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Despite many nano-based strategies devoted to delivering cisplatin for tumor therapy, its clinical benefits are compromised by poor tissue penetration and limited DNA adducts formation of the drug. Herein, a cisplatin loading nanomotor based janus structured Ag-polymer is developed for cisplatin delivery of deeper tissue and increased DNA adducts formation. The nanomotor displayed a self‐propelled tumor penetration fueled by hydrogen peroxide (H2O2) in tumor tissues, which is catalytically decomposed into a large amount of oxygen bubbles by Ag nanoparticles (NPs). Notably, cisplatin could elevate the intracellular H2O2 level through cascade reactions, further promote the degradation of Ag NPs accompanied with the Ag+ release, which could downregulate intracellular Cl− through the formation of AgCl precipitate, thereby enhancing cisplatin dechlorination and Pt–DNA formation. Moreover, polymer can also inhibit the activity of ALKBH2 (a Fe2+-dependent DNA repair enzyme) by chelating intracellular Fe2+ to increase the proportion of irreparable Pt–DNA cross-links. It is found that deep tissue penetration, as well as the increased formation and maintenance of Pt–DNA adducts induced by the nanomotor afford 80% of tumor growth inhibition with negligible toxicity. This work provides an important perspective of resolving chemotherapeutic barriers for boosting cisplatin therapy. [ABSTRACT FROM AUTHOR]

Efficient nuclear DNA damage and release is highly recommended to improve the photodynamic immunotherapy by eliciting innate immune response yet remains challenging. Herein, an intracellular self‐assembly driven nucleus‐targeted photo‐immune stimulator (PIS) with chromatin decompaction function is reported for innate and adaptive antitumor immunity co‐activation. The PIS consists of vorinostat (SAHA)‐loaded manganese‐porphyrin metal‐organic framework (Mn (III)‐TCPP MOF) with further modification of AS1411 aptamer. The PIS can be efficiently internalized by tumor cells and disassembled under the intracellular overexpressed glutathione (GSH). Notably, the released AS1411 is able to be self‐assembled with photosensitizer TCPP in situ within cells, driving nucleus‐targeted delivery of TCPP; meanwhile, the loaded SAHA can induce chromatin decompaction, cooperatively promoting TCPP‐mediated photodynamic nuclear DNA damage and cytosolic release under laser irradiation. In addition, the released manganese ions (Mn2+) further enhance the cytosolic DNA/cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon gene (STING) pathway mediated innate immunity, which synergizes with PDT‐induced immunogenic cell death to achieve co‐activation of innate and adaptive immunity. Compared to traditional PDT, the self‐assembly driven nucleus‐targeted PDT system with chromatin decompaction show significantly enhanced efficacy for inhibiting primary tumor growth and distant metastasis in several xenograft tumor models, mechanistically by promoting the maturation of dendritic cells and tumor infiltration of natural killer cell, cytotoxic T lymphocytes. [ABSTRACT FROM AUTHOR]

Most top-performed human pose estimation methods tend to have a high computational load, which is difficult to transform to resource-limited platforms. To conquer this issue, we propose an ultra-lightweight human pose estimation method based on unbiased data processing called UULPN. Firstly, we design a lightweight bottleneck block with a re-parameterized structure. Through simple linear operations, it generates a large number of feature maps and increases the diversity of feature maps. Secondly, we introduce a multi-branch structure and a single-branch structure in the bottleneck block. In the training phase, a multi-branch structure is adopted to increase the prediction accuracy. In the deploying phase, a single-branch structure is used to improve the model inference speed. These two structures realize the decoupling of the training phase and the deployment phase through the reparameterization technology. In the case of decreased computational cost, they have increased the predicted accuracy. Finally, we present a novel unbiased data processing method to solve quantization errors, which are introduced in the process of image encoding and decoding. Extensive experiment results on the MPII and COCO pose estimation benchmarks indicate that UULPN achieves almost equivalent results with the state-of-the-art methods with less computational cost. In particular, the computational cost of UULPN is almost 31% of HRNet, and the estimated accuracy on the COCO val2017 dataset is up to 74.1%, which is almost the same as HRNet-W32 at the resolution of 256 × 192. It shows that the research further develops in depth, which is of great significance. The code and the proposed method are available on https://github.com/Johnren1111/UULPN. [ABSTRACT FROM AUTHOR]

Despite the promise of tumor starvation therapies, they are often associated with nonspecific and incomplete energy blockade. Here, a novel paradigm of starvation therapy is proposed to synergize the "Zn2+ interference"‐mediated glycolysis inhibition and Zn2+‐activating GLUT1 (Glucose transporter 1) tumor specific depletion for systematic energy exhaustion. It is discovered that ZIF‐8 (zinc imidazolate metal–organic frameworks) can induce abrupt intracellular Zn2+ elevation preferentially in melanoma cells, and then achieve effective glycolysis blockade through "Zn2+ interference"‐triggered decrease of NAD+ and inactivation of GAPDH, making it a powerful tumor energy nanoinhibitor. Meanwhile, Zn2+‐activating DNAzymes for specifically cleaving GLUT1 mRNA is designed. This DNAzyme can only be activated under intracellular Zn2+ overloading, and then directionally cut off glucose supply, which further restrains the adaptive up‐regulation of glycolytic flux after glycolysis inhibition in tumors. Afterward, DNAzymes are loaded in ZIF‐8 concurrently tethered by hyaluronic acid (HA), constructing a "nanoenabled energy interrupter ". Such a rational design presents a preferential accumulation tendency to tumor sites due to the active CD44‐targeting mechanisms, specifically achieves remarkable systematic energy exhaustion in melanoma cells, and affords 80.8% in tumor growth suppression without systemic toxicity in vivo. This work verifies a fascinating therapeutic platform enabling ion interference‐inductive starvation strategy for effective tumor therapy. [ABSTRACT FROM AUTHOR]

The mining industry production is an important pillar industry in China, while its extensive production activities have led to several ecological and environmental problems. Earth observation technology using high-resolution satellite imagery can help us efficiently obtain information on surface elements, surveying and monitoring various land occupation issues arising from open-pit mining production activities. Conventional pixel-based interpretation methods for high-resolution remote sensing images are restricted by "salt and pepper" noise caused by environmental factors, making it difficult to meet increasing requirements for monitoring accuracy. With the Jingxiang phosphorus mining area in Jingmen Hubei Province as the studied area, this paper uses a multi-scale segmentation algorithm to extract large-scale main characteristic information using a layered mask method based on the hierarchical structure of the image object. The remaining characteristic elements were classified and extracted in combination with the random forest model and characteristic factors to obtain land occupation information related mining industry production, which was compared with the results of the Classification and Regression Tree model. 23 characteristic factors in three aspects were selected, including spectral, geometric and texture characteristics. The methods employed in this study achieved 86% and 0.78 respectively in overall extraction accuracy analysis and the Kappa coefficient analysis, compared to 79% and 0.68 using the conventional method. [ABSTRACT FROM AUTHOR]

In this article, the eye-in-hand visual trajectory tracking control problem of wheeled mobile robots (WMRs) is considered. Different from the conventional vision-based approaches, the monocular camera is not required to be mounted at the center of WMR, and thus the derived visual model is subject to not only the nonholonomic constraint but also the unknown camera extrinsic parameters. To ensure the WMR can track a desired trajectory effectively, a combined observation/control strategy is proposed. First, a concurrent learning observer is designed to identify the camera extrinsic parameters with measurable visual signals. Then, with the aid of the estimated parameters, a nonlinear controller is presented to achieve the tracking task. The closed-loop system stability is analyzed with Lyapunov methods, showing that both the estimation and tracking errors are asymptotically convergent to zero. Simulation and experimental results are provided to validate the developed approach. [ABSTRACT FROM AUTHOR]

This study introduces four rock–soil characteristics factors, that is, Lithology, Rock Structure, Rock Infiltration, and Rock Weathering, which based on the properties of rock formations, to predict Landslide Susceptibility Mapping (LSM) in Three Gorges Reservoir Area from Zigui to Badong. Logistic regression, artificial neural network, support vector machine is used in LSM modeling. The study consists of three main steps. In the first step, these four factors are combined with the 11 basic factors to form different factor combinations. The second step randomly selects training (70% of the total) and validation (30%) datasets out of grid cells corresponding to landslide and non-landslide locations in the study area. The final step constructs the LSM models to obtain different landslide susceptibility index maps and landslide susceptibility zoning maps. The specific category precision, receiver operating characteristic curve, and 5 other statistical evaluation methods are used for quantitative evaluations. The evaluation results show that, in most cases, the result based on Rock Structure are better than the result obtained by traditional method based on Lithology, have the best performance. To further study the influence of rock–soil characteristic factors on the LSM, these four factors are divided into "Intrinsic attribute factors" and "External participation factors" in accordance with the participation of external factors, to generate the LSMs. The evaluation results show that the result based on Intrinsic attribute factors are better than the result based on External participation factors, indicating the significance of Intrinsic attribute factors in LSM. The method proposed in this study can effectively improve the scientificity, accuracy, and validity of LSM. [ABSTRACT FROM AUTHOR]

The ability to 'see' genetic information directly in single cells can provide invaluable insights into complex biological systems. In this review, we discuss recent advances of in situ imaging technologies for visualizing the subtlest sequence alteration, single-nucleotide variation (SNV), at single-cell level. The mechanism of recently developed methods for SNV discrimination are summarized in detail. With recent developments, single-cell SNV imaging methods have opened a new door for studying the heterogenous and stochastic genetic information in individual cells. Furthermore, SNV imaging can be used on morphologically preserved tissue, which can provide information on histological context for gene expression profiling in basic research and genetic diagnosis. Moreover, the ability to visualize SNVs in situ can be further developed into in situ sequencing technology. We expect this review to inspire more research work into in situ SNV imaging technologies for investigating cellular phenotypes and gene regulation at single-nucleotide resolution, and developing new clinical and biomedical applications. [ABSTRACT FROM AUTHOR]

This paper proposes a trifocal tensor-based approach for six-degree-of-freedom visual servoing. The trifocal tensor model among the current, desired, and reference views is constructed to describe the geometric relationship of the system. More precisely, to ensure the computation consistency of trifocal tensor, a virtual reference view is introduced by exploiting the transfer relationships between the initial and desired images. Instead of resorting to explicit estimation of the camera pose, a set of visual features with satisfactory decoupling properties are constructed from the tensor elements. Based on the selected features, a visual controller is developed to regulate the camera to a desired pose, and an adaptive update law is used to compensate for the unknown distance scale factor. Furthermore, the system stability is analyzed via Lyapunov-based techniques, showing that the proposed controller can achieve almost global asymptotic stability. Both simulation and experimental results are provided to demonstrate the effectiveness and robustness of our approach under different conditions and case studies. [ABSTRACT FROM AUTHOR]

The spatial organization of cell‐surface receptors plays an important role in defining cell fate. Recently, the development of strategies for the direct regulation of receptor clustering using nanomaterials has aroused enormous interest. In this review, we discuss the mechanisms and features of recently developed nanomaterial‐based strategies to control the nanoscale distribution of cell binding ligands and regulate cell behavior. We expect this review to inspire innovative work on manipulating cell functions by controlling the clustering of cell surface receptors. Controlling cell fate: The mechanisms and features of nanomaterials for controlling the nanoscale distribution of cell binding ligands and regulating the cell behavior are summarized and discussed in this Minireview. [ABSTRACT FROM AUTHOR]

In this paper, a homography-based visual servo controller is developed for a rigid body to track a moving object in three-dimensional space with a fixed relative pose. Specifically, a monocular camera is mounted on the rigid body, and the desired relative pose is expressed by a pre-recorded reference image. Homography is exploited to obtain the orientation and scaled position for controller design. Considering the unknown moving object's velocities and distance information, a continuous nonlinear visual controller is developed using the robust integral of the signum of the error methodology. To facilitate the stability analysis, the system uncertainties regarding the moving object's velocities and distance information are divided into the error-unrelated system uncertainties and the error-related system uncertainties. After that, the upper bounds of the error-related system uncertainties are derived with composited system errors. An asymptotic tracking of the leading object is proved based on the Lyapunov methods and the derived upper bounds. In addition, the proposed controller is extended to address the trajectory tracking problem. Simulation results validate the effectiveness of the proposed approach. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Efficient gene modification in BSF has also recently been reported (Zhan I et al. i , [45]; Kou I et al. i , [17]), highlighting the possibility of revealing the functions of genes and selecting more economically beneficial strains. Dear Editor, Economic and population growth increasingly consume resources from the environment and present a major challenge regarding the management of waste. The comprehensive database BSFbase integrates multiple lines of omics data and other informative data on BSF. As modification by gene editing is an increasingly popular way of improving breeds, BSFbase provides a clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR-associated protein 9 (Cas9) protocol and video protocol in "Source" with the aim of facilitating the effective application of this technology to BSF. [Extracted from the article]

Quantification of miRNAs in blood can be potentially used for early disease detection, surveillance monitoring and drug response evaluation. However, quantitative and robust measurement of miRNAs in blood is still a major challenge in large part due to their low concentration and complicated sample preparation processes typically required in conventional assays. Here, we present the ‘Integrated Comprehensive Droplet Digital Detection’ (IC 3D) system where the plasma sample containing target miRNAs is encapsulated into microdroplets, enzymatically amplified and digitally counted using a novel, high-throughput 3D particle counter. Using Let-7a as a target, we demonstrate that IC 3D can specifically quantify target miRNA directly from blood plasma at extremely low concentrations ranging from 10s to 10 000 copies per mL in ≤3 hours without the need for sample processing such as RNA extraction. Using this new tool, we demonstrate that target miRNA content in colon cancer patient blood is significantly higher than that in healthy donor samples. Our IC 3D system has the potential to introduce a new paradigm for rapid, sensitive and specific detection of low-abundance biomarkers in biological samples with minimal sample processing. [ABSTRACT FROM AUTHOR]

Dynamic average consensus is a decentralized control/estimation framework where a group of agents cooperatively track the average of local time-varying reference signals. In this paper, we develop a novel state decomposition-based privacy preservation scheme to protect the privacy of agents when sharing information with neighboring agents. Specifically, we first show that an external eavesdropper can successfully wiretap the reference signals of all agents in a conventional dynamic average consensus algorithm. To protect privacy against the eavesdropper, a state decomposition scheme is developed where the original state of each agent is decomposed into two sub-states: one succeeds the role of the original state in inter-node interactions, while the other sub-state only communicates with the first one and is invisible to other neighboring agents. Rigorous analyses are performed to show that (1) the proposed privacy scheme preserves the convergence of the average consensus; and (2) the privacy of the agents is protected such that an eavesdropper cannot discover the private reference signals with guaranteed accuracy. The developed privacy-preserving dynamic average consensus framework is then applied to the formation control of multiple non-holonomic mobile robots, in which the efficacy of the scheme is demonstrated. Numerical simulation is provided to illustrate the effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

B Tumor Starvation Therapy b In article number 2103534 by Zhenzhong Zhang, Junjie Liu, Jinjin Shi, and co-workers, a "nano-enabled energy interrupter"-initiated novel paradigm of tumor starvation therapy is proposed. Nano-enabled Tumor Systematic Energy Exhaustion via Zinc (II) Interference Mediated Glycolysis Inhibition and Specific GLUT1 Depletion (Adv. Sci. 7/2022) The energy interrupter shows a preferential tumor systemic energy exhaustion without obvious side effects by synergizing the "Zn SP 2+ sp interference"-mediated glycolysis inhibition and Zn SP 2+ sp -activating GLUT1 (glucose transporter 1) tumor specific depletion. [Extracted from the article]

There is a growing need for robotic apple harvesting due to decreasing availability and rising cost in labor. Towards the goal of developing a viable robotic system for apple harvesting, this paper presents synergistic mechatronic design and motion control of a robotic apple harvesting prototype, which lays a critical foundation for future advancements. Specifically, we develop a deep learning-based fruit detection and localization system using a RGB-D camera. A three degree-of-freedom manipulator is designed with a hybrid pneumatic/motor actuation mechanism to achieve dexterous movements. A vacuum-based end-effector is used for apple detaching. These three components are integrated into a robotic apple harvesting prototype with simplicity, compactness, and robustness. Moreover, a nonlinear control scheme is developed for the manipulator to achieve accurate and agile motion control. Field experiments are conducted to demonstrate the performance of the developed apple harvesting robot. • The synergistic development of a robotic apple harvesting prototype is presented. • A control strategy is designed by fully exploiting the mechanical structure of the manipulator. • The experimental studies validate the design concept and underpin future research. [ABSTRACT FROM AUTHOR]

Precise and efficient regulation of microglia is vital for ischemic stroke therapy and prognosis. The infiltration of neutrophils into the brain provides opportunities for regulatory drugs across the blood–brain barrier, while hindered by neutrophil extracellular traps (NETs) and targeted delivery of intracerebral drugs to microglia. This study reports an efficient neutrophil hijacking nanoplatform (referred to as APTS) for targeted A151 (a telomerase repeat sequence) delivery to microglia without the generation of NETs. In the middle cerebral artery occlusion (MCAO) mouse model, the delivery efficiency to ischemic stroke tissues increases by fourfold. APTS dramatically reduces the formation of NETs by 2.2‐fold via reprogramming NETosis to apoptosis in neutrophils via a reactive oxygen species scavenging‐mediated citrullinated histone 3 inhibition pathway. Noteworthy, A151 within neutrophils is repackaged into apoptotic bodies following the death pattern reprogramming, which, when engulfed by microglia, polarizes microglia to an anti‐inflammatory M2 phenotype. After four times treatment, the cerebral infarction area in the APTS group decreases by 5.1‐fold. Thus, APTS provides a feasible, efficient, and practical drug delivery approach for reshaping the immune microenvironment and treating brain disorders in the central nervous system. [ABSTRACT FROM AUTHOR]

Glycemic variability (GV) has been related to complications in patients with diabetes. The aim of the systematic review and meta-analysis was to investigate whether GV is also associated with the incidence of diabetic peripheral neuropathy (DPN). A systematic search of Medline, Web of Science, Embase, and Cochrane Library database was conducted to identify relevant observational studies with longitudinal follow-up. The Newcastle-Ottawa Scale was used for study quality evaluation. A random-effects model was utilized to pool the results, accounting for heterogeneity. Ten observational studies including 72 565 patients with diabetes were included. The quality score was 8–9, indicating generally good quality of the included studies. With a mean follow-up duration of 7.1 years, 11 532 patients (15.9%) were diagnosed as DPN. Compared to patients with low GV, patients with high GV were associated with an increased risk incidence of DPN (risk ratio: 1.51, 95% confidence interval: 1.23 to 1.85, p<0.001; I2=78%). In addition, subgroup analysis showed consistent results in patients with type 1 and type 2 diabetes, and in studies evaluating the short-term and long-term GV (p for subgroup difference=0.82 and 0.53). Finally, results of subgroup analysis also suggested that the association between GV and risk of DPN were not significantly affected by study design, follow-up durations, diagnostic methods for DPN, adjustment of mean glycated hemoglobin A1c, or study quality scores (p for subgroup difference all>0.05). A high GV may be associated with an increased incidence of DPN. [ABSTRACT FROM AUTHOR]

Single-nucleotide variants (SNVs) are the most common type variation of sequence alterations at a specific location in the genome, thus involving significant clinical and biological information. The assay of SNVs has engaged great awareness, because many genome-wide association studies demonstrated that SNVs are highly associated with serious human diseases. Moreover, the investigation of SNV expression levels in single cells are capable of visualizing genetic information and revealing the complexity and heterogeneity of single-nucleotide mutation-related diseases. Thus, developing SNV assay approaches in vitro , particularly in single cells, is becoming increasingly in demand. In this review, we summarized recent progress in the enzyme-free and enzyme-mediated strategies enabling SNV assay transition from sensing interface to the test tube and single cells, which will potentially delve deeper into the knowledge of SNV functions and disease associations, as well as discovering new pathways to diagnose and treat diseases based on individual genetic profiles. The leap of SNV assay achievements will motivate observation and measurement genetic variations in single cells, even within living organisms, delve into the knowledge of SNV functions and disease associations, as well as open up entirely new avenues in the diagnosis and treatment of diseases based on individual genetic profiles. [ABSTRACT FROM AUTHOR]

Ten-eleven translocation (TET) proteins, encoding dioxygenase for DNA hydroxymethylation, are important players in nervous system development and disease. In addition to their proverbial enzymatic role, TET proteins also possess non-enzymatic activity and function in multiple protein–protein interaction networks, which remains largely unknown during oligodendrocyte differentiation. To identify partners of TET1 in the myelinating cells, we performed proteome-wide analysis using co-immunoprecipitation coupled to mass spectrometry (IP-MS) in purified oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs), respectively. Following a stringent selection of MS data based on identification reliability and protein enrichment, we identified a core set of 1211 partners that specifically interact with TET1 within OPCs and OLs. Analysis of the biological process and pathways associated with TET1-interacting proteins indicates a significant enrichment of proteins involved in regulation of cellular protein localization, cofactor metabolic process and regulation of catabolic process, et al. We further validated TET1 interactions with selected partners. Overall, this comprehensive analysis of the endogenous TET1 interactome during oligodendrocyte differentiation suggest its novel mechanism in regulating oligodendrocyte homeostasis and provide comprehensive insight into the molecular pathways associated with TET1. [ABSTRACT FROM AUTHOR]

• WMPAE inhibited the growth of Aphanizomenon flos-aquae. • WMPAE decreased the cell viability promptly, induced cell shape and caused the intracellular structural damage. • WMPAE increased the activities of intracellular antioxidant enzymes, caused lipid peroxidation. • WMPAE exerted detrimental effects on photosynthetic efficiency. • Our results presented multiple physiological responses of Aphanizomenon flos-aquae to WMPAE. Natural algaecides are more likely to be specific and biodegradable, and may offer an environmentally friendly method for control of cyanobacterial blooms. We explored, for the first time, the potential for watermelon peel aqueous extract (WMPAE) to control the growth of the harmful blue-green alga Aphanizomenon flos-aquae. The growth inhibition and several physiological parameters of A. flos-aquae , in response to WMPAE, were analyzed. Results showed that WMPAE significantly inhibited the growth of A. flos-aquae in a concentration-dependent way. The highest inhibition reached 94 % after 3 days' treatment with 6 g L−1 of WMPAE and a significant effect was obtained with lower doses and shorter times as well. The cell viability decreased quickly, cell shape changed, and intracellular structural damage occurred. At the same time, the antioxidant enzymes (superoxide dismutase SOD, catalase CAT and peroxidase POD) and malondialdehyde (MDA) levels all increased significantly, indicating that WMPAE between 2–6 g L−1 induced severe oxidative stress and damage to A. flos-aquae. Moreover, production of the four pigments chlorophyll a (Chl a), carotenoids, phycocyanin (PC), and allophycocyanin (APC) were all stimulated, though photosynthesis of A. flos-aquae was clearly inhibited. The maximum quantum yield of photosystem II (F v / F m) and the effective quantum yield of photosystem II ( F v ' / F m ') declined sharply, suggesting the decreased photosystem capacity of A. flos-aquae to convert light energy into chemical energy. In addition, non-photochemical quenching (N P Q) of A. flos-aquae increased after a very short time exposure to WMPAE, and decreased significantly with prolonged exposure time, which indicated the failure of photo protection mechanisms. These results suggest that the loss of cell viability, and increases in oxidative stress, and damage to intracellular structure and photosynthetic systems might be the mechanisms for the inhibitory effects. Our results suggested that WMPAE could be a novel and effective approach for controlling the growth of A. flos-aquae in aquatic environments. [ABSTRACT FROM AUTHOR]

• Type I (electron transfer) PDT of C60 is significantly enhanced by gold nanoparticles. • C60@GNPs can be excited under near-infrared light, which has a high tissue penetration. • C60@GNPs with near-infrared light irradiation can obtain oxygen non-dependent of PDT. Recently, fullerene (C60) has been widely used as a nano photosensitizer (PS) for tumor related photodynamic therapy (PDT). However, current PDT based on C60 is severely restricted by the visible light source (shallow tissue penetrating depth) and oxygen dependent (tumor hypoxia). Therefore, taking advantages of the surface plasmon resonance (SPR) effect of gold nanoparticles (GNPs) and "electronic sponge" property of C60, a C60 based hybrid nanostructured photosensitizer (C60@GNPs) with high light stability, near infrared light (NIR) excitation, and oxygen non-dependent properties was rational designed according to the mechanism of PDT. Compared with C60, after GNPs in-situ synthesis, the PDT mechanism of C60@GNPs changed from type II to type I, and the main product of PDT changed from singlet oxygen to hydroxyl radicals. Furthermore, C60@GNPs hybrid could efficiently generate hydroxyl radicals under NIR light excitation even in the hypoxia condition. These results suggest that C60@GNPs hybrid has a great potential for in vivo PDT applications. [ABSTRACT FROM AUTHOR]

Single cell analysis is of great significance to biological and biomedical research. With recent development, lots of in situ amplification methods have been applied for imaging the spatial location of specific biomolecules in situ in single cells. In particular, RCA is a simple and efficient isothermal amplification method, which can locally amplify the fluorescent signal in situ. Due to the ability of detecting single molecules directly in cells and tissues, RCA has been widely used for illustrating many important biological processes. In this review, we summarize recent development of RCA-based method for single cell analysis and discuss their applications. Moreover, we emphasize the utilization of RCA for in situ sequencing, which is a very interesting and emerging research field. • The basic mechanism of rolling circle amplification (RCA) for in situ single cell imaging is summarized. • RCA can be used for analysis of various targets in situ in single cells, including gene expression, single-nucleotide variation, mRNA splicing and protein post-translation modification. • The utilization of RCA for in situ sequencing are discussed. [ABSTRACT FROM AUTHOR]

• Mesoporous MnO2 nanoparticle was employed as the carrier and quencher of photosensitizer. • Tumor marker MUC-1 activated ROS generation system was constructed based on the gatekeeper effect of aptamer. • MCF-7 was killed selectively via the tumor cell activated photodynamic therapy. Herein, we report a turn-on strategy for selectively killing the tumor cell via combining the singlet-oxygen quenching MnO 2 and tumor cell-targeting aptamer. The photosensitizers were in the quenching state when loaded in the mesoporous MnO 2 (mMnO 2) nanoparticles and sealed by the aptamer on the particle surface. The aptamer can selectively recognize the specific membrane protein on the tumor cell and release the photosensitizers, activating the photosensitizer and killing the tumor cells. The specific binding-induced "off-on" switching of singlet oxygen generation reduced the damage to the nearby healthy cells to a large extent. The high loading ability for photosensitizer and the GSH consumption property of mMnO 2 endow the system with high local concentration of singlet-oxygen for killing the target tumor cell. The high selectivity and efficiency of the constructed singlet oxygen regulating system will pave a new way for utilizing PDT in cancer precise treatment. [ABSTRACT FROM AUTHOR]

N6‐methyladenosine (m6A) modification—the most prevalent mammalian RNA internal modification—plays key regulatory roles in mRNA metabolism. Current approaches for m6A modified RNA analysis limit at bulk‐population level, resulting in a loss of spatiotemporal and cell‐to‐cell variability information. Here we proposed a m6A‐specific in situ hybridization mediated proximity ligation assay (m6AISH‐PLA) for cellular imaging of m6A RNA, allowing to identify m6A modification at specific location in RNAs and image m6A RNA with single‐cell and single‐molecule resolution. Using m6AISH‐PLA, we investigated the m6A level and subcellular location of HSP70 RNA103‐m6A in response to heat shock stress, and found an increased m6A modified ratio and an increased distribution ratio in cytoplasm under heat shock. m6AISH‐PLA can serve in the study of m6A RNA in single cells for deciphering epitranscriptomic mechanisms and assisting clinical diagnosis. [ABSTRACT FROM AUTHOR]

N6‐methyladenosine (m6A) modification—the most prevalent mammalian RNA internal modification—plays key regulatory roles in mRNA metabolism. Current approaches for m6A modified RNA analysis limit at bulk‐population level, resulting in a loss of spatiotemporal and cell‐to‐cell variability information. Here we proposed a m6A‐specific in situ hybridization mediated proximity ligation assay (m6AISH‐PLA) for cellular imaging of m6A RNA, allowing to identify m6A modification at specific location in RNAs and image m6A RNA with single‐cell and single‐molecule resolution. Using m6AISH‐PLA, we investigated the m6A level and subcellular location of HSP70 RNA103‐m6A in response to heat shock stress, and found an increased m6A modified ratio and an increased distribution ratio in cytoplasm under heat shock. m6AISH‐PLA can serve in the study of m6A RNA in single cells for deciphering epitranscriptomic mechanisms and assisting clinical diagnosis. [ABSTRACT FROM AUTHOR]

Amplifying intracellular oxidative stress by organelle‐targeted reactive oxygen species (ROS) production combined with tumor cell‐specific gene disruption is a promising strategy for tumor treatment. However, due to the vulnerability of CRISPR/Cas9 ribonucleoproteins (RNPs) to ROS, co‐delivery of CRISPR/Cas9 RNPs and ROS generators to enhance the sensitivity of tumor cells to oxidative stress remains challenging. Herein, a cascade‐responsive "oxidative stress amplifier" (named DR‐TAF‐pHT/FA) is proposed, which can successively respond to cathepsin B, localized laser irradiation and ATP to generate ROS on the lysosomal membrane of tumor cells and release Cas9/sgNrf2 RNPs for efficient gene disruption. It is demonstrated that, under near infrared (NIR) irradiation, DR‐TAF‐pHT/FA achieves targeted rupture of lysosomal membranes, inducing significant intracellular oxidative stress. Meanwhile, due to the protective function of TAF coating (TA‐Fe3+ coordination self‐assembled networks), Cas9/sgNrf2 RNPs can safely escape into the cytoplasm and be released in response to ATP, further amplifying oxidative stress and promoting tumor cell apoptosis through efficient Nrf2 gene disruption. Treatment with DR‐TAF‐pHT/FA + NIR significantly improves tumor ablation efficiency and extends median survival time (over 70 days) in Hela xenograft models. This "oxidative stress amplifier" provides a new paradigm for multimodal and synergistic tumor therapy through precise lysosomal membrane bursting together with efficient Nrf2 gene disruption. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a progressive histological manifestation that happens in almost all chronic liver diseases. An unabated liver fibrosis may eventually develop into liver cirrhosis or hepatocellular carcinoma. Yet, the strategy for reversal of liver fibrosis is still limited. Herein, a biomimetic nano‐regulator (P‐ZIF8‐cirDNAzyme) is developed to affect both collagen synthesis and degradation in liver to remodel collagen microenvironment. It is found that Zn (II) interference can efficiently inhibit collagen synthesis in activated hepatic stellate cells (aHSC) by inactivating proline 4 hydroxylase and affecting many fibrosis‐related signaling pathways. Meanwhile, Zn (II)‐dependent circular DNAzymes (cirDNAzymes) are used to efficiently silence tissue inhibitors of metalloproteinase‐1, accelerating the degradation of collagen. They act in concert to recover the balance between collagen deposition and degradation. Additionally, ZIF‐8‐cirDNAzyme is coated by platelet membrane (PM) for precisely targeting aHSC via PM's inflammatory tropism and CD62p–CD44 interaction. In carbon tetrachloride‐induced fibrotic mice, P‐ZIF‐8‐cirDNAzyme shows a potent anti‐fibrotic effect, greatly reducing the expression of collagen by 73.12% and restoring liver function nearly to normal. This work proposes a prospective platform enabling ion interference and gene silencing, collectively acting in aHSC for reversal of liver fibrosis. [ABSTRACT FROM AUTHOR]

This paper concerns the road reconstruction problem of on-road vehicles with shadows. To deal with the effects of shadows, images are transformed to the proposed illuminant invariant color space and are fused with raw images to obtain more details in both dark and bright regions. Then, the road region is reconstructed from a geometry point of view. Based on the two-view geometric model, the scene can be described by the projective parallax information with respect to a reference plane, which is the grounding plane of the vehicle in this paper. The road reconstruction is performed row-by-row recursively. For each row, a row-wise image registration method is used to estimate the parallax information, based on which height information with respect to the reference plane can be calculated. Based on the distributions of height information and image intensity, the road region is detected and is used to direct the image registration of the next row. This process stops when the road region is small enough and the entire road region is obtained. The proposed approach is general in the sense that it works with shadows for different road types and camera configurations. Experimental results are provided to show the effectiveness and robustness of the proposed method. [ABSTRACT FROM AUTHOR]

Abundant cancer-associated fibroblasts (CAFs) in highly fibrotic breast cancer constitute an immunosuppressive barrier for T cell activity and are closely related to the failure of immune checkpoint blockade therapy (ICB). Inspired by the similar antigen-processing capacity of CAFs to professional antigen-presenting cells (APCs), a "turning foes to friends" strategy is proposed by in situ engineering immune-suppressed CAFs into immune-activated APCs for improving response rates of ICB. To achieve safe and specific CAFs engineering in vivo , a thermochromic spatiotemporal photo-controlled gene expression nanosystem was developed by self-assembly of molten eutectic mixture, chitosan and fusion plasmid. After photoactivatable gene expression, CAFs could be engineered as APCs via co-stimulatory molecule (CD86) expression, which effectively induced activation and proliferation of antigen-specific CD8 + T cells. Meanwhile, engineered CAFs could also secrete PD-L1 trap protein in situ for ICB, avoiding potential autoimmune-like disorders caused by "off-target" effects of clinically applied PD-L1 antibody. The study demonstrated that the designed nanosystem could efficiently engineer CAFs, significantly enhance the percentages of CD8+ T cells (4-folds), result in about 85% tumor inhibition rate and 83.3% survival rate at 60 days in highly fibrotic breast cancer, further inducing long-term immune memory effects and effectively inhibiting lung metastasis. [Display omitted] • No-destructive and precise photoactivatable gene expression. • In situ engineering immune-suppressed CAFs as immune-activated APCs. • In situ blockading of PD-1/PD-L1 interaction. [ABSTRACT FROM AUTHOR]

Deoxyribonucleic acid (DNA) methylation is one of the epigenetic characteristics that result in heritable and revisable phenotype changes but without sequence changes in DNA. Aberrant methylation occurring at a specific locus was reported to be associated with cancers, insulin resistance, obesity, Alzheimer's disease, Parkinson's disease, etc. Therefore, locus‐specific DNA methylation can serve as a valuable biomarker for disease diagnosis and therapy. Recently, Clustered regularly interspaced short palindromic repeats (CRISPR)‐Cas systems are applied to develop biosensors for DNA, ribonucleic acid, proteins, and small molecules detection. Because of their highly specific binding ability and signal amplification capacity, CRISPR‐Cas assisted biosensor also serve as a potential tool for locus‐specific detection of DNA methylation. In this perspective, based on the detection principle, a detailed classification and comprehensive discussion of recent works about the latest advances in locus‐specific detection of DNA methylation using CRISPR‐Cas systems are provided. Furthermore, current challenges and future perspectives of CRISPR‐based locus‐specific detection of DNA methylation are outlined. [ABSTRACT FROM AUTHOR]

This paper presents a road reconstruction algorithm based on two-view geometry. A general geometric model for both planar and nonplanar scenes is proposed with respect to a reference plane. Then, points in the scene can be described geometrically by the projective parallax with respect to the reference plane. In practice, the grounding plane of the vehicle is selected as the reference plane. A row-wise image registration method is proposed to estimate the parallax information effectively. Based on the geometric model, points in the scene can be reconstructed as relative position and height information with respect to the reference plane. For road detection, the scene can be segmented where the height changes abruptly. Then, the road region is obtained by a diffusion strategy. The road surface can be reconstructed using the proposed model. Experiments are conducted to show the effectiveness and robustness of the proposed approach. The proposed approach is general in the sense that it does not rely on the priors of road appearance and structure, and it is not restricted to specific stereo camera configurations making it extendable to other multicamera systems. [ABSTRACT FROM AUTHOR]

During tunnel boring machine (TBM) construction, the rock breaking effect of the disc cutter in complex formations affects the progress and cost of the entire project. Therefore, it is necessary to better understand the rock breaking mechanism of TBM in complex formations. In this study, matrix discrete element method (MatDEM) software is used to study the rock breaking mechanism of the disc cutter at the interface of soil and rock. Based on the theoretical study and analysis of rock breaking process of the disc cutter in the soil-rock composite formations, the three-dimensional dynamic rock breaking process of the disc cutter in soil-rock formations with different rock dip angles (0°, 15°, 30°, 45°, 60°, 75°) is simulated by using MatDEM, and the simulation results are analyzed from three aspects: the unit force, the fracture number of unit connection, and the system energy. The main conclusions are as follows: when the disc cutter is used to roll and break the rock at the soil-rock interface of composite formations, the unit force and the fracture number of unit connection are positively related to the contact area S of the rock and blade at the front edge of the disc cutter. The energy to break the rock by the disc cutter is mainly affected by the broken rock volume per unit time Vdt. The greater the Vdt is, the more energy the disc cutter needs to break the rock is. The total force P is affected by the contact area S (β, t). The change of the maximum total force is small when β = 15°, 30°, and 45°, and is obviously lower at 60° and 75°, respectively. [ABSTRACT FROM AUTHOR]

The power industry in China is the foremost emitter of carbon, necessitating a clean transition in its power generation segment for successful decarbonization. Identifying and quantitative analysis the critical factors that shape the transition and their operational mechanisms will help achieve a secure low-carbon transformation of the energy system. Nonetheless, the body of extensive research in this particular field remains notably limited. To bridge this gap, this paper initiates by developing a comprehensive mechanism framework (REEP) for the transition towards cleaner power generation including Resource endowment (abbreviated as R), Electricity market (abbreviated as E), Economic development (abbreviated as E) and Policy implementation (abbreviated as P) four fields. This framework is based on monthly power generation data derived from four categories of power generation sources at the provincial level in China, spanning the years 2014–2019. It dynamically and quantitative elucidates the multifaceted impacts of various influencing factors on the evolution of the power generation structure. Based on the REEP framework, we observe the power generation structure evolution trends. The study's findings underscore the significance of resource endowment as a paramount internal factor influencing the clean evolution of the power generation structure, while economic development emerges as a pivotal external driving force propelling its transformation. Despite wind and solar power generation accounting for a relatively small proportion at the end of the 14th Five Year Plan period, it is imperative for China to continue promoting the extensive development of renewable energy. While we should coordinate national power transmission and distribution on the foundation of incentivizing technological innovation in emission reduction and the development of energy storage technology. This approach is essential to comprehensively advance the low-carbon and stable development of the energy system, ultimately facilitating the realization of the dual-carbon goal. [ABSTRACT FROM AUTHOR]

The article titled "Retraction Note: Copper-based metal–organic framework impedes triple-negative breast cancer metastasis via local estrogen deprivation and platelets blockade" has been retracted by the Editors-in-Chief of the Journal of Nanobiotechnology. The authors discovered errors in several figures, and further checks by the publisher revealed inconsistencies in the presented data. The Editors-in-Chief no longer have confidence in the data and the authors have agreed to the retraction. Springer Nature, the publisher, remains neutral in regards to jurisdictional claims and institutional affiliations. [Extracted from the article]

Background: Tyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits are often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and focal adhesion kinase (FAK). Here we present the preclinical evaluation of APG-2449, which exhibits antiproliferative activity in cells carrying ALK fusion or secondary mutations.Methods: KINOMEscan® and LANCE TR-FRET were used to characterize targets and selectivity of APG-2449. Water-soluble tetrazolium salt (WST-8) viability assay and xenograft tumorigenicity were employed to evaluate therapeutic efficacy of monotherapy or drug combination in preclinical models of solid tumors. Western blot, pharmacokinetic, and flow cytometry analyses, as well as RNA sequencing were used to explore pharmacokinetic-pharmacodynamic correlations and the mechanism of actions driving drug combination synergy.Results: In mice bearing wild-type or ALK/ROS1-mutant non-small-cell lung cancer (NSCLC), APG-2449 demonstrates potent antitumor activity, with correlations between pharmacokinetics and pharmacodynamics in vivo. Through FAK inhibition, APG-2449 sensitizes ovarian xenograft tumors to paclitaxel by reducing CD44+ and aldehyde dehydrogenase 1-positive (ALDH1+) cancer stem cell populations, including ovarian tumors insensitive to carboplatin. In epidermal growth factor receptor (EGFR)-mutated NSCLC xenograft models, APG-2449 enhances EGFR TKI-induced tumor growth inhibition, while the ternary combination of APG-2449 with EGFR (osimertinib) and mitogen-activated extracellular signal-regulated kinase (MEK; trametinib) inhibitors overcomes osimertinib resistance. Mechanistically, phosphorylation of ALK, ROS1, and FAK, as well as their downstream components, is effectively inhibited by APG-2449.Conclusions: Taken together, our studies demonstrate that APG-2449 exerts potent and durable antitumor activity in human NSCLC and ovarian tumor models when administered alone or in combination with other therapies. A phase 1 clinical trial has been initiated to evaluate the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK+ NSCLC refractory to earlier-generation ALK inhibitors.Trial Registration: Clinicaltrial.gov registration: NCT03917043 (date of first registration, 16/04/2019) and Chinese clinical trial registration: CTR20190468 (date of first registration, 09/04/2019). [ABSTRACT FROM AUTHOR]

Metastasis is one of the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Abnormally estrogen level and activated platelets are the key driving forces for TNBC metastasis. Herein, an "ion/gas" bioactive nanogenerator (termed as IGBN), comprising a copper-based MOF and loaded cisplatin-arginine (Pt-Arg) prodrug is developed for metastasis-promoting tumor microenvironment reprogramming and TNBC therapy. The copper-based MOF not only serves as a drug carrier, but also specifically produces Cu2+ in tumors, which catalytic oxidizing estrogen to reduce estrogen levels in situ. Meanwhile, the rationally designed Pt-Arg prodrug reduced into cisplatin to significantly promote the generation of H2O2 in the tumor, then permitting self-augmented cascade NO gas generation by oxidizing Arg through a H2O2 self-supplied way, thus blocking platelet activation in tumor. We clarified that IGBN inhibited TNBC metastasis through local estrogen deprivation and platelets blockade, affording 88.4% inhibition of pulmonary metastasis in a 4T1 mammary adenocarcinoma model. Notably, the locally copper ion interference, NO gas therapy and cisplatin chemotherapy together resulted in an enhanced therapeutic efficacy in primary tumor ablation without significant toxicity. This "ion/gas" bioactive nanogenerator offers a robust and safe strategy for TNBC therapy. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Inspired by the adaptation of cells to the surrounding environment, the combination of cell membrane and nanomaterials has gradually become a new type of biomimetic nanocomposite. The construction of endogenous membrane biomimetic nanocarriers (EMBNs) not only retains the structure of membrane surface protein, but also has the properties of nanoparticles (NPs), also provides the ability of natural interaction between nanomaterials and organisms, thus overcoming the severe challenges faced by traditional nanodelivery systems in clinical application. In this paper, the construction methods of EMBNs are reviewed, focusing on a simple method to prepare membrane proteins. Secondly, EMBNs were classified according a variety of cell membranes. Finally, the unique advantages of EMBNs in nanomedicine are introduced, including improving biocompatibility, homologous targeting ability, prolonging blood circulation time and immune escape ability. In nanomedicine, such as targeted delivery, phototherapy, immunotherapy and tumor imaging, multifaceted biological interfaces through membrane masking provide a new approach for the development of multifunctional NPs. [ABSTRACT FROM AUTHOR]

The clinical outcomes of programmed cell death protein‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) blockade are usually limited by the multiple immune evasion mechanism of the tumor, as well as the immune storm caused by "off‐target" effects of the PD‐1/PD‐L1 antibody. Here, a previously unknown strategy is proposed to synergize the "Ca2+ interference" mediated M2‐like tumor‐associated macrophages (TAM) re‐education and Ca2+‐activating locally PD‐L1 depletion for immunotherapy. The authors discover that calcium‐containing nanoparticles can induce significant "Ca2+ interference" effect and simultaneously reset TAM toward the M1 phenotype through activation of multiple inflammation‐related signaling pathways, as well as NLRP3 inflammasomes, and promoting in situ tumor‐associated antigen release. In addition, a circular aptamer‐DNAzyme conjugate (cAD) is designed with a tumor‐targeting ability and its catalytic shear activity can be specifically activated by Ca2+, which reduces potential autoimmune‐like disorders of PD‐L1 antibody. By simply integrating the ultra‐high pH‐sensitive calcium peroxide nanoparticles with cAD into one nanosystem, it is demonstrated that the nanosystem not only arrest primary tumor progression and lung metastasis but also provides a long‐term immunological memory, which can protect against tumor rechallenge. Therefore, this work provides an attractive strategy for boosting tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Highlights: [•] We highlight droplet microfluidics in cancer research, diagnosis and therapy. [•] Droplet microfluidics is suitable for single-molecule and single-cell analysis. [•] Molecular and cellular heterogeneity can be dissected using droplet microfluidics. [ABSTRACT FROM AUTHOR]

By using the cold metal transfer welding technique, an S215 Al-bronze repair layer (∼850 μm in thickness) was successfully fabricated on the surface of 27SiMn steel. The microstructure of the repair layer was characterized by X-ray diffraction, electron channeling contrast imaging, energy dispersive spectrometry and electron backscatter diffraction techniques. Corrosion resistance and hardness of the repair layer were evaluated using an electrochemical workstation and a Vickers hardness tester, respectively. The repair layer mainly consists of near equiaxed Cu-phase grains and dispersed α-Fe particles (with interlaced fine laths as internal substructures) resulting from the liquid phase separation of the Cu Fe system during rapid solidification. The corrosion resistance of the repair layer (E corr : −463.2 mV and I corr : 1.263 μA/cm2) is found substantially superior to that of the substrate (E corr :−658.9 mV and I corr : 3.310 μA/cm2). The corrosion rate of the repair layer is reduced by ∼59.2 % compared to the substrate. This improvement is related to the formation of protective passive films (Cu/Al-oxides) on the repair layer during electrochemical corrosion. This research should be able to provide valuable insights for preparing corrosion-resistant repair layers for steels. • A defect-free Al-bronze repair layer was prepared on 27SiMn steel by cold metal transfer • Repair layer consists of Cu-phase grains and dispersed α-Fe particles with lath substructures • Repair layer exhibits superior electrochemical corrosion resistance compared to substrate • Enhanced corrosion resistance is due to protective passive films formed on repair layer [ABSTRACT FROM AUTHOR]

Following ischemic stroke, brain‐resident activated microglia and peripherally infiltrated inflammatory cells create a complicated and overactivated brain immune microenvironment, which causes neuron death and dramatically hinders neurological functional recovery. Herein, an engineering CXCL12 biomimetic decoy‐integrated versatile immunosuppressive nanoparticle (VIN) for management of the overactivated brain immune microenvironment is reported. The shell of VIN (membrane of CXCR4 overexpressed mesenchymal stem cells), can not only improve the homing of nanoparticles to the cerebral ischemic lesions, but also efficiently adsorb and neutralize CXCL12 to cut off infiltration of peripheral‐neutrophils and mononuclear macrophages. The loaded A151 (cGAS inhibitor, telomerase repeat sequences) can inhibit cGAS‐STING pathway in microglia, leading to microglia polarization toward an anti‐inflammatory M2‐like phenotype. Interestingly, A151 can be efficiently loaded onto the polydopamine nanospheres (PDA, the core of VIN) through the bridge of Zn2+. In the inflammatory site, PDA is oxidized by reactive oxygen species (ROS), with the disappearance of Zn2+ complexation effect, and then A151 realizes a controlled release. In a model of rat ischemic stroke, VIN integrates inflammation tropism, peripherally inflammatory cells filtrate, brain‐resident activated microglia polarization, as well as, ROS scavenging, exerting outstanding therapeutic effects on ameliorating the mortality, reducing the infarct volume, and protecting neurogenic functions of neurons. [ABSTRACT FROM AUTHOR]

In their Communication on page 22646, Jinghong Li et al. propose a powerful in situ imaging method, termed m SP 6 sp A-specific in situ hybridization mediated proximity ligation assay (m SP 6 sp AISH-PLA), that enables the identification of m SP 6 sp A modifications at a specific location in RNAs and the imaging of m SP 6 sp A RNA with single-cell and single-molecule resolution. Keywords: in situ imaging; m6A; proximity ligation; single-molecule; spatiotemporal information EN in situ imaging m6A proximity ligation single-molecule spatiotemporal information 22589 22589 1 10/06/21 20211011 NES 211011 B N b SP B 6 b sp B -methyladenosine b (m SP 6 sp A)-modified RNA analysis is limited at the bulk-population level, thus not giving access to spatiotemporal and cell-to-cell variability information. Cover Picture: Single-Cell Imaging of m6A Modified RNA Using m6A-Specific In Situ Hybridization Mediated Proximity Ligation Assay (m6AISH-PLA) (Angew. [Extracted from the article]

Titelbild: Single-Cell Imaging of m6A Modified RNA Using m6A-Specific In Situ Hybridization Mediated Proximity Ligation Assay (m6AISH-PLA) (Angew. In ihrer Zuschrift auf S. 22828 postulieren Jinghong Li et al. eine leistungsstarke In-situ-Imaging-Methode, die als "m SP 6 sp A-specific in situ hybridization mediated proximity ligation assay" (m SP 6 sp AISH-PLA) bezeichnet wird und die Identifizierung von m SP 6 sp A-Modifikationen an spezifischen Stellen in RNA und die Bildgebung von m SP 6 sp A-RNA mit Einzelzell- und Einzelmolekül-Auflösung ermöglicht. In ihrer Zuschrift auf S. 22828 postulieren Jinghong Li et al. eine leistungsstarke In-situ-Imaging-Methode, die als "m SP 6 sp A-specific in situ hybridization mediated proximity ligation assay" (m SP 6 sp AISH-PLA) bezeichnet wird und die Identifizierung von m SP 6 sp A-Modifikationen an spezifischen Stellen in RNA und die Bildgebung von m SP 6 sp A-RNA mit Einzelzell- und Einzelmolekül-Auflösung ermöglicht. [Extracted from the article]

Cross-platform difficulties, data privacy, and authentication security are common problems in the Internet of Things (IoT) environment. Despite the fact that blockchain technology has brought new opportunities to the development of the IoT by enhancing interoperability, improving privacy and security, there are still problems such as diversity, lack of communication and sharing. To solve the security authentication problem in the IoT environment and the cross-chain communication problem in the blockchain platform, an Identity-Based Encryption (IBE) based cross-chain communication mechanism of Blockchain in IoT (IBE-BCIOT). This mechanism elects the proxy nodes of each blockchain in multiple blockchains, and passes theIDof the proxy node, as the public key, to the cross-chain notary. Then, the cross-chain notary calculates the corresponding private key through the IBE mechanism, and returns it to the proxy node in a secure way, to achieve safe and efficient communication between blockchains. Next, the IBE-BCIOT mechanism provides two cross-chain communication schemes: the direct cross-chain communication scheme among the proxy nodes, and the indirect cross-chain communication scheme through the notary. We also build a blockchain-based on the FICSO BCOS platform to implement the IBE-BCIOT mechanism and analyze its security. The performance of the proposed two cross-chain communication schemes was verified in experiments of the IoT environment. The experimental results show that IBE-BCIOT is an effective IoT cross-chain communication mechanism. [ABSTRACT FROM AUTHOR]

In this paper, a 2-point algorithm is proposed to estimate the relative pose as well as the absolute scale between two vehicle-mounted cameras efficiently. The system model is deduced by combining a two-view geometric model and the planar motion constraint to reduce the degrees of freedom. 2-point correspondences are utilized to calculate the rotation information independently from the translation information, which indicates that the proposed algorithm can deal with pure rotation scenes. Besides, provided that the camera’s configuration satisfies a certain condition, the absolute scale can be recovered. An approximation algorithm is developed and combined with the random sample and consensus scheme to deal with the uneven ground surfaces in practice. As only 2-point correspondences are required, less iterations are demanded in the estimating procedure compared with many other existing related algorithms. Both simulation and experiments are implemented to evaluate the proposed algorithm, in which the synthetic data, virtual robot experimentation platform, KITTI Vision Benchmark, and SUMMIT-XL platform are acquired. According to the results, the proposed algorithm performs better than many related algorithms including the well-known 5-point algorithm in many cases, especially when the camera’s trajectory contains sharp corners. [ABSTRACT FROM AUTHOR]

The clustered regularly interspaced short palindromic repeats (CRISPR) system provides a new molecular diagnostic tool for construction of biosensor platforms due to its high programmability and target specificity. Herein, we developed a CRISPR-empowered electrochemical biosensor by combining the advantages of CRISPR/Cas13a and primer exchange reaction (PER), named PER-E-CRISPR, for target amplification-free and sensitive detection of miR-21. Dual-signal amplification procedures involve the binding of target miR-21 induced by CRISPR-based amplification, along with the hybridization of multiple short single-stranded DNA strands with PER concatemers. When target miR-21 is present, CRISPR/Cas13a specifically recognizes the target miRNA, triggering the trans -cleavage activity of CRISPR/Cas13a. Then Cas13a/crRNA/miRNA cleaved the predesigned ribonucleotide site in hairpin 1 (HP1) and released trigger to open hairpin 2 (HP2) modified on the electrode surface. Then PER bridge sequence contained in HP2 is exposed and hybridized with PER concatemers, following multiple short single-stranded DNA tagged with methylene blue (ssDNA-MB) bond with the PER concatemers. Under optimized conditions, PER-E-CRISPR assay for detecting miR-21 exhibits linearity in dynamic range from 10−13 to 10−7 M, and we obtained a limit of detection (LOD) of 30.2 fM. The established PER-E-CRISPR biosensor shows perfect practical performance in actual plasma, which may have great promising prospects for miRNA detection in the field of molecular diagnosis. [Display omitted] • CRISPR-empowered electrochemical biosensor with dual-signal amplification. • Nucleic acid amplification-free and sensitive detection of miRNA by PER-E-CRISPR. • Pre-synthesis of PER concatemer significantly improve the detection signal. [ABSTRACT FROM AUTHOR]

Ensemble learning methods can be used to evaluate landslide susceptibility when combined with remote sensing (RS) and geographic information systems (GIS). In this study, the rotation forest (ROF) and random forest (RF) ensemble learning models were applied to evaluate landslide susceptibility. The experiments selected the factors by analysing the linear relationship between the factors, explored the optimal proportions of non-landslide samples and landslide samples based on an unbalanced sample dataset, and used the factors before and after the selection to generate landslide susceptibility maps (LSMs) in the Zigui-Badong area. The results show that a suitable ratio between the sample types in the training set can achieve good results for both sensitivity and specificity. The RF models of the study area with 21 factors and 16 factors had sensitivities of 94.22% and 93.59%, respectively. The ROF models with 21 factors and 16 factors had sensitivities of 90.63% and 88.84%, respectively. Although both the RF and ROF models exhibited high accuracy, the RF model achieved a more reasonable and accurate LSM. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EV) have attracted increasing attention as tumour biomarkers due to their unique biological property. However, conventional methods for EV analysis are mainly based on bulk measurements, which masks the EV‐to‐EV heterogeneity in tumour diagnosis and classification. Herein, a localized fluorescent imaging method (termed Digital Profiling of Proteins on Individual EV, DPPIE) was developed for analysis of multiple proteins on individual EV. In this assay, an anti‐CD9 antibody engineered biochip was used to capture EV from clinical plasma sample. Then the captured EV was specifically recognized by multiple DNA aptamers (CD63/EpCAM/MUC1), followed by rolling circle amplification to generate localized fluorescent signals. By‐analyzing the heterogeneity of individual EV, we found that the high‐dimensional data collected from each individual EV would provide more precise information than bulk measurement (ELISA) and the percent of CD63/EpCAM/MUC1‐triple‐positive EV in breast cancer patients was significantly higher than that of healthy donors, and this method can achieve an overall accuracy of 91%. Moreover, using DPPIE, we are able to distinguish the EV between lung adenocarcinoma and lung squamous carcinoma patients. This individual EV heterogeneity analysis strategy provides a new way for digging more information on EV to achieve multi‐cancer diagnosis and classification. [ABSTRACT FROM AUTHOR]