Cobalt MOF-Based Porous Carbonaceous Spheres for Multimodal Soft Actuator Exhibiting Intricate Biomimetic Motions.

The advancement of active electrode materials is essential to meet the demand for multifaceted soft robotic interactions. In this study, a new type of porous carbonaceous sphere (PCS) for a multimodal soft actuator capable of both magnetoactive and electro-ionic responses is reported. The PCS, derived from the simultaneous oxidative and reductive breakdown of specially designed cobalt-based metal-organic frameworks (Co-MOFs) with varying metal-to-ligand ratios, exhibits a high specific surface area of 529 m2 g-1 and a saturated magnetization of 142.7 Am2 kg-1. The size of the PCS can be controlled through the Ostwald ripening mechanism, while the porous structure can be regulated by adjusting the metal-to-ligand mol ratio. Its exceptional compatibility with poly(3,4-ethylene-dioxythiophene)-poly(styrenesulfonate) enables the creation of uniform electrode, crucial for producing soft actuators that work in both magnetic and electrical fields. Operated at an ultralow voltage of 1 V, the PCS-based actuator generates a blocking force of 47.5 mN and exhibits significant bending deflection even at an oscillation frequency of 10 Hz. Employing this simultaneous multimodal actuation ensures the dynamic and complex motions of a balancing bird robot and a dynamic eagle robot. This advancement marks a significant step toward the realization of more dynamic and versatile soft robotic systems.

Adipose Tissue Macrophage Polarization Is Altered during Recovery after Exercise: A Large-Scale Flow Cytometric Study.

We performed a large-scale flow cytometric analysis to determine whether M1 macrophage (M1Ø) and M2 macrophage (M2Ø) polarization in white adipose tissue (WAT) was altered immediately after exercise. Additionally, we comprehensively investigated the effects of obesity, exercise intensity, and recovery time on macrophage polarization in WAT. A single exercise bout of various intensities (ND, non-exercise control; -LIE, low-intensity exercise; -MIE, mid-intensity exercise; -HIE, high-intensity exercise) was performed by normal mice (ND) and obese mice (HFD). To confirm differences in M1Ø/M2Ø polarization in WAT based on the recovery time after a single exercise bout, WAT was acquired at 2 h, 24 h, and 48 h after exercise (total n = 168, 7 mice × 4 groups × 2 diets × 3 recovery time). The harvested WAT was immediately analyzed by flow cytometry, and macrophages were fluorescently labeled using F4/80, as well as M1Ø with CD11c and M2Øs with CD206. After a single bout of exercise, the M2Ø/M1Ø polarization ratio of WAT increases in both normal and obese mice, but differences vary depending on recovery time and intensity. Regardless of obesity, our findings showed that there could be a transient increase in M1Ø in WAT over a short recovery time (24 h) post-exercise (in ND-MIE, ND-HIE, and HFD-HIE). Furthermore, it was observed that the greater the exercise intensity in obese mice, the more effective the induction of M2Ø polarization immediately after exercise, as well as the maintenance of high M2Ø polarization, even after a prolonged recovery time.

Janus CoMOF-SEBS Membrane for Bifunctional Dielectric Layer in Triboelectric Nanogenerators.

Considerable research has been conducted on the application of functional nano-fillers to enhance the power generation capabilities of triboelectric nanogenerators (TENGs). However, these additives often exhibit a decrease in output power at higher concentration. Here, a Janus cobalt metal-organic framework-SEBS (JCMS) membrane is reported as a dual-purpose dielectric layer capable of efficiently capturing and blocking charges for high-performance TENGs. The JCMS is produced asymmetrically through gravitational sedimentation, employing spherical CoMOFs within a diluted SEBS solution. Beyond its dual dielectric characteristics, the JCMS showcases exceptional mechanical durability, displaying notable stretchability of up to 475% and remarkable resilience when subjected to diverse mechanical pressures. Consequently, the JCMS-TENG produces a maximum peak-to-peak voltage of 936 V, a current of 42.8 µA, and a power density of 10.89 W m- 2 when exposed to an external force of 10 N at a 5 Hz frequency. This investigation highlights the potential of JCMS-TENGs with unique structures, known for their exceptional energy harvesting capabilities, mechanical strength, and flexibility. Additionally, the promising prospects of easily produced asymmetric structures is emphasized with bifunctionalities for developing efficient and flexible MOFs-based TENGs. These advancements are well-suited for self-powered wearables, rehabilitation devices, and energy harvesters.

Exercise intensity impacts the improvement of metabolic dysfunction-associated steatotic liver disease via variations of monoacylglycerol O-acyltransferase 1 expression.

BACKGROUND: The involvement of monoacylglycerol O-acyltransferase 1 (MOGAT1) in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) has been recognized. While exercise is recommended for the improvement of obesity and MASLD, the impact of exercise intensity remains unclear. This study aimed to examine the influence of exercise intensity on MOGAT1 expression in high-fat diet (HFD)-induced obese mice with MASLD. METHOD: Male C57BL/6 mice aged 6 weeks were subjected to either a regular or HFD with 60 % fat content for 8 weeks. The mice were categorized into 5 groups based on their diet and exercise intensity: normal diet group (ND), HFD group, low-intensity exercise with HFD group (HFD+LIE), moderate-intensity exercise with HFD group (HFD+MIE), and high-intensity exercise (HIE) with HFD group (HFD+HIE). The duration of running was adjusted to ensure uniform exercise load across groups (total distance = 900 m): HFD+LIE at 12 m/min for 75 min, HFD+MIE at 15 m/min for 60 min, and HFD+HIE at 18 m/min for 50 min. RESULTS: Lipid droplet size and MASLD activity score were significantly lower in the HFD+HIE group compared to other exercise-intensity groups (p < 0.05). Among the 3 intensity exercise groups, the lowest MOGAT1 protein expression was found in the HFD+HIE group (p < 0.05). CONCLUSION: This study reveals that high-intensity exercise has the potential to mitigate MASLD development, partly attributed to the downregulation of MOGAT1 expression.

Pharmaceutical and Immunological Evaluation of Cholera Toxin A1 Subunit as an Adjuvant of Hepatitis B Vaccine Microneedles.

PURPOSE: For successful delivery of a solid vaccine formulation into the skin using microneedles, the solubility of an adjuvant should be considered because the decrease in the dissolution rate by the addition of adjuvant decreases the delivery efficiency of the vaccine. METHODS: In this study, cholera toxin A subunit 1 (CTA1) was examined as an adjuvant to Hepatitis B vaccine (HBV) microneedles because of its good water solubility, improved safety, and positive effect as shown in intramuscular administration of a liquid vaccine. RESULTS: All solid formulations with CTA 1 dissolved in in vivo mouse skin within 30 min, and they were successfully delivered into the skin. In experiments with mice, the addition of CTA1 led to improved IgG immune response compared to the use of an aluminum hydroxide-based formulation and intramuscular administration of HBV. In addition, CTA1 induced CD8 + T cell response as much as in which the aluminum hydroxide-based formulation induced. CONCLUSIONS: CTA1 is an adjuvant that satisfies both the delivery efficiency and the immunological characteristics required for vaccine microneedles. CTA1 will be used as a potential adjuvant through vaccine microneedles.

Secreted aspartyl protease 3 regulated by the Ras/cAMP/PKA pathway promotes the virulence of Candida auris.

The surge of multidrug-resistant fungal pathogens, especially Candida auris, poses significant threats to global public health. Candida auris exhibits resistance to multiple antifungal drugs, leading to major outbreaks and a high mortality rate. With an urgent call for innovative therapeutic strategies, this study focused on the regulation and pathobiological significance of secreted aspartyl proteinases (SAPs) in C. auris, as these enzymes play pivotal roles in the virulence of some fungal species. We delved into the Ras/cAMP/PKA signaling pathway's influence on SAP activity in C. auris. Our findings underscored that the Ras/cAMP/PKA pathway significantly modulates SAP activity, with PKA catalytic subunits, Tpk1 and Tpk2, playing a key role. We identified a divergence in the SAPs of C. auris compared to Candida albicans, emphasizing the variation between Candida species. Among seven identified secreted aspartyl proteases in C. auris (Sapa1 to Sapa7), Sapa3 emerged as the primary SAP in the pathogen. Deletion of Sapa3 led to a significant decline in SAP activity. Furthermore, we have established the involvement of Sapa3 in the biofilm formation of C. auris. Notably, Sapa3 was primarily regulated by Tpk1 and Tpk2. Deletion of SAPA3 significantly reduced C. auris virulence, underscoring its pivotal role in C. auris pathogenicity. The outcomes of this study provide valuable insights into potential therapeutic targets, laying the groundwork for future interventions against C. auris infection.

Protein Kinase A Controls the Melanization of Candida auris through the Alteration of Cell Wall Components.

Candida auris, a multidrug-resistant fungal pathogen, significantly threatens global public health. Recent studies have identified melanin production, a key virulence factor in many pathogenic fungi that protects against external threats like reactive oxygen species, in C. auris. However, the melanin regulation mechanism remains elusive. This study explores the role of the Ras/cAMP/PKA signaling pathway in C. auris melanization. It reveals that the catalytic subunits Tpk1 and Tpk2 of protein kinase A (PKA) are essential, whereas Ras1, Gpr1, Gpa2, and Cyr1 are not. Under melanin-promoting conditions, the tpk1Δ tpk2Δ strain formed melanin granules in the supernatant akin to the wild-type strain but failed to adhere them properly to the cell wall. This discrepancy is likely due to a decreased expression of chitin-synthesis-related genes. Our findings also show that Tpk1 primarily drives melanization, with Tpk2 having a lesser impact. To corroborate this, we found that C. auris must deploy Tpk1-dependent melanin deposition as a defensive mechanism against antioxidant exposure. Moreover, we confirmed that deletion mutants of multicopper oxidase and ferroxidase genes, previously assumed to influence C. auris melanization, do not directly contribute to the process. Overall, this study sheds light on the role of PKA in C. auris melanization and enhances our understanding of the pathogenicity mechanisms of this emerging fungal pathogen.

Easy-To-Wear Auxetic SMA Knot-Architecture for Spatiotemporal and Multimodal Haptic Feedbacks.

Wearable haptic interfaces prioritize user comfort, but also value the ability to provide diverse feedback patterns for immersive interactions with the virtual or augmented reality. Here, to provide both comfort and diverse tactile feedback, an easy-to-wear and multimodal wearable haptic auxetic fabric (WHAF) is prepared by knotting shape-memory alloy wires into an auxetic-structured fabric. This unique meta-design allows the WHAF to completely expand and contract in 3D, providing superior size-fitting and shape-fitting capabilities. Additionally, a microscale thin layer of Parylene is coated on the surface to create electrically separated zones within the WHAF, featuring zone-specified actuation for conveying diverse spatiotemporal information to users with using the WHAF alone. Depending on the body part it is worn on, the WHAF conveys either cutaneous or kinesthetic feedback, thus, working as a multimodal wearable haptic interface. As a result, when worn on the forearm, the WHAF intuitively provides spatiotemporal information to users during hands-free navigation and teleoperation in virtual reality, and when worn on the elbow, the WHAF guides users to reach the desired elbow flexion, like a personal exercise advisor.

Deciphering the regulatory mechanisms of the cAMP/protein kinase A pathway and their roles in the pathogenicity of Candida auris.

The emergence of multidrug-resistant fungal pathogens is a significant concern for global public health. Candida auris poses a considerable threat as a multidrug-resistant fungal pathogen. Our recent study revealed that the adenylyl cyclase Cyr1 and protein kinase A (PKA) pathways play distinct and redundant roles in drug resistance and pathogenicity of C. auris. However, the upstream and negative feedback regulatory mechanisms of C. auris are not yet fully understood. In this study, we discovered that the small GTPase Ras1, along with its nucleotide exchange factor Cdc25 and GTPase-activating protein Ira2, plays a major role in regulating cAMP/PKA-dependent traits, while G-protein-coupled receptor Gpr1 and heterotrimeric G-protein α subunit Gpa2 play a minor role. Pde2 plays a major role in negative feedback regulation of the cAMP/PKA pathway, while Pde1 plays a minor role. Hyperactivation of the Ras/cAMP/PKA pathway by deleting PDE2 or BCY1 renders C. auris cells thermosensitive and susceptible to nutrient deficiency, which leads to attenuated virulence. Our study demonstrates the distinct contributions of hyperactivation of the Ras/cAMP/PKA signaling pathway to C. auris pathogenesis and suggests potential therapeutic targets for C. auris-mediated candidiasis. IMPORTANCE Candida auris is a major concern as a multidrug-resistant fungal pathogen. While our previous studies highlighted the crucial roles of the cAMP/protein kinase A (PKA) pathway in regulating drug resistance, stress responses, morphogenesis, ploidy change, biofilm formation, and pathogenicity in this pathogen, their regulatory mechanism remains unclear. In our study, we provided evidence that the cAMP/PKA signaling pathway in C. auris is primarily governed by the small GTPase RAS rather than a G-protein-coupled receptor. Additionally, we discovered that the negative feedback regulation of cAMP, controlled by phosphodiesterases, is vital for C. auris virulence by promoting resistance to high temperatures and nutrient deficiencies. These findings underscore the diverse pathobiological significance of the Ras/cAMP/PKA signaling pathway in C. auris, shedding light on potential therapeutic targets and strategies for combating this multidrug-resistant fungal pathogen.

Recent Advances in Triboelectric Nanogenerators: From Technological Progress to Commercial Applications.

Serious climate changes and energy-related environmental problems are currently critical issues in the world. In order to reduce carbon emissions and save our environment, renewable energy harvesting technologies will serve as a key solution in the near future. Among them, triboelectric nanogenerators (TENGs), which is one of the most promising mechanical energy harvesters by means of contact electrification phenomenon, are explosively developing due to abundant wasting mechanical energy sources and a number of superior advantages in a wide availability and selection of materials, relatively simple device configurations, and low-cost processing. Significant experimental and theoretical efforts have been achieved toward understanding fundamental behaviors and a wide range of demonstrations since its report in 2012. As a result, considerable technological advancement has been exhibited and it advances the timeline of achievement in the proposed roadmap. Now, the technology has reached the stage of prototype development with verification of performance beyond the lab scale environment toward its commercialization. In this review, distinguished authors in the world worked together to summarize the state of the art in theory, materials, devices, systems, circuits, and applications in TENG fields. The great research achievements of researchers in this field around the world over the past decade are expected to play a major role in coming to fruition of unexpectedly accelerated technological advances over the next decade.

Changes in aquaporins expression due to acute water restriction in naturally aging mice

Aquaporins (AQPs) are water channels in the cell membrane that regulate osmosis in response to rapid changes in intracellular and extracellular fluid concentration caused by extrinsic factors. While there are so many studies on the association of AQPs with muscular atrophy, sarcopenia, and Duchenne muscular dystrophy (DMD), the expression of AQP has not been verified in naturally aging mice or humans. Notably, due to the characteristics of AQPs, the difference in function cannot be evaluated without extrinsic factors such as acute water restriction. The purpose of this study was to investigate the changes in AQPs expression and function due to natural aging under acute water restriction conditions in aging mice. The expression of AQP4 was shown to decrease with aging similar to previous studies. However, for the first time, this study results confirmed that AQP1 expression increased in aging mice. In addition, the expression of Aqp1 decreased in the acute water restricted group compared to the control group after acute water restriction in aging mice. These results suggest that although the expression of AQP1 increases with aging, its function is reduced. We also confirmed that overexpression of Aqp1 can inhibit myotube differentiation and that knockdown can promote myotube differentiation through in vitro experiments. In conclusion, based on our results, we suggest that the AQP1 is an important factor in sarcopenia caused by natural aging accompanied by chronic dehydration. (AU)

Distinct effect of exercise modes on mood-related behavior in mice.

Exercise can afford several benefits to combat mood disorders in both rodents and humans. Engagement in various physical activities upregulates levels of neurotrophic factors in several brain regions and improves mental health. However, the type of exercise that regulates mood and the underlying mechanisms in the brain remain elusive. Herein, we performed two distinct types of exercise and RNA sequencing analyses to investigate the effect of exercise on mood-related behaviors and explain the distinct patterns of gene expression. Specifically, resistance exercise exhibited reduced immobility time in the forced swim test when compared with both no exercise and treadmill exercise (in the aerobic training [AT] group). Interestingly, anxiety-like behaviors in the open field and nest-building tests were ameliorated in the AT group when compared with those in the control group; however, this was not observed in the RT group. To elucidate the mechanism underlying these different behavioral changes caused by distinct exercise types, we examined the shift in the gene expression pattern in the hippocampus, a brain region that plays a critical role in regulating mood. We discovered that 38 and 40 genes were altered in the AT and RT groups, respectively, compared with the control group. Both exercises regulated 16 common genes. Compared with the control group, mitogen-activated protein kinase (MAPK) was enriched in the AT group and phosphatidylinositol-3-kinase (PI3K)/AKT and neurotrophin signaling pathways were enriched in the RT group, as determined by bioinformatics pathway analysis. PCR results revealed that Cebpß expression was increased in AT group, and Dcx expression was upregulated in both groups. Our findings indicate that different exercise types may exert substantially distinct effects on mood-like behaviors. Accordingly, appropriate types of exercise can be undertaken based on the mood disorder to be regulated.

Changes in aquaporins expression due to acute water restriction in naturally aging mice.

Aquaporins (AQPs) are water channels in the cell membrane that regulate osmosis in response to rapid changes in intracellular and extracellular fluid concentration caused by extrinsic factors. While there are so many studies on the association of AQPs with muscular atrophy, sarcopenia, and Duchenne muscular dystrophy (DMD), the expression of AQP has not been verified in naturally aging mice or humans. Notably, due to the characteristics of AQPs, the difference in function cannot be evaluated without extrinsic factors such as acute water restriction. The purpose of this study was to investigate the changes in AQPs expression and function due to natural aging under acute water restriction conditions in aging mice. The expression of AQP4 was shown to decrease with aging similar to previous studies. However, for the first time, this study results confirmed that AQP1 expression increased in aging mice. In addition, the expression of Aqp1 decreased in the acute water restricted group compared to the control group after acute water restriction in aging mice. These results suggest that although the expression of AQP1 increases with aging, its function is reduced. We also confirmed that overexpression of Aqp1 can inhibit myotube differentiation and that knockdown can promote myotube differentiation through in vitro experiments. In conclusion, based on our results, we suggest that the AQP1 is an important factor in sarcopenia caused by natural aging accompanied by chronic dehydration.

Daily Walking Accompanied with Intermittent Resistance Exercise Prevents Osteosarcopenia: A Large Cohort Study.

BACKGROUND: This study aimed to analyze the effects of walking and resistance exercises on bone structure, bone mineral density (BMD), and skeletal muscle mass. We used data from the fourth Korean National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 3,477 participants aged ≥19 years underwent hip structural analysis (HSA), BMD, and skeletal muscle index (SMI). All radiologic evaluations were performed using dual energy X-ray absorptiometry (DXA). The Korean short version of the International Physical Activity Questionnaire was used to measure physical activity status. The physical activity recommendations of the American College of Rheumatology Work Group Panel were used to evaluate the extent of activity. RESULTS: The BMD and SMI in the group in which walking activity was performed 5 days or more per week for at least 30 min per day were significantly higher than those in the group in which walking activity was not performed. HSA and SMI in the group in which resistance exercise was performed 2 days or more per week for at least 30 min per day were found to be significantly higher than those in the group in which strengthening exercises were not performed. CONCLUSIONS: If resistance exercise and walking are combined, bone loss and muscle loss are prevented maintaining cortical thickness in the elderly. Walking for more than 5 days a week and resistance exercise for more than 2 days a week will help to maintain the skeletal muscle as well as the cortex around the femur neck, thus helping to prevent fragility fractures in older individuals.

Unraveling Capsule Biosynthesis and Signaling Networks in Cryptococcus neoformans.

The polysaccharide capsule of Cryptococcus neoformans-an opportunistic basidiomycete pathogen and the major etiological agent of fungal meningoencephalitis-is a key virulence factor that prevents its phagocytosis by host innate immune cells. However, the complex signaling networks for their synthesis and attachment remain elusive. In this study, we systematically analyzed capsule biosynthesis and signaling networks using C. neoformans transcription factor (TF) and kinase mutant libraries under diverse capsule-inducing conditions. We found that deletion of GAT201, YAP1, BZP4, and ADA2 consistently caused capsule production defects in all tested media, indicating that they are capsule-regulating core TFs. Epistatic and expression analyses showed that Yap1 and Ada2 control Gat201 upstream, whereas Bzp4 and Gat201 independently regulate capsule production. Next, we searched for potential upstream kinases and found that mutants lacking PKA1, BUD32, POS5, IRE1, or CDC2801 showed reduced capsule production under all three capsule induction conditions, whereas mutants lacking HOG1 and IRK5 displayed enhanced capsule production. Pka1 and Irk5 controlled the induction of GAT201 and BZP4, respectively, under capsule induction conditions. Finally, we monitored the transcriptome profiles governed by Bzp4, Gat201, and Ada2 under capsule-inducing conditions and demonstrated that these TFs regulate redundant and unique sets of downstream target genes. Bzp4, Ada2, and Gat201 govern capsule formation in C. neoformans by regulating the expression of various capsule biosynthesis genes and chitin/chitosan synthesis genes in a positive and negative manner, respectively. In conclusion, this study provides further insights into the complex regulatory mechanisms of capsule production-related signaling pathways in C. neoformans. IMPORTANCE Over the past decades, human fungal pathogens, including C. neoformans, have emerged as a major public threat since the AIDS pandemic, only to gain more traction in connection to COVID-19. Polysaccharide capsules are rare fungal virulence factors that are critical for protecting C. neoformans from phagocytosis by macrophages. To date, more than 75 proteins involved in capsule synthesis and cell wall attachment have been reported in C. neoformans; however, their complex upstream signaling networks remain elusive. In this study, we demonstrated that Ada2, Yap1, Bzp4, and Gat201 were key capsule-inducing transcriptional regulators. Yap1 and Ada2 function upstream of Gat201, whereas Bzp4 and Gat201 function independently. Genome-wide transcriptome profiling revealed that Bzp4, Gat201, and Ada2 promote capsule production and attachment by positively and negatively regulating genes involved in capsule synthesis and chitin/chitosan synthesis, respectively. Thus, this study provides comprehensive insights into the complex capsule-regulating signaling pathway in C. neoformans.

Preparation of particle-attached microneedles using a dry coating process.

The standard process for manufacturing microneedles containing API requires a way to process the API, including dissolving the API in a co-solvent and a drying process. In this study, the authors introduce a novel microneedle system that involves physically attaching API particles to the biocompatible adhesive surface of the microneedles. To manufacture particle-attached microneedles, an adhesive surface was prepared by coating polydimethylsiloxane (PDMS) mixed with an elastomer base and a curing agent at a ratio of 40:1 (PDMS40) onto polylactic acid microneedles (PLA), and then attaching ovalbumin (OVA) particles with a mean diameter of 10 µm to the PDMS adhesive layer. The OVA particles were delivered for 5 min into porcine skin with a delivery efficiency of 93% ex vivo and into mouse skin with a delivery efficiency of over 90% in vivo. Finally, mouse experiments with OVA particle-attached microneedles showed a value of OVA antibody titer similar to that produced by intramuscular administration. Particle-attached microneedles are a novel microneedle system with a dry coating process and rapid API delivery into the skin. Particle-attached microneedles can provide a wide range of applications for administering drugs and vaccines.

Effects of lifelong spontaneous exercise on skeletal muscle and angiogenesis in super-aged mice.

There has been an increasing awareness of sarcopenia, which is characterized by a concomitant decrease in skeletal muscle mass and quality due to aging. Resistance exercise is considered more effective than aerobic exercise in terms of therapeutic exercise. To confirm the effect of long-term aerobic exercise in preventing sarcopenia, we evaluated the skeletal muscle mass, quality, and angiogenic capacity of super-aged mice that had undergone lifelong spontaneous exercise (LSE) through various experiments. Our findings show that LSE could maintain skeletal muscle mass, quality, and fitness levels in super-aged mice. In addition, ex vivo experiments showed that the angiogenic capacity was maintained at a high level. However, these results were not consistent with the related changes in the expression of genes and/or proteins involved in protein synthesis or angiogenesis. Based on the results of previous studies, it seems certain that the expression at the molecular level does not represent the phenotypes of skeletal muscle and angiogenesis. This is because aging and long-term exercise are variables that can affect both protein synthesis and the expression patterns of angiogenesis-related genes and proteins. Therefore, in aging and exercise-related research, various physical fitness and angiogenesis variables and phenotypes should be analyzed. In conclusion, LSE appears to maintain the potential of angiogenesis and slow the aging process to maintain skeletal muscle mass and quality. Aerobic exercise may thus be effective for the prevention of sarcopenia.

A Dual-Responsive Magnetoactive and Electro-Ionic Soft Actuator Derived from a Nickel-Based Metal-Organic Framework.

There is growing demand for multiresponsive soft actuators for the realization of natural, safe, and complex motions in robotic interactions. In particular, soft actuators simultaneously stimulated by electrical and magnetic fields are always under development owing to their simple controllability and reliability during operation. Herein, magnetically and electrically driven dual-responsive soft actuators (MESAs) derived from novel nickel-based metal-organic frameworks (Ni-MOFs-700C), are reported. Nanoscale Ni-MOFs-700C has excellent electrochemical and magnetic properties that allow it to be used as a multifunctional material under both magnetoactive and electro-ionic actuations. The dual-responsive MESA exhibits a bending displacement of 30 mm and an ultrafast rising time of 1.5 s under a very low input voltage of 1 V and also exerts a bending deflection of 12.5 mm at 50 mT under a high excitation frequency of 5 Hz. By utilizing a dual-responsive MESA, the hovering motion of a hummingbird robot is demonstrated under magnetic and electrical stimuli.

Spherical Micro/Nano Hierarchical Structures for Energy and Water Harvesting Devices.

Three-dimensional (3D) hierarchical structures have been explored for various applications owing to the synergistic effects of micro- and nanostructures. However, the development of spherical micro/nano hierarchical structures (S-HSs), which can be used as energy/water harvesting systems and sensing devices, remains challenging owing to the trade-off between structural complexity and fabrication difficulty. This paper presents a new strategy for facile, scalable S-HS fabrication using a thermal expansion of microspheres and nanopatterned structures. When a specific temperature is applied to a composite film of microspheres and elastomers with nanopatterned surfaces, microspheres are expanded and 3D spherical microstructures are generated. Various nanopatterns and densities of spherical microstructures can thereby be quantitatively controlled. The fabricated S-HSs have been used in renewable electrical energy harvesting and sustainable water management applications. Compared to a triboelectric nanogenerator (TENG) with bare film, the S-HS-based TENG exhibited 4.48 times higher triboelectric performance with high mechanical durability. Furthermore, an S-HS is used as a water harvesting device to capture water in a fog environment. The water collection rate is dramatically enhanced by the increased surface area and locally concentrated vapor diffusion flux due to the spherical microstructures.

Identification and Management of Pathogenic Variants in BRCA1, BRCA2, and PALB2 in a Tumor-Only Genomic Testing Program.

PURPOSE: Tumor-only genomic testing can uncover somatic and germline pathogenic variants [pathogenic/likely pathogenic (P/LP)] in cancer predisposition genes. We describe the prevalence of P/LPs in BRCA1/2 and PALB2 (B1B2P2) across malignancies and the frequency of clinical germline testing (CGT) in patients with P/LPs in B1B2P2 identified on tumor-only testing. EXPERIMENTAL DESIGN: Among 7,575 patients with cancer tested between 2016 and 2018 with the OncoPanel tumor-only sequencing assay, we characterized P/LP frequencies by tumor type, receipt of CGT prior to or within 12 months after OncoPanel, and factors associated with CGT. RESULTS: 272 (3.6%) patients had OncoPanel-detected P/LPs in B1B2P2: 37.5% of P/LPs were in BRCA-related cancers; the remainder were in non-BRCA tumors. P/LPs were detected in ≥5% of breast, pancreatic, prostate, ovarian, nonmelanoma skin, endometrial, small cell lung, and colorectal cancers. 37.9% of patients with P/LPs received CGT prior to OncoPanel; an additional 10.7% underwent CGT within 12 months of OncoPanel. Among 132 with CGT, 88.6% had ≥1 clinical factor for CGT compared with 47.1% who did not undergo CGT. Patients with BRCA tumors were more likely to have CGT compared with those without (81.4% vs. 29.0%, P < 0.0001). Among patients with CGT, 70.5% (93/132) of P/LPs were germline. CONCLUSIONS: Tumor-only genomic testing identified P/LPs in B1B2P2 in 3.6% of patients. 52.9% of patients with tumor-detected P/LPs and without CGT did not meet personal or family history criteria for CGT. In addition, some patients with tumor-detected P/LPs were not referred for CGT, especially those with non-BRCA tumors. Given implications for treatment selection and familial cancer risk, processes to reliably trigger CGT from tumor-genomic findings are needed.