The radiation of electromagnetic and mechanical waves depends not only on the intrinsic properties of the emitter but also on the surrounding environment. This principle has laid the foundation for ...the development of lasers, quantum optics, sonar, musical instruments and other fields related to wave–matter interaction. In the conventional wisdom, the environment is defined exclusively by its eigenstates, and an emitter radiates into and interacts with these eigenstates. Here we show experimentally that this scenario breaks down at a non-Hermitian degeneracy known as an exceptional point. We find a chirality-reversal phenomenon in a ring cavity where the radiation field reveals the missing dimension of the Hilbert space, known as the Jordan vector. This phenomenon demonstrates that the radiation field of an emitter can become fully decoupled from the eigenstates of its environment. The generality of this striking phenomenon in wave–matter interaction is experimentally confirmed in both electromagnetic and acoustic systems. Our finding transforms the fundamental understanding of light–matter interaction and wave–matter interaction in general, and enriches the intriguing physics of exceptional points.The modes of the radiation field generated from an emitter are usually determined by the eigenstates of the surrounding environment. However, this scenario breaks down in a non-Hermitian system, at the spectral degeneracy known as an exceptional point.
ObjectivePatients with increased PD-L1+ host cells in tumours are more potent to benefit from antiprogrammed death-1/programmed death ligand-1 (PD-L1) treatment, but the underlying mechanism is still ...unclear. We aim to elucidate the nature, regulation and functional relevance of PD-L1+ host cells in hepatocellular carcinoma (HCC).DesignA total of untreated 184 HCC patients was enrolled randomly. C57BL/6 mice are given injection of Hepa1-6 cells to form autologous hepatoma. ELISpot, flow cytometry and real-time PCR are applied to analyse the phenotypic characteristics of PD-L1+ cells isolated directly from HCC specimens paired with blood samples or generated from ex vivo and in vitro culture systems. Immunofluorescence and immunohistochemistry are performed to detect the presence of immune cells on paraffin-embedded and formalin-fixed samples. The underlying regulatory mechanisms of metabolic switching are assessed by both in vitro and in vivo studies.ResultsWe demonstrate that PD-L1+ host macrophages, which constructively represent the major cellular source of PD-L1 in HCC tumours, display an HLA-DRhighCD86high glycolytic phenotype, significantly produce antitumourigenic IL-12p70 and are polarised by intrinsic glycolytic metabolism. Mechanistically, a key glycolytic enzyme PKM2 triggered by hepatoma cell derived fibronectin 1, via a HIF-1α-dependent manner, concurrently controls the antitumourigenic properties and inflammation-mediated PD-L1 expression in glycolytic macrophages. Importantly, although increased PKM2+ glycolytic macrophages predict poor prognosis of patients, blocking PD-L1 on these cells eliminates PD-L1-dominant immunosuppression and liberates intrinsic antitumourigenic properties.ConclusionsSelectively modulating the ‘context’ of glycolytic macrophages in HCC tumours might restore their antitumourigenic properties and provide a precise strategy for anticancer therapy.
In-situ formation of appropriate interfacial carbides by matrix-alloying with carbide-forming elements offers an efficient approach to improve the interfacial bonding of graphene/CuX composites. ...However, the carbide formation commonly occurs at graphene edge/matrix interface, which is not enough to achieve the sufficient interfacial bonding because the vast majority of graphene/matrix interface is basal-plane/matrix interface rather than edge/matrix interface. To alleviate this limitation, we reported a new design of creating defects on graphene basal-plane (CDGB) to optimize the interface and mechanical properties of graphene/CuCr composites. Plasma treatment was employed to create the structural defects (∼7 nm nanopores) on graphene basal-plane. When incorporating the plasma-treated graphene into the CuCr matrix, the Cr7C3 carbides were found to be in-situ formed at both basal-plane/matrix and edge/matrix interfaces. Ex-situ and in-situ tensile tests both demonstrated that the plasma-treated graphene led to the composite that showed a larger strength enhancement and a higher load transfer capability than untreated counterpart, which was ascribed to the largely improved interfacial bonding contributed by the Cr7C3 formed at basal-plane/matrix interface. This study suggests that the CDBG via plasma treatment affords a feasible solution for the interface optimization of graphene/CuX composites with enhanced mechanical properties.
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To date, photothermal sensitizers include organic and inorganic nanomaterials for biomedical applications. However, the impediments of low biodegradability and potential toxicity hinder their further ...applications in clinics. Liquid metal nanospheres show superior photothermal effects under near-infrared laser irradiation, in addition, a transformation in shape can be triggered, which also promotes biodegradability that helps to avoid potential systemic toxicity. Here, we fabricated tunable liquid metal nanoparticles having sphere-shaped to rod-shaped characteristics, resulting in good biocompatibility, favorable photothermal conversion efficiency, and targeting capability to tumors. The synthesis strategy is easy to achieve through one-step sonication. We systematically evaluated the photothermal properties of these liquid metal nanoparticles as well as their destructive effects on tumors in a quantitative way both in vitro and in vivo under laser exposure. Results have shown for the first time in mice that gallium nanorods, regulated and controlled through the production of GaO(OH), displayed outstanding photothermal conversion efficiency and exhibited distinct temperature elevation compared to gallium nanospheres and gallium-indium alloy nanorods. These shape transformable and biocompatible gallium nanorods establish the basis for the future laser ablation of tumors to achieve enhanced therapeutic outcomes. This shape tunability of a smart nano-liquid metal directly contributes to enhanced photothermal therapy in mice and opens new opportunities for potential applications with tumor therapy and imaging.
Context: Increasing incidence and impact of inflammatory diseases have encouraged the search of new pharmacological strategies to face them. Licorice has been used to treat inflammatory diseases ...since ancient times in China.
Objective: To summarize the current knowledge on anti-inflammatory properties and mechanisms of compounds isolated from licorice, to introduce the traditional use, modern clinical trials and officially approved drugs, to evaluate the safety and to obtain new insights for further research of licorice.
Methods: PubMed, Web of Science, Science Direct and ResearchGate were information sources for the search terms 'licorice', 'licorice metabolites', 'anti-inflammatory', 'triterpenoids', 'flavonoids' and their combinations, mainly from year 2010 to 2016 without language restriction. Studies were selected from Science Citation Index journals, in vitro studies with Jadad score less than 2 points and in vivo and clinical studies with experimental flaws were excluded.
Results: Two hundred and ninety-five papers were searched and 93 papers were reviewed. Licorice extract, 3 triterpenes and 13 flavonoids exhibit evident anti-inflammatory properties mainly by decreasing TNF, MMPs, PGE2 and free radicals, which also explained its traditional applications in stimulating digestive system functions, eliminating phlegm, relieving coughing, nourishing qi and alleviating pain in TCM. Five hundred and fifty-four drugs containing licorice have been approved by CFDA. The side effect may due to the cortical hormone like action.
Conclusion: Licorice and its natural compounds have demonstrated anti-inflammatory activities. More pharmacokinetic studies using different models with different dosages should be carried out, and the maximum tolerated dose is also critical for clinical use of licorice extract and purified compounds.
In many parts of the world, apple trees suffer from severe foliar damage each year due to infection of Alternaria blotch (Alternaria alternata f. sp. Mali), resulting in serious economic losses to ...growers. Traditional methods for disease detection and severity classification mostly rely on manual labor, which is slow, labor-intensive and highly subjective. There is an urgent need to develop an effective protocol to rapidly and accurately evaluate disease severity. In this study, DeeplabV3+, PSPNet and UNet were used to assess the severity of apple Alternaria leaf blotch. For identifications of leaves and disease areas, the dataset with a total of 5382 samples was randomly split into 74% (4004 samples) for model training, 9% (494 samples) for validation, 8% (444 samples) for testing and 8% (440 samples) for overall testing. Apple leaves were first segmented from complex backgrounds using the deep-learning algorithms with different backbones. Then, the recognition of disease areas was performed on the segmented leaves. The results showed that the PSPNet model with MobileNetV2 backbone exhibited the highest performance in leaf segmentation, with precision, recall and MIoU values of 99.15%, 99.26% and 98.42%, respectively. The UNet model with VGG backbone performed the best in disease-area prediction, with a precision of 95.84%, a recall of 95.54% and a MIoU value of 92.05%. The ratio of disease area to leaf area was calculated to assess the disease severity. The results showed that the average accuracy for severity classification was 96.41%. Moreover, both the correlation coefficient and the consistency correlation coefficient were 0.992, indicating a high agreement between the reference values and the value that the research predicted. This study proves the feasibility of rapid estimation of the severity of apple Alternaria leaf blotch, which will provide technical support for precise application of pesticides.
Abstract
Licorice is one of the oldest and most frequently used herbs in traditional Chinese medicine. It contains more than 20 triterpenoids and 300 flavonoids. In recent years, a lot of studies ...have reported that the active compounds isolated from licorice possess antitumor, antimicrobial, antiviral, anti-inflammatory, immunoregulatory, and several other activities that contribute to the recovery and protection of the nervous, alimentary, respiratory, endocrine, and cardiovascular systems. In this paper, nine different pharmacological activities of licorice are summarized. The active compounds responsible for these pharmacological activities, the molecular mechanisms, and
in vivo
and
in vitro
studies are listed in detail. Furthermore, the clinical therapeutics and toxicity studies of licorice are also discussed. We hope this work can provide a basis for further studies concerning with the safe and effective use of licorice.
Flexible materials with the ability to be bent, strained, or twisted play a critical role in soft robots and stretchable electronics. Although tremendous efforts are focused on developing new ...stretchable materials with excellent stability, inevitable mechanical damage due to long term deformation is still an urgent problem to be tackled. Here, a magnetic healing method based on Fe‐doped liquid metal (Fe‐GaIn) conductive ink via a noncontact way is proposed. Further, multifunctional flexible electronics are designed with combined performances of superior remote self‐healing under magnetic field, water‐degradable, and thermal transfer printing, which attribute to three parts of the materials including Fe‐GaIn conductive ink, degradable PVA substrate, and adhesive fructose. The as‐made light emitting diodes (LED) circuit is demonstrated with both structural and functional repairing after single or multipoint damage. The self‐healing time from multipoint damage is pretty fast within 10 s. Due to the water‐soluble PVA film, the recycling process is simple via immersing into water. Through heating, the electric circuit on fructose can be transferred to other flexible substrate with high efficiency, which broadens the practical applications of the present system. The novel and multifunctional electronics hold great promise for self‐healing electronics, transient electronics, and soft robots.
Multifunctional flexible electronics involving integrated features of remote self‐healing, water‐degradable and thermal transfer printing are developed. Here, a magnetic healing approach is proposed based on Fe‐doped liquid metal (Fe‐GaIn) conductive ink, which is demonstrated with both structural and functional repair under magnetic field with a magnet after single or multipoint damage.
Deoxynivalenol (DON) in raw and processed grain poses significant risks to human and animal health. In this study, the feasibility of classifying DON levels in different genetic lines of barley ...kernels was evaluated using hyperspectral imaging (HSI) (382-1030 nm) in tandem with an optimized convolutional neural network (CNN). Machine learning methods including logistic regression, support vector machine, stochastic gradient descent, K nearest neighbors, random forest, and CNN were respectively used to develop the classification models. Spectral preprocessing methods including wavelet transform and max-min normalization helped to enhance the performance of different models. A simplified CNN model showed better performance than other machine learning models. Competitive adaptive reweighted sampling (CARS) in combination with successive projections algorithm (SPA) was applied to select the best set of characteristic wavelengths. Based on seven wavelengths selected, the optimized CARS-SPA-CNN model distinguished barley grains with low levels of DON (<5 mg/kg) from those with higher levels (5 mg/kg < DON ≤ 14 mg/kg) with an accuracy of 89.41%. The lower levels of DON class I (0.19 mg/kg ≤ DON ≤ 1.25 mg/kg) and class II (1.25 mg/kg < DON ≤ 5 mg/kg) were successfully distinguished based on the optimized CNN model, yielding a precision of 89.81%. The results suggest that HSI in tandem with CNN has great potential for discrimination of DON levels of barley kernels.
In this study, the toxicity effects on circulatory system and respiratory system, and the acute toxicity test of recombinant neorudin (EPR-hirudin, EH) in cynomolgus monkeys were evaluated to provide ...reference information for clinical studies. Eighteen cynomolgus monkeys were randomly divided into three groups for single intravenous administration of 3, 30 mg/kg EH and normal saline, respectively. The changes of respiratory frequency, respiratory intensity, blood pressure and electrocardiogram before and after administration were recorded. In acute toxicity test, six cynomolgus monkeys were intravenously received EH at a single dose of 171, 257, 385, 578, 867 and 1300 mg/kg respectively. The vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of the animals were determined before administration and on the 7th and 14th day after administration. As the results showed that there were no significant abnormal changes in respiratory frequency, respiratory intensity, blood pressure or electrocardiogram in cynomolgus monkeys after receiving EH at 3 mg/kg and 30 mg/kg, and there was no statistical difference between the treated groups and normal saline group. In the acute toxicity test, no significant abnormalities were observed in vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of six cynomolgus monkeys at day 7 and 14 after EH administration. Furthermore, autopsies of all cynomolgus monkeys showed no abnormalities. The results of toxicokinetics showed that AUClast of the drug increased in proportion to the EH dose in the range of 171-578 mg/kg, and increased in over proportion to the EH dose in the range of 578-1300 mg/kg. The variation of Cmax was basically consistent with AUClast. In a sum, A single intravenous injection of 3 and 30 mg/kg of EH did not affect the circulatory system and respiratory system in cynomolgus monkeys and the maximum tolerated dose of EH in cynomolgus monkey is over 1300 mg/kg (equivalent to 619-1300 times of the proposed clinical equivalent dose).