Metformin represses the carcinogenesis potentially induced by 50 Hz magnetic fields in aged mouse fibroblasts via inhibition of NF-kB.

Aging is a risk factor for various human disorders, including cancer. Current literature advocates that the primary principles of aging depend on the endogenous stress-induced DNA damage caused by reactive oxygen species 50 Hz low-frequency magnetic field was suggested to induce DNA damage and chromosomal instability. NF-kB, activated by DNA damage, is upregulated in age-related cancers and inhibition of NF-kB results in aging-related delayed pathologies. Metformin (Met), an NF-kB inhibitor, significantly reduces both NF-kB activation and expression in aging and cancer. This in vitro study, therefore, was set out to assess the effects of 5mT MF in 50 Hz frequency and Met treatment on the viability and proliferation of aged mouse NIH/3T3 fibroblasts and expression of RELA/p65, matrix metalloproteinases MMP2 and MMP9, and E-cadherin (CDH1) genes. The trypan blue exclusion assay was used to determine cell viability and the BrdU incorporation assay to determine cell proliferation. The MMP-2/9 protein analysis was carried out by immunocytochemistry, NF-kB activity by ELISA and the expressions of targeted genes by qRT-PCR methods. Four doses of Met (500 uM, 1 mM, 2 mM and 10 mM) suppressed both the proliferation and viability of fibroblasts exposed to the MF in a dose-dependent pattern, and the peak inhibition was recorded at the 10 mM dose. Met reduced the expression of NF-kB, and MMP2/9, elevated CDH1 expression and suppressed NF-kB activity. These findings suggest that Met treatment suppresses the carcinogenic potential of 50 Hz MFs in aged mouse fibroblasts, possibly through modulation of NF-kB activation and epithelial-mesenchymal transition modulation.

Alternating magnetic fields (AMF) and linezolid reduce Staphylococcus aureus biofilm in a large animal implant model.

OBJECTIVES: We aimed to evaluate the effectiveness of alternating magnetic fields (AMF) combined with antibiotics in reducing Staphylococcus aureus biofilm on metal implants in a large animal model, compared to antibiotics alone. METHODS: Metal plates were inoculated with a clinical MRSA strain and then implanted into thirty-three ewes divided into three groups: positive control, linezolid only, and a combination of linezolid and AMF. Animals had either titanium or cobalt-chrome plates and were sacrificed at 5 or 21 days post-implantation. Blood and tissue samples were collected at various time points post-AMF treatment. RESULTS: In vivo efficacy studies demonstrated significant biofilm reduction on titanium and cobalt-chrome implants with AMF-linezolid combination treatment compared to controls. Significant bacterial reductions were also observed in surrounding tissues and bones. Cytokine analysis showed improved inflammatory responses with combination therapy, and histopathology confirmed reduced inflammation, necrosis, and bacterial presence, especially at 5 days post-implantation. CONCLUSIONS: This study demonstrates that combining AMF with antibiotics significantly reduces biofilm-associated infections on metal implants in a large animal model. Numerical simulations confirmed targeted heating, and in vivo results showed substantial bacterial load reduction and reduced inflammatory response. These findings support the potential of AMF as a non-invasive treatment for prosthetic joint infections.

Enhanced triplet superconductivity in next-generation ultraclean UTe2.

The unconventional superconductor UTe[Formula: see text] exhibits numerous signatures of spin-triplet superconductivity-a rare state of matter which could enable quantum computation protected against decoherence. UTe[Formula: see text] possesses a complex phase landscape comprising two magnetic field-induced superconducting phases, a metamagnetic transition to a field-polarized state, along with pair- and charge-density wave orders. However, contradictory reports between studies performed on UTe[Formula: see text] specimens of varying quality have severely impeded theoretical efforts to understand the microscopic origins of the exotic superconductivity. Here, we report a comprehensive suite of high magnetic field measurements on a generation of pristine quality UTe[Formula: see text] crystals. Our experiments reveal a significantly revised high magnetic field superconducting phase diagram in the ultraclean limit, showing a pronounced sensitivity of field-induced superconductivity to the presence of crystalline disorder. We employ a Ginzburg-Landau model that excellently captures this acute dependence on sample quality. Our results suggest that in close proximity to a field-induced metamagnetic transition the enhanced role of magnetic fluctuations-that are strongly suppressed by disorder-is likely responsible for tuning UTe[Formula: see text] between two distinct spin-triplet superconducting phases.

Piezo tube stacked scanning tunneling microscope for use in extreme and confined environments.

Scanning Tunneling Microscopy (STM) is widely used for observing atomic structures due to its ultra-high spatial resolution. As the core units of STM, the coarse stepper motor and imaging unit, have conflicting size requirements for piezo tubes. Longer piezo tubes yield greater output force and easier movement for the motor, while shorter tubes enhance imaging precision and stability for the scanner. Traditional STMs typically employ a large piezo tube for coarse stepping and a smaller one for independent imaging to address this issue. Here, we present the new design of a piezo tube stacked STM, in which two independent piezo tubes act together during tip-sample approach process and only one shorter tube works during scanning imaging. Both tubes are fixed to the framework, ensuring high rigidity and compactness. The new design enables us to achieve both coarse stepping and imaging functions with a total length of only 25 mm for the two tubes, effectively reducing the length of whole STM, facilitating its integration into narrow low-temperature spaces for imaging applications. Using this device, we obtained high-quality atomic images of graphite sample surfaces at room temperature. Continuous scanning imaging of the same area on Au film at 300 K demonstrates the STM's high stability in both X-Y and Z directions. Atomic images, I-V spectra, and di/dv spectra obtained at 2 K on graphite surface illustrate the excellent application potential of this device in low-temperature environments. Finally, atomic images obtained of graphite in sweeping the magnetic fields from 0 T to 11 T in a huge vibrational dry magnet prove the new STM's excellent performance in extreme conditions.

Field-domain rapid-scan EPR at 240GHz for studies of protein functional dynamics at room temperature.

We present field-domain rapid-scan (RS) electron paramagnetic resonance (EPR) at 8.6T and 240GHz. To enable this technique, we upgraded a home-built EPR spectrometer with an FPGA-enabled digitizer and real-time processing software. The software leverages the Hilbert transform to recover the in-phase (I) and quadrature (Q) channels, and therefore the raw absorptive and dispersive signals, χ' and χ'', from their combined magnitude (I2+Q2). Averaging a magnitude is simpler than real-time coherent averaging and has the added benefit of permitting long-timescale signal averaging (up to at least 2.5×106 scans) because it eliminates the effects of source-receiver phase drift. Our rapid-scan (RS) EPR provides a signal-to-noise ratio that is approximately twice that of continuous wave (CW) EPR under the same experimental conditions, after scaling by the square root of acquisition time. We apply our RS EPR as an extension of the recently reported time-resolved Gd-Gd EPR (TiGGER) [Maity et al., 2023], which is able to monitor inter-residue distance changes during the photocycle of a photoresponsive protein through changes in the Gd-Gd dipolar couplings. RS, opposed to CW, returns field-swept spectra as a function of time with 10ms time resolution, and thus, adds a second dimension to the static field transients recorded by TiGGER. We were able to use RS TiGGER to track time-dependent and temperature-dependent kinetics of AsLOV2, a light-activated phototropin domain found in oats. The results presented here combine the benefits of RS EPR with the improved spectral resolution and sensitivity of Gd chelates at high magnetic fields. In the future, field-domain RS EPR at high magnetic fields may enable studies of other real-time kinetic processes with time resolutions that are otherwise difficult to access in the solution state.

The Physiological Impact of Melatonin, Its Effect on the Course of Diseases and Their Therapy and the Effect of Magnetic Fields on Melatonin Secretion-Potential Common Pathways of Influence.

Melatonin is a relic, due to its millions-of-years-old presence in chemical reactions, found in evolutionarily diverse organisms. It has a multidirectional biological function. It controls diurnal rhythms, redox homeostasis, intestinal motor functions, mitochondrial biogenesis and fetal development and has antioxidant effects. It also has analgesic and therapeutic effects. The purpose of this paper is to describe the role of melatonin in vital processes occurring in interaction with the environment, with particular reference to various magnetic fields ubiquitous in the life of animate matter, especially radio frequency/extra low frequency (RF/ELF EMF) and static magnetic fields. The most important part of this article is to describe the potential effects of magnetic fields on melatonin secretion and the resulting possible health effects. Melatonin in some cases positively amplifies the electromagnetic signal, intensifying health effects, such as neurogenesis, analgesic effects or lowering blood pressure. In other cases, it is a stimulus that inhibits the processes of destruction and aggravation of lesions. Sometimes, however, in contrast to the beneficial effects of electromagnetic fields in therapy, they intensify pathogenic effects, as in multiple sclerosis by intensifying the inflammatory process.

Are Aminoglycoside Antibiotics TRPing Your Metabolic Switches?

Transient receptor potential (TRP) channels are broadly implicated in the developmental programs of most tissues. Amongst these tissues, skeletal muscle and adipose are noteworthy for being essential in establishing systemic metabolic balance. TRP channels respond to environmental stimuli by supplying intracellular calcium that instigates enzymatic cascades of developmental consequence and often impinge on mitochondrial function and biogenesis. Critically, aminoglycoside antibiotics (AGAs) have been shown to block the capacity of TRP channels to conduct calcium entry into the cell in response to a wide range of developmental stimuli of a biophysical nature, including mechanical, electromagnetic, thermal, and chemical. Paradoxically, in vitro paradigms commonly used to understand organismal muscle and adipose development may have been led astray by the conventional use of streptomycin, an AGA, to help prevent bacterial contamination. Accordingly, streptomycin has been shown to disrupt both in vitro and in vivo myogenesis, as well as the phenotypic switch of white adipose into beige thermogenic status. In vivo, streptomycin has been shown to disrupt TRP-mediated calcium-dependent exercise adaptations of importance to systemic metabolism. Alternatively, streptomycin has also been used to curb detrimental levels of calcium leakage into dystrophic skeletal muscle through aberrantly gated TRPC1 channels that have been shown to be involved in the etiology of X-linked muscular dystrophies. TRP channels susceptible to AGA antagonism are critically involved in modulating the development of muscle and adipose tissues that, if administered to behaving animals, may translate to systemwide metabolic disruption. Regenerative medicine and clinical communities need to be made aware of this caveat of AGA usage and seek viable alternatives, to prevent contamination or infection in in vitro and in vivo paradigms, respectively.

Science development study for the Atacama Large Aperture Submillimeter Telescope (AtLAST): Solar and stellar observations.

Observations at (sub-)millimeter wavelengths offer a complementary perspective on our Sun and other stars, offering significant insights into both the thermal and magnetic composition of their chromospheres. Despite the fundamental progress in (sub-)millimeter observations of the Sun, some important aspects require diagnostic capabilities that are not offered by existing observatories. In particular, simultaneously observations of the radiation continuum across an extended frequency range would facilitate the mapping of different layers and thus ultimately the 3D structure of the solar atmosphere. Mapping large regions on the Sun or even the whole solar disk at a very high temporal cadence would be crucial for systematically detecting and following the temporal evolution of flares, while synoptic observations, i.e., daily maps, over periods of years would provide an unprecedented view of the solar activity cycle in this wavelength regime. As our Sun is a fundamental reference for studying the atmospheres of active main sequence stars, observing the Sun and other stars with the same instrument would unlock the enormous diagnostic potential for understanding stellar activity and its impact on exoplanets. The Atacama Large Aperture Submillimeter Telescope (AtLAST), a single-dish telescope with 50m aperture proposed to be built in the Atacama desert in Chile, would be able to provide these observational capabilities. Equipped with a large number of detector elements for probing the radiation continuum across a wide frequency range, AtLAST would address a wide range of scientific topics including the thermal structure and heating of the solar chromosphere, flares and prominences, and the solar activity cycle. In this white paper, the key science cases and their technical requirements for AtLAST are discussed.

Observations of our Sun and other stars at wavelengths of around one millimeter, i.e. in the range between infrared and radio waves, present a valuable complementary perspective. Despite significant technological advancements, certain critical aspects necessitate diagnostic capabilities not offered by current observatories. The proposed Atacama Large Aperture Submillimeter Telescope (AtLAST), featuring a 50-meter aperture and slated for construction at a high altitude in Chile's Atacama desert, promises to address these observational needs. Equipped with novel detectors that would cover a wide frequency range, AtLAST could unlock a plethora of scientific studies contributing to a better understanding of our host star. Simultaneous observations over a broad frequency range at rapid succession would enable the imaging of different layers of the Sun, thus elucidating the three-dimensional thermal and magnetic structure of the solar atmosphere and providing important clues for many long-standing central questions such as how the outermost layers of the Sun are heated to very high temperatures, the nature of large-scale structures like prominences, and how flares and coronal mass ejections, i.e. enormous eruptions, are produced. The latter is of particular interest to modern society due to the potentially devastating impact on the technological infrastructure we depend on today. Another unique possibility would be to study the Sun's long-term evolution in this wavelength range, which would yield important insights into its activity cycle. Moreover, the Sun serves as a fundamental reference for other stars as, due to its proximity, it is the only star that can be investigated in such detail. The results for the Sun would therefore have direct implications for understanding other stars and their impact on exoplanets. This article outlines the key scientific objectives and technical requirements for solar observations with AtLAST.

Cellular and Molecular Effects of Magnetic Fields.

Recently, magnetic fields (MFs) have received major attention due to their potential therapeutic applications and biological effects. This review provides a comprehensive analysis of the cellular and molecular impacts of MFs, with a focus on both in vitro and in vivo studies. We investigate the mechanisms by which MFs influence cell behavior, including modifications in gene expression, protein synthesis, and cellular signaling pathways. The interaction of MFs with cellular components such as ion channels, membranes, and the cytoskeleton is analyzed, along with their effects on cellular processes like proliferation, differentiation, and apoptosis. Molecular insights are offered into how MFs modulate oxidative stress and inflammatory responses, which are pivotal in various pathological conditions. Furthermore, we explore the therapeutic potential of MFs in regenerative medicine, cancer treatment, and neurodegenerative diseases. By synthesizing current findings, this article aims to elucidate the complex bioeffects of MFs, thereby facilitating their optimized application in medical and biotechnological fields.

Anti-tumor effect of innovative tumor treatment device OM-100 through enhancing anti-PD-1 immunotherapy in glioblastoma growth.

Glioblastoma (GBM) is associated with a median survival rate of less than 15 months, necessitating innovative treatment approaches. This study investigates the safety and efficacy of the low-frequency magnetic field (LFMF) OM-100 instrument in GBM therapy. In vitro experiments utilized normal astrocyte and GBM cell lines, determining that OM-100 at 100 kHz for 72 h selectively targeted GBM cells without harming normal cells. Subsequent analyses revealed OM-100's impact on cell viability, apoptosis, migration, invasion, reactive oxide species levels, and PD-L1 expression. In vivo studies on mice with U87-induced GBM demonstrated OM-100's synergy with anti-PD-1 therapy, leading to significant tumor volume reduction and increased apoptosis. Notably, OM-100 exhibited safety in healthy mice. Overall, OM-100 could enhance anti-PD-1 immunotherapy effectiveness probably by directly inhibiting tumor proliferation and migration as well as promoting PD-L1 expression, offering a promising therapeutic strategy for GBM treatment.