Mycobacterium abscessus (MAB) is a species of nontuberculous mycobacteria (NTM) and a major causative pathogen of pulmonary diseases especially in patients with cystic fibrosis. MAB infection is notoriously difficult to treat because of its intrinsic or inducible resistance to most antibiotics. The rough (R) morphotype of MAB, lacking cell surface glycopeptidolipids (GPLs), is associated with more severe and persistent infection than the smooth (S) type; however, the mechanisms underlying the R type’s virulence and the relation with GPLs remain unclear. In this study, we found that R-type MAB is much more proapoptotic than the S type, as a result of GPL-mediated inhibition of macrophage apoptosis. Polar GPLs inhibited an apoptotic response (induced by proapoptotic stimuli) by suppressing ROS production and the cytochrome c release and by preserving mitochondrial transmembrane potential. Furthermore, GPLs were found to be targeted to mitochondria and interacted with cyclophilin D; their acetylation was essential for this interaction. Finally, GPLs inhibited the intracellular growth and bacterial spreading of R-type MAB among macrophages via apoptosis inhibition. These findings suggest that GPLs limit MAB virulence by inhibiting apoptosis and the spread of bacteria and therefore provide a novel insight into the mechanism underlying virulence of MAB.

In this paper, a total of 57 micro and nano scale hybrid manufacturing processes are reviewed. These processes are categorized in terms of process timing and process type. Process timing is one of the most important aspects of manufacturing, and three different process schemes -concurrent, main/assistive (M/S) separate, and main/main (M/M) separate -are considered. The process type is categorized as either geometrically additive or subtractive, and all hybrid processes are categorized into combinations of additive, subtractive, and assistive process. Features and advantages are described for each of these classifications. Machining is found to be the most common process for both micro and nano-scale hybrid manufacturing. Of micro scale hybrid manufacturing schemes, 74.4% use assistive processes as a secondary process because the main purpose of most micro scale hybrid manufacturing is to improve the quality of the process. In nano scale manufacturing, 61.5% of hybrid manufacturing schemes employ assistive processes, since these processes typically focus on the fabrication of parts that are difficult to fabricate using a single, existing process. Based on a summary of published work, future trends in hybrid manufacturing at the micro and nano scale are suggested.

Mycobacterium avium complex induces macrophage apoptosis. However, the M. avium components that inhibit or trigger apoptosis and their regulating mechanisms remain unclear. We recently identified the immunodominant MAV2054 protein by fractionating M. avium culture filtrate protein by multistep chromatography; this protein showed strong immuno-reactivity in M. avium complex pulmonary disease and in patients with tuberculosis. Here, we investigated the biological effects of MAV2054 on murine macrophages. Recombinant MAV2054 induced caspase-dependent macrophage apoptosis. Enhanced reactive oxygen species production and JNK activation were essential for MAV2054-mediated apoptosis and MAV2054-induced interleukin-6, tumour necrosis factor, and monocyte chemoattractant protein-1 production. MAV2054 was targeted to the mitochondrial compartment of macrophages treated with MAV2054 and infected with M. avium. Dissipation of the mitochondrial transmembrane potential (ΔΨm) and depletion of cytochrome c also occurred in MAV2054-treated macrophages. Apoptotic response, reactive oxygen species production, and ΔΨm collapse were significantly increased in bone marrow-derived macrophages infected with Mycobacterium smegmatis expressing MAV2054, compared to that in M. smegmatis control. Furthermore, MAV2054 expression suppressed intracellular growth of M. smegmatis and increased the survival rate of M. smegmatis-infected mice. Thus, MAV2054 induces apoptosis via a mitochondrial pathway in macrophages, which may be an innate cellular response to limit intracellular M. avium multiplication.

Shape memory alloys (SMAs) are widely utilized as an actuation source in microscale devices, since they have a simple actuation mechanism and high-power density. However, they have limitations in terms of strain range and actuation speed. High-speed microscale SMA actuators are developed having diamond-shaped frame structures with a diameter of 25 µm. These structures allow for a large elongation range compared with bulk SMA materials, with the aid of spring-like behavior under tensile deformation. These actuators are validated in terms of their applicability as an artificial muscle in microscale by investigating their behavior under mechanical deformation and changes in thermal conditions. The shape memory effect is triggered by delivering thermal energy with a laser. The fast heating and cooling phenomenon caused by the scale effect allows high-speed actuation up to 1600 Hz. It is expected that the proposed actuators will contribute to the development of soft robots and biomedical devices.

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Existing proofs-of-concept have shown that microrobots can perform cell manipulation and enucleation, [4] selective gene transmission, [5] in vivo biopsy, [6] and cellular stimulation. [7] As the robots are too tiny to carry motors, control devices, and energy storages, they are commonly propelled using a magnetic gradient imparting a direct pull [8] or using a homogenous rotating field that in turn makes the microrobots rotate. [9] Developments in manufacturing technology made major contributions to the abovementioned achievements. Manufacturing processes can be categorized as top-down or bottom-up. The bottomup methods, such as precision additive manufacturing are widely applied. [10,11] Even, it tries to utilize smart material for developing 4D printing. [12] Two-photon lithography is a representative, additive microscale manufacturing process that uses laser scanning to polymerize photosensitive materials. Although this method can create a complete 3D structure, limitations exist on material selection, mostly polymers.On the other hand, top-down processes including focused ion beam (FIB) milling can be used to fabricate robots from a range of materials, including biocompatible or biodegradable materials. Furthermore, smart materials, such as shape memory alloys (SMAs), shape memory polymers (SMPs), and piezoelectric materials, can be used as actuators of the microrobot.The creation of movement in liquid is the first challenge when miniaturizing robots to microscales. As the size shrinks, the low Reynolds number due to more viscous effect and Brownian motion become major challenges. An efficient microscale robot thus requires a swimming strategy operative at low Reynolds numbers, and a navigation strategy that overcomes Brownian motion. As a traditional powering method to robot cannot be fitted at such small-scales, innovative design and actuation methods are required to satisfy the challenges of power and actuation. Various microrobots highlighting specific navigation principles have been developed over the past decade. [2] There are three categories of navigation strategies in microrobots: self-propulsion, external propulsion, and a hybrid strategy. [13] Self-propulsion is generated by result of local, smallscale chemical reactions on the robot surface; chemical energy is converted into kinetic energy. Generating local concentration Microrobotics has many potential applications, such as environmental remediation, in the biomedical arena. However, existing microrobots exhibit practical limitations including inadequate biocompatibility and imprecise control. Here, a microrobot made of shape memory alloy (SMA) actuator which can be driven by laser scanning to perform microscale motions is introduced. The 65 µm long microrobot having crawling-like motion can demonstrate the movement with 10.0 µm s −1 of the maximum speed. The microrobot is controlled by a laser affording wireless, spatiotemporally selective capabilities. During actuation, the robot exhibits crawling-like motions including trigger via the SMA as ...

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