Search

Background/aimsEsophageal cancer (EC) is a prevalent malignancy worldwide and is ranked as the sixth most common cause of cancer-related deaths, where nearly half of the new cases are reported in China annually. The detection of esophageal cancer (EC) is crucial for improving patient survival.However, EEC is a highly aggressive form of cancer with a poor prognosis, even among experienced endoscopists. Therefore, computer-aided diagnosis (CAD) has emerged as a valuable tool to assist endoscopists in the accurate and rapid detection of EEC.MethodsWe have developed a novel three-way fusion CAD system for detecting EEC, which allows physicians to take a comprehensive approach by investigating both local and overall boundaries in the clinical setting.ResultsIn terms of achieving an accurate treatment boundary in clinical practice, we obtained a top performance of 0.9236 mAP on ME-NBI from the local perspective using a novel dual-annotation method that we innovated. The treatment boundary mAP should be even higher than this by definition. From the overall perspective, we also achieved a top performance of 0.862 mAP on LCE.ConclusionsOur three-way fusion CAD system has demonstrated excellent diagnostic performance for EEC detection using deep learning, providing accurate treatment boundaries on both image and patient level. This shows great potential for clinical application. Moving forward, we plan to collect and analyze patient data from a broader area to achieve real-time performance in clinical settings.

Benzisothiazole dioxide compound was reported to agonize HIF-2 stabilization and improve EPO production, thus conceiving a potential strategy to treat disease with chronic hypoxia exemplified by renal anemia. Herein, on the bases of multiple molecular and cellular assays, a series of benzisothiazole derivatives have been synthesized and their structure-activity relationship was evaluated. The SAR and molecular docking studies have revealed the structural insights on the rational design of HIF-2 agonist and discovered a more potential 5-bromine substituted analogue, which showed 2-4 times improvement of HIF-2 downstream gene transcriptions, including EPO production. The present results suggest the therapeutic potential of the compounds for diseases related to EPO insufficiency.

Flexible dielectric polymers with high energy storage density are needed for film capacitor applications including hybrid electric vehicles and medical apparatuses. Poly(vinylidene fluoride) (PVDF) is regarded as a promising candidate owing to its intrinsic high polarisation, outstanding processability, good mechanical properties, and high dielectric breakdown strength. However, normal PVDF suffers from low energy density (Ue) and charge–discharge efficiency (η) at high electric fields. In this study, these restrictions are successfully overcome using a novel facile one-step Roll & Press method. A record high energy storage density of 50.2 J cm−3 with an outstanding charge–discharge efficiency of 80% is achieved at 1000 kV mm−1 in relaxor-like PVDF, which is ascribed to reversible polar nanostructures generated by the constraining effect originating from continuous folded boundaries in the multilayer structure during rolling and pressing. The superior energy storage performance of Roll & Pressed PVDF surpasses those of all other polymer-based materials reported. Additionally, a ready-to-use capacitor is assembled using the Roll & Press technique with electrodes constructed using a stretchable carbon nanotube veil (CNT veil), which exhibits strong interfacial interactions with the PVDF film and results in excellent energy storage performance. The universal applicability of the Roll & Press method and superior energy storage properties makes PVDF a strong candidate for modern energy storage systems.

Hypoxia-inducible factors (HIFs) are α/β heterodimeric transcription factors modulating cellular responses to the low oxygen condition. Among three HIF-α isoforms, HIF-3α is the least studied to date. Here we show that oleoylethanolamide (OEA), a physiological lipid known to regulate food intake and metabolism, binds selectively to HIF-3α. Through crystallographic analysis of HIF-3 α/β heterodimer in both apo and OEA-bound forms, hydrogen-deuterium exchange mass spectrometry (HDX-MS), molecular dynamics (MD) simulations, and biochemical and cell-based assays, we unveil the molecular mechanism of OEA entry and binding to the PAS-B pocket of HIF-3α, and show that it leads to enhanced heterodimer stability and functional modulation of HIF-3. The identification of HIF-3α as a selective lipid sensor is consistent with recent human genetic findings linking HIF-3α with obesity, and demonstrates that endogenous metabolites can directly interact with HIF-α proteins to modulate their activities, potentially as a regulatory mechanism supplementary to the well-known oxygen-dependent HIF-α hydroxylation.

Poly(vinylidene fluoride) (PVDF) and PVDF-based copolymers with trifluoroethylene (PVDF-TrFE) have attracted considerable academic and industrial interest due to their ferroelectric properties, which are only present in very few polymers. However, the underlying fundamentals of molecular ordering and induced polarizations are complex and not fully understood. Herein, PVDF, PVDF-TrFE and their blends, prepared using melt extrusion and hot pressing, have been selected to obtain controlled case studies with well-defined chain ordering and microstructures. Impedance analysis and terahertz time-domain spectroscopy (THz-TDS) are exploited to investigate electric polarization in PVDF-based polymers at different length scales. The extruded ferroelectric films show in-plane chain orientation and higher domain wall density compared to hot pressed films with randomly-distributed polymer chains, which favors the polarization at low frequencies (Hz to MHz), as concluded from the higher dielectric constants and more prominent high electric field polarization switching features. However, the domain walls cannot respond at high frequencies, which leads to lower dielectric constants in the extruded films at THz frequencies.

Flexible polymer-based dielectric capacitors with superior power density and stability are irreplaceable components in modern electrical devices. Among all dielectrics, ferroelectric relaxor materials are the most competitive candidates due to their high discharged energy density Ue and efficiency arising from their reversible polar nanodomains at high electric field. Poly(vinylidenedifluoride – trifluoroethylene - chlorotrifluoroethylene) (P(VDF-TrFE-CTFE)), one of the most well-known ferroelectric relaxor polymers, suffers from some limitations, including, poor processability, relatively low breakdown strength and high cost, which inhibit its potential commercial use. In this work, these restrictions have been effectively addressed via a low-cost binary polymer blending route. Owing to the high compatibility and strong interactions between P(VDF-TrFE-CTFE) and Poly(vinylidene difluoride-hexafluoropropylene) (P(VDF-HFP)), the nanostructure of blends can be modulated, which significantly enhanced the reversible polarization Pin-max to 0.132 C/m2 at the breakdown strength Eb of 600 kV/mm, leading to a high energy density of 21.9 J/cm3 in oriented P(VDF-TrFE-CTFE)/P(VDF-HFP) (50/50 wt%) blended films. The simplicity of the blending approach and the industrial viability of the processing technique, melt-extrusion, combined with high discharged energy density make oriented P(VDF-TrFE-CTFE)/P(VDF-HFP) (50/50 wt%) blended films a potential candidate for advanced energy storage applications.

Polymer based dielectric materials with simultaneously high thermal conductivity and low dielectric loss are highly desirable in various applications like energy storage, thermal management and electronic packaging. Polymer dielectrics generally benefit from good electrical insulation, high breakdown strength, high toughness and low density but suffer from very low thermal conductivity (0.1–0.5 W m −1 K −1). Herein we propose a new strategy to overcome this compromise; solid-state drawing of ultra-high molecular weight polyethylene (UHMWPE) films doped with a small amount of nanodiamonds (NDs). The resulting orientation of UHMWPE macromolecules and the nanofiller significantly improves the thermal conductivity along the stretching direction, while the dodecane surface functionalization of the NDs endows a robust interface between the matrix and filler, which minimizes the thermal resistance and dielectric loss. Our composites film (2 wt% NDs) shows an ultra-high thermal conductivity of 60 W m −1 K −1 in the drawing direction and very low dielectric loss, both at low and high electric field. More generally, herein we demonstrates that the interfaces introduced by the nanofillers do not necessarily cause an increase in dielectric loss at high electric field and a decrease in thermal conductivity, providing a new direction for the design of novel polymer based dielectric and functional materials.

Pim-1 kinase is a serine/threonine kinase which is vital in many tumors. The Pim-1 inhibitor 10-DEBC and its derivatives discovered in our previous work were modified through macrocyclization strategy. A series of benzo[b]pyridine[4,3-e][1,4]oxazine macrocyclic compounds were designed, synthesized, and evaluated as novel Pim-1 kinase inhibitors. Among these compounds, compound H5 exhibited the highest activity with an IC

Cryptands, seen as a kind of crown ether derivatives, have attracted much attention because of their three dimensional spatial structures and additional binding sites. Moreover, by changing functional groups on the third arm, various stimuli-responsive host–guest systems were obtained, which have played key roles in the construction of functional supramolecular systems. The recent advances in supramolecular systems constructed by crown ether-based cryptands, and further applications, especially in supramolecular polymers are summarized in this digest paper.

Two kinds of fluorescent BMP32C10-based cryptands 1 and 2 have been developed. Cryptand 1 contains a binaphthol group, while cryptand 2 bears a coumarin group in their third arms. Based on this design, novel self-assemblies constructed from cryptand 1 or 2 and basic N-heteroaromatic guests 3-6 were successfully obtained. Moreover, the threading/dethreading processes of the host-guest complexes could be well switched by the alternate addition of acid/base, and accompanied by concurrent changes in fluorescence.

During infection, nicotinamide adenine dinucleotide phosphate-oxidase of innate immune cells generates important microbicidal reactive oxygen species (ROS) such as hypochlorous acid (HOCl) to kill the invading pathogens. However, excess amounts of HOCl induce oxidative damage of functional biomolecules such as DNA and proteins, which may cause chronic inflammatory diseases. Herein, we outline protocols for the preparation of a rhodamine-based HOCl probe, as well as applications thereof, with which to detect HOCl in living cells and organisms. The probe (R19S) can be prepared from a commercially available rhodamine, rhodamine 6G, in two steps. When R19S is treated with HOCl, the sulfur atom is replaced by an oxygen atom, resulting in opening of the lactone ring; thus, nonfluorescent R19S is converted to highly fluorescent rhodamine 19 (R19). R19S exhibits high selectivity for HOCl over other ROS and high sensitivity in a weakly acidic environment. In addition, we describe fluorescence imaging assays of HOCl in mouse neutrophils and Drosophila targeted using this probe. The approximate amount of time required to synthesize the probe is 2-3 d, after which it can be used for up to 5 h in the bioimaging of living cells.

In this paper, highly sensitive and selective fluorescent probe 1 for GSH is designed and synthesized based on modulation of the excited-state intramolecular proton transfer (ESIPT) process of 2-(2′-hydroxy-3′-ethoxyphenyl)benzothiazole. Upon introducing GSH in neutral solution containing CTAB micelles, dinitrophenyl, the protecting group of the probe, is removed via the nucleophilic substitution, thereby retrieving the ESIPT process of 2-(2′-hydroxy-3′-ethoxyphenyl)benzothiazole, which results in a fluorescence enhancement at 485 nm. Additionally, the fluorescence intensity of the probe is linearly proportional to GSH concentration ranging from 0 to 100 μM and the obtained detection limit is as low as 0.81 μM. The enhanced selectivity toward GSH over Cys and Hcy is also attributed to one more carboxyl group in GSH. Importantly, the probe is successfully utilized for monitoring GSH in living HeLa cells.

High power dielectric capacitors with high energy density are needed in order to develop modern electronic and electrical systems, including hybrid vehicles, telecommunication infrastructures and portable electronic devices. Relaxor ferroelectric polymers (RFP) are considered to be the most promising candidates for the next generation of capacitors owing to their relatively high energy storage density. However, the commercialization of RFP capacitors in power systems is hindered by their high cost and low dielectric breakdown strength. In this study, inexpensive, free-standing nano-crystalline (~3.3 nm) poly (vinylidene fluoride) (PVDF) films with high β phase content (~98%), “relaxor-like” ferroelectric behaviour and high breakdown strength (880 kV/mm) were fabricated using the facile Press & Folding (P&F) technique. An internal stress dominated polarization switching model is proposed to explain the origin of the relaxor-like ferroelectric behaviour. The internal stress generated during pressing alters the intermolecular chain distance of the (200) plane of β-PVDF from 4.24 A in internal stress free films to 4.54 A in P&F films, corresponding to a tensile strain and residual stress of 7.11% and 142 MPa, respectively. The internal stress acts to partially reverse the polarization on reversal of the applied electric field. This, combined with preferred in-plane orientation of the crystallites, results in a polar nanostructure with high polarization reversibility at high electric fields. A giant discharged energy storage density of 39.8 J/cm3 at 880 kV/mm was achieved for P&F films, which surpasses all previously reported polymer-based materials.

A perylene-based probe was developed for uridine diphosphate (UDP) sensing and cell imaging. The probe presented about 4-fold fluorescence enhancement in the presence or absence of 100 equiv UDP. The selectivity toward UDP over other phosphor-containing anions was observed. The selective UDP sensing was speculated to be related to the binding affinities of Zn 2+ ions in sensor with the uridine and phosphate moieties of UDP. Furthermore, this probe was also applied to image of UDP in living cells.

In this work, we developed three fluorescent probes (F-1, F-2, and F-3) based on fluorescein, mono-formylated fluorescein, and bis-formylated fluorescein for hydrogen sulfide (H

Reactive oxygen (ROS) and nitrogen (RNS) species cause oxidative and nitrosative stresses, respectively. These stresses are implicated not only in diverse physiological processes but also in various pathological processes, including cancer and neurodegenerative disorders. In addition, some ROS and RNS in the environment are pollutants that threaten human health. As a consequence of these effects, sensitive methods, which can be employed to selectively monitor ROS and RNS in live cells, tissues and organisms as well as in environmental samples, are needed so that their biological roles can be understood and their concentrations in environmental samples can be determined. In this review, fluorescent, luminescent and colorimetric ROS and RNS probes, which have been developed since 2011, are comprehensively discussed.