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As effective ways to regulate protein levels, targeted protein degradation technologies have attracted great attention in recent years. Here, we established a novel integrin-facilitated lysosomal degradation (IFLD) strategy to degrade extracellular and cell membrane proteins using bifunctional compounds as molecular degraders. By conjugation of a target protein-binding ligand with an integrin-recognition ligand, the resulting molecular degrader proved to be highly efficient to induce the internalization and subsequent degradation of extracellular or cell membrane proteins in an integrin- and lysosome-dependent manner. As demonstrated in the development of BMS-L1-RGD, which is an efficient programmed death-ligand 1 (PD-L1) degrader validated both

A survey was conducted to investigate the effects of cadmium (Cd), arsenic (As), chromium (Cr), lead (Pb), and copper (Cu) in medicine and food homologous substances (MFHs) on human health. Nine common and typical MFHs (Dendrobium, Bulbus lilii, Poria, Semen nelumbinis, Radix puerariae, Gardenia jasminoides, Hordeum vulgare L, Semen coicis, and Ganoderma Karst) in the form of medicinal slices ready for decoction were purchased from pharmacies. Five among the MFHs (Dendrobium, Bulbus lilii, Poria, Semen nelumbinis, and Radix puerariae) were further obtained from a local field as raw materials for comparison. The results showed that raw materials of MFHs collected from the field had higher contents of heavy metal and greater health risks than medicinal slices purchased from pharmacy. Generally, the heavy metal residues in MFHs of different medicinal parts were different, and MFHs from roots or stems had significantly higher contents of heavy metals than those from fruits or seeds. Most importantly, the contents of Cd in Bulbus lilii and As in wild Poria from field were higher than the contents described in the Pharmacopoeia of the People's Republic of China (ChP). Non-carcinogenic and carcinogenic risk assessments revealed that Poria from field had larger non-carcinogenic and carcinogenic risks to human health; Bulbus lilii showed no non-carcinogenic risk but exhibited carcinogenic risks, whereas Cr showed carcinogenic risks in all samples. Given that MFHs are incorporated in regular foods, care should be taken to minimize health hazards caused by heavy metals to human. This study creates awareness on the safety issues associated with MFHs, and provides basic information for establishing the maximum allowable contents of medicinal and food substances in normal diets.

In the new era, the arrival of 5G has added a lot of fun and beauty to our lives, allowing us to enjoy the happiness brought by the network even more. The 5th Generation mobile technology (5G for short) is a new generation of broadband mobile communication technology with features such as higher speed, lower latency, and massive connectivity. Moreover, this is a network infrastructure that, in fact, realizes the interconnections among humans, computer machines, and sensors/things, i.e., Internet of things. The world can now be characterized as a whole global village. The 5 G, mobile edge computing networks, and cloud-edge collaborative computing allow us to communicate and share information on the cloud networks, allowing us to better understand the global village. Based on cloud-edge collaborative computing for 5G edge networks, this study builds a task scheduling algorithm, which will help us to check network defects and make better use of the 5G technology to serve customers. Experimental results demonstrate the extra efficiency of the proposed algorithm over the closest rivals.

Ultrasound is a critical non-invasive test for preoperative diagnosis of ovarian cancer. Deep learning is making advances in image-recognition tasks; therefore, we aimed to develop a deep convolutional neural network (DCNN) model that automates evaluation of ultrasound images and to facilitate a more accurate diagnosis of ovarian cancer than existing methods.In this retrospective, multicentre, diagnostic study, we collected pelvic ultrasound images from ten hospitals across China between September 2003, and May 2019. We included consecutive adult patients (aged ≥18 years) with adnexal lesions in ultrasonography and healthy controls and excluded duplicated cases and patients without adnexa or pathological diagnosis. For DCNN model development, patients were assigned to the training dataset (34 488 images of 3755 patients with ovarian cancer, 541 442 images of 101 777 controls). For model validation, patients were assigned to the internal validation dataset (3031 images of 266 patients with ovarian cancer, 5385 images of 602 with benign adnexal lesions), external validation datasets 1 (486 images of 67 with ovarian cancer, 933 images of 268 with benign adnexal lesions), and 2 (1253 images of 166 with ovarian cancer, 5257 images of 723 benign adnexal lesions). Using these datasets, we assessed the diagnostic value of DCNN, compared DCNN with 35 radiologists, and explored whether DCNN could augment the diagnostic accuracy of six radiologists. Pathological diagnosis was the reference standard.For DCNN to detect ovarian cancer, AUC was 0·911 (95% CI 0·886-0·936) in the internal dataset, 0·870 (95% CI 0·822-0·918) in external validation dataset 1, and 0·831 (95% CI 0·793-0·869) in external validation dataset 2. The DCNN model was more accurate than radiologists at detecting ovarian cancer in the internal dataset (88·8% vs 85·7%) and external validation dataset 1 (86·9% vs 81·1%). Accuracy and sensitivity of diagnosis increased more after DCNN-assisted diagnosis than assessment by radiologists alone (87·6% [85·0-90·2] vs 78·3% [72·1-84·5], p0·0001; 82·7% [78·5-86·9] vs 70·4% [59·1-81·7], p0·0001). The average accuracy of DCNN-assisted evaluations for six radiologists reached 0·876 and were significantly augmented when they were DCNN-assisted (p0·05).The performance of DCNN-enabled ultrasound exceeded the average diagnostic level of radiologists matched the level of expert ultrasound image readers, and augmented radiologists' accuracy. However, these observations warrant further investigations in prospective studies or randomised clinical trials.National Key Basic Research Program of China, National Sci-Tech Support Projects, and National Natural Science Foundation of China.

The optimal path planning for EVs (electric vehicles) has gained great attention during the last decade due to the zero pollution emission characteristics and limited power capacity of EV batteries. In this paper, an optimal route search is proposed considering multiple charging stations in a dynamic urban environment, while it is still applicable when the initial available amount of the battery fails to cover a certain travel range. The TRDP (transit route design problem) and TNDP (transit node design problem) are used to search for the most feasible routes based on time and driving range via the improved route-assisted rapid random tree (RA-RRT*) algorithm. Considering the status of charge of an EV’s battery during optimal routes search, three states are investigated between the destination and the aggregators: (1) bypassing the aggregators, (2) stopping over a single aggregator, and (3) stopping over multiple aggregators. During the states (2) and (3), it is required that the EVs be charged at the charging stations obtained by the RA-RRT* algorithm while approaching the destination. The proposed algorithm is tested on a random dataset under certain conditions, that is, traffic flow with congestion and assigned target locations from a given map data, with comparison experiments for efficacy verification.

A far-red-absorbing photosensitiser that can be activated by human NAD(P)H:quinone oxidoreductase 1 has been designed, synthesised and examined for its in vitro and in vivo responsive properties.

Due to its multifaceted impact in various applications, icing and ice dendrite growth has been the focus of numerous studies in the past. Dendrites on wetting (hydrophilic) and nonwetting (hydrophobic) surfaces are sharp, pointy, branching, and hairy. Here, we show a unique dendrite morphology on state-of-the-art micro/nanostructured oil-impregnated surfaces, which are commonly referred to as slippery liquid-infused porous surfaces or liquid-infused surfaces. Unlike the dendrites on traditional textured hydrophilic and hydrophobic surfaces, the dendrites on oil-impregnated surfaces are thick and lumpy without pattern. Our experiments show that the unique ice dendrite morphology on lubricant-infused surfaces is due to oil wicking into the porous dendritic network because of the capillary pressure imbalance between the surface texture and the dendrites. We characterized the shape complexity of the ice dendrites using fractal analysis. Experiments show that ice dendrites on textured oil-impregnated surfaces have lower fractal dimensions than those on traditional lotus leaf-inspired air-filled porous structures. Furthermore, we developed a regime map that can be used as a design guideline for micro/nanostructured oil-impregnated surfaces by capturing the complex effects of oil chemistry, oil viscosity, and wetting ridge volume on dendrite growth and morphology. The insights gained from this work inform strategies to reduce lubricant depletion, a major bottleneck for the transition of micro/nanostructured oil-impregnated surfaces from bench-top laboratory prototypes to industrial use. This work will assist the development of next-generation depletion-resistant lubricant-infused ice-repellent surfaces.

An analytical expression of a single Airyprime beam propagating in free space is derived. Upon propagation in free space, a single Airyprime beam in arbitrary transverse direction is the coherent superposition of the Airyprime and the Airy-related modes, which results in the interference enhancement effect under the appropriate condition. The Airy-related mode is the conventional propagating Airy mode with an additional π/2 phase shift and a weight coefficient of half the normalized propagation distance. Due to the peak light intensity in the initial plane being set to be 1, the strength of interference enhancement effect is characterized by the maximum light intensity. The maximum light intensity of a single Airyprime beam propagating in free space is independent of the scaling factor and is only decided by the exponential decay factor. When the exponential decay factor is above the saturated value, the interference enhancement effect disappears. When the exponential decay factor decreases from the saturated value, the maximum light intensity of a single propagating Airyprime beam increases, and the position of maximum light intensity is getting farther away. With the increase of the scaling factor, the position of maximum light intensity of a single propagating Airyprime beam is extended. The intensity distribution and the transverse Poynting vector of a single propagating Airyprime beam are demonstrated in different observation planes of free space. The flow direction of transverse energy flux effectively supports the interference enhancement effect of a single propagating Airyprime beam. The Airyprime beam is experimentally generated, and the interference enhancement effect is experimentally confirmed. The interference enhancement effect is conducive to the practical application of a single Airyprime beam.

In this paper, the lone generation of a new kind of beam named finite energy Airyprime (FEA) beam through the Airy transformation of the coherent superposition of four different elegant Hermite-Gaussian modes is reported for the first time. Analytical expressions of the centroid, the r.m.s beam width, the divergence angle, and the beam propagation factor of the FEA beam are derived in the output plane of Airy transformation, respectively. The effects of the Airy control parameters on the intensity distribution, the centroid, the r.m.s beam width, and the beam propagation factor are examined in detail through numerical examples. Unlike the Airy beam, the FEA beam upon free space propagation will be associated with an additional Airy mode, and the beam pattern of the FEA beams propagating in free space will evolve into a solid beam spot with two tails along two transverse directions, as well as the the intensity of main lobe of the FEA beam decays much slowly during free space propagation. Further, an experiment setup is established to generate the FEA beam via Airy transformation of four mixed elegant Hermite-Gaussian modes. The propagation characteristics such as the intensity distribution, the r.m.s beam width and the beam propagation factor are measured. The experimental results agree well with the theoretical predictions. Our study affords an effective and novel approach to generate the FEA beam, and is beneficial to expand the potential application of the FEA beam.

Attitudes are deemed critical psychological variables that can determine end users’ acceptance and adoption of robots. This study explored the heterogeneity of the Chinese public’s attitudes toward robots in healthcare and examined demographic characteristics associated with the derived profile membership. The data were collected from a sample of 428 Chinese who participated in an online survey. Latent profile analysis identified three distinct subgroups regarding attitudes toward robots—optimistic (36.9%), neutral (47.2%), and ambivalent (15.9%). Interestingly, although participants in the ambivalent attitude profile held more negative attitudes toward interaction with or social influence of healthcare robots, their attitudes tended to be positive when it came to emotional interactions with healthcare robots. All the respondents reported negative attitudes toward the social influence of healthcare robots. Multivariable regression analysis results showed that there were significant differences in age, education level, monthly income, experience with computers, experience with wearable devices, and whether to follow robot-related news or not. This study confirmed the heterogeneity of the Chinese public’s attitudes toward robots in healthcare and highlighted the importance of emotional interaction with and social influence of healthcare robots, which might facilitate a better understanding of the needs and expectations of potential end users for robots in healthcare to make them more acceptable in different situations.

When a small portion of the decision makers hold the correct information and the majority hold the opposite, the correct ranking of the alternatives for the group decision-making cannot be obtained with the current methods. A novel method is thus developed to tackle this challenge in this article. The priori probabilities of each alternative can be calculated via the opinions of the group decision makers, which are presented as the pairwise comparisons of the alternatives in the form of the linguistic preference relation. Based on the aggregated probabilities of the alternatives in the group of the decision makers, the normalized-prediction selection rate (NPSR) is defined and calculated accordingly. The alternative with maximal NPSR is selected as the correct answer, whereas the accuracy of the correct alternative selection (CAS) is guaranteed by two propositions. The iterative algorithm is first devised to determine the ranking of the alternatives depending on the CAS. For the proposed method, the decision makers require no modification of the opinions as can avoid the consensus problem, and the CAS can be obtained under the circumstances that the correct information is held by the minority of the group. Finally, the experiment has been conducted to demonstrate the efficacy of the proposed method to obtain the CAS, and the main limitations of proposed method are carefully addressed as well.

Researchers are puzzled whether the enhancement of the abruptly autofocusing ability caused by a linear chirp factor is accompanied by the shortening or the extension of the focal length. In this Letter, a circular Airyprime beam is chosen as the research object to reveal this mystery. Extension or shortening of the focal length in the enhancement of the abruptly autofocusing ability depends on the exponential decay factor a and the dimensionless radius of the primary ring. When a is small enough, there exists a critical value for the dimensionless radius. If the dimensionless radius is greater than the critical value, the focal length is shortened in the enhancement of the abruptly autofocusing ability. If the dimensionless radius is less than the critical value, the focal length is extended in the enhancement of the abruptly autofocusing ability. As a increases, the critical value for the dimensionless radius decreases until it reaches zero. The physical mechanism of extension or shortening of the focal length in the enhancement of the abruptly autofocusing ability is elucidated.

Considering the multi-feature fusion via information synergy entropy (ISE) based interval intuitionistic fuzzy (IIF) technique for order preference by similarity to ideal solution, the paper propose a method to identify the operating condition identification in a complex environment. In this method, the evaluation information contained in the decision matrices is characterized by an IIF number, and the related attribute weights are incompletely known. First, the ISE concept is proposed to calculate the weight of each attribute value which is used to construct a weighted collective decision matrix. Both intuitionistic and fuzzy information are incorporated into the matrix to describe the uncertainty in the IIF sets to improve the decision accuracy. Next, an improved Euclidean distance is used to calculate the degree of relative closeness so as to rank the decision alternatives, which can overcome the drawback of division by zero. Then the superheat identification is used as a case study to illustrate optimal operating condition determination of aluminium electrolysis cell. Experimental results have demonstrated the validity and applicability of the proposed operating condition determination algorithm.

Fallowing is an improvement process aimed at promoting the soil health and the sustainability of cultivated land. How it affects the soil health-related abiotic properties and microbial community composition under different levels of cadmium (Cd) contamination is not well known. This study involved applying consistent fallowing practices to paddy soils of low and high Cd content, in order to examine changes in the soil Cd, nutrient, and microbial community using a high-throughput sequencing method. Fallowing significantly decreased available Cd and phosphorus (P) content, but increased ammonium nitrogen (N) on lightly contaminated plots, whereas only P variables changed significantly for heavily contaminated plots. Furthermore, fallowing significantly decreased bacterial Shannon diversity on lightly contaminated plots and altered bacterial community composition on heavily contaminated plots, but it had no impact on archaeal or fungal communities, indicating that bacteria are more sensitive to fallowing than archaea and fungi. Specifically, fallowing significantly promoted some copiotrophic bacteria (Alphaproteobacteria and Betaproteobacteria) but suppressed some oligotrophic taxa (Chloroflexi phylum and OTU5837 belonging to the phylum Acidobacteria) on highly contaminated plots. Interestingly, the soil microbial community in the lightly contaminated plots was mainly affected by soil pH, C, and N properties, whereas on heavily contaminated plots, it was largely influenced by soil Cd and P variables. Overall, these findings showed that fallowing significantly improved soil N availability but decreased Cd availability in lightly contaminated conditions, while shifts in microbial community composition under heavily contaminated conditions may indirectly enhance soil nutrient availability and reduce available Cd. These findings highlight the significance of fallowing to promote the health and the sustainability of Cd-contaminated cultivated land.

Coibamide A (1) is a highly N-methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (1a), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of 1a, two novel peptide-drug conjugates RGD-SS-CA (2) and RGD-VC-CA (3) were designed, synthesized, and evaluated. Composed of cyclodepsipeptide 1a, a tumor-homing RGD motif, and a conditionally labile linker, the conjugates are expected to release 1a tracelessly in specific tumor microenvironments. Compared with RGD-VC-CA (3), RGD-SS-CA (2) proved to be superior in in vitro drug release and cytotoxicity tests. Notably, intravenous injection of RGD-SS-CA (2) into mice-bearing human tumor xenografts induced significant tumor growth suppression with negligible toxicity. Therefore, as a novel prodrug of the coibamide A analogue, conjugate 2 has great potential for further exploration in cancer drug discovery.

A nanoprobe based on polydopamine-coated gold nanobipyramids surface modified with molecules of a phenylboronic acid-substituted distyryl boron dipyrromethene has been fabricated and characterised using various physical and spectroscopic methods. It serves as an ultrasensitive sensor for sialic acids on the surface of cancer cells based on its dual surface-enhanced Raman scattering and fluorescence response. This biomarker can also trigger the photodynamic activity of these nanobipyramids, effectively eradicating the cancer cells mainly through apoptosis as shown by various bioassays.

Local climate zones (LCZ) describe urban surface structures, supporting studies of urban heat islands, sustainable urbanization, and energy balance. The existing studies mapped LCZs from satellite images using scene-based classification, which trained deep-learning classifiers by labeled image patches, segmented satellite images into patches by sliding windows to match the size of training data, and finally classified the segmented patches to obtain LCZ maps. However, sliding windows are different from the real footprints of LCZs, which leads to large errors in classification. To address this problem, this article proposes a parcel-based method for LCZ classification using Sentinel-2 images, road networks, and elevation data. First, the Sentinel-2 images are segmented by the road network to obtain the land parcels as classification units. Second, each image parcel is standardized to match the training dataset, So2Sat LCZ42. Third, the trained convolutional neural network (CNN) is used to classify the standardized parcels into LCZs. Finally, the building height information derived from elevation data is used to refine the LCZs by a rule-based classifier. The results of the four test sites show that the overall accuracy of our method is 0.75, higher than the sliding-window-based method's accuracy of 0.47. Additional simulation experiments demonstrated that parcels derived from road networks can reduce the mixture effect in image patches, and parcel standardization can ensure the transferability of the CNN model trained by regular image patches. Considering that the road network and elevation data are widely available, the proposed method has the potential of mapping LCZs in large areas.

A novel nanosystem of polydopamine-coated gold nanorods (AuNR@PDA) immobilised with molecules of hairpin DNA-conjugated distyryl boron dipyrromethene (DSBDP) was designed and fabricated for detection of microRNA-21 (miR-21). By using this oncogenic stimulus, the photodynamic effect of the DSBDP-based photosensitiser was also activated. In the presence of miR-21, the fluorescence intensity of the nanosystem was increased due to the dissociation of the conjugate from AuNR@PDA upon hybridisation. The intracellular fluorescence intensity triggered by intracellular miR-21 was in the order: MCF-7 > HeLa > HEK-293, which was in accordance with their miR-21 expression levels. The specificity was demonstrated by comparing the results with those of an analogue with a scrambled DNA sequence. The nanosystem could also result in miR-21-mediated photodynamic eradication of miR-21-overexpressed MCF-7 cells. After intravenous injection of the nanosystem into HeLa tumour-bearing nude mice, the fluorescence intensity of the tumour was increased over 24 h and was about 3-fold stronger than that of the scrambled analogue. Upon irradiation, the nanosystem could also greatly reduce the size of the tumour without causing significant tissue damage in the major organs. The overall results showed that this nanoplatform can serve as a specific and potent theranostic agent for simultaneous miR-21 detection and miR-21-mediated photodynamic therapy.