Opsonization Inveigles Macrophages Engulfing Carrier-Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy.

Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease-modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G-conjugated bilirubin/JPH203 self-assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra-articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa-B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier-free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.

Specialized spatially-arranged non-circular fibers enhance filtration performance of African shrimp (Atya gabonensis).

African shrimp (Atya gabonensis) inhabit clear freshwaters, where the notably low concentration of food may pose a challenge to the efficacy of filter fibers on the chela for filter-feeding. Here, we investigate how the distinctive cross-sectional characteristics and spatial arrangement of the African shrimp's non-circular fibers contribute to the enhanced filtration performance of these specialized fibers. The unilateral thickening of the wall along the long axis of the elliptical cross-section of African shrimp fibers markedly enhances the filtration performance. The staggered and twisted arrangement of the fibers optimizes the surrounding flow field, achieving a favorable balance between pressure drop and collection efficiency, consequently improving their filtration performance in collecting fine particles (diameter: 2-10µm). Moreover, the arrangement of the fibers substantially increases the effective flow-facing filtering area of the fiber bundles, thus facilitating their efficiency in collecting larger particles (diameter > 10µm). The unique fiber properties of the African shrimp offer novel insights for the design and optimization of new fiber-filtering robots, presenting a wide range of potential applications, such as marine in-situ resource extraction, medical filtration, and industrial filtration.

Morphological and structural characteristics of the elytra reduce impact damage to ladybird beetles.

Beetle elytra act as natural protective covers and effectively shield their flexible abdomens and fragile hindwings from damage. The existing studies have attributed this contribution of the elytra to its honeycomb structures. In this combined experimental and theoretical study, we used the seven-spotted ladybird beetle to demonstrate that both biological morphology and the hollow structure of the dome-like elytra combined to reduce damage during falling. The falling ladybird beetles had a high probability (59.52%) of hitting the ground with the costal edge of the elytra. This strategy could assist with converting the translational energy into rotational kinetic energy, resulting in the reduction of the impulse during falling. In addition, the hollow structures on the elytra could further absorb the residual impact energy. In the future, this biological paradigm could be used as a basis for the development of falling/landing techniques for advanced robots.

One Endothelium-Targeted Combined Nucleic Acid Delivery System for Myocardial Infarction Therapy.

Acute myocardial infarction (MI) and ischemic heart disease are the leading causes of heart failure and mortality. Currently, research on MI treatment is focused on angiogenic and anti-inflammatory therapies. Although endothelial cells (ECs) are critical for triggering inflammation and angiogenesis, no approach has targeted them for the treatment of MI. In this study, we proposed a nonviral combined nucleic acid delivery system consisting of an EC-specific polycation (CRPPR-grafted ethanolamine-modified poly(glycidyl methacrylate), CPC) that can efficiently codeliver siR-ICAM1 and pCXCL12 for the treatment of MI. Animals treated with the combination therapy exhibited better cardiac function than those treated with each nucleic acid alone. In particular, the combination therapy of CPC/siR-ICAM1 and CPC/pCXCL12 significantly improved cardiac systolic function, anti-inflammatory responses, and angiogenesis compared to the control group. In conclusion, CPC-based combined gene delivery systems show impressive performance in the treatment of MI and provide a programmed strategy for the development of codelivery systems for various EC-related diseases.

Bilirubin ameliorates osteoarthritis via activating Nrf2/HO-1 pathway and suppressing NF-κB signalling.

Osteoarthritis (OA) is a chronic degenerative joint disease that affects worldwide. Oxidative stress plays a critical role in the chronic inflammation and OA progression. Scavenging overproduced reactive oxygen species (ROS) could be rational strategy for OA treatment. Bilirubin (BR) is a potent endogenous antioxidant that can scavenge various ROS and also exhibit anti-inflammatory effects. However, whether BR could exert protection on chondrocytes for OA treatment has not yet been elucidated. Here, chondrocytes were exposed to hydrogen peroxide with or without BR treatment. The cell viability was assessed, and the intracellular ROS, inflammation cytokines were monitored to indicate the state of chondrocytes. In addition, BR was also tested on LPS-treated Raw264.7 cells to test the anti-inflammation property. An in vitro bimimic OA microenvironment was constructed by LPS-treated Raw264.7 and chondrocytes, and BR also exert certain protection for chondrocytes by activating Nrf2/HO-1 pathway and suppressing NF-κB signalling. An ACLT-induced OA model was constructed to test the in vivo therapeutic efficacy of BR. Compared to the clinical used HA, BR significantly reduced cartilage degeneration and delayed OA progression. Overall, our data shows that BR has a protective effect on chondrocytes and can delay OA progression caused by oxidative stress.

Metabolomics identifies and validates serum androstenedione as novel biomarker for diagnosing primary angle closure glaucoma and predicting the visual field progression.

Background: Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG. Methods: Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots. Results: Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression. Conclusions: Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression. Funding: This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).

Botrytis cinerea type II inhibitor of apoptosis BcBIR1 enhances the biocontrol capacity of Coniothyrium minitans.

Apoptosis-like programmed cell death is associated with fungal development, ageing, pathogenicity and stress responses. Here, to explore the potential of Botrytis cinerea type II inhibitor of apoptosis (IAP) BcBIR1 in elevating the biocontrol efficacy of Coniothyrium minitans, the BcBIR1 gene was heterologously expressed in C. minitans. Results indicated that the strains expressing BcBIR1 had higher rates of conidiation, mycelial growth and biomass growth than the wild-type strain. Moreover, BcBIR1 was found to inhibit apoptosis, indicating its role as an IAP in C. minitans. Under various abiotic stresses, the growth rates of BcBIR1-expressing strains were significantly higher than that of the wild-type strain. Moreover, the conidial survival rate of the BcBIR1-expressing strains treated with ultraviolet irradiation was enhanced. In antifungal activity assay, the culture filtrates of BcBIR1-expressing strains displayed a stronger inhibitory effect on B. cinerea and Sclerotinia sclerotiorum than the wild-type strain. The study also found that BcBIR1 expression increased the mycoparasitism against the sclerotia, but not the hyphae of S. sclerotiorum. Taken together, these results suggest that BcBIR1 enhances vegetative growth, conidiation, anti-apoptosis activity, abiotic stress resistance, antifungal activity and mycoparasitism in C. minitans. As an IAP, BcBIR1 may improve the control capacity of C. minitans against S. sclerotiorum.

A self-locking mechanism of the frog-legged beetle Sagra femorata.

Insect legs play a crucial role in various modes of locomotion, including walking, jumping, swimming, and other forms of movement. The flexibility of their leg joints is critical in enabling various modes of locomotion. The frog-legged leaf beetle Sagra femorata possesses remarkably enlarged hind legs, which are considered to be a critical adaptation that enables the species to withstand external pressures. When confronted with external threats, S. femorata initiates a stress response by rapidly rotating its hind legs backward and upward to a specific angle, thereby potentially intimidating potential assailants. Based on video analysis, we identified 4 distinct phases of the hind leg rotation process in S. femorata, which were determined by the range of rotation angles (0°-168.77°). Utilizing micro-computed tomography (micro-CT) technology, we performed a 3-dimensional (3D) reconstruction and conducted relative positioning and volumetric analysis of the metacoxa and metatrochanter of S. femorata. Our analysis revealed that the metacoxa-trochanter joint is a "screw-nut" structure connected by 4 muscles, which regulate the rotation of the legs. Further testing using a 3D-printed model of the metacoxa-trochanter joint demonstrated its possession of a self-locking mechanism capable of securing the legs in specific positions to prevent excessive rotation and dislocation. It can be envisioned that this self-locking mechanism holds potential for application in bio-inspired robotics.

Honeybee comb-inspired stiffness gradient-amplified catapult for solid particle repellency.

Natural surfaces that repel foreign matter are ubiquitous and crucial for living organisms. Despite remarkable liquid repellency driven by surface energy in many organisms, repelling tiny solid particles from surfaces is rare. The main challenge lies in the unfavourable scaling of inertia versus adhesion in the microscale and the inability of solids to release surface energy. Here we report a previously unexplored solid repellency on a honeybee's comb: a catapult-like effect to immediately eject pollen after grooming dirty antennae for self-cleaning. Nanoindentation tests revealed the 38-µm-long comb features a stiffness gradient spanning nearly two orders of magnitude from ~25 MPa at the tip to ~645 MPa at the base. This significantly augments the elastic energy storage and accelerates the subsequent conversion into kinetic energy. The reinforcement in energy storage and conversion allows the particle's otherwise weak inertia to outweigh its adhesion, thereby suppressing the unfavourable scaling effect and realizing solid repellency that is impossible in conventional uniform designs. We capitalize on this to build an elastomeric bioinspired stiffness-gradient catapult and demonstrate its generality and practicality. Our findings advance the fundamental understanding of natural catapult phenomena with the potential to develop bioinspired stiffness-gradient materials, catapult-based actuators and robotic cleaners.

Inversion study on elastic-plastic material parameters of red sandstone in uniaxial compression test.

In order to obtain the real material parameters of heterogeneous rock, the material parameters of red sandstone specimens under uniaxial compression tests are inverted based on the Digital Image Correlation (DIC) method and the Finite Element Model Updating (FEMU) method. The DIC method is employed to calculate the displacement field of red sandstone specimens during uniaxial compression loading. Concurrently, a uniaxial compression elastic-plastic finite element numerical model with non-uniform material parameters is developed based on the FEMU method. The model adopts the Mohr-Coulomb yield criterion and adjusts the boundary conditions in real-time to maintain consistency with the test. The vertical displacement field of the numerical model is juxtaposed with that of the test to construct the objective function. Optimization is achieved using the Artificial Fish Swarm algorithm, which enables the acquisition of the non-uniform distribution and evolution process of the material parameters of specimens at different loading moments. The results indicate that this method can spatially obtain the non-uniform distribution field of material parameters and temporally track the evolution of material parameters during the loading process. This research lays a solid foundation for enhancing the accuracy of intelligent coal mining and dynamic disaster monitoring and early warning in coal mines.

The effect of homocysteine-lowering therapy on the formation of carotid atherosclerosis: A follow-up study in the rural areas of northwest China.

Objective: To explore the risk factors for carotid atherosclerosis in the rural areas of Northwest China, and to assess whether reducing serum homocysteine can prevent carotid atherosclerosis in subjects with hyperhomocysteinemia. Method: This observational study with 767 participants aged 40 years or older was conducted over 3 years. Color Doppler ultrasonography was performed to measure carotid atherosclerosis. We recorded biochemical indexes and carotid ultrasound results in the first and fourth years. Result: A total of 767 individuals (48.5 % men) were analyzed. Older age, hypertension, and higher levels of baseline low-density lipoprotein cholesterol (LDL-C) were risk factors for increased carotid intima-media thickness (CIMT), carotid plaque, and carotid stenosis (All P < 0.05). No association was found between decreased serum homocysteine (Hcy) levels and CIMT, carotid plaque, or carotid stenosis in individuals with hyperhomocysteinemia. Conclusion: Older age, hypertension, and higher baseline levels of LDL-C were independent risk factors for carotid atherosclerosis. Reducing serum Hcy levels may not prevent carotid atherosclerosis in the general population with hyperhomocysteinemia.

Animating fossilized invertebrates by motion reconstruction.

Taking the motion reconstruction of the Cretaceous hell ants as an example, this study shows how to achieve motion reconstruction in fossil invertebrates and discusses potential challenges and opportunities.

Quinolines: A Promising Heterocyclic Scaffold for Cancer Therapeutics.

The quinoline scaffold is a widely recognized heterocycle with applications across various disease categories, ranging from malaria and viral infections to bacterial infections, high cholesterol, and even tumors. Consequently, quinoline plays a crucial role in the development of new drugs, and the field greatly benefits from advancements in computer-aided drug design. This review aims to provide insights into the evolution of quinoline and its derivatives, offering a comprehensive exploration of both marketed and developing drugs. Furthermore, the function and mechanism of quinoline compounds are introduced. Many studies rely on cell experiments to demonstrate drug cytotoxicity. In the concluding section of this review, the interaction between quinoline compounds and targets is simulated using computer-aided drug design methods. A thorough analysis is conducted on the potential influencing factors affecting the binding state between quinoline compounds and targets. Notably, the Pi-Alkyl interaction emerges as a significant contributor, while hydrogen bonding is identified as a pivotal bond in these interactions. This review serves as a valuable overview of the potential contributions of quinoline compounds to cancer treatment. It seamlessly combines the essential functions of marketed quinoline drugs with the promise held by emerging quinoline-based compounds. Additionally, the simulation of interactions between quinoline compounds and proteins through computer-aided design enhances our understanding of these compounds' efficacy.

Adult rhinoceros beetles use a sweeping pattern to ingest high-viscosity fluid.

More than half of all insect species utilize various natural liquids as primary diet. The concentrated liquids with energy-dense nutrition can provide highly favorable rewards, however, their high-viscosity poses challenges to the insect for ingesting. Here we show that rhinoceros beetles, Trypoxylus dichotomus (Coleoptera: Scarabaeidae), are capable of ingesting sugar solutions with viscosities spanning four orders of magnitude, exhibiting extraordinary adaptability to diverse natural liquid sources. We discovered a previously unidentified maxillae-sweeping motion that beetles preferentially adopt to consume highly viscous liquids, achieving a higher feeding rate than the more common direct sucking. By utilizing morphological characterizations, flow visualization, and fluid-structure coupling simulation, we revealed the underlying mechanisms of how this maxillary movement facilitates the transportation of viscous liquid. Our findings not only shed light on the multi-functionality of beetle mouthparts but also provide insights into the adaptability of generalized mouthparts to a broad range of fluid sources.

High stability in filtration apparatus of African shrimp.

The African shrimp (Atya gabonensis) uses elongated setae to filter feed, adapting to high flow velocities. The setae's stability stems from carefully designed geometric and structural parameters, notably a specialized wall and distribution principle. This study highlights the robust filtration mechanism in the shrimp and potential for developing stable structures in underwater environments.

Honey bees switch mechanisms to drink deep nectar efficiently.

The feeding mechanisms of animals constrain the spectrum of resources that they can exploit profitably. For floral nectar eaters, both corolla depth and nectar properties have marked influence on foraging choices. We report the multiple strategies used by honey bees to efficiently extract nectar at the range of sugar concentrations and corolla depths they face in nature. Honey bees can collect nectar by dipping their hairy tongues or capillary loading when lapping it, or they can attach the tongue to the wall of long corollas and directly suck the nectar along the tongue sides. The honey bee feeding apparatus is unveiled as a multifunctional tool that can switch between lapping and sucking nectar according to the instantaneous ingesting efficiency, which is determined by the interplay of nectar-mouth distance and sugar concentration. These versatile feeding mechanisms allow honey bees to extract nectar efficiently from a wider range of floral resources than previously appreciated and endow them with remarkable adaptability to diverse foraging environments.

Development and validation of a routine blood parameters-based model for screening the occurrence of retinal detachment in high myopia in the context of PPPM.

Background/aims: Timely detection and treatment of retinal detachment (RD) could effectively save vision and reduce the risk of progressing visual field defects. High myopia (HM) is known to be associated with an increased risk of RD. Evidently, it should be clearly discriminated the individuals with high or low risk of RD in patients with HM. By using multi-parametric analysis, risk assessment, and other techniques, it is crucial to create cutting-edge screening programs that may be utilized to improve population eye health and develop person-specific, cost-effective preventative, and targeted therapeutic measures. Therefore, we propose a novel, routine blood parameters-based prediction model as a screening program to help distinguish who should offer detailed ophthalmic examinations for RD diagnosis, prevent visual field defect progression, and provide personalized, serial monitoring in the context of predictive, preventive, and personalized medicine (PPPM/3 PM). Methods: This population-based study included 20,870 subjects (HM = 19,284, HMRD = 1586) who underwent detailed routine blood tests and ophthalmic evaluations. HMRD cases and HM controls were matched using a nested case-control design. Then, the HMRD cases and HM controls were randomly assigned to the discovery cohort, validation cohort 1, and validation cohort 2 maintaining a 6:2:2 ratio, and other subjects were assigned to the HM validation cohort. Receiver operating characteristic curve analysis was performed to select feature indexes. Feature indexes were integrated into seven algorithm models, and an optimal model was selected based on the highest area under the curve (AUC) and accuracy. Results: Six feature indexes were selected: lymphocyte, basophil, mean platelet volume, platelet distribution width, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Among the algorithm models, the algorithm of conditional probability (ACP) showed the best performance achieving an AUC of 0.79, a diagnostic accuracy of 0.72, a sensitivity of 0.71, and a specificity of 0.74 in the discovery cohort. A good performance of the ACP model was also observed in the validation cohort 1 (AUC = 0.81, accuracy = 0.72, sensitivity = 0.71, specificity = 0.73) and validation cohort 2 (AUC = 0.77, accuracy = 0.71, sensitivity = 0.70, specificity = 0.72). In addition, ACP model calibration was found to be good across three cohorts. In the HM validation cohort, the ACP model achieved a diagnostic accuracy of 0.81 for negative classification. Conclusion: We have developed a routine blood parameters-based model with an ACP algorithm that could potentially be applied in the clinic with a PPPM approach for serial monitoring and predicting the occurrence of RD in HM and can facilitate the prevention of HM progression to RD. According to the current study, routine blood measures are essential in patient risk classification, predictive diagnosis, and targeted therapy. Therefore, for high-risk RD persons, novel screening programs and prompt treatment plans are essential to enhance individual outcomes and healthcare offered to the community with HM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00319-3.

Three-Dimensional Gait Analysis and sEMG Measures for Robotic-Assisted Gait Training in Subacute Stroke: A Randomized Controlled Trial.

Background: The efficacy of robotic-assisted gait training (RAGT) should be considered versatilely; among which, gait assessment is one of the most important measures; observational gait assessment is the most commonly used method in clinical practice, but it has certain limitations due to the deviation of subjectivity; instrumental assessments such as three-dimensional gait analysis (3DGA) and surface electromyography (sEMG) can be used to obtain gait data and muscle activation during walking in stroke patients with hemiplegia, so as to better evaluate the rehabilitation effect of RAGT. Objective: This single-blind randomized controlled trial is aimed at analyzing the impact of RAGT on the 3DGA parameters and muscle activation in patients with subacute stroke and evaluating the clinical effect of improving walking function of RAGT. Methods: This randomized controlled trial evaluated the improvement of 4-week RAGT on patients with subacute stroke by 3DGA and surface electromyography (sEMG), combined with clinical scales: experimental group (n = 18, 20 sessions of RAGT) or control group (n = 16, 20 sessions of conventional gait training). Gait performance was evaluated by the 3DGA, and clinical evaluations based on Fugl-Meyer assessment for lower extremity (FMA-LE), functional ambulation category (FAC), and 6-minute walk test (6MWT) were used. Of these patients, 30 patients underwent sEMG measurement synchronized with 3DGA; the cocontraction index in swing phase of the knee and ankle of the affected side was calculated. Results: After 4 weeks of intervention, intragroup comparison showed that walking speed, temporal symmetry, bilateral stride length, range of motion (ROM) of the bilateral hip, flexion angle of the affected knee, ROM of the affected ankle, FMA-LE, FAC, and 6MWT in the experimental group were significantly improved (p < 0.05), and in the control group, significant improvements were observed in walking speed, temporal symmetry, stride length of the affected side, ROM of the affected hip, FMA-LE, FAC, and 6MWT (p < 0.05). Intergroup comparison showed that the experimental group significantly outperformed the control group in walking speed, temporal symmetry of the spatiotemporal parameters, ROM of the affected hip and peak flexion of the knee in the kinematic parameters, and the FMA-LE and FAC in the clinical scale (p < 0.05). In patients evaluated by sEMG, the experimental group showed a noticeable improvement in the cocontraction index of the knee (p = 0.042), while no significant improvement was observed in the control group (p = 0.196), and the experimental group was better than the control group (p = 0.020). No noticeable changes were observed in the cocontraction index of the ankle in both groups (p > 0.05). Conclusions: Compared with conventional gait training, RAGT successfully improved part of the spatiotemporal parameters of patients and optimized the motion of the affected lower limb joints and muscle activation patterns during walking, which is crucial for further rehabilitation of walking ability in patients with subacute stroke. This trial is registered with ChiCTR2200066402.

Rapid manoeuvre of fan worms (Annelida: Sabellidae) through tubes.

Multiple variables determine the success of an escape response of an animal, and the rapidity of the escape manoeuvre is often the most important. Fan worms (Annelida: Sabellidae) can rapidly withdraw their tentacles, which are covered in heavily ciliated ramifications called pinnules, into their tubes to protect them from approaching threats. Here, we explore the dynamic and mechanistic features behind this escape manoeuvre. The escape responses of fan worms were recorded by high-speed videography and quantified by computerized motion analysis, showing an ultrahigh retraction speed of 272±135 mm s-1 (8±4 body lengths s-1). We found that fan worms possess powerful muscle-driven systems, which can generate contractive forces up to 36 times their body weight. In order to achieve these rapid, forceful movements through seawater without damaging their tentacles, fan worms have developed functional morphological adaptations to reduce fluidic drag, including the flattening of their radiolar pinnules and the deformation of bodily segmental ridges. Our hydrodynamic models indicate that these mechanical processes can decrease fluidic drag by 47%, trapped mass by 75% and friction coefficient by 89%. These strategies allow fan worms to execute rapid escape responses and could inspire the design of fast in-pipe robots.

Immunostimulant In Situ Fibrin Gel for Post-operative Glioblastoma Treatment by Macrophage Reprogramming and Photo-Chemo-Immunotherapy.

Tumor recurrence remains the leading cause of treatment failure following surgical resection of glioblastoma (GBM). M2-like tumor-associated macrophages (TAMs) infiltrating the tumor tissue promote tumor progression and seriously impair the efficacy of chemotherapy and immunotherapy. In addition, designing drugs capable of crossing the blood-brain barrier and eliciting the applicable organic response is an ambitious challenge. Here, we propose an injectable nanoparticle-hydrogel system that uses doxorubicin (DOX)-loaded mesoporous polydopamine (MPDA) nanoparticles encapsulated in M1 macrophage-derived nanovesicles (M1NVs) as effectors and fibrin hydrogels as in situ delivery vehicles. In vivo fluorescence imaging shows that the hydrogel system triggers photo-chemo-immunotherapy to destroy remaining tumor cells when delivered to the tumor cavity of a model of subtotal GBM resection. Concomitantly, the result of flow cytometry indicated that M1NVs comprehensively improved the immune microenvironment by reprogramming M2-like TAMs to M1-like TAMs. This hydrogel system combined with a near-infrared laser effectively promoted the continuous infiltration of T cells, restored T cell effector function, inhibited the infiltration of myeloid-derived suppressor cells and regulatory T cells, and thereby exhibited a strong antitumor immune response and significantly inhibited tumor growth. Hence, MPDA-DOX-NVs@Gel (MD-NVs@Gel) presents a unique clinical strategy for the treatment of GBM recurrence.