Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
Abstract
Structural phase transitions serve as the basis for many functional applications including shape memory alloys (SMAs), switches based on metal-insulator transitions (MITs), etc. In such ...materials, lattice incompatibility between transformed and parent phases often results in a thermal hysteresis, which is intimately tied to degradation of reversibility of the transformation. The non-linear theory of martensite suggests that the hysteresis of a martensitic phase transformation is solely determined by the lattice constants, and the conditions proposed for geometrical compatibility have been successfully applied to minimizing the hysteresis in SMAs. Here, we apply the non-linear theory to a correlated oxide system (V
1−
x
W
x
O
2
), and show that the hysteresis of the MIT in the system can be directly tuned by adjusting the lattice constants of the phases. The results underscore the profound influence structural compatibility has on intrinsic electronic properties, and indicate that the theory provides a universal guidance for optimizing phase transforming materials.
Dynamical quantum phase transitions are closely related to equilibrium quantum phase transitions for ground states. Here, we report an experimental observation of a dynamical quantum phase transition ...in a spinor condensate with correspondence in an excited state phase diagram, instead of the ground state one. We observe that the quench dynamics exhibits a nonanalytical change with respect to a parameter in the final Hamiltonian in the absence of a corresponding phase transition for the ground state there. We make a connection between this singular point and a phase transition point for the highest energy level in a subspace with zero spin magnetization of a Hamiltonian. We further show the existence of dynamical phase transitions for finite magnetization corresponding to the phase transition of the highest energy level in the subspace with the same magnetization. Our results open a door for using dynamical phase transitions as a tool to probe physics at higher energy eigenlevels of many-body Hamiltonians.
Rapid worldwide spread of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic.
This review article provides emergency physicians with an overview of the most current understanding ...of COVID-19 and recommendations on the evaluation and management of patients with suspected COVID-19.
Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing COVID-19, is primarily transmitted from person-to-person through close contact (approximately 6 ft) by respiratory droplets. Symptoms of COVID-19 are similar to other viral upper respiratory illnesses. Three major trajectories include mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ARDS). Emergency physicians should focus on identifying patients at risk, isolating suspected patients, and informing hospital infection prevention and public health authorities. Patients with suspected COVID-19 should be asked to wear a facemask. Respiratory etiquette, hand washing, and personal protective equipment are recommended for all healthcare personnel caring for suspected cases. Disposition depends on patient symptoms, hemodynamic status, and patient ability to self-quarantine.
This narrative review provides clinicians with an updated approach to the evaluation and management of patients presenting to the emergency department with suspected COVID-19.
The role of autotransplantation in end-stage hepatic alveolar echinococcosis (AE) is unclear. We aimed to present our 15-case experience and propose selection criteria for autotransplantation. All ...patients were considered to have unresectable hepatic AE by conventional resection due to critical invasion to retrohepatic vena cava, hepatocaval region along with three hepatic veins, and the tertiary portal and arterial branches. All patients successfully underwent ex vivo extended right hepatectomy and autotransplantation without intraoperative mortality. The median autograft weight was 706 g (380–1000 g); operative time was 15.5 hours (11.5–20.5 hours); and anhepatic time was 283.8 minutes (180–435 min). Postoperative hospital stay was 32.3 days (12–60 days). Postoperative complication Clavien–Dindo grade IIIa or higher occurred in three patients including one death that occurred 12 days after the surgery due to acute liver failure. One patient was lost to follow-up after the sixth month. Thirteen patients were followed for a median of 21.6 months with no relapse. This is the largest reported series of patients with end-stage hepatic AE treated with liver autotransplantation. The technique requires neither organ donor nor postoperative immunosuppressant. The early postoperative mortality was low with acceptable morbidity. Preoperative precise assessment and strict patient selection are of utmost importance.
Topological order can be found in a wide range of physical systems, from crystalline solids, photonic meta-materials and even atmospheric waves to optomechanic, acoustic and atomic systems. ...Topological systems are a robust foundation for creating quantized channels for transporting electrical current, light, and atmospheric disturbances. These topological effects are quantified in terms of integer-valued 'invariants', such as the Chern number, applicable to the quantum Hall effect, or the Formula: see text invariant suitable for topological insulators. Here, we report the engineering of Rashba spin-orbit coupling for a cold atomic gas giving non-trivial topology, without the underlying crystalline structure that conventionally yields integer Chern numbers. We validated our procedure by spectroscopically measuring both branches of the Rashba dispersion relation which touch at a single Dirac point. We then measured the quantum geometry underlying the dispersion relation using matter-wave interferometry to implement a form of quantum state tomography, giving a Berry's phase with magnitude π. This implies that opening a gap at the Dirac point would give two dispersions (bands) each with half-integer Chern number, potentially implying new forms of topological transport.
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have gained increasingly global attention in recent years. Due to their unique amphiphilic properties and stability, PFASs are recognized as ...highly persistent, toxic, and environmentally bioaccumulative. Among several physicochemical technologies, adsorption has been extensively used and proved to be an effective method for removing PFASs from aqueous environment. In this review article, the technical feasibility of the use of different adsorbents, such as activated carbon, ion exchange resins, minerals, molecularly imprinted polymer (MIP), carbon nanotubes (CNTs), and a wide range of potentially low-cost biosorbents, for PFASs removal from water or wastewater is critically reviewed. The evaluation and comparison of their PFASs sorption behavior in terms of kinetics and isotherms is presented. The mechanisms involved in PFASs adsorption processes, such as diffusion, electrostatic interaction, hydrophobic interaction, ion exchange and hydrogen bond, are discussed. The effects of the parameters variability on sorption process are highlighted. Based on the literature reviewed, a few recommendations for future research on PFASs adsorption are also elaborated.
Capsule: The adsorption behavior and mechanisms of perfluoroalkyl and polyfluoroalkyl substances (PFASs) on various adsorbents are reviewed.
Display omitted
•Resins and CNTs exhibit higher adsorption capacity than other adsorbents.•Biosorbents have great potential for efficient PFAS removal with cost-effectiveness.•Adsorption mechanisms involve electrostatic interaction, hydrophobic interaction and ion exchange.•The environmental parameters can influence PFASs adoption performance.
The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and ...required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota and treatment with Akkermansia and Parabacteroides each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum, and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA/glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity, and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice.
Display omitted
•Changes in the gut microbiota are required for the anti-seizure effects of the KD•Specific KD-associated bacteria mediate and confer the anti-seizure effects of the KD•KD microbiota regulate amino acid γ-glutamylation and hippocampal GABA/glutamate
The beneficial effects of a ketogenic diet on epileptic seizures are mediated by the gut microbiome through their modulation of hippocampal GABA/glutamate ratios.
Estuaries have been sites of intensive human activities during the past century. Tracing the evolution of subaqueous topography in estuaries on a decadal timescale enables us to understand the ...effects of human activities on estuaries. Bathymetric data from 1955 to 2010 show that land reclamation decreased the subaqueous area of Lingding Bay, in the Pearl River estuary, by ~170 km
and decreased its water volume by 615 × 10
m
, representing a net decrease of 11.2 × 10
m
per year and indicating the deposition of approximately 14.5 Mt/yr of sediment in Lingding Bay during that period. Whereas Lingding Bay was mainly governed by natural processes with slight net deposition before 1980, subsequent dredging and large port engineering projects changed the subaqueous topography of the bay by shallowing its shoals and deepening its troughs. Between 2012 and 2013, continuous dredging and a surge of sand excavation resulted in local changes in water depth of ± 5 m/yr, far exceeding the magnitude of natural topographic evolution in Lingding Bay. Reclamation, dredging, and navigation-channel projects removed 8.4 Mt/yr of sediment from Lingding Bay, representing 29% of the sediment input to the bay, and these activities have increased recently.
Waning immunity and declining anatomic and physiologic defenses render the elder vulnerable to a wide range of infectious diseases. Clinical presentations are often atypical and muted, favoring ...global changes in mental status and function over febrile responses or localizing symptoms. This review encompasses early recognition, evaluation, and appropriate management of these common infections specifically in the context of elders presenting to the emergency department. With enhanced understanding and appreciation of the unique aspects of infections in the elderly, emergency physicians can play an integral part in reducing the morbidity and mortality associated with these often debilitating and life-threatening diseases.
PDF
