LIFU/MMP-2 dual-responsive release of repurposed drug disulfiram from nanodroplets for inhibiting vasculogenic mimicry and lung metastasis in triple-negative breast cancer.

BACKGROUND: Vasculogenic mimicry (VM), when microvascular channels are formed by cancer cells independent of endothelial cells, often occurs in deep hypoxic areas of tumors and contributes to the aggressiveness and metastasis of triple-negative breast cancer (TNBC) cells. However, well-developed VM inhibitors exhibit inadequate efficacy due to their low drug utilization rate and limited deep penetration. Thus, a cost-effective VM inhibition strategy needs to be designed for TNBC treatment. RESULTS: Herein, we designed a low-intensity focused ultrasound (LIFU) and matrix metalloproteinase-2 (MMP-2) dual-responsive nanoplatform termed PFP@PDM-PEG for the cost-effective and efficient utilization of the drug disulfiram (DSF) as a VM inhibitor. The PFP@PDM-PEG nanodroplets effectively penetrated tumors and exhibited substantial accumulation facilitated by PEG deshielding in a LIFU-mediated and MMP-2-sensitive manner. Furthermore, upon exposure to LIFU irradiation, DSF was released controllably under ultrasound imaging guidance. This secure and controllable dual-response DSF delivery platform reduced VM formation by inhibiting COL1/pro-MMP-2 activity, thereby significantly inhibiting tumor progression and metastasis. CONCLUSIONS: Considering the safety of the raw materials, controlled treatment process, and reliable repurposing of DSF, this dual-responsive nanoplatform represents a novel and effective VM-based therapeutic strategy for TNBC in clinical settings.

A memristive all-inclusive hypernetwork for parallel analog deployment of full search space architectures.

In recent years, there has been a significant advancement in memristor-based neural networks, positioning them as a pivotal processing-in-memory deployment architecture for a wide array of deep learning applications. Within this realm of progress, the emerging parallel analog memristive platforms are prominent for their ability to generate multiple feature maps in a single processing cycle. However, a notable limitation is that they are specifically tailored for neural networks with fixed structures. As an orthogonal direction, recent research reveals that neural architecture should be specialized for tasks and deployment platforms. Building upon this, the neural architecture search (NAS) methods effectively explore promising architectures in a large design space. However, these NAS-based architectures are generally heterogeneous and diversified, making it challenging for deployment on current single-prototype, customized, parallel analog memristive hardware circuits. Therefore, investigating memristive analog deployment that overrides the full search space is a promising and challenging problem. Inspired by this, and beginning with the DARTS search space, we study the memristive hardware design of primitive operations and propose the memristive all-inclusive hypernetwork that covers 2×1025 network architectures. Our computational simulation results on 3 representative architectures (DARTS-V1, DARTS-V2, PDARTS) show that our memristive all-inclusive hypernetwork achieves promising results on the CIFAR10 dataset (89.2% of PDARTS with 8-bit quantization precision), and is compatible with all architectures in the DARTS full-space. The hardware performance simulation indicates that the memristive all-inclusive hypernetwork costs slightly more resource consumption (nearly the same in power, 22%∼25% increase in Latency, 1.5× in Area) relative to the individual deployment, which is reasonable and may reach a tolerable trade-off deployment scheme for industrial scenarios.

Long-term table tennis training alters dynamic functional connectivity and white matter microstructure in large scale brain regions.

Table tennis training has been employed as an exercise treatment to enhance cognitive brain functioning in patients with mental illnesses. However, research on its underlying mechanisms remains limited. In this study, we investigated functional and structural changes in large-scale brain regions between 20 table tennis players (TTPs) and 21 healthy controls (HCs) using 7-Tesla magnetic resonance imaging (MRI) techniques. Compared with those of HCs, TTPs exhibited significantly greater fractional anisotropy (FA) and axial diffusivity (AD) values in multiple fiber tracts. We used the locations with the most significant structural changes in white matter as the seed areas and then compared static and dynamic functional connectivity (sFC and dFC). Brodmann 11, located in the orbitofrontal cortex, showed altered dFC values to large-scale brain regions, such as the occipital lobe, thalamus, and cerebellar hemispheres, in TTPs. Brodmann 48, located in the temporal lobe, showed altered dFC to the parietal lobe, frontal lobe, cerebellum, and occipital lobe. Furthermore, the AD values of the forceps minor (Fmi) and right anterior thalamic radiations (ATRs) were negatively correlated with useful field of view (UFOV) test scores in TTPs. Our results suggest that table tennis players exhibit a unique pattern of dynamic neural activity, this provides evidence for potential mechanisms through which table tennis interventions can enhance attention and other cognitive functions.

Effects of impulse on prescribed-time synchronization of switching complex networks.

The specified convergence time, designated by the user, is highly attractive for many high-demand applications such as industrial robot control, missile guidance, and autonomous vehicles. For the application of neural networks in the field of secure communication and power systems, the importance of prescribed-time synchronization(PTs) and stable performance of the system is more prominent. This paper introduces a prescribed-time controller without the fractional power function and sign function, which can reach synchronization at a prescribed time and greatly reduce the chattering phenomenon of neural networks. Additionally, by constructing synchronizing/desynchronizing impulse sequences, the PTs of switching complex networks(SCN) is achieved with impulse effects, where the time sequences of switching and impulse occurrences in the networks are constrained by the average dwell time. This approach effectively reduces the impact of frequent mode switching on network synchronization, and the synchronization time can be flexibly adjusted within any physically allowable range to accommodate different application requirements. Finally, the effectiveness of the proposed control strategy is demonstrated by two examples.

Interaction Between Microbubbles and Microwave Ablation: A Phantom and Rabbit Model.

OBJECTIVES: This study aimed to explore the interactions between microbubbles and microwave ablation (MWA). METHODS: The study employed custom-made phantoms (in vitro) and white New Zealand rabbits (in vivo). MWA was performed with or without microbubbles in the phantoms (2 × 105 particles mL-1) and rabbit livers (intravenous injection of 0.05 mL/kg SonoVue). During the MWA, K-type thermocouple probes were used to monitor the MWA-induced temperature increase. Contrast-enhanced ultrasound imaging (CEUS) was used to monitor and analyze the microbubbles signal intensity. After MWA, the ablation-zone volumes were evaluated and compared between the groups with and without microbubbles. RESULTS: In both the phantom models and rabbits, microbubbles showed no significant influence on MWA, including the ablation range and MWA-induced temperature increase. In phantoms and rabbit livers filled with microbubbles, MWA caused the formation of a gradually expanding microbubble-defect region over the ablation time. An increase in the temperature caused microbubble destruction. CONCLUSIONS: Microbubbles had no significant influence on MWA. However, MWA induced the destruction of microbubbles in a temperature-dependent manner. Thus, the poor thermotolerance of microbubbles is a non-negligible barrier when using CEUS to monitor the ablation range during MWA in real-time.

The relationship between ablation range and ablation energy in papillary thyroid microcarcinoma: a comparison between microwave ablation and laser ablation.

OBJECTIVES: To study the relationship between the ablation range and applied energy of laser ablation (LA) and microwave ablation (MWA) in papillary thyroid microcarcinoma (PTMC). METHODS: A total of 201 PTMC patients were treated with LA (n = 102) or MWA (n = 99) with single-applicator fixed ablation. The ablation range was determined by contrast-enhanced ultrasound. The ratios of ablation volume, longitudinal diameter, and orthogonal diameter to ablation energy (RAV/E, RAL/E, RAO/E) were analyzed and compared between MWA and LA. The effects of PTMC characteristics and Hashimoto's thyroiditis (HT) on ablation efficiency were evaluated by linear regression. RESULTS: The RAV/E was 0.72 (0.65-0.84) mm3/J for MWA and 0.48 (0.39-0.54) mm3/J for LA. HT was significantly correlated with RAV/E of LA (coefficient = - 0.367, p < 0.0001). RAL/E did not differ significantly between MWA and LA (MWA 0.026 mm/J, LA 0.025 mm/J; p = 0.957). However, MWA had a greater RAO/E than LA (MWA 0.014 mm/J, LA 0.012 mm/J; p < 0.0001). The plateau values of MWA and LA on the ablation orthogonal diameter were 10.7 mm and 8.69 mm, respectively. CONCLUSIONS: MWA showed a higher RAV/E than LA. More intuitively, MWA had a better ablation performance than LA on the orthogonal axis rather than the longitudinal axis. Theoretically, MWA and LA could achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin. HT had a negative effect on LA but not on MWA. CLINICAL RELEVANCE STATEMENT: This study establishes strong connections between ablation energy and ablation range in papillary thyroid microcarcinoma (PTMC) in vivo, possibly contributing to the supplementation of the PTMC Ablation Consensus or Guidelines and providing a scientific basis for choosing clinical ablation parameters in PTMC. KEY POINTS: • Both microwave ablation (MWA) and laser ablation (LA) have excellent performance on the ablation longitudinal axis (easily exceeding 10 mm) for papillary thyroid microcarcinoma (PTMC). • MWA performed much better than LA on the ablation orthogonal axis. • MWA and LA are expected to achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin.

Tensile Stress-Activated and Exosome-Transferred YAP/TAZ-Notch Circuit Specifies Type H Endothelial Cell for Segmental Bone Regeneration.

The Ilizarov technique has been continuously innovated to utilize tensile stress (TS) for inducing a bone development-like regenerative process, aiming to achieve skeletal elongation and reconstruction. However, it remains uncertain whether this distraction osteogenesis (DO) process induced by TS involves the pivotal coupling of angiogenesis and osteogenesis mediated by type H endothelial cells (THECs). In this study, it is demonstrated that the Ilizarov technique induces the formation of a metaphysis-like architecture composed of THECs, leading to segmental bone regeneration during the DO process. Mechanistically, cell-matrix interactions-mediated activation of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) transcriptionally upregulates the expression of Notch1 and Delta-like ligand 4, which act as direct positive regulators of THECs phenotype, in bone marrow endothelial cells (BMECs) upon TS stimulation. Simultaneously, the Notch intracellular domain enhances YAP/TAZ activity by transcriptionally upregulating YAP expression and stabilizing TAZ protein, thus establishing the YAP/TAZ-Notch circuit. Additionally, TS-stimulated BMECs secrete exosomes enriched with vital molecules in this positive feedback pathway, which can be utilized to promote segmental bone defect healing, mimicking the therapeutic effects of Ilizarov technique. The findings advance the understanding of TS-induced segmental bone regeneration and establish the foundation for innovative biological therapeutic strategies aimed at activating THECs.

Ferroptosis in Osteocytes as a Target for Protection Against Postmenopausal Osteoporosis.

Ferroptosis is a necrotic form of iron-dependent regulatory cell death. Estrogen withdrawal can interfere with iron metabolism, which is responsible for the pathogenesis of postmenopausal osteoporosis (PMOP). Here, it is demonstrated that estrogen withdrawal induces iron accumulation in the skeleton and the ferroptosis of osteocytes, leading to reduced bone mineral density. Furthermore, the facilitatory effect of ferroptosis of osteocytes is verified in the occurrence and development of postmenopausal osteoporosis is associated with over activated osteoclastogenesis using a direct osteocyte/osteoclast coculture system and glutathione peroxidase 4 (GPX4) knockout ovariectomized mice. In addition, the nuclear factor erythroid derived 2-related factor-2 (Nrf2) signaling pathway is confirmed to be a crucial factor in the ferroptosis of osteocytic cells. Nrf2 regulates the expression of nuclear factor kappa-B ligand (RANKL) by regulating the DNA methylation level of the RANKL promoter mediated by DNA methyltransferase 3a (Dnmt3a), which is as an important mechanism in osteocytic ferroptosis-mediated osteoclastogenesis. Taken together, this data suggests that osteocytic ferroptosis is involved in PMOP and can be targeted to tune bone homeostasis.

Finite element modeling and analysis of effect of preexisting cervical degenerative disease on the spinal cord during flexion and extension.

Recent studies have emphasized the importance of dynamic activity in the development of myelopathy. However, current knowledge of how degenerative factors affect the spinal cord during motion is still limited. This study aimed to investigate the effect of various types of preexisting herniated cervical disc and the ligamentum flavum ossification on the spinal cord during cervical flexion and extension. A detailed dynamic fluid-structure interaction finite element model of the cervical spine with the spinal cord was developed and validated. The changes of von Mises stress and maximum principal strain within the spinal cord in the period of normal, hyperflexion, and hyperextension were investigated, considering various types and grades of disc herniation and ossification of the ligamentum flavum. The flexion and extension of the cervical spine with spinal canal encroachment induced high stress and strain inside the spinal cord, and this effect was also amplified by increased canal encroachments and cervical hypermobility. The spinal cord might evade lateral encroachment, leading to a reduction in the maximum stress and principal strain within the spinal cord in local-type herniation. Although the impact was limited in the case of diffuse type, the maximum stress tended to appear in the white matter near the encroachment site while compression from both ventral and dorsal was essential to make maximum stress appear in the grey matter. The existence of canal encroachment can reduce the safe range for spinal cord activities, and hypermobility activities may induce spinal cord injury. Besides, the ligamentum flavum plays an important role in the development of central canal syndrome.Significance. This model will enable researchers to have a better understanding of the influence of cervical degenerative diseases on the spinal cord during extension and flexion.

The biomechanical effect of different types of ossification of the ligamentum flavum on the spinal cord during cervical dynamic activities.

Ossification of the ligamentum flavum (OLF) is thought to be an influential etiology of myelopathy, as thickened ligamentum flavum causes the stenosis of the vertebral canal, which could subsequently compress the spinal cord. Unfortunately, there was little information available on the effects of cervical OLF on spinal cord compression, such as the relationship between the progression of cervical OLF and nervous system symptoms during dynamic cervical spine activities. In this research, a finite element model of C1-C7 including the spinal cord featured by dynamic fluid-structure interaction was reconstructed and utilized to analyze how different types of cervical OLF affect principal strain and stress distribution in spinal cord during spinal activities towards six directions. For patients with cervical OLF, cervical extension induces higher stress within the spinal cord among all directions. From the perspective of biomechanics, extension leads to stress concentration in the lateral corticospinal tracts or the posterior of gray matter. Low energy damage to the spinal cord would be caused by the high and fluctuating stresses during cervical movements to the affected side for patients with unilateral OLF at lower grades.

Target-triggered enzyme-free amplification for highly efficient AND-gated bioimaging in living cells.

Rapid, simultaneous, and sensitive detection of biomolecules has important application prospects in disease diagnosis and biomedical research. However, because the content of intracellular endogenous target biomolecules is usually very low, traditional detection methods can't be used for effective detection and imaging, and to enhance the detection sensitivity, signal amplification strategies are frequently required. The hybridization chain reaction (HCR) has been used to detect many disease biomarkers because of its simple operation, good reproducibility, and no enzyme involvement. Although HCR signal amplification methods have been employed to detect and image intracellular biomolecules, there are still false positive signals. Therefore, a target-triggered enzyme-free amplification system (GHCR system) was developed, as a fluorescent AND-gated sensing platform for intracellular target probing. The false positive signals can be well avoided and the accuracy of detection and imaging can be improved by using the design of the AND gate. Two cancer markers, GSH and miR-1246, were used as two orthogonal inputs for the AND gated probe. The AND-gated probe only works when GSH and miR-1246 are the inputs at the same time, and FRET signals can be the output. In addition to the use of AND-gated imaging, FRET-based high-precision ratiometric fluorescence imaging was employed. FRET-based ratiometric fluorescent probes have a higher ability to resist interference from the intracellular environment, they can avoid false positive signals well, and they are expected to have good specificity. Due to the advantages of HCR, AND-gated, and FRET fluorescent probes, the GHCR system exhibited highly efficient AND-gated FRET bioimaging for intracellular endogenous miRNAs with a lower detection limit of 18 pM, which benefits the applications of ratiometric intracellular biosensing and bioimaging and offers a novel concept for advancing the diagnosis and therapeutic strategies in the field of cancer.

Impacts of Climate Changes on Geographic Distribution of Primula filchnerae, an Endangered Herb in China.

Primula filchnerae, an endangered plant endemic to China, has drawn people's attention in recent years due to its ornamental value in flower. It was rarely recorded since being described in 1902, but it was rediscovered in 2009 and is now known from a limited number of sites located in Hubei and Shaanxi Provinces. Since the species is still poorly known, a number of unanswered questions arise related to it: How has P. filchnerae responded to past climate change and how might it respond in the future? Why was P. filchmerae so rarely collected during the past century? We assembled geographic coordinates for P. filchnerae through the field surveys and website searches, and then used a maximum entropy model (MaxEnt) to simulate its potential suitable distribution in six periods with varied carbon emission levels by combining bioclimatic and environmental factors. MaxEnt showed that Min Temperature of the Coldest Month (bio6) and Precipitation of the Coldest Quarter (bio19) affected P. filchnerae's distribution most, with an aggregate contribution >60% and suitable ranges above -5 °C and below 40 mm, respectively. We also analyzed potential habitat distribution in various periods with differing impacts of climate change compared to today's suitable habitats, and in most cases, Shaanxi and Sichuan remained the most stable areas and with possible expansion to the north under various carbon emission scenarios, but the 2050s SSP5-8.5 scenario may be an exception. Moreover, we used MaxEnt to evaluate population shifts, with various scenarios indicating that geometric center would be concentrated in Sichuan Province in China. Finally, conservation strategies are suggested, including the creation of protected areas, long-term monitoring, raising public awareness of plant conservation, situ conservation measures, assisted migration, and species introduction. This study demonstrates how P. filchnerae may have adapted to changes in different periods and provides a scientific basis for germplasm conservation and management.

Dual-Mode Gold Nanocluster-Based Nanoprobe Platform for Two-Photon Fluorescence Imaging and Fluorescence Lifetime Imaging of Intracellular Endogenous miRNA.

Bioimaging is widely used in various fields of modern medicine. Fluorescence imaging has the advantages of high sensitivity, high selectivity, noninvasiveness, in situ imaging, and so on. However, one-photon (OP) fluorescence imaging has problems, such as low tissue penetration depth and low spatiotemporal resolution. These disadvantages can be solved by two-photon (TP) fluorescence imaging. However, TP imaging still uses fluorescence intensity as a signal. The complexity of organisms will inevitably affect the change of fluorescence intensity, cause false-positive signals, and affect the accuracy of the results obtained. Fluorescence lifetime imaging (FLIM) is different from other kinds of fluorescence imaging, which is an intrinsic property of the material and independent of the material concentration and fluorescence intensity. FLIM can effectively avoid the fluctuation of TP imaging based on fluorescence intensity and the interference of autofluorescence. Therefore, based on silica-coated gold nanoclusters (AuNCs@SiO2) combined with nucleic acid probes, the dual-mode nanoprobe platform was constructed for TP and FLIM imaging of intracellular endogenous miRNA-21 for the first time. First, the dual-mode nanoprobe used a dual fluorescence quencher of BHQ2 and graphene oxide (GO), which has a high signal-to-noise ratio and anti-interference. Second, the dual-mode nanoprobe can detect miR-21 with high sensitivity and selectivity in vitro, with a detection limit of 0.91 nM. Finally, the dual-mode nanoprobes performed satisfactory TP fluorescence imaging (330.0 µm penetration depth) and FLIM (τave = 50.0 ns) of endogenous miR-21 in living cells and tissues. The dual-mode platforms have promising applications in miRNA-based early detection and therapy and hold much promise for improving clinical efficacy.

Effect of Different Types of Ossification of the Posterior Longitudinal Ligament on the Dynamic Biomechanical Response of the Spinal Cord: A Finite Element Analysis.

Ossification of the posterior longitudinal ligament (OPLL) has been identified as an important cause of cervical myelopathy. However, the biomechanical mechanism between the OPLL type and the clinical characteristics of myelopathy remains unclear. The aim of this study was to evaluate the effect of different types of OPLL on the dynamic biomechanical response of the spinal cord. A three-dimensional finite element model of the fluid-structure interaction of the cervical spine with spinal cord was established and validated. The spinal cord stress and strain, cervical range of motion (ROM) in different types of OPLL models were predicted during dynamic flexion and extension activity. Different types of OPLL models showed varying degrees of increase in stress and strain under the process of flexion and extension, and there was a surge toward the end of extension. Larger spinal cord stress was observed in segmental OPLL. For continuous and mixed types of OPLL, the adjacent segments of OPLL showed a dramatic increase in ROM, while the ROM of affected segments was limited. As a dynamic factor, flexion and extension of the cervical spine play an amplifying role in OPLL-related myelopathy, while appropriate spine motion is safe and permitted. Segmental OPLL patients are more concerned about the spinal cord injury induced by large stress, and patients with continuous OPLL should be noted to progressive injuries of adjacent level.

Static and dynamic resting-state brain activity patterns of table tennis players in 7-Tesla MRI.

Table tennis involves quick and accurate motor responses during training and competition. Multiple studies have reported considerably faster visuomotor responses and expertise-related intrinsic brain activity changes among table tennis players compared with matched controls. However, the underlying neural mechanisms remain unclear. Herein, we performed static and dynamic resting-state functional magnetic resonance imaging (rs-fMRI) analyses of 20 table tennis players and 21 control subjects using 7T ultra-high field imaging. We calculated the static and dynamic amplitude of low-frequency fluctuations (ALFF) of the two groups. The results revealed that table tennis players exhibited decreased static ALFF in the left inferior temporal gyrus (lITG) compared with the control group. Voxel-wised static functional connectivity (sFC) and dynamic functional connectivity (dFC) analyses using lITG as the seed region afforded complementary and overlapping results. The table tennis players exhibited decreased sFC in the right middle temporal gyrus and left inferior parietal gyrus. Conversely, they displayed increased dFC from the lITG to prefrontal cortex, particularly the left middle frontal gyrus, left superior frontal gyrus-medial, and left superior frontal gyrus-dorsolateral. These findings suggest that table tennis players demonstrate altered visuomotor transformation and executive function pathways. Both pathways involve the lITG, which is a vital node in the ventral visual stream. These static and dynamic analyses provide complementary and overlapping results, which may help us better understand the neural mechanisms underlying the changes in intrinsic brain activity and network organization induced by long-term table tennis skill training.

Simultaneous and rapid screening of live and dead E. coli O157:H7 with three signal outputs: An all-in-one biosensor using phage-apoferritin@CuO2 signal tags on MXenes-modified electrode platform.

Simultaneous detection of live and dead bacteria is a huge challenge for food safety. To solve this issue, an all-in-one biosensor for bacteria was developed using the phage-apoferritin@CuO2 (phage-Apo@CP) probe on an antimicrobial peptide (AMP)/MXenes-modified detection platform. With the specific recognition of AMP and phage-Apo@CP, the biosensor for the target Escherichia coli O157:H7 (E. coli O157:H7) presented multi-mode (bioluminescent, colorimetric, and electrochemical) signals to simultaneously measure live and dead bacteria. The bioluminescent signal caused by the adenosine triphosphate (ATP) from the bacteria was used to quantify live bacteria. The colorimetric and voltammetric signals triggered by ·OH and Cu2+ from the probe with the assistance of acid could rapidly screen and quantitative determination of total E. coli O157:H7 concentration. Thus, the dead one was obtained according to the total and live ones. All three signals could be mutually corrected to improve the accuracy. The biosensor was successfully used for on-site measurement of live and dead E. coli O157:H7 in food samples with the limit of detection of 30 CFU/mL for live ones and 6 CFU/mL for total bacteria within 50 min. This work presents a novel pathway for rapid and simultaneous quantification of both live and dead bacteria.

Development of HSP90 inhibitors-SN38 conjugates for cancer treatment.

Presently, chemotherapy remains to be one of the most important therapeutic approaches for malignant tumors. Ligands based drug conjugates are showing considerable promise as potential therapeutic agents delivery systems for cancer. Here, a series of HSP90 inhibitors-SN38 conjugates were developed through cleavable linkers for tumor-specific delivery of SN38 and reducing its side effects. In vitro assays showed that these conjugates exhibited acceptable stability in PBS and plasma, appreciable HSP90 binding affinity, and potent cytotoxic abilities. Cellular uptake behaviors also indicated that these conjugates could selectively target cancer cells in a time-dependent manner via HSP90. Among them, compound 10b with a glycine linkage exhibits appreciable in vitro and in vivo pharmacokinetic profiles, and excellent in vivo antitumor activity in Capan-1 xenograft models, demonstrating the selective targeting and accumulation of the active payload at tumor sites. Above all, these results suggest that compound 10b has the potential as a potent anticancer drug, meriting further evaluation in the future.

A Cartesian-Based Trajectory Optimization with Jerk Constraints for a Robot.

To address the time-optimal trajectory planning (TOTP) problem with joint jerk constraints in a Cartesian coordinate system, we propose a time-optimal path-parameterization (TOPP) algorithm based on nonlinear optimization. The key insight of our approach is the presentation of a comprehensive and effective iterative optimization framework for solving the optimal control problem (OCP) formulation of the TOTP problem in the (s,s˙)-phase plane. In particular, we identify two major difficulties: establishing TOPP in Cartesian space satisfying third-order constraints in joint space, and finding an efficient computational solution to TOPP, which includes nonlinear constraints. Experimental results demonstrate that the proposed method is an effective solution for time-optimal trajectory planning with joint jerk limits, and can be applied to a wide range of robotic systems.

Low-intensity focused ultrasound targeted microbubble destruction reduces tumor blood supply and sensitizes anti-PD-L1 immunotherapy.

Immune checkpoint blockade (ICB) typified by anti-PD-1/PD-L1 antibodies as a revolutionary treatment for solid malignancies has been limited to a subset of patients due to poor immunogenicity and inadequate T cell infiltration. Unfortunately, no effective strategies combined with ICB therapy are available to overcome low therapeutic efficiency and severe side effects. Ultrasound-targeted microbubble destruction (UTMD) is an effective and safe technique holding the promise to decrease tumor blood perfusion and activate anti-tumor immune response based on the cavitation effect. Herein, we demonstrated a novel combinatorial therapeutic modality combining low-intensity focused ultrasound-targeted microbubble destruction (LIFU-TMD) with PD-L1 blockade. LIFU-TMD caused the rupture of abnormal blood vessels to deplete tumor blood perfusion and induced the tumor microenvironment (TME) transformation to sensitize anti-PD-L1 immunotherapy, which markedly inhibited 4T1 breast cancer's growth in mice. We discovered immunogenic cell death (ICD) in a portion of cells induced by the cavitation effect from LIFU-TMD, characterized by the increased expression of calreticulin (CRT) on the tumor cell surface. Additionally, flow cytometry revealed substantially higher levels of dendritic cells (DCs) and CD8+ T cells in draining lymph nodes and tumor tissue, as induced by pro-inflammatory molecules like IL-12 and TNF-α. These suggest that LIFU-TMD as a simple, effective, and safe treatment option provides a clinically translatable strategy for enhancing ICB therapy.

Adaptive fixed-time output synchronization for complex dynamical networks with multi-weights.

This paper addresses fixed-time output synchronization problems for two types of complex dynamical networks with multi-weights (CDNMWs) by using two types of adaptive control methods. Firstly, complex dynamical networks with multiple state and output couplings are respectively presented. Secondly, several fixed-time output synchronization criteria for these two networks are formulated based on Lyapunov functional and inequality techniques. Thirdly, by employing two types of adaptive control methods, fixed-time output synchronization issues of these two networks are dealt with. At last, the analytical results are verified by two numerical simulations.