Biohybrid microrobots locally and actively deliver drug-loaded nanoparticles to inhibit the progression of lung metastasis.

Lung metastasis poses a formidable challenge in the realm of cancer treatment, with conventional chemotherapy often falling short due to limited targeting and low accumulation in the lungs. Here, we show a microrobot approach using motile algae for localized delivery of drug-loaded nanoparticles to address lung metastasis challenges. The biohybrid microrobot [denoted "algae-NP(DOX)-robot"] combines green microalgae with red blood cell membrane-coated nanoparticles containing doxorubicin, a representative chemotherapeutic drug. Microalgae provide autonomous propulsion in the lungs, leveraging controlled drug release and enhanced drug dispersion to exert antimetastatic effects. Upon intratracheal administration, algae-NP(DOX)-robots efficiently transport their drug payload deep into the lungs while maintaining continuous motility. This strategy leads to rapid drug distribution, improved tissue accumulation, and prolonged retention compared to passive drug-loaded nanoparticles and free drug controls. In a melanoma lung metastasis model, algae-NP(DOX)-robots exhibit substantial improvement in therapeutic efficacy, reducing metastatic burden and extending survival compared to control groups.

Continuous Ketone Monitoring via Wearable Microneedle Patch Platform.

Ketone bodies (KBs), especially ß-hydroxybutyrate (BHB), have gained tremendous attention as potential biomarkers as their presence in bodily fluids is closely associated with health and wellness. While a variety of blood fingerstick test strips are available for self-testing of BHB, there are major needs for wearable devices capable of continuously tracking changing BHB concentrations. To address these needs, we present here the first demonstration of a wearable microneedle-based continuous ketone monitoring (CKM) in human interstitial fluid (ISF) and illustrate its ability to closely follow the intake of ketone drinks. To ensure highly stable and selective continuous detection of ISF BHB, the new enzymatic microneedle BHB sensor relies on a gold-coated platinum working electrode modified with a reagent layer containing toluidine blue O (TBO) redox mediator, ß-hydroxybutyrate dehydrogenase (HBD) enzyme, a nicotinamide adenine dinucleotide (NAD+) cofactor, along with carbon nanotubes (CNTs), chitosan (Chit), and a poly(vinyl chloride) (PVC) outer protective layer. The skin-worn microneedle sensing device operates with a miniaturized electrochemical analyzer connected wirelessly to a mobile electronic device for capturing, processing, and displaying the data. Cytotoxicity and skin penetration studies indicate the absence of potential harmful effects. A pilot study involving multiple human subjects evaluated continuous BHB monitoring in human ISF, against gold standard BHB meter measurements, revealing the close correlation between the two methods. Such microneedle-based CKM offers considerable promise for dynamic BHB tracking toward the management of diabetic ketoacidosis and personal nutrition and wellness.

Significance of Gastrokine-1 Polymorphism Rs4254535 as a Prognostic Marker and its Association with Clinical Characteristics in Chinese Lung Cancer Patients.

Background: The single nucleotide polymorphism (SNP) of Gastrokine-1 (GKN1) is associated with lung cancer but its association with prognosis is not clear. Methods: Genomic DNA was extracted from the blood samples of 888 patients with lung cancer. The association between GKN1 polymorphism rs4254535 and prognostic was analyzed by the Kaplan-Meier (KM) method, Log-rank test, and Cox proportional hazards model. Results: In females and patients diagnosed with late-stage lung cancer, the CC genotype (CC vs TT, adjusted odds ratio [HR] = 0.57, 95% Confidence Interval [CI]: 0.33-0.99, P = 0.045; HR = 0.66, 95% CI: 0.48-0.92, P = 0.014) and recessive CC genotype (CC vs TT + TC, HR = 0.55, 95% CI: 0.32-0.94, P = 0.028; HR = 0.64, 95% CI: 0.47-0.89, P = 0.006) of rs4254535 conferred a better prognosis, compared with the TT and TT + TC genotype. Rs4254535 dominate TC + CC genotype, recessive CC genotype, and C allele who were adenocarcinoma patients had a significantly better prognosis. The recessive CC genotype of non-smoking patients has a better prognosis, compared to the TT + TC genotype. Additionally, in the dominant TT + TC genotype and C allele, no family history patients had a significantly better prognosis, compared to the TT genotype. Conclusion: For lung cancer patients, GKN1 polymorphism rs4254535 may be a protective genetic marker and predicts the prognosis of lung cancer patients.

Biohybrid Microalgae Robots: Design, Fabrication, Materials, and Applications.

The integration of microorganisms and engineered artificial components has shown considerable promise for creating biohybrid microrobots. The unique features of microalgae make them attractive candidates as natural actuation materials for the design of biohybrid microrobotic systems. In this review, microalgae-based biohybrid microrobots are introduced for diverse biomedical and environmental applications. The distinct propulsion and phototaxis behaviors of green microalgae, as well as important properties from other photosynthetic microalga systems (blue-green algae and diatom) that are crucial to constructing powerful biohybrid microrobots, will be described first. Then the focus is on chemical and physical routes for functionalizing the algae surface with diverse reactive materials toward the fabrication of advanced biohybrid microalgae robots. Finally, representative applications of such algae-driven microrobots are presented, including drug delivery, imaging, and water decontamination, highlighting the distinct advantages of these active biohybrid robots, along with future prospects and challenges.

Prognostic implications of the EGFR polymorphism rs763317 and clinical variables among young Chinese lung cancer population.

The 5-year survival rate for patients with lung cancer, the world's second most frequent malignant tumor, is less than 20%, and its prognosis cannot be clearly predicted. Our aim was to analyze the epidermal growth factor receptor (EGFR) rs763317 (G>A) single nucleotide polymorphism and its association with prognosis in Chinese Han lung cancer patients. 839 patients with primary lung cancer were recruited, and genomic DNA was extracted and genotyped by SNPscan. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the association between prognosis and EGFR polymorphism rs763317. A significant association after stratification by age, significantly increased lung cancer risk was associated with the AA homozygous genotype of rs763317 (adjusted hazard ratio = 2.53, 95% CI: 1.31-4.88, p=0.005), and conferred a poor survival for lung cancer patients (MST: median survival time: 13.6 months) compared with GG genotype (MST: 41.5 months), and in the recessive model AA genotype (AA vs. GG + GA; adjusted hazard ratio = 2.57, 95% CI: 1.34-4.93, p=0.004) who were young (<60 years) had a significantly increased risk of death. The EGFR polymorphism rs763617 might serve as a significant genetic marker for predicting the prognosis of lung cancer.

Research on line loss analysis and intelligent diagnosis of abnormal causes in distribution networks: artificial intelligence based method.

The primary source of energy losses in distribution networks (DNs) is rooted in line losses, which is crucial to conduct a thorough and reasonable examination of any unusual sources of line losses to guarantee the power supply in a timely and safe manner. In recent studies, identifying and analyzing abnormal line losses in DNs has been a widely and challenging research subject. This article investigates a key technology for the line loss analyses of DNs and intelligent diagnosis of abnormal causes by implementing artificial intelligence (AI), resulting in several prominent results. The proposed algorithm optimizes the parameters of the support vector machine (SVM) and suggests an intelligent diagnosis algorithm called the Improved Sparrow Search Algorithm and Support Vector Machine (ISSA-SVM). The ISSA-SVM algorithm is trained to calculate the data anomalies of line losses when changing loads and exhibiting exceptional performance to identify abnormal line losses. The accuracy of abnormality identification employing the ISSA-SVM algorithm reaches an impressive 98%, surpassing the performances of other available algorithms. Moreover, the practical performance of the proposed approach for analyzing large volumes of abnormal line loss data daily in DNs is also noteworthy. The ISSA-SVM accurately identifies the root causes of abnormal line losses and lowers the error in calculating abnormal line loss data. By combining different types of power operation data and creating a multidimensional feature traceability model, the study successfully determines the factors contributing to abnormal line losses. The relationship between transformers and voltage among various lines is determined by using the Pearson correlation, which provides valuable insights into the relationship between these variables and line losses. The algorithm's reliability and its potential to be applied to real-world scenarios bring an opportunity to improve the efficiency and safety of power supply systems. The ISSA that incorporates advanced techniques such as the Sobol sequence, golden sine algorithm, and Gaussian difference mutation appears to be a promising tool.

Extremophile-based biohybrid micromotors for biomedical operations in harsh acidic environments.

The function of robots in extreme environments is regarded as one of the major challenges facing robotics. Here, we demonstrate that acidophilic microalgae biomotors can maintain their swimming behavior over long periods of time in the harsh acidic environment of the stomach, thus enabling them to be applied for gastrointestinal (GI) delivery applications. The biomotors can also be functionalized with a wide range of cargos, ranging from small molecules to nanoparticles, without compromising their ability to self-propel under extreme conditions. Successful GI delivery of model payloads after oral administration of the acidophilic algae motors is confirmed using a murine model. By tuning the surface properties of cargos, it is possible to modulate their precise GI localization. Overall, our findings indicate that multifunctional acidophilic algae-based biomotors offer distinct advantages compared to traditional biohybrid platforms and hold great potential for GI-related biomedical applications.

Prognostic value of GPC5 polymorphism rs2352028 and clinical characteristics in Chinese lung cancer patients.

Background: GPC5 rs2352028 is associated with the risk of lung cancer, but its relationship with lung cancer prognosis is unclear. Materials & methods: The authors collected blood samples from 888 patients with lung cancer and used a Cox proportional hazards model to analyze the association between prognosis and GPC5 polymorphism rs2352028. Results: GPC5 rs2352028 C > T was associated with a better prognosis. Patients with CT genotype had longer overall survival than those with CC genotype. Additionally, older and early-stage patients with CT + TT genotype had a lower risk of death than those with CC genotype. Conclusion: GPC5 rs2352028 C > T may play a protective role in patients with lung cancer and GPC5 rs2352028 may be a potential genetic marker for lung cancer prognosis.

Gastrointestinal tract drug delivery using algae motors embedded in a degradable capsule.

The use of micromotors for active drug delivery via oral administration has recently gained considerable interest. However, efficient motor-assisted delivery into the gastrointestinal (GI) tract remains challenging, owing to the short propulsion lifetime of currently used micromotor platforms. Here, we report on an efficient algae-based motor platform, which takes advantage of the fast and long-lasting swimming behavior of natural microalgae in intestinal fluid to prolong local retention within the GI tract. Fluorescent dye or cell membrane-coated nanoparticle functionalized algae motors were further embedded inside a pH-sensitive capsule to enhance delivery to the small intestines. In vitro, the algae motors displayed a constant motion behavior in simulated intestinal fluid after 12 hours of continuous operation. When orally administered in vivo into mice, the algae motors substantially improved GI distribution of the dye payload compared with traditional magnesium-based micromotors, which are limited by short propulsion lifetimes, and they also enhanced retention of a model chemotherapeutic payload in the GI tract compared with a passive nanoparticle formulation. Overall, combining the efficient motion and extended lifetime of natural algae-based motors with the protective capabilities of oral capsules results in a promising micromotor platform capable of achieving greatly improved cargo delivery in GI tissue for practical biomedical applications.

Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia.

Bioinspired microrobots capable of actively moving in biological fluids have attracted considerable attention for biomedical applications because of their unique dynamic features that are otherwise difficult to achieve by their static counterparts. Here we use click chemistry to attach antibiotic-loaded neutrophil membrane-coated polymeric nanoparticles to natural microalgae, thus creating hybrid microrobots for the active delivery of antibiotics in the lungs in vivo. The microrobots show fast speed (>110 µm s-1) in simulated lung fluid and uniform distribution into deep lung tissues, low clearance by alveolar macrophages and superb tissue retention time (>2 days) after intratracheal administration to test animals. In a mouse model of acute Pseudomonas aeruginosa pneumonia, the microrobots effectively reduce bacterial burden and substantially lessen animal mortality, with negligible toxicity. Overall, these findings highlight the attractive functions of algae-nanoparticle hybrid microrobots for the active in vivo delivery of therapeutics to the lungs in intensive care unit settings.

An integrated wearable microneedle array for the continuous monitoring of multiple biomarkers in interstitial fluid.

Implementations of wearable microneedle-based arrays of sensors for the monitoring of multiple biomarkers in interstitial fluid have lacked system integration and evidence of robust analytical performance. Here we report the development and testing of a fully integrated wearable array of microneedles for the wireless and continuous real-time sensing of two metabolites (lactate and glucose, or alcohol and glucose) in the interstitial fluid of volunteers performing common daily activities. The device works with a custom smartphone app for data capture and visualization, comprises reusable electronics and a disposable microneedle array, and is optimized for system integration, cost-effective fabrication via advanced micromachining, easier assembly, biocompatibility, pain-free skin penetration and enhanced sensitivity. Single-analyte and dual-analyte measurements correlated well with the corresponding gold-standard measurements in blood or breath. Further validation of the technology in large populations with concurrent validation of sensor readouts through centralized laboratory tests should determine the robustness and utility of real-time simultaneous monitoring of several biomarkers in interstitial fluid.

Biomembrane-Functionalized Micromotors: Biocompatible Active Devices for Diverse Biomedical Applications.

There has been considerable interest in developing synthetic micromotors with biofunctional, versatile, and adaptive capabilities for biomedical applications. In this perspective, cell membrane-functionalized micromotors emerge as an attractive platform. This new class of micromotors demonstrates enhanced propulsion and compelling performance in complex biological environments, making them suitable for various in vivo applications, including drug delivery, detoxification, immune modulation, and phototherapy. This article reviews various proof-of-concept studies based on different micromotor designs and cell membrane coatings in these areas. The review focuses on the motor structure and performance relationship and highlights how cell membrane functionalization overcomes the obstacles faced by traditional synthetic micromotors while imparting them with unique capabilities. Overall, the cell membrane-functionalized micromotors are expected to advance micromotor research and facilitate its translation towards practical uses.

ACE2 Receptor-Modified Algae-Based Microrobot for Removal of SARS-CoV-2 in Wastewater.

The coronavirus SARS-CoV-2 can survive in wastewater for several days with a potential risk of waterborne human transmission, hence posing challenges in containing the virus and reducing its spread. Herein, we report on an active biohybrid microrobot system that offers highly efficient capture and removal of target virus from various aquatic media. The algae-based microrobot is fabricated by using click chemistry to functionalize microalgae with angiotensin-converting enzyme 2 (ACE2) receptor against the SARS-CoV-2 spike protein. The resulting ACE2-algae-robot displays fast (>100 µm/s) and long-lasting (>24 h) self-propulsion in diverse aquatic media including drinking water and river water, obviating the need for external fuels. Such movement of the ACE2-algae-robot offers effective "on-the-fly" removal of SARS-CoV-2 spike proteins and SARS-CoV-2 pseudovirus. Specifically, the active biohybrid microrobot results in 95% removal of viral spike protein and 89% removal of pseudovirus, significantly exceeding the control groups such as static ACE2-algae and bare algae. These results suggest considerable promise of biologically functionalized algae toward the removal of viruses and other environmental threats from wastewater.

Flow shear stress controls the initiation of neovascularization via heparan sulfate proteoglycans within a biomimetic microfluidic model.

Endothelial cells (ECs) in vivo are subjected to three forms of shear stress induced by luminal blood flow, transendothelial flow and interstitial flow simultaneously. It is controversial that shear stress, especially the component induced by luminal flow, was thought to inhibit the initialization of angiogenesis and trigger arteriogenesis. Here, we combined microfabrication techniques and delicate numerical simulations to reconstruct the initial physiological microenvironment of neovascularization in vitro, where ECs experience high luminal shear stress, physiological transendothelial flow and various vascular endothelial growth factor (VEGF) distributions simultaneously. With the biomimetic microfluidic model, cell alignment and endothelial sprouting assays were carried out. We found that luminal shear stress inhibits endothelial sprouting and tubule formation in a dose-dependent manner. Although a high concentration of VEGF increases EC sprouting, neither a positive nor a negative VEGF gradient additionally affects the degree of sprouting, and luminal shear stress significantly attenuates neovascularization even in the presence of VEGF. Heparinase was used to selectively degrade the heparan sulfate proteoglycan (HSPG) coating on ECs and messenger RNA profiles in ECs were analyzed. It turned out that HSPGs could act as a mechanosensor to sense the change of fluid shear stress, modulate multiple EC gene expressions, and hence affect neovascularization. In summary, distraction from the stabilized state, such as decreased luminal shear stress, increased VEGF and the destructed mechanotransduction of HSPGs would induce the initiation of neovascularization. Our study highlights the key role of the magnitude and forms of shear stress in neovascularization.

Enzyme-powered Janus platelet cell robots for active and targeted drug delivery.

Transforming natural cells into functional biocompatible robots capable of active movement is expected to enhance the functions of the cells and revolutionize the development of synthetic micromotors. However, present cell-based micromotor systems commonly require the propulsion capabilities of rigid motors, external fields, or harsh conditions, which may compromise biocompatibility and require complex actuation equipment. Here, we report on an endogenous enzyme-powered Janus platelet micromotor (JPL-motor) system prepared by immobilizing urease asymmetrically onto the surface of natural platelet cells. This Janus distribution of urease on platelet cells enables uneven decomposition of urea in biofluids to generate enhanced chemophoretic motion. The cell surface engineering with urease has negligible impact on the functional surface proteins of platelets, and hence, the resulting JPL-motors preserve the intrinsic biofunctionalities of platelets, including effective targeting of cancer cells and bacteria. The efficient propulsion of JPL-motors in the presence of the urea fuel greatly enhances their binding efficiency with these biological targets and improves their therapeutic efficacy when loaded with model anticancer or antibiotic drugs. Overall, asymmetric enzyme immobilization on the platelet surface leads to a biogenic microrobotic system capable of autonomous movement using biological fuel. The ability to impart self-propulsion onto biological cells, such as platelets, and to load these cellular robots with a variety of functional components holds considerable promise for developing multifunctional cell-based micromotors for a variety of biomedical applications.

Coronavirus Disease 2019: Initial Detection on Chest CT in a Retrospective Multicenter Study of 103 Chinese Patients.

PURPOSE: To evaluate the performance of chest CT regarding the initial presentation of patients suspected of having coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Data from 103 patients who were under investigation for COVID-19 based on inclusion criteria according to the World Health Organization Interim Guidance were retrospectively collected from January 21, 2020, to February 14, 2020. All patients underwent chest CT scanning and reverse-transcription polymerase chain reaction (RT-PCR) testing for COVID-19 at hospital presentation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) (with 95% confidence intervals) were calculated to evaluate the performance of CT. Subgroup analyses were also performed based on the geographical distribution of these cases in the province of Henan, China. RESULTS: There were 88/103 (85%) patients with COVID-19 confirmed by RT-PCR testing. The overall sensitivity, specificity, PPV, and NPV were 93% (85%, 97%), 53% (27%, 77%), 92% (83%, 96%), and 42% (18%, 70%), respectively. Similar results were shown in both geographic regions. The respective sensitivity, specificity, PPV, and NPV for chest CT in the districts of Xinyang and Zhumadian (n = 56) were 92% (80%, 97%), 63% (26%, 90%), 93% (81%, 98%), and 56% (23%, 85%), while these indicators in the district of Anyang (n = 47) were 95% (81%, 99%), 43% (12%, 80%), 90% (76%, 97%), and 60% (17%-93%). There were no significant differences in the prevalence of positive examinations in the two geographic subgroups for CT (P = .423) or RT-PCR (P = .931). CONCLUSION: Although initial chest CT obtained at hospital presentation showed high sensitivity in patients under investigation for COVID-19 in the two geographic regions in Henan Province, the NPV was only modest, suggesting a low value of CT as a screening tool.© RSNA, 2020.

Bioinspired helical graft with taper to enhance helical flow.

Helical flow has been introduced to improve the hemodynamic performance of vascular devices such as arterial grafts, stents and arteriovenous shunts to overcome the flow induced thrombus formation and intimal hyperplasia. However, the quite low intensity of helical flow in the existing devices may limit their function. To obtain desirably high intensity, inspired by the helical flow and tapered configuration of the arterial system, we proposed a new conceptual design of the medical devices, which take the form of a tapered helical shape. We demonstrated its effectiveness in arterial grafts by numerically comparing the hemodynamic performance of helical grafts with different smooth tapers. The results show that the helicity density quantifying the helical flow enlarges sharply with the increase of the taper under both steady and pulsatile flow conditions. Moreover, the amplified helical flow induced by the taper would lead to highly elevated wall shear stress, remarkably reduced oscillating shear index and relative residence time at both the grafts and the anastomosis of the host vessel. The present findings therefore indicated that the new helical graft with taper would significantly enhance the helical flow in the grafts and host vessel, which may reduce the possibility of thrombus formation in the graft and intimal hyperplasia in the host vessel and hence improve the graft patency. In addition, the concept of helical shape with taper may also be applied to design arterial stents and arteriovenous shunts to obtain better hemodynamic performance.