Template-guided Silicon Micromotor Assembly for Enhanced Cell Manipulation.

Light-driven micro/nanorobots (LMNRs) are tiny, untethered machines with great potential in fields like precision medicine, nano manufacturing, and various other domains. However, their practicality hinges on developing light-manipulation strategies that combine versatile functionalities, flexible design options, and precise controllability. Our study introduces an innovative approach to construct micro/nanorobots (MNRs) by utilizing micro/nanomotors as fundamental building blocks. Inspired by silicon Metal-Insulator-Semiconductor solar cell principles, we design a new type of optomagnetic hybrid micromotors (OHMs). These OHMs have been skillfully optimized with integrated magnetic constituent, resulting in efficient light propulsion, precise magnetic navigation, and the potential for controlled assembly. One of the key features of the OHMs is their ability to exhibit diverse motion modes influenced by fracture surfaces and interactions with the environment, streamlining cargo conveyance along "micro expressway" - the predesigned microchannels. Further enhancing their versatility, a template-guided assembly strategy facilitates the assembly of these micromotors into functional microrobots, encompassing various configurations such as "V-shaped", "N-shaped", and 3D structured microrobots. The heightened capabilities of these microrobots, underscore the innovative potential inherent in hybrid micromotor design and assembly, which provides a foundational platform for the realization of multi-component microrobots. Our work moves a step toward forthcoming microrobotic entities boasting advanced functionalities.

Magnetically Manipulated Optoelectronic Hybrid Microrobots for Optically Targeted Non-Genetic Neuromodulation.

Optically controlled neuromodulation is a promising approach for basic research of neural circuits and the clinical treatment of neurological diseases. However, developing a non-invasive and well-controllable system to deliver accurate and effective neural stimulation is challenging. Micro/nanorobots have shown great potential in various biomedical applications because of their precise controllability. Here, a magnetically-manipulated optoelectronic hybrid microrobot (MOHR) is presented for optically targeted non-genetic neuromodulation. By integrating the magnetic component into the metal-insulator-semiconductor junction design, the MOHR has excellent magnetic controllability and optoelectronic properties. The MOHR displays a variety of magnetic manipulation modes that enables precise and efficient navigation in different biofluids. Furthermore, the MOHR could achieve precision neuromodulation at the single-cell level because of its accurate targeting ability. This neuromodulation is achieved by the MOHR's photoelectric response to visible light irradiation, which enhances the excitability of the targeted cells. Finally, it is shown that the well-controllable MOHRs effectively restore neuronal activity in neurons damaged by ß-amyloid, a pathogenic agent of Alzheimer's disease. By coupling precise controllability with efficient optoelectronic properties, the hybrid microrobot system is a promising strategy for targeted on-demand optical neuromodulation.

Achiral Au(I) Cyclic Trinuclear Complexes with High-Efficiency Circularly Polarized Near-Infrared TADF.

Realizing high photoluminescence quantum yield (PLQY) in the near-infrared (NIR) region is challenging and valuable for luminescent material, especially for thermally activated delay fluorescence (TADF) material. In this work, we report two achiral cyclic trinuclear Au(I) complexes, Au3 (4-Clpyrazolate)3 and Au3 (4-Brpyrazolate)3 (denoted as Cl-Au and Br-Au), obtained through the reaction of 4-chloro-1H-pyrazole and 4-bromo-1H-pyrazole with Au(I) salts, respectively. Both Cl-Au and Br-Au exhibit TADF with high PLQY (>70 %) in the NIR I (700-900 nm) (λmax = 720 nm) region, exceeding other NIR-TADF emitters in the solid state. Photophysical experiments and theoretical calculations confirmed the efficient NIR-TADF properties of Cl-Au and Br-Au were attributed to the small energy gap ΔE(S1-T2) (S = singlet, T = triplet) and the large spin-orbital coupling induced by ligand-to-metal-metal charge transfer of molecular aggregations. In addition, both complexes crystallize in the achiral Pna21 space group (mm2 point group) and are circularly polarized light (CPL) active with maxima luminescent dissymmetry factor |glum | of 3.4 × 10-3 (Cl-Au) and 2.7 × 10-3 (Br-Au) for their crystalline powder samples, respectively. By using Cl-Au as the emitting ink, 3D-printed luminescent logos are fabricated, which own anti-counterfeiting functions due to its CPL behavior dependent on the crystallinity.

Histamine H1 receptor antagonist attenuates catecholamine surge and organ injury after severe burns.

Severe burns induce a catecholamine surge, causing severe damage to the organism and raising the possibility of multisystem organ failure. Few strategies are generally acceptable to reduce catecholamine surge and organ injury post-burn. We have previously shown that histamine can amplify the catecholamine surge. In addition, promethazine, a first-generation histamine H1 receptor antagonist, alleviates catecholamine surge and organ injury after severe burns in rats. However, evidence is lacking on whether promethazine benefits patients after severe burns. Currently, sedation and analgesia (such as midazolam and fentanyl) are commonly required for patients after severe burns. It remains unclear if patients after severe burns derive clinical benefit from histamine H1 receptor antagonists combined with sedation and analgesia. This study investigates the therapeutic effect of promethazine on patients after severe burns. Moreover, we test the therapeutic effect of cetirizine, a second-generation histamine H1 receptor antagonist, combined with sedation and analgesia in rats after severe burns. We find that promethazine-pethidine treatment shows a tendency for a lower level of total bilirubin than midazolam-fentanyl in patients 7-day after severe burn. Our study confirms that cetirizine combined with midazolam and fentanyl reduces catecholamine surge and liver and lung damage after severe burns in rats; the effects are better than midazolam and fentanyl treatment. In summary, for the first time, we suggest that histamine H1 receptor antagonist has the potential clinical value of reducing liver injury in patients after severe burns. In addition, we reveal that cetirizine combined with midazolam and fentanyl may be an ideal strategy for treating severe burns.

MOF-Integrated Hierarchical Composite Fiber for Efficient Daytime Radiative Cooling and Antibacterial Protective Textiles.

Incorporating passive radiative cooling into textiles is an effective way to improve individual personalized thermophysiological comfort for the human body. Based on radiative cooling textile design, rational functionalization further facilitates practical applications, especially for medical protective products with customized requirements. Herein, we present a hierarchical polyurethane/metal-organic framework (MOF) composite nanofiber membrane with an integrated radiative cooling effect and photocatalytic antibacterial property. Fabricated by a scalable electrospinning method, the hierarchical nanofiber membrane shows high solar reflectance of 97% and improved thermal emissivity of 93% attributed to the abundant chemical bonds in ZIF-8 nanoparticles, rendering a temperature drop of ∼7.2 °C under direct sunlight and ∼5.5 °C at night. In addition, the photocatalytic activity of ZIF-8 ensures a 96% bacterial mortality rate for preventing bacterial infection. In practical application, our composite fabric can prevent superheating by 4.4 °C compared with the traditional protective suit under direct sunlight. Along with its anti-infection ability, the composite fabric is desirable for medical protective textiles. The innovative integration of passive radiative cooling design and functional MOFs breaks through the traditional cooling mode and provides huge substantial advantages for smart textiles and personal cooling applications.

Sorafenib inhibits doxorubicin-induced PD-L1 upregulation to improve immunosuppressive microenvironment in Osteosarcoma.

PURPOSE: Although undergoing conventional chemotherapy significantly improves the prognosis of Osteosarcoma, chemoresistance and failure of therapy is still a significant challenge. Furthermore, conventional chemotherapy, like doxorubicin, would upregulate the expression of programmed death-ligand 1 (PD-L1) which caused an immunosuppressive microenvironment and unsatisfied treatment result in Osteosarcoma. Thus, it is urgent to explore a strategy to overcome this disadvantage. METHODS: Human Osteosarcoma cell line MG63 and mouse Osteosarcoma cell line K7 were included in this study. Subcutaneous tumor model was used by injection of K7 cells in BALB/C mice to test the effect of doxorubicin and sorafenib on tumor growth. PD-L1 expression was tested in vitro (flow cytometry, western blot and PCR) and in vivo (flow cytometry and immunohistochemistry). Proportion of immune cells (CD4, CD8, Tregs, and cytotoxic T lymphocytes) in vivo was analyzed with flow cytometry. RESULTS: Combination of sorafenib and doxorubicin inhibited tumor growth significantly in vivo. Doxorubicin increased PD-L1 expression in vitro and in vivo, while sorafenib inhibited doxorubicin-induced PD-L1 upregulation in vitro and in vivo. Proportion of interferon-γ-secreting CD8 + T lymphocytes in tumor tissue was increased significantly when sorafenib was combined with doxorubicin, while proportion of CD4, CD8, and Tregs was not significantly changed. Extracellular signal-regulated kinases (ERK) pathway could be one of the key mechanisms by which doxorubicin induced upregulation of PD-L1 in Osteosarcoma cells. CONCLUSION: Combination of sorafenib and conventional chemotherapeutic reagents is a potent strategy to improve treatment effectiveness by modulating tumor microenvironment in Osteosarcoma through increasing proportion of cytotoxic T lymphocytes.

Lactylation of PKM2 Suppresses Inflammatory Metabolic Adaptation in Pro-inflammatory Macrophages.

Emerging evidence suggests that metabolic adaptation is a vital hallmark and prerequisite for macrophage phenotype transition. Pyruvate kinase M2 (PKM2) is an essential molecular determinant of metabolic adaptions in pro-inflammatory macrophages. Post-translational modifications play a central role in the regulation of PKM2. However, doubt remains on whether lactylation in PKM2 exists and how lactylation modulates the function of PKM2. For the first time, our study reports that lactate inhibits the Warburg effect by activating PKM2, promoting the transition of pro-inflammatory macrophages towards a reparative phenotype. We identify PKM2 as a lactylation substrate and confirm that lactylation occurs mainly at the K62 site. We find that lactate increases the lactylation level of PKM2, which inhibits its tetramer-to-dimer transition, promoting its pyruvate kinase activity and reducing nuclear distribution. In short, our study reports a novel post-translational modification type in PKM2 and clarifies its potential role in regulating inflammatory metabolic adaptation in pro-inflammatory macrophages.

Photobiomodulation promotes angiogenesis in wound healing through stimulating the nuclear translocation of VEGFR2 and STAT3.

In recent years, Photobiomodulation (PBM) has gained prevalence as a kind of physical therapy for wound healing, however, concerning specific cellular mechanisms induced by PBM remains uncertain. The objective of this study is to evaluate the mechanisms of action of PBM (632.8 nm) on angiogenesis in wound healing in vitro and vivo. In the present work, we indicated that PBM with 1.0 J/cm2 irradiation dose exerts positive effects on cell viability, migration, proliferation and tube formation in human umbilical vein endothelial cells (HUVECs). Furthermore, we demonstrate that the VEGFA/VEGFR2/STAT3 pathway plays an important role in PBM effecting cellular function and promoting angiogenesis in wound healing. In addition, we also found that PBM activated the VEGFA/VEGFR2/STAT3 pathway by stimulating VEGFR2 and STAT3 nuclear translocation in the presence of importin-ß. Our research offer a new insight into the potential molecular mechanisms in which PBM promotes angiogenesis in wound healing.

Self-driven magnetorobots for recyclable and scalable micro/nanoplastic removal from nonmarine waters.

Micro/nanoplastic (MNP) contamination in nonmarine waters has evolved into a notable ecotoxicological threat to the global ecosystem. However, existing strategies for MNP removal are typically limited to chemical flocculation or physical filtering that often fails to decontaminate plastic particulates with ultrasmall sizes or ultralow concentrations. Here, we report a self-driven magnetorobot comprising magnetizable ion-exchange resin sphere that can be used to dynamically remove or separate MNPs from nonmarine waters. As a result of the long-range electrophoretic attraction established by recyclable ion-exchange resin, the magnetorobot shows sustainable removal efficiency of >90% over 100 treatment cycles, with verified broad applicability to varying plastic compositions, sizes, and shapes as well as nonmarine water samples. Our work may facilitate industry-scale MNP removal with affordable cost and minimal secondary pollution and suggests an appealing strategy based on self-propelled micro/nanorobots to sample and assess nanoplastics in aqueous environment.

Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance in osteosarcoma.

Metastasis and drug resistance are the leading causes of poor prognosis in patients with osteosarcoma. Identifying the relevant factors that drive metastasis and drug resistance is the key to improving the therapeutic outcome of osteosarcoma. Here, we reported that autophagy was highly activated in metastatic osteosarcoma. We found increased autophagolysosomes in metastatic osteosarcoma cell lines by using electron microscopy, Western blot, and immunofluorescence experiments. We further examined the expression of the autophagy-related genes Beclin1 and LC3B in 82 patients through immunohistochemistry and found that Beclin1 and LC3B were highly related to unfavorable prognosis of osteosarcoma. Knockdown of Beclin1 and LC3B reduced invasion, metastasis, and proliferation in metastatic osteosarcoma cells. In vitro and in vivo studies also demonstrated that inhibiting by 3-MA inhibited cell growth and metastasis. Moreover, we demonstrated that autophagy-related genes were activated by SEs and that the inhibition of SEs by JQ-1 decreased the metastasis of osteosarcoma. Overall, our findings highlighted the association of autophagy with osteosarcoma progression and shed new light on autophagy-targeting therapy for osteosarcoma.

LYTIC COCKTAIL ATTENUATES CATECHOLAMINE SURGE AFTER SEVERE BURNS BY BLOCKING HISTAMINE H1 RECEPTOR/PKA/CREB/TYROSINE HYDROXYLASE SIGNALING IN CHROMAFFIN CELLS.

ABSTRACT: Severe burns develop a catecholamine surge, inducing severe damage to the organism, raising the possibility of multisystem organ failure, and even death. The mechanisms of catecholamine surge have not been fully elucidated, and few strategies are generally acceptable to reduce catecholamine surge postburn. Thus, it is valuable to investigate the underlying mechanisms of catecholamine surge postburn to develop targeted interventions to attenuate it. We have found that the lytic cocktail alleviates the surge of catecholamine and organ injury after severe burn; however, the underlying mechanisms were still unclear. Moreover, the lytic cocktail has side effects, such as significant arterial hypotension and breathing depression, limiting its clinical application. This study aims to investigate the therapeutic mechanism of the lytic cocktail in regulating catecholamine levels postburn. We find that promethazine, a classic histamine H1 receptor blocker and a component of the lytic cocktail, can effectively reduce catecholamine surge and organ injury postburn. Our study confirms that blood histamine levels increase after severe burns. We find that histamine can amplify the catecholamine surge by elevating tyrosine hydroxylase expression and catecholamine synthesis in chromaffin cells through the histamine H1 receptor/Protein Kinase A /cAMP-response element binding protein signaling pathway. In summary, for the first time, we find that histamine plays a vital role in catecholamine surge postburn. We also confirm that the lytic cocktail effectively alleviates catecholamine surge and organ injury postburn through promethazine.

Rationally Tuning Phase Separation in Polymeric Membranes toward Optimized All-day Passive Radiative Coolers.

The all-day passive radiative cooler has emerged as one of the state-of-the-art energy-saving cooling tool kits but routinely suffers from limited processability, high cost, and complicated fabrication processes, which impede large-scale applications. To address these challenges, this work exploits a polymer-based passive radiative cooler with optimized turbidity, reconfigurability, and recyclability. These cooling membranes are fabricated via selective condensation of octyl side chain-modified polyvinyl alcohol through a non-solvent-induced phase separation method. The rational tuning over spatial organization and distribution of the air-polymer interface renders optimized bright whiteness with solar reflectance at 96%. Meanwhile, the abundant -C-O-C- bonds endow such membranes with infrared thermal emittance over 90%. The optimized membrane realizes a subambient cooling of ∼5.7 °C with an average cooling power of ∼81 W m-2 under a solar intensity of ∼528 W m-2. Furthermore, the supramolecule nature of the developed passive radiative cooling membrane bears enhanced shape malleability and recyclability, substantially enhancing its conformability to the complex geometry and extending its life for an eco-friendly society.

Inhibiting Hyper-O-GlcNAcylation of c-Myc accelerate diabetic wound healing by alleviating keratinocyte dysfunction.

BACKGROUND: Diabetic foot ulcers characterized by delayed healing are one of the main complications of diabetes. Epidermal keratinocyte dysfunction has been found to play a pivotal role in the poor healing ability of diabetic wounds. In this study, we aimed to explore the relationship between c-Myc and its O-linked N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) modification and keratinocyte dysfunction in diabetic wounds. METHODS: Clinical wound samples were collected and a full-thickness skin defect wound model of diabetic rats was established. Re-epithelialization of wounds was observed by H&E staining and expressions of proliferating cell nuclear antigen, transglutaminase 1, loricrin, c-Myc and O-GlcNAc were measured by immunohistochemistry. The functional changes of proliferation, migration and differentiation of human immortalized epidermal cells (HaCaT) cells after overexpression or knockdown of c-Myc were observed. O-GlcNAcylation of c-Myc was confirmed using immunoprecipitation and proximity ligation assay. Stability of the c-Myc protein was measured using cycloheximide. Wound healing was observed after topical application of compounds that inhibited c-Myc or O-GlcNAc on diabetic wounds. RESULTS: Keratinocytes at the diabetic wound margin were characterized by active proliferation and division, slow migration and poor differentiation. Similar phenomena were observed in HaCaT cells cultured in 30 mM glucose and keratinocytes at the wound margin of the diabetic rats. The expression of c-Myc was increased in keratinocytes at the wound margin of diabetic rats, patients, and in HaCaT cells cultured with 30 mM glucose. Increased expression of c-Myc promoted the proliferation while inhibiting the migration and differentiation of the HaCaT cells, and inhibition of c-Myc promoted diabetic wound healing. Increased O-GlcNAcylation of c-Myc with 30 mM glucose stabilized the c-Myc proteins. Inhibition of O-GlcNAc ameliorated keratinocyte dysfunction and promoted diabetic wound healing. CONCLUSIONS: Increased expression of c-Myc promoted abnormal proliferation and inhibited migration and differentiation of keratinocytes at the diabetic wound margin. Increased O-GlcNAcylation of c-Myc with 30 mM glucose stabilized the c-Myc proteins. Inhibition of c-Myc or O-GlcNAc alleviated delayed diabetic wound healing. These findings make c-Myc and O-GlcNAc potential therapeutic targets for diabetic wounds.

c-Myc Upregulated by High Glucose Inhibits HaCaT Differentiation by S100A6 Transcriptional Activation.

Keratinocyte differentiation dysfunction in diabetic skin is closely related to impaired skin barrier functions. We investigated the effects of c-Myc and S100A6 on Human immortal keratinocyte line (HaCaT) or keratinocyte differentiation and potential mechanisms. The expression levels of differentiation makers such as transglutaminase 1 (TGM1), loricrin (LOR), and keratin 1 (K1) were significantly reduced, while the expression of c-Myc was significantly increased in HaCaT cells cultured in high glucose and wound margin keratinocytes from diabetic rats and human patients. Overexpression of c-Myc caused differentiation dysfunction of HaCaT, while knocking down c-Myc promoted differentiation. High glucose increased the expression of c-Myc and inhibited differentiation in HaCaT cells by activating the WNT/ß-catenin pathway. Moreover, inhibition of c-Myc transcriptional activity alleviated the differentiation dysfunction caused by high glucose or overexpression of c-Myc. c-Myc binds to the S100A6 promoter to directly regulate S100A6 expression and high glucose promoted S100A6 transcription. The expression of S100A6 was increased in HaCaT cultured with high glucose and wound margin keratinocytes from diabetic rats and human patients. However, the expression of S100A6 was decreased during normal HaCaT differentiation. HaCaT cells treated with S100A6 recombinant protein showed differentiation dysfunction. The expressions of TGM1, LOR and K1 in knockdown S100A6 HaCaT cells were higher than those in the control group. Overexpression of c-Myc or high glucose caused differentiation dysfunction of HaCaT cells, and was rescued by knocking down S100A6. These findings illustrate a new mechanism by which c-Myc upregulated by high glucose inhibits HaCaT differentiation by directly activating S100A6 transcription. Thus, c-Myc and S100A6 may be potential targets for the treatment of chronic diabetic wounds.

Ion-exchange enabled synthetic swarm.

Active matters are out-of-equilibrium systems that convert energy from the environment to mechanical motion. Non-reciprocal interaction between active matters may lead to collective intelligence beyond the capability of individuals. In nature, such emergent behaviours are ubiquitously observed in animal colonies, giving these species remarkable adaptive capability. In artificial systems, however, the emergence of non-trivial collective intelligent dynamics remains undiscovered. Here we show that a simple ion-exchange reaction can couple self-propelled ZnO nanorods and sulfonated polystyrene microbeads together. Chemical communication is established that enhances the reactivity and motion of both nanorods and the microbeads, resulting in the formation of an active swarm of nanorod-microbead complexes. We demonstrate that the swarm is capable of macroscopic phase segregation and intelligent consensus decision-making.

Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1.

Acute lung injury (ALI) is the leading cause of death in sepsis patients. Exosomes participate in the occurrence and development of ALI by regulating endothelial cell inflammatory response, oxidative stress and apoptosis, causing serious pulmonary vascular leakage and interstitial edema. The current study investigated the effect of exosomal miRNAs on endothelial cells during sepsis. We found a significant increase in miR-1-3p expression in cecal ligation and puncture (CLP) rats exosomes sequencing and sepsis patients' exosomes, and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) in vitro. However, the specific biological function of miR-1-3p in ALI remains unknown. Therefore, mimics or inhibitors of miR-1-3p were transfected to modulate its expression in HUVECs. Cell proliferation, apoptosis, contraction, permeability, and membrane injury were examined via cell counting kit-8 (CCK-8), flow cytometry, phalloidin staining, Transwell assay, lactate dehydrogenase (LDH) activity, and Western blotting. The miR-1-3p target gene was predicted with miRNA-related databases and validated by luciferase reporter. Target gene expression was blocked by siRNA to explore the underlying mechanisms. The results illustrated increased miR-1-3p and decreased stress-associated endoplasmic reticulum protein 1 (SERP1) expression both in vivo and in vitro. SERP1 was a direct target gene of miR-1-3p. Up-regulated miR-1-3p inhibits cell proliferation, promotes apoptosis and cytoskeleton contraction, increases monolayer endothelial cell permeability and membrane injury by targeting SERP1, which leads to dysfunction of endothelial cells and weakens vascular barrier function involved in the development of ALI. MiR-1-3p and SERP1 may be promising therapeutic candidates for sepsis-induced lung injury.

Isolation of extracellular vesicle with different precipitation-based methods exerts a tremendous impact on the biomarker analysis for clinical plasma samples.

BACKGROUND: Extracellular vesicles(EVs) is an emerging approach of cancer liquid biopsy. Although the precipitation-based method with commercial kits has gained popularity as the second most commonly used technique, these protocols vary tremendously with many included reagents still unknown to the community. METHODS: In this study, we assigned each of the 3 clinical plasma samples into 6 aliquots to assess five commercial EV isolation kits, in comparison with ultracentrifugation(UC). We implemented a standardized EV preparation and transcriptome analysis workflow except the EV isolation methods used. The metrics of EVs and its RNA cargo (evRNA) were compared to assess the technical variations versus the biological variations in the clinical setting. RESULTS: Although the size range of the isolated EVs demonstrated a similar distribution, we found significant technical variability among these methods, in terms of EV amount, purity, subpopulations and RNA integrity. Such variabilities were further relayed to a drastic divergence of evRNA expression on a transcriptome-wide fashion. CONCLUSIONS: Our study demonstrated a highly variable result from polymeric precipitation-based EV isolation methods, making EVs based biomarker analysis difficult to interpret and reproduce. We highlighted the importance of benchmarking and transparent reporting of the precipitation-based protocols in the liquid biopsy research.

Rational Design of Reversible Redox Shuttle for Highly Efficient Light-Driven Microswimmer.

The light-driven micro/nanomotor (LMNM) is machinery that harvests photon energy and generates self-propulsion in varieties of liquid media. Though visions are made that these tiny swimming machines can serve future medicine for accurate drug delivery and noninvasive microsurgery, their biomedical application is still impeded by the insufficient propulsion efficiency. Here we provide a holistic model of LMNM by considering (i) photovoltaic, (ii) electrochemical, and (iii) electrokinetic processes therein. Such a quantitative model revealed the pivotal role of reaction kinetics and diffusion properties of shuttle ions in the propulsion efficiency of LMNM. With the guidance of this model, a group of ferrocene-based reversible redox shuttles, which generate slow-diffusion ions, was identified, showcasing a high locomotion velocity of ∼500 µm/s (∼100 body length per second) at an ultralow concentration (70 µM). Owing to the in-depth understanding of the fundamental energy conversion processes in LMNM, we anticipate that the development of other high-performance supporting chemicals and LMNM systems will be greatly motivated, foreseeing the advent of LMNM systems with superior efficiency.

Bimetallic coatings synergistically enhance the speeds of photocatalytic TiO2 micromotors.

The design of powerful, more biocompatible microrobots calls for faster catalytic reactions. Here we demonstrate a two-fold increase in the speed of photocatalytic TiO2-metal Janus micromotors via a Au/Ag bi-layered coating. Electrochemical measurements show that such a bimetallic coating is a better photocatalyst than either metal alone. Similarly, an additional sputtered Ag layer could also significantly increase the speed of Pt-PS or TiO2-Pt micromotors, suggesting that applying bimetallic coatings is a generalizable strategy in the design of faster catalytic micromotors.

MicroRNA-200a induces immunosuppression by promoting PTEN-mediated PD-L1 upregulation in osteosarcoma.

In this study, we identified microRNAs that regulate the expression of programmed death-ligand 1(PD-L1) in osteosarcoma and investigated their role in PD-L1-targeted immunotherapy. MicroRNA sequencing analysis showed that the expression of PD-L1 is regulated by microRNA-200a in U2OS, 143B, and K7 osteosarcoma cells. MicroRNA-200a overexpression induced the upregulation of PD-L1 in the osteosarcoma cells. CD8+ T cells co-cultured with microRNA-200a-overexpressing osteosarcoma cells showed reduced survival, proliferation, and secretion of granzyme B and perforin. The same phenomenon was also observed in the K7-derived syngeneic mouse model, as microRNA-200a promoted tumor growth by increasing the percentage of Foxp3+ regulatory T lymphocytes while reducing the proportions of CD4+, CD8+, and IFN-γ+ cytotoxic T lymphocytes. But microRNA-200a overexpression group was also more responsive to PD-L1-targeted immunotherapy than the controls. In addition, the tumor tissues from 32 osteosarcoma patients showed that high expression of microRNA-200a and PD-L1 was associated with poor tumor necrosis rate after chemotherapy. Moreover, we confirmed that tensin homolog deleted on chromosome ten (PTEN) could act as the target gene for microRNA-200a during the upregulation of PD-L1. Thus, our findings provide important and novel insight into a regulatory axis involving microRNA-200a/PTEN/ PD-L1 axis, which determines osteosarcoma growth and the efficacy of PD-L1-targeted immunotherapy.