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Ferroptosis offers a novel method for overcoming therapeutic resistance of cancers to conventional cancer treatment regimens. Its effective use as a cancer therapy requires a precisely targeted approach, which can be facilitated by using nanoparticles and nanomedicine, and their use to enhance ferroptosis is indeed a growing area of research. While a few review papers have been published on iron-dependent mechanism and inducers of ferroptosis cancer therapy that partly covers ferroptosis nanoparticles, there is a need for a comprehensive review focusing on the design of magnetic nanoparticles that can typically supply iron ions to promote ferroptosis and simultaneously enable targeted ferroptosis cancer nanomedicine. Furthermore, magnetic nanoparticles can locally induce ferroptosis and combinational ferroptosis with diagnostic magnetic resonance imaging (MRI). The use of remotely controllable magnetic nanocarriers can offer highly effective localized image-guided ferroptosis cancer nanomedicine. Here, recent developments in magnetically manipulable nanocarriers for ferroptosis cancer nanomedicine with medical imaging are summarized. This review also highlights the advantages of current state-of-the-art image-guided ferroptosis cancer nanomedicine. Finally, image guided combinational ferroptosis cancer therapy with conventional apoptosis-based therapy that enables synergistic tumor therapy is discussed for clinical translations.

Abstract Indoor photovoltaics are limited by their inherently low‐photogenerated carrier density, leading to heightened carrier recombination and adverse leakage currents compared with conventional solar cells operating under 1 sun condition. To address these problems, this work incorporates a porous insulating interlayer (Al2O3) in perovskite devices, which effectively mitigates recombination and parasitic leakage current. A systematic investigation of the relationship between shunt resistance, photocarrier generation, and recombination at different light intensities demonstrates the effectiveness of the alumina interlayer in perovskite solar cells under low‐light conditions. Moreover, the practicability of the alumina interlayer was demonstrated through its successful implementation in a large‐area perovskite solar module (PSM). With bandgap engineering, the optimized PSM achieves a remarkable power conversion efficiency of 33.5% and a record‐breaking power density of 107.3 μW cm−2 under 1000 lux illumination. These results underscore the potential of alumina interlayers in improving energy harvesting performance, particularly in low‐light indoor environments.

Organic pollutants in wastewater pose serious threats to human health and the environment. Nevertheless, potent strategies are being devised to tackle this critical issue. Specifically, advanced oxidation processes driven by solar energy and photocatalysts show promise for the degradation of organic pollutants. In particular, porous nanomaterials are effective as photocatalysts because of their high surface area, light‐harvesting properties, and ability to generate reactive oxygen species. To further expedite the development of feasible and sustainable organic‐pollutant‐degrading schemes, this article reports a strategy rooted in selective core etching for fabricating a core‐satellite‐type porous Fe3O4–Au nanocomposite. The Fe3O4 core behaves as a semiconductor to generate electron–hole pairs, whereas the Au satellite units serve as hot‐electron donors under visible‐light irradiation. The nanocomposite exhibits exceptional photocatalytic activity, degrading methylene blue molecules by 97% in just 1 h under visible light, and maintains its photocatalytic performance even after five rounds of recycling. Moreover, the nanocomposite achieves 90% tetracycline decomposition within 2 h. In addition to exhibiting noteworthy photocatalytic activity, the nanocomposite is magnetically separable, facilitating its recovery and reuse and exhibiting remarkable stability and cost‐effectiveness. These attributes underscore the practical viability of the core‐satellite‐type Fe3O4–Au nanocomposite in wastewater treatment.

Summary: Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of kidney failure and death in patients with chronic kidney disease (CKD) but are underused. We evaluated the number of patients with CKD in Australia that would be eligible for treatment and estimated the number of cardiorenal and kidney failure events that could be averted with improved uptake of SGLT2 inhibitors. Methods: This cross-sectional observational study leveraged nationally representative primary care data from 392 Australian general practices (MedicineInsight) between 1 January 2020 and 31 December 2021. We identified patients that would have met inclusion criteria of key SGLT2 inhibitor trials and applied these data to age and sex-stratified estimates of CKD prevalence for the Australian population (using national census data), estimating the number of preventable events using trial event rates. Key outcomes included cardiorenal events (CKD progression, kidney failure, or death due to cardiovascular or kidney disease) and kidney failure. Findings: In MedicineInsight, 44.2% of adults with CKD would have met CKD eligibility criteria for an SGLT2 inhibitor; baseline use was 4.1%. Applying these data to the Australian population, 230,246 patients with CKD would have been eligible for treatment with an SGLT2 inhibitor. Optimal implementation of SGLT2 inhibitors (75% uptake) could reduce cardiorenal and kidney failure events annually in Australia by 3644 (95% CI 3526–3764) and 1312 (95% CI 1242–1385), respectively. Interpretation: Improved uptake of SGLT2 inhibitors for patients with CKD in Australia has the potential to prevent large numbers of patients experiencing CKD progression or dying due to cardiovascular or kidney disease. Identifying strategies to increase the uptake of SGLT2 inhibitors is critical to realising the population-level benefits of this drug class. Funding: University of New South Wales Scientia Program and Boehringer Ingelheim Eli Lilly Alliance.

Planar magnetic microswimmers bear great potential for in vivo biomedical applications as they can be mass‐produced at minimal costs using standard photolithography techniques. Therefore, it is central to understand how to control their motion. This study examines the propulsion of planar V‐shaped microswimmers in an aqueous solution powered by a conically rotating magnetic field and compares the experimental results with theory. Propulsion is investigated upon altering the cone angle of the driving field. It is shown that a V‐shaped microswimmer magnetized along its symmetry axis exhibits unidirectional in‐sync propulsion with a constant (frequency‐independent) velocity in a limited band of actuation frequencies. It is also demonstrated that the motion of individual and multiple in‐plane magnetized planar microswimmers in a conically rotating field can be efficiently controlled.

Abstract Dental caries is the most common human disease caused by oral biofilms despite the widespread use of fluoride as the primary anticaries agent. Recently, an FDA-approved iron oxide nanoparticle (ferumoxytol, Fer) has shown to kill and degrade caries-causing biofilms through catalytic activation of hydrogen peroxide. However, Fer cannot interfere with enamel acid demineralization. Here, we show notable synergy when Fer is combined with stannous fluoride (SnF2), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, we discover that the stability of SnF2 is enhanced when mixed with Fer in aqueous solutions while increasing catalytic activity of Fer without any additives. Notably, Fer in combination with SnF2 is exceptionally effective in controlling dental caries in vivo, even at four times lower concentrations, without adverse effects on host tissues or oral microbiome. Our results reveal a potent therapeutic synergism using approved agents while providing facile SnF2 stabilization, to prevent a widespread oral disease with reduced fluoride exposure.

Postmenopausal osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-driven bone formation, presents substantial health implications. In this study, we investigated the role of black goat extract (BGE), derived from a domesticated native Korean goat, estrogen-like activity, and osteoprotective effects in vitro. BGE’s mineral and fatty acid compositions were analyzed via the ICP-AES method and gas chromatography–mass spectrometry, respectively. In vitro experiments were conducted using MCF-7 breast cancer cells, MC3T3-E1 osteoblasts, and RAW264.7 osteoclasts. BGE exhibits a favorable amount of mineral and fatty acid content. It displayed antimenopausal activity by stimulating MCF-7 cell proliferation and augmenting estrogen-related gene expression (ERα, ERβ, and pS2). Moreover, BGE positively impacted osteogenesis and mineralization in MC3T3-E1 cells through Wnt/β-catenin pathway modulation, leading to heightened expression of Runt-related transcription factor 2, osteoprotegerin, and collagen type 1. Significantly, BGE effectively suppressed osteoclastogenesis by curtailing osteoclast formation and activity in RAW264.7 cells, concurrently downregulating pivotal signaling molecules, including receptor activator of nuclear factor κ B and tumor necrosis factor receptor-associated factor 6. This study offers a shred of preliminary evidence for the prospective use of BGE as an effective postmenopausal osteoporosis treatment.

Abstract Background Chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) has been studied in patients with head and neck cancer. Its impact on patients with oral cavity cancer was not specified. Methods We consecutively reviewed medical files of patients with untreated oral cavity cancer who received neoadjuvant TPF chemotherapy in our department from January 2017 to April 2020. Outcomes included the objective response to TPF chemotherapy, factors associated with the response, and progression and survival in different response groups. Results A total of 167 patients were included, with half of stage IV disease. Complete or partial response was observed in 51 patients. A total of 91 patients had stable disease, and 25 patients had progressive disease. The response was not associated with age, sex, anatomic subsite, and the tumor's T stage. It was related with N stage (p

Background: Diabetes is a common condition that often requires increasing intensity of glucose lowering regimens. We describe the population trends in the intensity of regimens, and associations of achieved HbA1c and treatment persistence. Methods: We performed an episode-based analysis of the EXTEND-45 dataset, assessing trends in glucose lowering therapy and the associated outcomes of HbA1c and treatment persistence. Trends from 2009 to 2014 were assessed for each intensity level of a glucose lowering therapy regimen, according to the year prescribed. Episodes were defined as the length of time that an individual adhered to a regimen through ongoing prescription, and this was used as to define persistence. Mean HbA1c were calculated for each episode. Persistence and HbA1c were compared across the different regimens of treatment intensity. Results: The intensity of glucose lowering therapy remained stable over time with around one third of episodes utilising a single glucose lowering agent. Mean HbA1c was higher for insulin-based treatment (mean 7.9 % SD = 1.3 %), and lowest for episodes of no glucose lowering treatment (mean 6.3 % (SD = 0.8 %). Around half of participants achieved glycemic targets of 7 %. While there was considerable variation in persistence, the median persistence was around 3 months (94 days, IQR 51–201 days). Conclusions: Therapeutic intensity for diabetes has remained stable over 9 years. Whilst there was considerable variability in persistence with glucose lowering regimens, the mean duration of all regimens was less than a year. Requirement for higher intensity treatment with insulin was related to poorer glycemic control.

Background Sodium glucose cotransporter‐2 inhibitors reduce systolic blood pressure (SBP), but whether they affect SBP variability is unknown. There also remains uncertainty regarding the prognostic value of SBP variability for different clinical outcomes. Methods and Results Using individual participant data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, we assessed the effect of canagliflozin on SBP variability in people with type 2 diabetes across 4 study visits over 1.5 years as measured by standard deviation, coefficient of variation, and variability independent of the mean. We used multivariable Cox regression models to estimate associations of SBP variability with cardiovascular, kidney, and mortality outcomes. In 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (−0.25 mm Hg [95% CI, –0.44 to −0.06]), but there was no effect on coefficient of variation (0.02% [95% CI, –0.12 to 0.16]) or variability independent of the mean (0.08 U [95% CI, –0.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02–1.38]) and all‐cause mortality (HR, 1.12 [95% CI, 1.01–1.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes. Conclusions In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit‐to‐visit SBP variability is independently associated with risks of hospitalization for heart failure and all‐cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP‐lowering effect. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01032629, NCT01989754, NCT02065791.

Rationale & Objective: The benefit–risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and

Abstract Chemically coated micro/nanoparticles are often used in medicine to enhance drug delivery and increase drug up-take into specific areas of the body. Using a recently discovered spontaneous symmetry breaking propulsion mechanism, we demonstrate that chemically coated microparticles can swim through mucus solution under precise navigation and that certain functionalizations can dynamically change propulsion behavior. For this investigation biotin, Bitotin-PEG3-amine, and biotin chitosan were chemically functionalized onto the surfaces of magnetic microparticles using an avidin–biotin complex. These chemicals were chosen because they are used prolifically in drug delivery applications, with PEG and chitosan having well known mucoadhesive effects. Coated microparticles were then suspended in mucus synthesized from porcine stomach mucins and propelled using rotating magnetic fields. The relationship between different chemical coatings, microparticle velocity, and controllability were thoroughly explored and discussed. Results indicate that the biotinylated surface coatings altered the propulsion behavior of microparticles, with performance differences interlinked to both magnetic field properties and localized mucus properties. Precisely controlled drug carrying microparticles are envisioned to help supplant traditional drug delivery methods and enhance existing medical techniques utilizing micro/nanoparticles.

Abstract Objective: The aim of this study was to assess the nature and consequences of student vaping in Australian primary and secondary schools by consulting staff working in these settings. Methods: A national sample of 196 school staff was accessed via a web panel provider and administered an online survey about students’ e‐cigarette use. Three‐quarters of the survey respondents were teachers/teacher aides, with the remainder divided between those in other student‐facing roles and office staff. Results: A majority (78%) of respondents expressed concern about current levels of vaping in schools. Around half reported negative outcomes relating to mental well‐being, social/peer interactions, and school performance. Only one‐third of respondents reported a vaping policy (35%) or vaping‐prevention education (31%) being in place at their schools. Conclusions: E‐cigarette use in schools is an area of concern for school staff, yet relevant policies and education programs appear to be lacking. Implications for public health: Schools represent a key context for encouraging health promoting behaviours and discouraging harmful behaviours, including vaping. These results highlight the need to monitor and address student e‐cigarette use in schools and provide staff with greater support to prevent the negative consequences associated with vaping by children at school and beyond.

Abstract Ferroptosis provides an opportunity to overcome the cancer cell therapeutic resistance and modulate the immune system. Here an interaction between ferroptosis of cancer cells and natural killer (NK) cells was investigated with a clinical grade iron oxide nanoparticle (ferumoxytol) for potential synergistic anti-cancer effect of ferroptosis and NK cell therapy in prostate cancer. When ferumoxytol mediated ferroptosis of cancer cells was combined with NK cells, the NK cells’ cytotoxic function was increased. Observed ferroptosis mediated NK cell activation was also confirmed with IFN-γ secretion and lytic degranulation. Upregulation of ULBPs, which is one of the ligands for NK cell activating receptor NKG2D, was observed in the co-treatment of ferumoxytol mediated ferroptosis and NK cells. Additionally, HMGB1 and PD-L1 expression of cancer cells were observed in the treatment of ferroptosis + NK cells. Finally, in vivo therapeutic efficacy of ferumoxytol mediated ferroptosis and NK cell therapy was observed with significant tumor volume regression in a prostate cancer mice model. These results suggest that the NK cells’ function can be enhanced with ferumoxytol mediated ferroptosis.

India has introduced comprehensive e-cigarette bans focused on protecting youth from vaping-related harm. Despite these bans, educated young people appear to be a relatively high user group, although little is known about their usage patterns. The aims of the present study were to examine educated young adults’ e-cigarette-related attitudes and behaviors and their support for various e-cigarette control policies. In total, 840 tertiary-educated young adults completed an online survey. Demographic characteristics, e-cigarette and tobacco use, beliefs about e-cigarettes, exposure to e-cigarette advertising, sources of access to e-cigarettes, numbers of family members and peers who vape, and support for a range of e-cigarette policies were assessed. One-third (33%) reported never having heard of e-cigarettes/vapes, 23% reported ever using e-cigarettes, 70% reported ever using tobacco, and 8% were dual users of both e-cigarettes and tobacco. Only 8% of e-cigarette users reported daily use. Vapers sourced e-cigarettes from retail outlets (vape shops, tobacconists) and their social networks (friends, siblings). Just under two-thirds of those who were aware of e-cigarettes believed them to be harmful and to contain chemicals. Among non-users, 31% were curious about using e-cigarettes and 23% intended to use in the following year, indicating high levels of susceptibility. The results suggest that despite a complete ban, young people are still able to access e-cigarettes in India. Greater education about harms associated with vaping and more intensive monitoring and enforcement could assist in reducing uptake in relatively high-prevalence groups such as educated young adults.

Oriented attachment is a non-classical growth mechanism of nanomaterials that can lead to tunable properties and functionalities. Here the authors show that the crystallographic alignment between magnetite mesocrystal building-blocks can be tuned by the surface ligands, influencing the resulting magnetic properties.

This study presents an innovative methodology that integrates experimental investigations with finite element simulations to ascertain the validity and reliability of Al 3104 sheet metals during cold deep drawing. Focusing on the nose plunger radius and coefficient of friction at a fixed speed and temperature (25 °C), five different scenarios are utilized to simulate the optimum parameters. Through a detailed strain history analysis from simulations, the initiation of bending in the corner is precisely identified, with a validation achieved through a strain analysis obtained via digital image correlation. The study delves into the influence of strain and strain rate on the microstructures and mechanical properties near the corner region. It highlights the superior efficacy of strain-based criteria in characterizing deformation behavior. Notably, the strain distributions during the onset of bending and severe bending align remarkably well with the established simulation data. In brief, this work introduces an integrated approach that harmoniously combines computational simulations with empirical observations, resulting in significant ramifications for precisely comprehending and forecasting the strain distribution in metal forming operations.

Individuals with end-stage kidney disease (ESKD) on dialysis are at a high risk of developing foot ulcerations and undergoing subsequent lower extremity amputation (LEA), which can exert significant impacts on their quality of life and contribute to rising healthcare costs. We aimed to identify risk factors associated with LEA in patients with ESKD to predict LEA progression and eventually prevent it. We used 18 years (2002–2019) of data from the Korean National Health Insurance Service (KNHIS). Data were collected from patients with ESKD who underwent renal replacement therapy (RRT) and had no history of amputation caused by trauma or toxins. The risk factors were compared between patients with or without LEA. We collected data from 220,838 patients newly diagnosed with ESKD, including 6348 in the LEA group and 214,490 in the non-LEA group. The total incidence of LEA was 2.9%. Older age, male gender, lower income, non-metropolitan residence, diabetes mellitus, dialysis treatment (compared to kidney transplantation), microvascular disease, peripheral vascular disease, endovascular procedure, and endovascular operation were associated with an increased risk of LEA. Thus, individuals with ESKD who are at a higher risk for LEA should be closely monitored, and kidney transplantation should be considered as a preventative measure.

Damage due to abnormal conditions in water distribution systems is attributable to direct causes, such as facility deterioration, as well as indirect causes, including inadequate management, natural disasters, and negligence of a manager. Such damage can be prevented from being spread by closing a shut-off valve to isolate the incident area, although additional damage may occur in the area isolated by the control valve due to water outage, thus requiring a structural solution. Therefore, this study proposed an optimal segment division technique that minimizes the damage due to water outage occurring in the isolated area by installing a shut-off valve at an appropriate location through an optimal valve location determination model designed based on various urban development scenarios. The proposed technique was applied to a benchmark network and J-city network in Korea for performance verification. This technique can be used to select the number of installable valves and find the optimal valve locations according to the urban development scenario.

Abstract Magnetic achiral planar microswimmers can be massively fabricated at low cost and are envisioned to be useful for in vivo biomedical applications. To understand locomotion in representative in vivo environments, we investigated the swimming performance of achiral planar microswimmers in methylcellulose solutions. We observed that these microswimmers displayed very similar swimming characteristics in methylcellulose solutions as in water. Furthermore, this study indicated that the range of precession angles increased as the concentration of MC solution increased. Last, it was demonstrated that achiral planar microswimmers with similar precession angles exhibited nearly the same dimensionless speeds in different concentrations of the methylcellulose solutions. Upon understanding swimmer kinematics, more effective control over the achiral planar microswimmers can be achieved to perform multiple biomedical tasks in in vivo environments.

Multifunctional magnetic nanoparticles (MNPs) exhibit unique properties, such as remote motion controllability, degradability, and diagnostic imaging, which are typically not shown in nonmagnetic nanomaterials. MNPs remotely controllable via magnetic fields offer advantages of high tissue penetrability and biocompatibility. In this review, recent advances of multifunctional MNPs exhibiting unique characteristic for therapeutic applications are summarized, which utilize the “dynamic” motion, iron ion degradation, or imaging‐guided targeting of the MNPs under diverse magnetic field modes. The magnetic field‐controlled MNP motion enables spatiotemporal and reversible in situ cell regulation and mechanosensitive molecule modulation or thermal energy generation. Furthermore, the iron‐based MNPs can produce degraded ions and reactive oxygen species to enable targeted ferroptosis therapy with medical imaging‐guided approaches. The state‐of‐the‐art imaging‐guided “dynamic” therapy using the MNPs that can provide in situ feedback at each therapeutic stage is highlighted. Potential hurdles in translating the magnetic dynamic imaging and therapy toward clinical practices are also discussed. The imaging capability of the MNPs during “dynamic” magneto‐cell regulation enables noninvasive, safe, localized, and on‐demand regulation for the state‐of‐the‐art regenerative therapy, immunotherapy, and cancer treatment.

Summary: Ammonia is a promising carbon-free hydrogen carrier. Owing to their nickel-rich anodes and high operating temperatures, solid oxide fuel cells (SOFCs) can directly utilize NH3 fuel—direct-ammonia SOFCs (DA-SOFCs). Lowering the operating temperature can diversify application areas of DA-SOFCs. We tested direct-ammonia operation using two types of thin-film SOFCs (TF-SOFCs) under 500 to 650°C and compared these with a conventional SOFC. The TF-SOFC with a nickel oxide gadolinium-doped ceria anode achieved a peak power density of 1330 mW cm−2 (NH3 fuel under 650°C), which is the best performance reported to date. However, the performance difference between the NH3 and H2 operations was significant. Electrochemical impedance analyses, ammonia conversion quantification, and two-dimensional multi-physics modeling suggested that reduced ammonia conversion at low temperatures is the main cause of the performance gap. A comparative study with previously reported DA-SOFCs clarified that incorporating a more active ammonia decomposition catalyst will further improve low-temperature DA-SOFCs.

This study investigates the motion characteristics of soft alginate microrobots in complex fluidic environments utilizing wireless magnetic fields for actuation. The aim is to explore the diverse motion modes that arise due to shear forces in viscoelastic fluids by employing snowman-shaped microrobots. Polyacrylamide (PAA), a water-soluble polymer, is used to create a dynamic environment with non-Newtonian fluid properties. Microrobots are fabricated via an extrusion-based microcentrifugal droplet method, successfully demonstrating the feasibility of both wiggling and tumbling motions. Specifically, the wiggling motion primarily results from the interplay between the viscoelastic fluid environment and the microrobots’ non-uniform magnetization. Furthermore, it is discovered that the viscoelasticity properties of the fluid influence the motion behavior of the microrobots, leading to non-uniform behavior in complex environments for microrobot swarms. Through velocity analysis, valuable insights into the relationship between applied magnetic fields and motion characteristics are obtained, facilitating a more realistic understanding of surface locomotion for targeted drug delivery purposes while accounting for swarm dynamics and non-uniform behavior.

This study aimed to establish an efficient plant regeneration system from leaf-derived embryogenic structure cultures of Daphne genkwa. To induce embryogenic structures, fully expanded leaf explants of D. genkwa were cultured on Murashige and Skoog (MS) medium supplemented with 0, 0.1, 0.5, 1, 2, and 5 mg·L−1 2,4-dichlorophenoxyacetic acid (2,4-D), respectively. After 8 weeks of incubation, the highest frequency of embryogenic structure formation reached 100% when the leaf explants were cultivated on MS medium supplemented with 0.1 to 1 mg·L−1 2,4-D. At higher concentrations of 2,4-D (over 2 mg·L−1 2,4-D), the frequency of embryogenic structure formation significantly declined. Similar to 2,4-D, indole butyric acid (IBA) and α-naphthaleneacetic acid (NAA) treatments were also able to form embryogenic structures. However, the frequency of embryogenic structure formation was lower than that of 2,4-D. In particular, the yellow embryonic structure (YES) and white embryonic structure (WES) were simultaneously developed from the leaf explants of D. genkwa on culture medium containing 2,4-D, IBA, and NAA, respectively. Embryogenic calluses (ECs) were formed from the YES after subsequent rounds of subculture on MS medium supplemented with 1 mg·L−1 2,4-D. To regenerate whole plants, the embryogenic callus (EC) and the two embryogenic structures (YES and WES) were transferred onto MS medium supplemented with 0.1 mg·L−1 6-benzyl aminopurine (BA). The YES had the highest plant regeneration potential via somatic embryo and shoot development compared to the EC and WES. To our knowledge, this is the first successful report of a plant regeneration system via the somatic embryogenesis of D. genkwa. Thus, the embryogenic structures and plant regeneration system of D. genkwa could be applied to mass proliferation and genetic modification for pharmaceutical metabolite production in D. genkwa.

Introduction: Caregivers are essential for the health, safety, and independence of many patients and incur financial and personal cost in this role, including increased burden and lower quality of life (QOL) compared to the general population. Extended-hours hemodialysis may be the preference of some patients, but little is known about its effects on caregivers. Methods: Forty caregivers of participants of the ACTIVE Dialysis trial, who were randomized to 12 months extended (median 24 hours/wk) or standard (12 hours/wk) hemodialysis, were included. Utility-based QOL was measured by EuroQOL–5 Dimension–3 Level (EQ-5D-3L) and Short Form–6 Dimensions (SF-6D) and health-related QOL (HRQOL) was measured by the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS) and the Personal Wellbeing Index (PWI) at enrolment and then every 3 months until the end of the study. Results: At baseline, utility-based QOL and HRQOL were similar in both groups. At follow-up, caregivers of people randomized to extended-hours dialysis experienced a greater decrease in utility-based QOL measured by EQ-5D-3L compared with caregivers of people randomized to standard hours (–0.18±0.30 vs. –0.02±0.16, P = 0.04). There were no differences between extended- and standard-hours groups in mean change in SF-6D (0.03±0.12 vs. –0.04±0.1, P = 0.8), PCS (–1.2±9.8 vs. –5.6±9.8, P = 0.2), MCS (–4.1±11.2 vs. –0.5±7.1, P = 0.4), and PWI (2.3±17.6 vs. 0.00±20.4, P = 0.9). Conclusion: Poorer utility-based QOL, as measured by the EQ-5D-3L, was observed in caregivers of patients receiving extended-hours hemodialysis in this small study. Though the findings are exploratory, the possibility that mode of dialysis delivery negatively impacts on caregivers supports the prioritization of research on burden and impact of service delivery in this population.

Abstract Neurodegenerative disorders are characterized by the decline of cognitive function and the progressive loss of memory. The dysfunctions of the cognitive and memory system are closely related to the decreases in brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) signalings. Ribes fasciculatum, a medicinal plant grown in diverse countries, has been reported to pharmacological effects for autoimmune diseases and aging recently. Here we found that afzelin is a major compound in Ribes fasciculatum. To further examine its neuroprotective effect, the afzelin (100 ng/µl, three times a week) was administered into the third ventricle of the hypothalamus of C57BL/6 mice for one month and scopolamine was injected (i.p.) to these mice to impair cognition and memory before each behavior experiment. The electrophysiology to measure long-term potentiation and behavior tests for cognitive and memory functions were performed followed by investigating related molecular signaling pathways. Chronic administration of afzelin into the brain ameliorated synaptic plasticity and cognitive/memory behaviors in mice given scopolamine. Studies of mice’s hippocampi revealed that the response of afzelin was accountable for the restoration of the cholinergic systems and molecular signal transduction via CREB-BDNF pathways. In conclusion, the central administration of afzelin leads to improved neurocognitive and neuroprotective effects on synaptic plasticity and behaviors partly through the increase in CREB-BDNF signaling.

Introduction: Several circulating markers, including autoantibodies to erythropoietin receptor (anti-EPOR antibodies), have been identified as useful biomarkers in predicting diabetic kidney disease progression. However, a direct comparison of their utility is lacking. We aimed to validate and to compare the prognostic value of anti-EPOR antibodies with that of other known biomarkers, using the ADVANCE trial and its long-term follow-up, ADVANCE-ON, cohorts. Methods: In this nested case-control study from the ADVANCE trial cohort, we included 165 case participants who had the composite kidney outcome (renal replacement therapy, renal death, or doubling of serum creatinine to ≥200 μmol/l) and 330 matched controls. We compared the associations of baseline plasma levels of anti-EPOR antibodies, tumor necrosis factor receptor (TNFR)-1 and -2, and bone morphogenetic protein (BMP)-7 with kidney outcomes. Results: Cases had higher baseline plasma levels of anti-EPOR antibodies than controls (median 1.7 vs. 0.6 enzyme-linked immunosorbent assay unit, P < 0.001). Higher levels of anti-EPOR antibodies were associated with an increased risk of kidney outcome (odds ratio 2.16 [95% confidence interval 1.51, 3.08], per 1 SD of log-transformed levels) after adjusting for conventional markers. Elevated circulating TNFR1 and TNFR2 levels, and lower BMP-7 levels at baseline, were associated with poor kidney outcome (odds ratios 2.06 [1.29, 3.30], 1.66 [1.13, 2.43], and 0.45 [0.32, 0.65], respectively). The addition of anti-EPOR antibodies into the model improved the prediction of kidney outcome, regardless of other biomarkers. Conclusion: Anti-EPOR antibodies provide a promising biomarker, as with TNFR1, TNFR2, and BMP-7, in predicting kidney disease progression in people with type 2 diabetes mellitus.

Abstract Background Autoantibody production against endogenous cellular components is pathogenic feature of systemic lupus erythematosus (SLE). Follicular helper T (TFH) cells aid in B cell differentiation into autoantibody-producing plasma cells (PCs). The IL-6 and IL-21 cytokine-mediated STAT3 signaling are crucial for the differentiation to TFH cells. Niclosamide is an anti-helminthic drug used to treat parasitic infections but also exhibits a therapeutic effect on autoimmune diseases due to its potential immune regulatory effects. In this study, we examined whether niclosamide treatment could relieve lupus-like autoimmunity by modulating the differentiation of TFH cells in two murine models of lupus. Methods 10-week-old MRL/lpr mice were orally administered with 100 mg/kg of niclosamide or with 0.5% methylcellulose (MC, vehicle) daily for 7 weeks. TLR7 agonist, resiquimod was topically applied to an ear of 8-week-old C57BL/6 mice 3 times a week for 5 weeks. And they were orally administered with 100 mg/kg of niclosamide or with 0.5% MC daily for 5 weeks. Every mouse was analyzed for lupus nephritis, proteinuria, autoantibodies, immune complex, immune cell subsets at the time of the euthanization. Results Niclosamide treatment greatly improved proteinuria, anti-dsDNA antibody levels, immunoglobulin subclass titers, histology of lupus nephritis, and C3 deposition in MRL/lpr and R848-induced mice. In addition, niclosamide inhibited the proportion of TFH cells and PCs in the spleens of these animals, and effectively suppressed differentiation of TFH-like cells and expression of associated genes in vitro. Conclusions Niclosamide exerted therapeutic effects on murine lupus models by suppressing TFH cells and plasma cells through STAT3 inhibition.

A self-propelling agent at small Reynolds numbers usually requires a fore-aft asymmetry in order to circumvent the scallop theorem. Here Rogowski et al. show that this need not be true for motion in non-linear viscoelastic fluids, where an initial symmetry may be broken spontaneously.

Background In patients with congenital melanocytic nevus (CMN), single-stage removal of large lesions can be difficult because the high tension created by excising and repairing a large lesion may result in scar widening. Herein, we introduce a method to effectively excise lesions while minimizing scarring and compare its outcomes to those of existing surgical methods. Methods We compared patients who underwent surgery using the anchoring technique (n=42) or the conventional elliptical technique (n=36). One side of the lesion was removed via en bloc resection up to the superficial fascia. The other side of the lesion was removed via de-epithelialization. The de-epithelialized dermal flap was then fixed by suturing it to the superficial fascia on the opposite side. The length of the lesion’s long axis and amount of scar widening were measured immediately after surgery and at 2, 6, and 12 months postoperatively. At 12 months, patients were assessed using the Patient and Observer Scar Assessment Scale. Results The lesion locations included the face, arms, legs, back, and abdomen. The anchoring method resulted in shorter and smaller scars than the conventional method. There were no cases of postoperative hematoma or wound dehiscence. Significant differences in postoperative scar widening were found in the arm and leg areas (P

This study evaluated the Hook-up installation of an offshore site construction process, which is the final step in an offshore site installation process. During Hook-up installation, the offshore structure can have a detrimental effect on the work stability due to low-frequency motion. Moreover, economic costs can be incurred by the increase in available days of a tugboat. Therefore, this study developed a numerical analysis program to assess the dynamic behavior of mooring systems during hook-up installation to analyze the generally performed installation process and determine when the tugboat should be released. In this program, the behavior of an offshore structure was calculated using Cummin’s time-domain motion equation, and the mooring system was calculated by Lumped mass method (LMM). In addition, a tugboat algorithm for hook-up installation was developed to apply the Hook-up procedure. The model used in the calculations was the barge type assuming FPSO (Floating production storage and off-loading) and has a taut mooring system connected to 16 mooring lines. The results of the simulation were verified by comparing with both MOSES, which is a commercial program, and a calculation method for restoring coefficient matrix, which was introduced by Patel and Lynch (1982). Finally, the offset of the structure according to the number of tugboats was calculated using the hook-up simulation, and the significant value was used to represent the calculation result.

Objective: To investigate long-term adherence to guideline-recommended cardioprotective medications following hospitalization for an acute myocardial infarction (AMI), and identify characteristics associated with adherence.Methods: An Australian population-based cohort study was used to identify participants who had their first AMI between 2006 and 2014 and were alive after 12 months. Linked routinely collected hospital, and prescription medication claims data was used to study adherence over time. Predictors and rates of adherence to both lipid-lowering medication and renin-angiotensin system blockade at 12 months post-AMI was assessed.Results: 14,200 people (mean age 69.9 years, 38.7% female) were included in our analysis. At 12 months post-AMI, 29.5% (95% CI: 28.8–30.3%) of people were adherent to both classes of medication. Individuals receiving treatment with both lipid-lowering medication and renin-angiotensin system blockade during the 6 months prior to their AMI were over 9 times more likely to be adherent to both medications at 12 months post-AMI (66.2% 95% CI: 64.8–67.5%) compared to those with no prior medication use (treatment naïve) (7.1%, 95% CI: 6.4–7.9%). Prior cardiovascular treatment was the strongest predictor of long-term adherence even after adjusting for age, sex, education and income.Conclusions: Despite efforts to improve long-term medication adherence in patients who have experienced an acute coronary event, considerable gaps remain. Of particular concern are people who are commencing guideline-recommended cardioprotective medication at the time of their AMI. The relationship between prior cardiovascular treatments and post AMI adherence offers insight into the support needs for the patient. Health care intervention strategies, strengthened by enabling policies, are needed to provide support to patients through the initial months following their AMI.

Abstract Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most prevalent inborn disorder. This X-chromosome-linked recessive disease affects more than 400 million people globally, and is associated with haemolytic anaemia after medication with the anti-latent malaria drug, primaquine. To prevent malaria, the Republic of Korea (ROK) Army administers malaria chemoprophylaxis. Due to the previously low G6PD deficiency prevalence in the ROK, prior to primaquine administration, testing for G6PD deficiency was not mandatory. In this study, to evaluate the risk from malaria chemoprophylaxis in the ROK, G6PD deficiency prevalence was investigated. Methods Blood specimens from 1632 soldiers entering training camp for the 3rd Infantry of the ROK Army were collected. CareStart™ Biosensor for G6PD and haemoglobin (Hb) was used to detect G6PD levels. G6PD variants using the DiaPlexC G6PD Genotyping kit (Asian type) and full-length sequencing were examined. Results Of 1632 blood specimens tested, none was observed to be G6PD deficient. The median value of all tested samples was 7.582 U/g Hb. An investigation of 170 G6PD DNA variants was analysed and categorized as partially low normal [n = 131, 30–80% (2.27–6.05 U/g Hb) of the median value], high [n = 3, > 150% (> 11.373 U/g Hb) of the median value], or normal [n = 36, 80–150% (6.05–11.373 U/g Hb) of the median value], and none was amplified by the DiaPlexC kit. Five silent mutations (C→T) in 131 partially low normal specimens were found at the 1311th nucleotide position by sequence analysis. Another 8 silent mutations (T93C) were also detected in 131 partially low normal specimens. Thus, it is inferred that these silent mutations could be related to G6PD activity. Conclusions This G6PD deficiency prevalence study, conducted among participants from the 3rd Infantry of the ROK Army, provided crucial evidence for the safety of malaria chemoprophylaxis. This study showed that the prevalence of G6PD deficiency among 1632 young soldiers was wholly absent. Although G6PD phenotypic mutations were not detected, many silent mutations (C1311T and T93C) were observed. Thus, it is inferred that malaria chemoprophylaxis is relatively safe against G6PD deficiency-mediated haemolytic anaemia. However, given the number of individuals whose G6PD were at the partially low normal range and the frequent detection of G6PD deficiency-related mutations, consistent monitoring of G6PD deficiency is needed.

In this paper, we proposed an algorithm that improves the heading accuracy of the global positioning system (GPS)/inertial navigation system (INS) integrated system used in automobiles by manipulating INS velocity and GPS velocity measurements. Two velocities are provided by the GPS receiver: the velocity calculated using the position difference and the velocity calculated using the Doppler shift. The velocity obtained using the position difference is an average velocity for a certain time period, which is inaccurate under dynamic conditions because of its time delay. In contrast, the velocity from the Doppler shift is an instantaneous velocity and has no time delay. However, it also relies on pseudo-range error and noise, which degrades the heading estimation accuracy in low dynamic situations. Thus, although the velocity measurements can improve heading accuracy, the navigation performance is often degraded when the velocity measurements are used for GPS/INS integration. To improve the heading accuracy by solving the aforementioned problems, we proposed a heading accuracy improvement algorithm that employs the average velocity measurements obtained using the averaged GPS velocity and the average velocity of the INS. Since the proposed average velocity measurements are calculated using long baseline, the proposed algorithm can improve the heading accuracy without using other sensors, especially in the case of low dynamic situations. It can be easily applied to the existing GPS/INS integrated system, making it suitable for use in automotive navigation systems. In this research, it is verified that the average velocity measurements can be substituted for Kalman filter measurements, and the performance improvements are confirmed through simulations and experiments.

Transient metastable intermediates play an important role in the crystallization process. Here, the authors unveil the microstructural changes in magnetite mesocrystals that depend on the intermediate polymorphism and the universal crystallite size effect on the magnetic coercivity of mesocrystals.

Abstract Developmental transitions are typically tightly controlled at the transcriptional level. Two of these transitions involve the induction of the embryo maturation program midway through seed development and its repression during the vegetative phase of plant growth. Very little is known about the factors responsible for this regulation during early embryogenesis, and only a couple of transcription factors have been characterized as repressors during the postgerminative phase. Arabidopsis 6b‐INTERACTING PROTEIN‐LIKE1 (ASIL1), a trihelix transcription factor, has been proposed to repress maturation both embryonically and postembryonically. Preliminary data also suggested that its closest paralog, ASIL2, might play a role as well. We used a transcriptomic approach, coupled with phenotypical observations, to test the hypothesis that ASIL1 and ASIL2 redundantly turn off maturation during both phases of growth. Our results indicate that, contrary to what was previously published, neither of the ASIL genes plays a role in the regulation of maturation, at any point during plant development. Analyses of gene ontology (GO)‐enriched terms and published transcriptomic datasets suggest that these genes might be involved in responses during the vegetative phase to certain biotic and abiotic stresses.

Cellular structures are central to the design of lightweight yet strong materials for engineering development. However, the material properties of cellular foams made of specific elements are placed in a narrow range in their density and corresponding mechanical properties. Here, this study presents an innovative design of creating closed-cellular structured (CCS) foams with a wide range of physical controllability. The CCS foams are prepared by assembly of solid bubbles consisting of reduced graphene oxide (rGO) and silica nanoparticles. By varying their compositional ratio, the resulting CCS foams exhibit completely discerned structural morphologies: Rhombic dodecahedral (RDH) internal cells for higher rGO content, whereas a fused face centered cubic (FCC)-like internal cells for a higher content of silica. As such, these tunable CCS foams manifest an extended relationship in density and resulting mechanical properties, spanning from a density of 2.3 mg/cm3 and corresponding Young's modulus of 0.102 MPa (for RDH) to 444.27 mg/cm3 and 180.3 MPa (for fused-FCC). Moreover, silica-containing CCS can exhibit a thermal insulation property with a greatly reduced thermal conductivity (κ) of 48 mW/m·K. therefore, this approach of creating the structurally tunable CCS foams would offer a concrete toolkit for designing high-performance cellular structures with on-demand physical/mechanical properties

Background: Most studies addressing hemodialysis initiation with a dialysis catheter focus on patients entering maintenance dialysis programs and exclude other patients, such as those with acute kidney injury (AKI), making interpretation and application of the results difficult for clinicians managing patients at the time of dialysis commencement. Objective: To compare the survival of all patients requiring a catheter for hemodialysis access according to the nature of clinical presentation. Design: Prospective observational. Setting: An Australian tertiary renal unit. Patients: All patients requiring a central venous catheter (CVC) for hemodialysis access between 2005 and 2015. Measurements: Baseline comorbidities, demographics, and nature of clinical presentation. Data regarding each episode of dialysis access insufficiency and each CVC were collected. The primary outcome was all-cause mortality. Methods: Patients were classified into 1 of 3 groups based on physician assessment at the time of presentation: patients believed to have AKI with expected renal recovery (AKI), patients considered to be entering the maintenance dialysis program without a functioning dialysis access (Maintenance Dialysis), patients unable to perform peritoneal dialysis, or use their existing hemodialysis access (Access Failure). Time-split multivariable Cox regression analyses were used to compare survival between groups. Results: A total of 557 eligible patients had complete prospective data regarding CVC use and were included in the analyses. The majority of patients were in the AKI (246/557, 44%) and Maintenance Dialysis groups (182/557, 33%) compared with the Access Failure group (129/557, 23%). During a median follow-up of 3 years, 302 (54%) of the 557 patients died. Following adjustment, risk of all-cause mortality was higher in the AKI group (hazard ratio [HR]: 2.01, 95% confidence interval [CI]: 1.31-3.60, P = .001) during the first 2 years after catheter insertion and lower in years 2 to 4 (HR: 0.42, 95% CI: 0.20-0.88, P = .02) than in the reference Maintenance Dialysis group. No difference in mortality risk between the Access Failure and reference group was found. Limitations: Single-center study. Possible residual confounding owing to the observational study design. Conclusions: Patients requiring acute or unplanned hemodialysis experience high mortality, and the nature of clinical presentation does influence outcomes. Most notable is the greater early mortality experienced by patients with AKI compared to other patient groups. Prospective definition of the nature of unplanned dialysis initiation is important to accurately measure and improve outcomes in this high-risk patient population. Human Research Ethics Committee Approval Number CH62/6/2017-042.

The development of marine technology is expected to increase the demand for marine plants because of increasing oil prices. Therefore, there is also expected to be an increase in the demand for cylindrical structures such as URF (umbilical, riser, flowline) structures and spars, which are used operating in various seas. However, a cylindrical structure experiences vortex induced motion (VIM) in a current. In particular, for risers and umbilicals, it is important to identify the characteristics of the VIM because interference between structures can occur. In addition, various studies have been conducted to reduce VIM because it is the cause of fatigue damage to structures. The helical strake, which was developed for VIM reduction, has an excellent VIM reduction performance, but is difficult to install on structures and has a negative effect on heave motion. Therefore, the purpose of this study was to supplement the shortcomings of the helical strake and develop a high-performance reduction device. In the reduction device developed in this study, a string is placed around the structure inside the flow, causing vibration. The vibration of this string causes a small turbulence in the flow field, reducing the VIM effect on the structure. Finally, in this study, the 2-DOF motion characteristics of models without a suppression device, models with a helical strake, and models with a string were investigated, and their reduction performances were compared through model tests.

This paper demonstrates a manipulation of snowman-shaped soft microrobots under a uniform rotating magnetic field. Each microsnowman robot consists of two biocompatible alginate microspheres with embedded magnetic nanoparticles. The soft microsnowmen were fabricated using a microfluidic device by following a centrifuge-based microfluidic droplet method. Under a uniform rotating magnetic field, the microsnowmen were rolled on the substrate surface, and the velocity response for increasing magnetic field frequencies was analyzed. Then, a microsnowman was rolled to follow different paths, which demonstrated directional controllability of the microrobot. Moreover, swarms of microsnowmen and single alginate microrobots were manipulated under the rotating magnetic field, and their velocity responses were analyzed for comparison.

Central sensitization (CS) has been extensively researched as a cause of persistent pain after total knee arthroplasty (TKA). This systematic review study sought to investigate the diagnosis of CS in patients who underwent TKA for knee osteoarthritis (OA) and the effect of CS on clinical outcomes after TKA. Three comprehensive databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched for studies that evaluated the outcomes of TKA in knee OA patients with CS. Data extraction, risk of bias assessment, and (where appropriate) meta-analysis were performed. The standardized mean difference (SMD) with a 95% confidence interval was used to assess the different scales of pain. A total of eight studies were selected, including two retrospective studies and five prospective observational studies. One study used additional randomized controlled trial data. Five studies were finally included in the meta-analysis. All studies had a minimum follow-up period of 3 months. The Central Sensitization Inventory (CSI), whole-body pain diagram, and quantitative sensory testing (QST) were used for measuring CS. The pooled analysis showed that patients with CS had more severe postoperative pain after TKA (SMD, 0.65; 95% CI, 0.40–0.90; p < 0.01) with moderate heterogeneity (I2 = 60%). In patients who underwent TKA with knee OA, CSI is most often used for the diagnosis of CS, and the QST and whole-body pain diagram are also used. CS is closely associated with more severe and persistent pain after TKA.

Cancer: Spotlighting hidden cancer-causing genes Mutation of a gene with no clear role in tumor development triggers a cascade of reactions that can cause liver cancer. Recent genome-wide analyses searching for genes connected to development of hepatocellular carcinoma, the most common type of liver cancer, have turned up some unexpected genes, such as the fat metabolism gene apolipoprotein A (APOB). To discover how APOB is related to liver tumor development, Sun Young Yim at the University of Texas MD Anderson Cancer Center, Houston, USA, and coworkers compared whole-genome profiles from human cancer patients with those of mice, in which cancer-related genetic patterns are better characterized. They found that mutation of APOB was associated with switching on of cancer-promoting genes, and switching off of genes that suppress tumor growth. These results reveal a behind-the-scenes regulator of cancer development.

Introduction An effective workforce is essential for optimal care of all forms of chronic diseases. The objective of this study was to assess workforce capacity for kidney failure (KF) care across world countries and regions.Methods Data were collected from published online sources and a survey was administered online to key stakeholders. All country-level data were analysed by International Society of Nephrology region and World Bank income classification.Results The general healthcare workforce varies by income level: high-income countries have more healthcare workers per 10 000 population (physicians: 30.3; nursing personnel: 79.2; pharmacists: 7.2; surgeons: 3.5) than low-income countries (physicians: 0.9; nursing personnel: 5.0; pharmacists: 0.1; surgeons: 0.03). A total of 160 countries responded to survey questions pertaining to the workforce for the management of patients with KF. The physicians primarily responsible for providing care to patients with KF are nephrologists in 92% of countries. Global nephrologist density is 10.0 per million population (pmp) and nephrology trainee density is 1.4 pmp. High-income countries reported the highest densities of nephrologists and nephrology trainees (23.2 pmp and 3.8 pmp, respectively), whereas low-income countries reported the lowest densities (0.2 pmp and 0.1 pmp, respectively). Low-income countries were most likely to report shortages of all types of healthcare providers, including nephrologists, surgeons, radiologists and nurses.Conclusions Results from this global survey demonstrate critical shortages in workforce capacity to care for patients with KF across world countries and regions. National and international policies will be required to build a workforce capacity that can effectively address the growing burden of KF and deliver optimal care.