Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.

The multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus.

Hepatocellular carcinoma biomarkers screening based on hydrogel photonic barcodes with tyramine deposition amplified ELISA.

Hepatocellular carcinoma (HCC), as one of the most lethal cancers, significantly impacts human health. Attempts in this area tends to develop novel technologies with sensitive and multiplexed detection properties for early diagnosis. Here, we present novel hydrogel photonic crystal (PhC) barcodes with tyramine deposition amplified enzyme-linked immunosorbent assay (ELISA) for highly sensitive and multiplexed HCC biomarker screening. Because of the abundant amino groups of acrylic acid (AA) component, the constructed hydrogel PhC barcodes with inverse opal structure could facilitate the loading of antibody probes for subsequent detection of tumor markers. By integrating tyramine deposition amplified ELISA on the barcode, the detection signal of tumor markers has been enhanced. Based on these features, it is demonstrated that the hydrogel PhC barcodes with tyramine deposition amplified ELISA could realize highly sensitive and multiplexed detection of HCC-related biomarkers. It was found that this method is flexible, sensitive and accurate, suitable for multivariate analysis of low abundance tumor markers and future cancer diagnosis. These features make the newly developed PhC barcodes an innovation platform, which possesses tremendous potential for practical application of low abundance targets.

Host protein EPCAM interacting with EtMIC8-EGF is essential for attachment and invasion of Eimeria tenella in chickens.

The five epidermal growth factor-like domains (EGF) of Eimeria tenella microneme protein 8 (EtMIC8) (EtMIC8-EGF) plays a vital role in host cell attachment and invasion. These processes require interactions between parasite proteins and receptors on the surface of host cells. In this study, five chicken membrane proteins potentially interacting with EtMIC8-EGF were identified using the GST pull-down assay and mass spectrometry analysis, and only chicken (Gallus gallus) epithelial cell adhesion molecule (EPCAM) could bind to EtMIC8-EGF. EPCAM-specific antibody and recombinant EPCAM protein (rEPCAM) inhibited the EtMIC8-EGF binding to host cells in a concentration-dependent manner. Furthermore, the rEPCAM protein showed a binding activity to sporozoites in vitro, and a significant reduction of E. tenella invasion in DF-1 cells was further observed after pre-incubation of sporozoites with rEPCAM. The specific anti-EPCAM antibody further significantly decreased weight loss, lesion score and oocyst output during E. tenella infection, displaying partial inhibition of E. tenella infection. These results indicate that chicken EPCAM is an important EtMIC8-interacting host protein involved in E. tenella-host cell adhesion and invasion. The findings will contribute to a better understanding of the role of adhesion-associated microneme proteins in E. tenella.

A Biomimetic Cardiac Fibrosis-on-a-Chip as a Visible Disease Model for Evaluating Mesenchymal Stem Cell-Derived Exosome Therapy.

Cardiac fibrosis acts as a serious worldwide health issue due to its prevalence in numerous forms of cardiac disease and its essential link to cardiac failure. Considering the efficiency of stem cell therapy for cardiac fibrosis, great efforts have been dedicated to developing accurate models for investigating their underlying therapeutic mechanisms. Herein we present an elaborate biomimetic cardiac fibrosis-on-a-chip based on Janus structural color film (SCF) to provide microphysiological visuals for stem cell therapeutic studies. By coculturing cardiomyocytes (CMs) and cardiac fibroblasts (FBs) on Janus SCF with fibrosis induction, the chip can recreate physiological intercellular crosstalk within the fibrotic microenvironment, elucidating the physiological alterations of fibrotic hearts. In particular, the Janus structural color film possesses superior perceptual capabilities for capturing and responding to a weak cardiac force, demonstrating synchronized structural color shifts. Based on these features, we have not only explored the dynamic relationship between color mapping and the evaluated disease phenotype but also demonstrated the self-reporting capacity of the cardiac fibrosis-on-a-chip for the assessment of mesenchymal stem cell-derived exosome therapy. These features suggest that such a chip can potentially facilitate the evolution of precision medicine strategies and create a protocol for preclinical cardiac drug screening.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023.

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

A candidate virulence factor of Eimeria tenella (EtROP30) predicted by virulence enhancement of transgenic Toxoplasma gondii.

Difficulties of in vitro culture and genetic manipulation of Eimeria tenella have hindered the screening of virulence factors in this parasite. In this study, the E. tenella rhoptry protein 30 (EtROP30) was expressed in Toxoplasma gondii (RH∆Ku80-EtROP30), and its effect on the proliferation and virulence of parasites was investigated. The results revealed that the expression of EtROP30 had no impact on the invasion and egress processes. However, the RH∆Ku80-EtROP30 strain formed larger plaques compared to the RH∆Ku80, indicating that the EtROP30 expression promotes T. gondii proliferation. Furthermore, the RH∆Ku80-EtROP30 strain exhibited greater pathogenicity, resulting in earlier mortality and shorter overall survival time compared to RH∆Ku80. These results imply that EtROP30 expression facilitates parasite intracellular proliferation and virulence in mice, suggesting that EtROP30 might be a candidate virulence factor of E. tenella.

The accuracy of intraocular lens power calculation formulas based on artificial intelligence in highly myopic eyes: a systematic review and network meta-analysis.

Objective: To systematically compare and rank the accuracy of AI-based intraocular lens (IOL) power calculation formulas and traditional IOL formulas in highly myopic eyes. Methods: We screened PubMed, Web of Science, Embase, and Cochrane Library databases for studies published from inception to April 2023. The following outcome data were collected: mean absolute error (MAE), percentage of eyes with a refractive prediction error (PE) within ±0.25, ±0.50, and ±1.00 diopters (D), and median absolute error (MedAE). The network meta-analysis was conducted by R 4.3.0 and STATA 17.0. Results: Twelve studies involving 2,430 adult myopic eyes (with axial lengths >26.0 mm) that underwent uncomplicated cataract surgery with mono-focal IOL implantation were included. The network meta-analysis of 21 formulas showed that the top three AI-based formulas, as per the surface under the cumulative ranking curve (SUCRA) values, were XGBoost, Hill-RBF, and Kane. The three formulas had the lowest MedAE and were more accurate than traditional vergence formulas, such as SRK/T, Holladay 1, Holladay 2, Haigis, and Hoffer Q regarding MAE, percentage of eyes with PE within ±0.25, ±0.50, and ±1.00 D. Conclusions: The top AI-based formulas for calculating IOL power in highly myopic eyes were XGBoost, Hill-RBF, and Kane. They were significantly more accurate than traditional vergence formulas and ranked better than formulas with Wang-Koch AL modifications or newer generations of formulas such as Barrett and Olsen. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022335969.

Ophthalmic nurses' knowledge, attitude, and practice toward venous thromboembolic prevention: a dual-center cross-sectional survey.

Background: Venous thromboembolism (VTE) is a severe preventable complication among ophthalmic surgical patients. The knowledge, attitude, and practice (KAP) of nurses play a key role in effective VTE prevention. However, little is known about the KAP of ophthalmic nurses' VTE prevention. This study aimed to examine the level of KAP toward VTE prevention among Chinese ophthalmic nurses and to investigate the influencing factors of their VTE practice. Methods: A total of 610 ophthalmic nurses from 17 cities in Hunan and Zhejiang Provinces, China, participated in this study. Data was collected via the Sojump online platform from March to April 2021. A self-administered VTE questionnaire was developed to assess nurses' KAP toward VTE prevention. Multiple linear regression analysis was used to analyze the influencing factors of ophthalmic nurses' VTE prevention practice. Results: The scores (correct rates) of ophthalmic nurses' knowledge, attitude, and practice were 103.87 ± 20.50 (76.4%), 21.96 ± 2.72, and 48.96 ± 11.23 (81.6%), respectively. The three lowest-scored knowledge items were related to VTE complications, physical prevention, and risk assessment. The three lowest-scored attitude items were related to nurses' training, VTE risk, and patient education. The three lowest-scored practice items were related to the assessment scale, VTE assessment, and patient education. Nurses' knowledge, attitude, and practice were significantly correlated with each other. Multiple linear regression analysis showed that Hunan Province (B = 2.77, p = 0.006), general hospital (B = 2.97, p = 0.009), outpatient department (B = 3.93, p = 0.021), inpatient department (B = 2.50, p = 0.001), previous VTE prevention training (B = 3.46, p < 0.001), VTE prevention management in hospital (B = 4.93, p < 0.001), better knowledge (B = 0.04, p = 0.038), and positive attitude towards VTE prevention (B = 1.35, p < 0.001) were all significantly and positively associated with higher practice scores in VTE prevention. Conclusions: Our study provided a comprehensive understanding of the ophthalmic nurses' knowledge, attitude, and practice in VTE prevention, as well as identified specific items in each dimension for improvement. In addition, our study showed multiple factors were associated with ophthalmic nurses' practice in VTE prevention, including environmental factors, training and management, knowledge and attitudes toward VTE prevention. Our findings provide important implications and guidance for future intervention programs to improve the ophthalmic nurses' knowledge, attitude, and practice in VTE prevention.

Biomimetic Gland Models with Engineered Stratagems.

As extensively distributed tissues throughout the human body, glands play a critical role in various physiological processes. Therefore, the construction of biomimetic gland models in vitro has aroused great interest in multiple disciplines. In the biological field, the researchers focus on optimizing the cell sources and culture techniques to reconstruct the specific structures and functions of glands, such as the emergence of organoid technology. From the perspective of biomedical engineering, the generation of biomimetic gland models depends on the combination of engineered scaffolds and microfluidics, to mimic the in vivo environment of glandular tissues. These engineered stratagems endowed gland models with more biomimetic features, as well as a wide range of application prospects. In this review, we first describe the biomimetic strategies for constructing different in vitro gland models, focusing on the role of microfluidics in promoting the structure and function development of biomimetic glands. After summarizing several common in vitro models of endocrine and exocrine glands, the applications of gland models in disease modelling, drug screening, regenerative medicine, and personalized medicine are enumerated. Finally, we conclude the current challenges and our perspective of these biomimetic gland models.

Tailoring biomaterials for biomimetic organs-on-chips.

Organs-on-chips are microengineered microfluidic living cell culture devices with continuously perfused chambers penetrating to cells. By mimicking the biological features of the multicellular constructions, interactions among organs, vascular perfusion, physicochemical microenvironments, and so on, these devices are imparted with some key pathophysiological function levels of living organs that are difficult to be achieved in conventional 2D or 3D culture systems. In this technology, biomaterials are extremely important because they affect the microstructures and functionalities of the organ cells and the development of the organs-on-chip functions. Thus, herein, we provide an overview on the advances of biomaterials for the construction of organs-on-chips. After introducing the general components, structures, and fabrication techniques of the biomaterials, we focus on the studies of the functions and applications of these biomaterials in the organs-on-chips systems. Applications of the biomaterial-based organs-on-chips as alternative animal models for pharmaceutical, chemical, and environmental tests are described and highlighted. The prospects for exciting future directions and the challenges of biomaterials for realizing the further functionalization of organs-on-chips are also presented.

TMT Labeling Reveals the Effects of Exercises on the Proteomic Characteristics of the Subcutaneous Adipose Tissue of Growing High-Fat-Diet-Fed Rats.

Aim: Growing period is an important period for fat remodeling. High-fat diet and exercise are reasons for adipose tissue (AT) remodeling, but existing evidence is not enough. Therefore, the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on the proteomic characteristics of the subcutaneous AT of growing rats on normal diet or high-fat diet (HFD) were determined. Methods: Four-week-old male Sprague-Dawley rats (n = 48) were subdivided into six groups: normal diet control group, normal diet-MICT group, normal diet-HIIT group, HFD control group, HFD-MICT group, and HFD-HIIT group. Rats in the training group ran on a treadmill 5 days a week for 8 weeks (MICT: 50 min at 60-70% VO2max intensity; HIIT: 7 min of warm-up and recovery at 70% VO2max intensity, 6 sets of 3 min of 30% VO2max followed by 3 min 90% VO2max). Following physical assessment, inguinal subcutaneous adipose tissue (sWAT) was collected for proteome analysis using tandem mass tag labeling. Results: MICT and HIIT attenuated body fat mass and lean body mass but did not affect weight gain. Proteomics revealed the impact of exercise on ribosome, spliceosome, and the pentose phosphate pathway. However, the effect was reversed on HFD and normal diet. The differentially expressed proteins (DEPs) affected by MICT were related to oxygen transport, ribosome, and spliceosome. In comparison, the DEPs affected by HIIT were related to oxygen transport, mitochondrial electron transport, and mitochondrion protein. In HFD, HIIT was more likely to cause changes in immune proteins than MICT. However, exercise did not seem to reverse the protein effects of HFD. Conclusion: The exercise stress response in the growing period was stronger but increased the energy metabolism and metabolism. MICT and HIIT can reduce fat, increase muscle percentage, and improve maximum oxygen uptake in rats fed with HFD. However, in rats with normal diet, MICT and HIIT triggered more immune responses of sWAT, especially HIIT. In addition, spliceosomes may be the key factors in AT remodeling triggered by exercise and diet.

A moderate anticoccidial effect of cedrol on Eimeria tenella in broiler chickens.

As drug-resistant strains of Eimeria have emerged and concerns about drug residues in poultry have grown, there is renewed interest in identifying natural alternatives to control coccidiosis. Cedrol, a natural sesquiterpene alcohol, was used in this study to test anticoccidial efficacy in chicks. Both the control and treatment groups were orally challenged with 2 × 104 oocysts per chicken. Chicks administered with cedrol had reduced oocyst count, an increase in the relative weight gain rate of chicks, and a decrease in severe swelling of the cecum. Based on the above, ACI was calculated and the cedrol group reached moderate anti-coccidial activity (169.34). In chickens treated with cedrol, there were no changes in serum biochemical parameters, but oxidative stress biomarkers and cytokine levels associated with anticoccidial response were altered. These changes suggest that the administered concentration of cedrol did not have any adverse effects on the chickens while enhancing their antioxidant capacity and immunity, leading to an improved anticoccidial ability. In conclusion, this study shows that the addition of cedrol in poultry production has an anticoccidial effect and successfully improves growth performance during the growth period.

Living Anisotropic Structural Color Hydrogels for Cardiotoxicity Screening.

Environmental toxins can result in serious and fatal damage in the human heart, while the development of a viable stratagem for assessing the effects of environmental toxins on human cardiac tissue is still a challenge. Herein, we present a heart-on-a-chip based on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured living anisotropic structural color hydrogels for cardiotoxicity screening. Such anisotropic structural color hydrogels with a conductive parallel carbon nanotube (CNT) upper layer, gelatin methacryloyl (GelMA) interlayer, and inverse opal bottom layer were fabricated by a sandwich replicating approach. The inverse opal structure endowed the anisotropic hydrogels with stable structural color property, while the parallel and conductive CNTs could induce the hiPSC-CMs to grow in a directional manner with consistent autonomous beating. Notably, the resultant hiPSC-CM-cultured hydrogel exhibited synchronous shifts in structural color, responding to contraction and relaxation of hiPSC-CMs, offering a visual platform for monitoring cell activity. Given these features, the hiPSC-CM-cultured living anisotropic structural color hydrogels were integrated into a heart-on-a-chip, which provided a superior cardiotoxicity screening platform for environmental toxins.

TgMORN2, a MORN Family Protein Involved in the Regulation of Endoplasmic Reticulum Stress in Toxoplasma gondii.

MORN proteins play a key role in the cytoskeletal structure of eukaryotes and are essential for the close arrangement of the endoplasmic reticulum and plasma membrane. A gene with nine MORN motifs (TGGT1_292120, named TgMORN2) was identified in the Toxoplasma gondii genome; it was presumed to belong to the MORN protein family and to have the function of forming the cytoskeleton, which affects the survival of T. gondii. However, the genetic deletion of MORN2 did not noticeably affect parasite growth and virulence. Using adjacent protein labeling techniques, we identified a network of TgMORN2 interactions, which mainly included endoplasmic reticulum stress (ER stress)-related proteins. In exploring these data, we found that the pathogenicity of the KO-TgMORN2 strain was significantly reduced in the case of tunicamycin-induced ER stress. Reticulon TgRTN (TGGT1_226430) and tubulin ß-Tubulin were identified as interaction proteins of TgMORN2. Collectively, TgMORN2 plays a role in ER stress, which lays a foundation for further research on the function of the MORN protein in T. gondii.

Influenza A Virus Weakens the Immune Response of Mice to Toxoplasma gondii, Thereby Aggravating T. gondii Infection.

This study aimed to investigate the relationship between the T. gondii type II strain (Pru) and respiratory viral infections, specifically focusing on the co-infection with PR8 (influenza A/Puerto Rico/8/34). In this study, we found that the number of T. gondii (Pru) in the lungs of co-infected mice was significantly higher and lesions were more severe than those in the group infected with T. gondii (Pru) alone, whereas IAV (influenza A virus) copy numbers of co-infected and PR8 alone infected groups were negligible, suggesting that infection with IAV increased the pathogenicity of T. gondii (Pru) in mice. The invasion and proliferation assays demonstrated no significant effect of co-infection on T. gondii (Pru) infection or replication in vitro. To further explore the factors causing the altered pathogenicity of T. gondii (Pru) caused by co-infection, we found that decreased expression levels of IL-1ß, IL-6, and IL-12 in the co-infected group were associated with the early immune responses against T. gondii (Pru), which affected the division of T. gondii (Pru). Moreover, the significant decrease in the CD4+/CD8+ ratio indicated a weakened long-term immune killing ability of the host against T. gondii (Pru) following IAV infection. In conclusion, a T. gondii type II strain (Pru) could not be properly cleared by the host immune system after IAV infection, resulting in toxoplasmosis and even death in mice.

Hierarchical Spinning of Janus Textiles with Anisotropic Wettability for Wound Healing.

Wound healing and tissue repair are recognized as basic human health problems worldwide. Attempts to accelerate the reparative process are focused on developing functional wound dressings. Herein, we present novel Janus textiles with anisotropic wettability from hierarchical microfluidic spinning for wound healing. The hydrophilic hydrogel microfibers from microfluidics are woven into textiles for freeze-drying treatment, followed by the deposition of electrostatic spinning nanofibers composed of hydrophobic polylactic acid (PLA) and silver nanoparticles. The electrospun nanofiber layer can be well coupled with the hydrogel microfiber layer to generate Janus textiles with anisotropic wettability due to the roughness of the hydrogel textile surface and the incomplete evaporation of PLA solution when reaching the surface. For wound treatment with the hydrophobic PLA side contacting the wound surface, the wound exudate can be pumped from the hydrophobic to the hydrophilic side based on the wettability differential derived drainage force. During this process, the hydrophobic side of the Janus textile can prevent excess fluid from infiltrating the wound again, preventing excessive moisture and preserving the breathability of the wound. In addition, the silver nanoparticles contained in the hydrophobic nanofibers could impart the textiles with good antibacterial effect, which further promote the wound healing efficiency. These features indicate that the described Janus fiber textile has great application potential in the field of wound treatment.

Melanin-Integrated Structural Color Hybrid Hydrogels for Wound Healing.

Hydrogel patches have outstanding values in wound treatment; challenges in this field are concentrated on developing functional and intelligent hydrogel patches with new antibacterial strategies for improving healing process. Herein, a novel melanin-integrated structural color hybrid hydrogel patches for wound healing is presented. Such hybrid hydrogel patches are fabricated by infusing asiatic acid (AA)-loaded low melting-point agarose (AG) pregel into the melanin nanoparticles (MNPs)-integrated fish gelatin inverse opal film. In this system, MNPs not only impart the hybrid hydrogels with properties of photothermal antibacterial and antioxidant, but also improve the visibility of structural colors by providing an inherent dark background. Besides, the photothermal effect of MNPs under near-infrared irradiation can also trigger liquid transformation of AG component in hybrid patch, resulting in the controllable release of its loaded proangiogenic AA. Attracting, this drug release induced refractive index variations in the patch can be detected as visible structural color shifting, which can be used to monitor their delivery processes. Benefiting from these features, the hybrid hydrogel patches are demonstrated to achieve excellent therapeutic effects for in vivo wound treatment. Thus, it is believed that the proposed melanin-integrated structural color hybrid hydrogels are valuable as multifunctional patches for clinical applications.

Bioinspired optical and electrical dual-responsive heart-on-a-chip for hormone testing.

Heart-on-chips have emerged as a powerful tool to promote the paradigm innovation in cardiac pathological research and drug development. Attempts are focused on improving microphysiological visuals, enhancing bionic characteristics, as well as expanding their biomedical applications. Herein, inspired by the bright feathers of peacock, we present a novel optical and electrical dual-responsive heart-on-a-chip based on cardiomyocytes hybrid bright MXene structural color hydrogels for hormone toxicity evaluation. Such hydrogels with inverse opal nanostructure are generated by using pregel to replicate MXene-decorated colloidal photonic crystal (PhC) array templates. The attendant MXene in the hydrogels could not only enhance the saturation of structural color, but also ensure the composite hydrogel with excellent electroconductivity to facilitate the synergetic beating of their surface cultured cardiomyocytes. In this case, the hydrogels would undergo a synchronous deformation and generate shift in corresponding photonic band gap and structural color, which could be employed as visual signal for self-reporting of the cardiomyocyte mechanics. Based on these features, we demonstrated the practical value of the optical and electrical dual-responsive structural color MXene hydrogels constructed heart-on-a-chip in hormone toxicity testing. These results indicated that the proposed heart-on-a-chip might find broad prospects in drug screening, biological research, and so on.

Rocket-Inspired Effervescent Motors for Oral Macromolecule Delivery.

Oral administration is among the most convenient ways with good patient compliance for drug delivery; while it remains a challenge to achieve desirable bioavailability of most macromolecules due to the complex gastrointestinal barriers. Here, inspired by the structure and function of rocket, a novel micromotor delivery system is presented with scaled-down rocket-like architecture and effervescent-tablets-derived fuel for efficient oral macromolecule delivery by penetrating intestinal barrier. These rocket-inspired effervescent motors (RIEMs) are composed of sharp needle tips for both loading cargoes and efficient penetrating, and tail wings for loading effervescent powders and avoiding perforation. When exposed to a water environment, the effervescent fuel generates intensive CO2 bubbles to propel the RIEMs to move at high speed. Thus, the RIEMs with their sharp tip can inject into the surrounding mucosa for effective drug release. Furthermore, benefiting from their tail-wing design, perforation can be effectively avoided during the injection process, ensuring the safety of the RIEMs in gastrointestinal active delivery. Based on these advantages, it is demonstrated that the RIEMs can efficiently move and stab into the intestinal mucosa for insulin delivery, exhibiting efficacy in regulating blood sugar glucose in a diabetic rabbit model. These features indicate that these RIEMs are versatile and valuable for clinical oral delivery of macromolecules.

Liquid Metal Droplets-Based Elastomers from Electric Toothbrush-Inspired Revolving Microfluidics.

Liquid metal (LM)-based elastomers have a demonstrated value in flexible electronics. Attempts in this area include the development of multifunctional LM-based elastomers with controllable morphology, superior mechanical performances, and great stability. Herein, inspired by the working principle of electric toothbrushes, a revolving microfluidic system is presented for the generation of LM droplets and construction of desired elastomers. The system involves revolving modules assembled by a needles array and 3D microfluidic channels. LM droplets can be generated with controllable size in a high-throughput manner due to the revolving motion-derived drag force. It is demonstrated that by employing a poly(dimethylsiloxane) (PDMS) matrix as the collection phase, the generated LM droplets can act as conductive fillers for the construction of flexible electronics directly. The resultant LM droplets-based elastomers exhibit high mechanical strength, stable electrical performance, as well as superior self-healing property benefiting from the dynamic exchangeable urea bond of the polymer matrix. Notably, due to the flexible programmable feature of the LM droplets embedded within the elastomers, various patterned LM droplets-based elastomers can be easily achieved. These results indicate that the proposed microfluidic LM droplets-based elastomers have a great potential for promoting the development of flexible electronics.