Search

Adoptive cell therapy using natural killer (NK) cells emerges as the next‐generation cancer immunotherapy. Based on the intrinsic capability of direct cancer cell necrosis without prior education, a chemotherapeutic, free‐drug delivery, NK‐cell‐based platform can be developed. However, weak targeting of NK cells to solid tumors is observed. In addition, to boost the tumor‐killing efficiency, another immune‐regulating function should be added to the cells. Herein, a NK‐cell‐based hybrid system (NK‐Robot) conjugated with magnetic nanoparticles (MNPs) that provides 1) efficient guidance of NK cells and 2) targeted delivery of MNPs in situ is demonstrated, taking advantage of a newly designed, stimuli‐responsive polymeric linker. Thus, NK cells are allowed to target tumors under magnetic control conditions, and the liberated MNPs effectively reeducate the tumor‐associated macrophages (M2) to antitumor macrophages (M1), beneficial for the immunotherapy of tumors. In vivo experiments on BALB/c nude mice further support the finding that NK‐Robots effectively inhibit tumor growth.

Abstract Background Exploring the relationship between parasitic plants and answering taxonomic questions is still challenging. The subtribe Scurrulinae (Loranthaceae), which has a wide distribution in Asia and Africa, provides an excellent example to illuminate this scenario. Using a comprehensive taxon sampling of the subtribe, this study focuses on infer the phylogenetic relationships within Scurrulinae, investigate the phylogeny and biogeography of the subtribe, and establish a phylogenetically-based classification incorporating both molecular and morphological evidence. We conducted phylogenetic, historical biogeography, and ancestral character state reconstruction analyses of Scurrulinae based on the sequences of six DNA regions from 89 individuals to represent all five tribes of the Loranthaceae and the dataset from eleven morphological characters. Results The results strongly support the non-monophyletic of Scurrulinae, with Phyllodesmis recognized as a separate genus from its allies Taxillus and Scurrula based on the results from molecular data and morphological character reconstruction. The mistletoe Scurrulinae originated in Asia during the Oligocene. Scurrulinae was inferred to have been widespread in Asia but did not disperse to other areas. The African species of Taxillus, T. wiensii, was confirmed to have originated in Africa from African Loranthaceae ca. 17 Ma, and evolved independently from Asian members of Taxillus. Conclusions This study based on comprehensive taxon sampling of the subtribe Scurrulinae, strongly supports the relationship between genera. The taxonomic treatment for Phyllodesmis was provided. The historical biogeography of mistletoe Scurrulinae was determined with origin in Asia during the Oligocene. Taxillus and Scurrula diverged during the climatic optimum in the middle Miocene. Taxillus wiensii originated in Africa from African Loranthaceae, and is an independent lineage from the Asian species of Taxillus. Diversification of Scurrulinae and the development of endemic species in Asia may have been supported by the fast-changing climate, including cooling, drying, and the progressive uplift of the high mountains in central Asia, especially during the late Pliocene and Pleistocene.

Colorectal cancer remains one of the main causes of cancer-related deaths worldwide. Although numerous nanomedicine formulations have been developed to tackle the disease, their low selectivity still limits effective therapeutic outcomes. In this study, we isolated extracellular vesicles (EVs) from CT26 colorectal cancer cells and 4T1 murine mammary carcinoma cells, loaded them with the chemotherapeutic agent (doxorubicin, DOX). Then we evaluated the cellular uptake of the extracellular vesicles both in 2D monolayer and 3D tumor spheroid setups using confocal laser scanning microscope and flow cytometry. In vivo tumor homing of the extracellular vesicles was verified on CT26 tumor bearing BALB/c mice using in vivo imaging system. Finally, in vivo therapeutic effects were evaluated and compared using the same animal models treated with five doses of EV formulations. CT26-EV-DOX exhibited excellent biocompatibility, a high drug-loading capacity, controlled drug release behavior, and a high capability for targeting colorectal cancer cells. In particular, we verified that CT26-EV-DOX could preferentially be up taken by their parent cells and could effectively target and penetrate 3D tumor spheroids resembling colorectal tumors in vivo in comparison with their 4T1 derived EV partner. Additionally, treatment of colorectal tumor-bearing BALB/c mice with of CT26-EV-DOX significantly inhibited the growth of the tumors during the treatment course. The developed CT26-EV-DOX nanoparticles may present a novel and effective strategy for the treatment of colorectal cancer.

Compared to other actuating methods, acoustic actuators offer the distinctive capability of the contactless manipulation of small objects, such as microscale and nanoscale robots. Furthermore, they have the ability to penetrate the skin, allowing for the trapping and manipulation of micro/nanorobots that carry therapeutic agents in diverse media. In this review, we summarize the current progress in using acoustic actuators for the manipulation of micro/nanorobots used in various biomedical applications. First, we introduce the actuating method of using acoustic waves to manipulate objects, including the principle of operation and different types of acoustic actuators that are usually employed. Then, applications involving manipulating different types of devices are reviewed, including bubble-based microrobots, bubble-free robots, biohybrid microrobots, and nanorobots. Finally, we discuss the challenges and future perspectives for the development of the field.

Macrophages, which are part of the mononuclear phagocytic system, possess sensory receptors that enable them to target cancer cells. In addition, they are able to engulf large amounts of particles through phagocytosis, suggesting a potential “Trojan horse” drug delivery approach to tumors by facilitating the engulfment of drug-hidden particles by macrophages. Recent research has focused on the development of macrophage-based microrobots for anticancer therapy, showing promising results and potential for clinical applications. In this review, we summarize the recent development of macrophage-based microrobot research for anticancer therapy. First, we discuss the types of macrophage cells used in the development of these microrobots, the common payloads they carry, and various targeting strategies utilized to guide the microrobots to cancer sites, such as biological, chemical, acoustic, and magnetic actuations. Subsequently, we analyze the applications of these microrobots in different cancer treatment modalities, including photothermal therapy, chemotherapy, immunotherapy, and various synergistic combination therapies. Finally, we present future outlooks for the development of macrophage-based microrobots.

University timetable scheduling, which is a typical problem that all universities around the world have to face every semester, is an NP-hard problem. It is the task of allocating the right timeslots and classrooms for various courses by taking into account predefined constraints. In the current literature, many approaches have been proposed to find feasible timetables. Among others, swarm-based algorithms are promising candidates because of their effectiveness and flexibility. This paper investigates proposing an approach to university timetable scheduling using a recent novel swarm-based algorithm named Spotted Hyena Optimizer (SHO) which is inspired by the hunting behaviour of spotted hyenas. Then, a combination of SA and SHO algorithms also investigated to improve the overall performance of the proposed method. We also illustrate the proposed method on a real-world university timetabling problem in Vietnam. Experimental results have indicated the efficiency of the proposed method in comparison to other competitive metaheuristic algorithm such as PSO algorithm in finding feasible timetables.

ABSTRACT Explaining where plants originated and how plants migrated between eastern Asia and other Northern Hemisphere regions is still challenging. The genus Arisaema is considered a good example to illuminate this process, due to its wide distribution in both the tropical and temperate zones. Based on comprehensive taxon sampling, the historical biogeography of Arisaema was conducted using the molecular data from four chloroplast DNA regions. The phylogeny of Arisaema was studied by using ML and BI methods. Divergence times of Arisaema species were estimated by the uncorrelated lognormal Bayesian method. The ancestral area reconstruction of Arisaema was performed with BioGeoBEARS and Bayes-DIVA. Our results indicated that the crown group of Arisaema originated in Southeast Asia ca. 31.28 Ma. After the initial origin, Arisaema was inferred to have become widespread in Southeast Asia. Members in Himalayas, Africa and North China, Japan, the Korean Peninsula region (NJK region) were derived from migrants originating in Southeast Asia. American members were derived from migrants originating in the NJK region. Arisaema originated in Southeast Asia during the Oligocene with the development of tropical rainforest and a warm, moist climate. During the Oligocene to Miocene, Southeast Asia was the original center for the diversification of Arisaema in the NJK region.

ABSTRACT Alpinia is considered the largest genus of Zingiberaceae with ca. 250 species occurring in tropical and subtropical Asia, Australia, and Pacific Islands. The historical biogeography of Alpinia was conducted to explain where Alpinia originated and how it migrated to other regions. The phylogeny, divergence times and ancestral area reconstruction of Alpinia were performed by using the molecular data based on the comprehensive taxon sampling. Our results provide an objective approach to understand the historical biogeography of Alpinia. The genus originated in Asia during the Late Cretaceous ca. 69 Ma and started to diverge after the K-Pg boundary during the early Paleocene with the presence and development of the tropical rainforest and a warm, moist climate. Alpinia migrated to Malesia and then dispersed to Australasia. The molecular analyses supported the diversification of Alpinia in Asia and Malesia. Additionally, the Indian Alpinia has likely a common ancestor with Renealmia and Aframomum, and it is possible that after originating in Asia, Alpinia migrated from Asia to India then to Africa during the early period of collision between the Indian subcontinent and Eurasia to form the common ancestor of Indian Alpinia, Renealmia, and Aframomum. Our phylogeny provides a framework for studies in biogeography, comparative ecology, and evolution.

The ultrasonic actuator can be used in medical applications because it is label-free, biocompatible, and has a demonstrated history of safe operation. Therefore, there is an increasing interest in using an ultrasonic actuator in the non-contact manipulation of micromachines in various materials and sizes for therapeutic applications. This research aims to design, fabricate, and characterize a single-sided transducer array with 56 channels operating at 500 kHz, which provide benefits in the penetration of tissue. The fabricated transducer is calibrated using a phase reference calibration method to reduce position misalignment and phase discrepancies caused by acoustic interaction. The acoustic fields generated by the transducer array are measured in a 300 mm × 300 mm × 300 mm container filled with de-ionized water. A hydrophone is used to measure the far field in each transducer array element, and the 3D holographic pattern is analyzed based on the scanned acoustic pressure fields. Next, the phase reference calibration is applied to each transducer in the ultrasonic actuator. As a result, the homogeneity of the acoustic pressure fields surrounding the foci area is improved, and the maximum pressure is also increased in the twin trap. Finally, we demonstrate the capability to trap and manipulate micromachines with acoustic power by generating a twin trap using both optical camera and ultrasound imaging systems in a water medium. This work not only provides a comprehensive study on acoustic actuators but also inspires the next generation to use acoustics in medical applications.

The use of untethered microrobots for precise synergistic anticancer drug delivery and controlled release has attracted attention over the past decade. A high surface area of the microrobot is desirable to achieve greater therapeutic effect by increasing the drug load. Therefore, various nano- or microporous microrobot structures have been developed to load more drugs. However, as most porous structures are not interconnected deep inside, the drug-loading efficiency may be reduced. Here, we propose a magnetically guided helical microrobot with a Gyroid surface for high drug-loading efficiency and precise drug delivery. All spaces inside the proposed microrobot are interconnected, thereby enabling drug loading deep inside the structure. Moreover, we introduce gold nanostars on the microrobot structure for near-infrared-induced photothermal therapy and triggering drug release. The results of this study encourage further exploration of a high loading efficiency in cell-based therapeutics, such as stem cells or immune cells, for microrobot-based drug-delivery systems.

Targeted drug delivery using microrobots manipulated by an external actuator has significant potential to be a practical approach for wireless delivery of therapeutic agents to the targeted tumor. This work aimed to develop a novel acoustic manipulation system and macrophage-based microrobots (Macbots) for a study in targeted tumor therapy. The Macbots containing superparamagnetic iron oxide nanoparticles (SPIONs) can serve as drug carriers. Under an acoustic field, a microrobot cluster of the Macbots is manipulated by following a predefined trajectory and can reach the target with a different contact angle. As a fundamental validation, we investigated an in vitro experiment for targeted tumor therapy. The microrobot cluster could be manipulated to any point in the 4 × 4 × 4 mm region of interest with a position error of less than 300 μm. Furthermore, the microrobot could rotate in the O-XY plane with an angle step of 45 degrees without limitation of total angle. Finally, we verified that the Macbots could penetrate a 3D tumor spheroid that mimics an in vivo solid tumor. The outcome of this study suggests that the Macbots manipulated by acoustic actuators have potential applications for targeted tumor therapy.

Several recent advances have emerged in biotherapy and the development of personal drugs. However, studies exploring effective manufacturing methods of personal drugs remain limited. In this study, solid drugs based on poly(ethylene glycol)diacrylate (PEGDA) hydrogel and doxorubicin were fabricated, and their final geometry was varied through UV-light patterning. The results suggested that the final drug concentration was affected by the geometrical volume as well as the UV-light exposure time. The analysis of PEGDA showed no effect on the surrounding cells, indicating its high biocompatibility. However, with the addition of doxorubicin, it showed an excellent therapeutic effect, indicating that drugs inside the PEGDA structure could be successfully released. This approach enables personal drugs to be fabricated in a simple, fast, and uniform manner, with perfectly tuned geometry.

Acoustic tweezers provide unique capabilities in medical applications, such as contactless manipulation of small objects (e.g., cells, compounds or living things), from nanometer-sized extracellular vesicles to centimeter-scale structures. Additionally, they are capable of being transmitted through the skin to trap and manipulate drug carriers in various media. However, these capabilities are hindered by the limitation of controllable degrees of freedom (DoFs) or are limited maneuverability. In this study, we explore the potential application of acoustical tweezers by presenting a five-DoF contactless manipulation acoustic system (AcoMan). The system has 30 ultrasound transducers (UTs) with single-side arrangement that generates active traveling waves to control the position and orientation of a fully untethered nanocarrier clusters (NCs) in a spherical workspace in water capable of three DoFs translation and two DoFs rotation. In this method, we use a phase modulation algorithm to independently control the phase signal for 30 UTs and manipulate the NCs’ positions. Phase modulation and switching power supply for each UT are employed to rotate the NCs in the horizontal plane and control the amplitude of power supply to each UT to rotate the NCs in the vertical plane. The feasibility of the method is demonstrated by in vitro and ex vivo experiments using porcine ribs. A significant portion of this study could advance the therapeutic application such a system as targeted drug delivery.

Capsule endoscopes (CEs) have emerged as an advanced diagnostic technology for gastrointestinal diseases in recent decades. However, with regard to robotic motions, they require active movability and multi-functionalities for extensive, untethered, and precise clinical utilization. Herein, we present a novel wireless biopsy CE employing active five degree-of-freedom locomotion and a biopsy needle punching mechanism for the histological analysis of the intestinal tract. A medical biopsy punch is attached to a screw mechanism, which can be magnetically actuated to extrude and retract the biopsy tool, for tissue extraction. The external magnetic field from an electromagnetic actuation (EMA) system is utilized to actuate the screw mechanism and harvest biopsy tissue; therefore, the proposed system consumes no onboard energy of the CE. This design enables observation of the biopsy process through the capsule’s camera. A prototype with a diameter of 12 mm and length of 30 mm was fabricated with a medical biopsy punch having a diameter of 1.5 mm. Its performance was verified through numerical analysis, as well as in-vitro and ex-vivo experiments on porcine intestine. The CE could be moved to target lesions and obtain sufficient tissue samples for histological examination. The proposed biopsy CE mechanism utilizing punch biopsy and its wireless extraction–retraction technique can advance untethered intestinal endoscopic capsule technology at clinical sites.

Bi2Te3‐based materials have drawn much attention from the thermoelectric community due to their excellent thermoelectric performance near room temperature. However, the stability of existing n‐type Bi2(Te,Se)3 materials is still low due to the evaporation energy of Se (37.70 kJ mol−1) being much lower than that of Te (52.55 kJ mol−1). The evaporated Se from the material causes problems in interconnects of the module while degrading the efficiency. Here, we have developed a new approach for the high‐performance and stable n‐type Se‐free Bi2Te3‐based materials by maximizing the electronic transport while suppressing the phonon transport, at the same time. Spontaneously generated FeTe2 nanoinclusions within the matrix during the melt‐spinning and subsequent spark plasma sintering is the key to simultaneous engineering of the power factor and lattice thermal conductivity. The nanoinclusions change the fermi level of the matrix while intensifying the phonon scattering via nanoparticles. With a fine‐tuning of the fermi level with Cu doping in the n‐type Bi2Te3–0.02FeTe2, a high power factor of ~41 × 10−4 Wm−1 K−2 with an average zT of 1.01 at the temperature range 300–470 K are achieved, which are comparable to those obtained in n‐type Bi2(Te,Se)3 materials. The proposed approach enables the fabrication of high‐performance n‐type Bi2Te3‐based materials without having to include volatile Se element, which guarantees the stability of the material. Consequently, widespread application of thermoelectric devices utilizing the n‐type Bi2Te3‐based materials will become possible. [ABSTRACT FROM AUTHOR]