1-fused apolipoprotein A-I-mimicking peptides (D4F) were exploited to impart tumor-homing and tumor-penetrating biological functions. The sub-100 nm drug vehicle possessed a long circulation time with uniform mono-dispersity but was stable enough to navigate freely, penetrate deeply into tumors and deliver its cargoes to the targeted sites. Moreover, ICG-encapsulated penetrable polymeric lipoprotein particles (PPL/ICG) could realize real-time fluorescence/photoacoustic imaging for monitoring in vivo dynamic distribution. Upon near-infrared (NIR) laser irradiation, PPL/ICG demonstrated a highly efficient phototherapeutic effect to eradicate orthotopic xenografted tumors, resulting in an 88.77% decrease from the initial tumor volume and inhibited tumor metastasis with good biosafety. Therefore, the described bio-strategy opens new avenues for creating polymeric lipoproteins with varied hybrid functionalities, which may be applied to provide a basis and inspiration for improved nanoparticle-based precision theranostic nanoplatforms.

14.
Mol Cell Biochem ; 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31446617

RESUMO

Atherosclerosis plays an important role in the pathology of coronary heart disease, cerebrovascular disease, and systemic vascular disease. Long non-coding RNAs (lncRNAs) are involved in most biological processes and are deregulated in many human diseases. However, the expression alteration and precise role of lncRNAs during atherosclerosis are unknown. We report here the systematic profiling of lncRNAs and mRNAs in an ApoE-deficient (ApoE-/-) mouse model of atherosclerosis. Clariom D solutions for the mouse Affymetrix Gene Chip were employed to analyze the RNAs from control and ApoE-/- mice. The functions of the differentially expressed mRNAs and lncRNAs and the relationships of their expression with atherosclerosis were analyzed by gene ontology, co-expression network, pathway enrichment, and lncRNA target pathway network analyses. Quantitative real-time PCR (QRT-PCR) was used to determine the expression of mRNAs and lncRNAs. A total of 2212 differentially expressed lncRNAs were identified in ApoE-/- mice, including 1186 up-regulated and 1026 down-regulated lncRNAs (|FC| ≥ 1.1, p < 0.05). A total of 1190 differentially expressed mRNAs were found in the ApoE-/- mice with 384 up-regulated and 806 down-regulated (|FC| ≥ 1.1, p < 0.05). Bioinformatics analyses demonstrated extensive co-expression of lncRNAs and mRNAs and concomitant deregulation of multiple signaling pathways associated with the initiation and progression of atherosclerosis. The identified differentially expressed mRNAs and lncRNAs as well as the related signaling pathways may provide systematic information for understanding the pathogenesis and identifying biomarkers for the diagnosis, treatment, and prognosis of atherosclerosis.

15.
Brain Imaging Behav ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31435899

RESUMO

Asymmetry has been proved to exist in the human brain structure, function and behavior. Most of the existing brain asymmetry findings are originated from the western populations, while studies about the brain structural and functional asymmetries in East Asians are limited. Extensive evidence suggested that cultural differences, e.g. education and language, may lead to differences in brain structure and function between races. Therefore, we hypothesized that differences in brain structural asymmetries exist between East Asians and Westerners. In this study, we performed a comprehensive surface-based morphometric (SBM) analysis of brain asymmetries in cortical thickness, volume and surface area in two well-matched groups of right-handed, Chinese (n = 45) and Caucasian (n = 45) young male adults (age = 22-29 years). Our results showed consistent inter-hemispheric asymmetries in the three brain morphological measures in multiple brain regions in the Chinese young adults, including the temporal, frontal, parietal, occipital, insular cortices and the cingulate gyrus. Comparing with the Caucasians, the Chinese group showed greater structural asymmetry in the frontal, temporal, occipital and insular cortices, and smaller asymmetry in the parietal cortex and cingulate gyrus. These findings could provide a new neuroanatomical basis for understanding the distinctions between East Asian and Caucasian in brain functional lateralization.

16.
Int Immunopharmacol ; 75: 105822, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31437793

RESUMO

Metformin, the most widely used medicine for type 2 diabetes, displays anti-inflammatory functions via activating AMP-activated protein kinase (AMPK). Circulating autoantibodies and disequilibrium of helper T cells and regulatory T cells are pathological hallmarks of myasthenia gravis (MG). Rectify the imbalance of different T cell populations has become an important therapeutic strategy to treat MG. In this study, we assessed the effect of metformin on the development of autoimmunity using an experimental autoimmune myasthenia gravis (EAMG) rat model. We first provided evidence that oral administration of metformin attenuated the onset of EAMG. This effect was accompanied by a substantial decrease of circulating auto-antibody levels with no effect on blood glucose level. While metformin treatment in vitro showed little effect on inducible Treg, metformin strongly inhibited Th17 cell differentiation through the increase of reactive oxygen species and AMPK. Furthermore, an attenuation of antigen-induced IgG2b antibody production by two different doses of metformin was also observed in the AChR-specific recall response. In conclusion, the above results indicate that metformin may have therapeutic value for the clinical treatment of MG.

17.
Water Sci Technol ; 80(1): 144-152, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31461431

RESUMO

Nitrogen removal is an obstacle for the wide application of wastewater ecological soil infiltration (WESI) system in domestic wastewater treatment. In this study, matrix dissolved oxygen (DO), nitrogen removal and nitrous oxide (N2O) emission in aerated pilot WESI systems were investigated under different aeration times (1, 2, 3, 4 and 6 h/d) and aeration rates (1, 2, 3 and 4 L/min). The results showed that aerobic conditions in upper matrix and anoxic or anaerobic conditions in the subsequent matrix were developed in an aerated/non-aerated cycle at the optimal aeration condition of aeration time of 4 h/d and aeration rate of 3 L/min. Simultaneously, high removal efficiency of chemical oxygen demand (COD) (97.9%), NH4+-N (98.2%), total nitrogen (TN) (90.7%) and low N2O emission rate (13.2 mg/(m2 d)) were obtained. The results would provide optimal aeration parameters for application of intermittent aerated WESI systems.


Assuntos
Nitrogênio/análise , Óxido Nitroso , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias , Desnitrificação , Solo
18.
Plant Signal Behav ; 14(11): 1659706, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31462133

RESUMO

In Arabidopsis, the floral meristem is essential for the production of floral organs. The floral meristem is initially maintained to contribute cells for floral organ formation. However, this stem cell activity needs be completely terminated at a certain floral developmental stage to ensure the proper development of floral reproductive organs. Here, we have reviewed recent findings on the complex regulation of floral meristem activities, which involve signaling cascades, transcriptional regulation, epigenetic mechanisms and hormonal control for floral meristem determinacy in Arabidopsis.

19.
Opt Lett ; 44(15): 3861-3864, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31368987

RESUMO

Here, on a platform of two split-ring resonator (SRR) disks in the microwave regime, we have numerically and experimentally investigated the coupling of toroidal localized spoof surface plasmons (LSSPs). The coupling effect is investigated both theoretically and experimentally. We observe that magnetic dipole coupling exists in the toroidal LSSPs coupling and causes a rearrangement of the toroidal LSSPs, which suppresses the propagation of toroidal LSSPs. To realize the propagation of toroidal LSSPs, we introduce conductive coupling into the SRR disks. The conductive coupling can correct magnetic dipole coupling and enhance toroidal LSSPs coupling. Both numerical simulations and experiments are in good agreement. The toroidal LSSPs can be effectively propagated, even in the three right-angle-bent SRR disks. This study paves the way toward a better understanding of toroidal LSSPs coupling and finds many applications in the transfer of electromagnetic energy using toroidal moments.

20.
Soft Matter ; 15(35): 6938-6945, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31432887

RESUMO

Collective cell migration in 3D extracellular matrix (ECM) is crucial to many physiological and pathological processes. Migrating cells can generate active pulling forces via actin filament contraction, which are transmitted to the ECM fibers and lead to a dynamically evolving force network in the system. Here, we elucidate the role of this force network in regulating collective cell behaviors using a minimal active-particle-on-network (APN) model, in which active particles can pull the fibers and hop between neighboring nodes of the network following local durotaxis. Our model reveals a dynamic transition as the particle number density approaches a critical value, from an "absorbing" state containing isolated stationary small particle clusters, to an "active" state containing a single large cluster undergoing constant dynamic reorganization. This reorganization is dominated by a subset of highly dynamic "radical" particles in the cluster, whose number also exhibits a transition at the same critical density. The transition is underlaid by the percolation of "influence spheres" due to the particle pulling forces. Our results suggest a robust mechanism based on ECM-mediated mechanical coupling for collective cell behaviors in 3D ECM.

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