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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]

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]

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.

Blood stream infection or sepsis is a major health problem worldwide, with extremely high mortality, which is partly due to the inability to rapidly detect and identify bacteria in the early stages of infection. Here we present a new technology termed 'Integrated Comprehensive Droplet Digital Detection' (IC 3D) that can selectively detect bacteria directly from milliliters of diluted blood at single-cell sensitivity in a one-step, culture- and amplification-free process within 1.5-4 h. The IC 3D integrates real-time, DNAzyme-based sensors, droplet microencapsulation and a high-throughput 3D particle counter system. Using Escherichia coli as a target, we demonstrate that the IC 3D can provide absolute quantification of both stock and clinical isolates of E. coli in spiked blood within a broad range of extremely low concentration from 1 to 10,000 bacteria per ml with exceptional robustness and limit of detection in the single digit regime.

Robust and effective fruit detection and localization is essential for robotic harvesting systems. While extensive research efforts have been devoted to improving fruit detection, less emphasis has been placed on the fruit localization aspect, which is a crucial yet challenging task due to limited depth accuracy from existing sensor measurements in the natural orchard environment with variable lighting conditions and foliage/branch occlusions. In this paper, we present the system design and calibration of an Active LAser-Camera Scanner (ALACS), a novel perception module for robust and high-precision fruit localization. The hardware of the ALACS mainly consists of a red line laser, an RGB camera, and a linear motion slide, which are seamlessly integrated into an active scanning scheme where a dynamic-targeting laser-triangulation principle is employed. A high-fidelity extrinsic model is developed to pair the laser illumination and the RGB camera, enabling precise depth computation when the target is captured by both sensors. A random sample consensus-based robust calibration scheme is then designed to calibrate the model parameters based on collected data. Comprehensive evaluations are conducted to validate the system model and calibration scheme. The results show that the proposed calibration method can detect and remove data outliers to achieve robust parameter computation, and the calibrated ALACS system is able to achieve high-precision localization with the maximum depth measurement error being less than 4 mm at distance ranging from 0.6 to 1.2 m. [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]

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]

Pathogenic bacterial infections are the second highest cause of death worldwide and bring severe challenges to public healthcare. Antibiotic resistance makes it urgent to explore new antibacterial therapy. As an essential metal element in both humans and bacteria, zinc ions have various physiological and biochemical functions. They can stabilize the folded conformation of metalloproteins and participate in critical biochemical reactions, including DNA replication, transcription, translation, and signal transduction. Therefore, zinc deficiency would impair bacterial activity and inhibit the growth of bacteria. Interestingly, excess zinc ions also could cause oxidative stress to damage DNA, proteins, and lipids by inhibiting the function of respiratory enzymes to promote the formation of free radicals. Such dual characteristics endow zinc ions with unparalleled advantages in the direction of antibacterial therapy. Based on the fascinating features of zinc ions, nanomaterial-based zinc ion interference therapy emerges relying on the outstanding benefits of nanomaterials. Zinc ion interference therapy is divided into two classes: zinc overloading and zinc deprivation. In this review, we summarized the recent innovative zinc ion interference strategy for the treatment of bacterial infections and focused on analyzing the antibacterial mechanism of zinc overloading and zinc deprivation. Finally, we discuss the current limitations of zinc ion interference antibacterial therapy and put forward problems of clinical translation for zinc ion interference antibacterial therapy. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BLCA) is among the most frequent types of cancer. Patients with BLCA have a significant recurrence rate and a poor post-surgery survival rate. Recent research has found a link between tumor immune cell infiltration (ICI) and the prognosis of BLCA patients. However, the ICI's picture of BLCA remains unclear. Methods: Common gene expression data were obtained by combining the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) expression databases. Two computational algorithms were proposed to unravel the ICI landscape of BLCA patients. The R package "limma" was applied to find differentially expressed genes (DEGs). ICI patterns were defined by the unsupervised clustering method. Principal-component analysis (PCA) was used to calculate the ICI score. In addition, the combined ICI score and tumor burden mutation (TMB) were utilized to assess BLCA patients' prognosis. The predictive value of ICI scores was verified by different clinical characteristics. Results: A total of 569 common gene expression data were retrieved from TCGA and GEO cohorts. CD8+ T cells were found to have a substantial positive connection with activated memory CD4+ T cells and immune score. On the contrary, CD8+ T cells were found to have a substantial negative connection with macrophages M0. Thirty-eight DEGs were selected. Two ICI patterns were defined by the unsupervised clustering method. Patients of BLCA were separated into two groups. The high ICI score group exhibited a better outcome than the low ICI score one (p < 0.001). Finally, the group with a high tumor mutation burden (TMB) as well as a high ICI score had the best outcome. (p < 0.001). Conclusions: Combining TMB and ICI scores resulted in a more accurate survival prediction, suggesting that ICI scores could be used as a prognostic marker for BLCA patients. [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]

Rational design of nanomedicine to accelerate thrombolysis and sequentially avoid thrombolysis-mediated reperfusion injury is still a challenge. Here, we develop a biomimetic nanovesicle (tPA/MNP@PM, tMP) by simple encapsulating melanin nanoparticles (MNP) and tPA with a platelet membrane vesicle (PM), which integrates the thrombus targeting property of PM, the photothermal conversion performance and free radical scavenging property of natural melanin for cascaded ischemic stroke treatment. Benefiting from natural thrombus-targeted adhesion capability of PM, nanovesicles could efficiently target thrombus site. Then near-infrared (NIR) mediated photothermal of MNP could lead to rupture of nanovesicles, thus achieving precise release of tPA in thrombus. Interestingly, local hyperthermia also increases the activity of tPA for accelerating thrombolysis. Afterwards, site specific released MNP (4.5 nm) accompanied by hemoperfusion can cross the BBB and accumulate in cerebral ischemia site, scavenging various free radicals and suppressing inflammation- and immune response–induced injury to achieve neuroprotection after thrombolysis. In addition, the biomimetic nanovesicle could block tPA-induced brain hemorrhage after stroke to improve thrombolytic therapy. The evaluation in ischemic stroke mice confirmed that the simple-prepared nanomedicine with cascaded thrombus targeting, precise thrombolysis and ischemia-reperfusion protection properties can significantly enhance the treatment effect of ischemic stroke. Ischemic stroke is recognized as a leading cause of death and disability in the world. Rational design of nanomedicine to accelerate thrombolysis and sequentially avoid thrombolysis-mediated reperfusion injury is still a challenge. Herein, a biomimetic nanovesicle (tMP) was developed for sequential ischemic stroke treatment. It could overcome the drawbacks of free tPA for safe thrombolysis: i) platelet membrane biomimetic coating significantly increases thrombus targeting; ii) NIR-mediated photothermal of natural melanin precise controlled release of tPA in thrombus in situ, and local hyperthermia also increases the thrombolytic activity of tPA. Notably, released melanin nanoparticles (4.5 nm) accompanied by hemoperfusion can across BBB and avoid ischemia-reperfusion injury through free radical scavenging and inflammation/immune response suppression. [Display omitted] [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]

5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA. A liposomal nanomedicine (MFLs@5-ALA/DFO) was designed for boosting the PDT of 5-ALA through intracellular iron ion regulation. [Display omitted] [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]

To meet the stability requirements for moving quadruped robots, it is important to design a rational structure for a single leg and plan the trajectory of the foot. First, a novel electrically driven leg mechanism for a quadruped robot is designed in this paper to reduce the inertia of the leg swing. Second, a modified foot trajectory based on a compound cycloid is proposed, which has swing-back and retraction motion and continuous velocity in the x-axis direction. Third, a Simulink platform is built to verify the correctness of the proposed foot trajectory. The simulation result shows that when the flight phase and the stand phase switch, the impact of torque is smaller than the foot trajectory before modification. Finally, an experimental platform is constructed, and a control algorithm is written into the controller to realize the foot proposed trajectory. The results of the experiment prove the feasibility of the leg mechanism and the rationality of the proposed foot trajectory. [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]