Search Results (7,257)

We study the problem of joint sensing and secure communications in a reconfigurable intelligent surface (RIS)-based symbiotic radio (SR) system. In the considered system, a dual-functional radar and communication base station (DFRC-BS) achieves secure communications with multiple user terminals (UTs), and at the same time, performs a target sensing task. An RIS simultaneously assists the secure communications between the DFRC-BS and the multiple UTs and conveys its own data to the UTs by modulating the radio frequency signal from the DFRC-BS. Two different SR settings are investigated, namely, parasitic SR (PSR) and commensal SR (CSR). In both the PSR and the CSR situations, the echo signal from the sensing target is interfered by the backscattered signal from the RIS. We propose two strategies for the DFRC-BS to handle with the interference from the RIS, namely, (1) directly sensing without interference cancelation, and (2) performing interference cancelation before sensing. For both the two strategies, we aim to maximize the sum secrecy rate from the DFRC-BS to the multiple UTs while ensuring satisfactory performances for the sensing and the backscatter links. A block coordinate ascend algorithm is proposed to solve the established non-convex optimization problems. Simulation results reveal that at the DFRC-BS, performing interference cancelation leads to an improved system performance. Furthermore, compared with PSR, CSR leads to a higher sum secrecy rate between the DFRC-BS and the UTs. Full article

Mesenchymal stem cells (MSCs) have been widely investigated in regenerative medicine owing to their immunomodulatory activity, paracrine signaling, and multilineage differentiation potential. However, accumulating clinical and preclinical evidence indicates that conventional MSC therapies based on single-cell injection often produce transient benefits due to rapid post-transplant cell loss and poor engraftment. These observations suggest that the limited efficacy of MSC therapy is not determined solely by cell type or disease context but may also be influenced by the delivery strategy. In this review, we focus on MSC-based cell sheet studies as an approach to improve cell retention and therapeutic persistence. Building on the clinical validation of cell sheet technology, we critically summarize preclinical evidence across distinct tissue environments. Preclinical studies in cardiac and cutaneous repair models demonstrate that MSC sheets enhance cell retention, sustain paracrine signaling, and promote tissue-level regeneration. Together, these findings highlight that effective MSC sheet therapy requires organ-specific, cell-source-dependent design strategies rather than a uniform approach across tissues. Finally, we propose that the MSC sheet engineering represents not a technical adjustment, but a conceptual shift from transient cell delivery toward structurally integrated, tissue-level regeneration engineering. Full article

Melanoma, a highly aggressive and metastatic cancer, poses significant challenges due to its propensity to spread to distant organs, with brain metastasis representing a particularly devastating complication. This review synthesizes preclinical and clinical evidence on the molecular, cellular, and microenvironmental mechanisms driving melanoma metastasis, emphasizing mechanisms of blood–brain barrier traversal, tumor-stroma co-option, and brain-specific genomic and transcriptional programs. We summarize advances in therapeutic strategies to combat melanoma brain metastasis including novel small molecules, immunotherapies, and combination approaches tailored for brain metastases. The review also highlights the immunological landscape of the brain, translational models, and multidisciplinary clinical management strategies. Finally, we identify critical research gaps, including the need for brain metastasis-specific clinical trials, AI-driven predictive models, and preventive strategies, to guide future efforts in improving outcomes for patients with melanoma brain metastasis. Full article

Key mechanisms underlying immune thrombocytopenia (ITP) pathophysiology include impaired platelet production and macrophage-mediated platelet destruction, the latter of which is the disease driver in more than half of patients. Traditional sequential treatment approaches achieve suboptimal responses in many patients. This review summarizes ITP pathogenesis and the treatment landscape and proposes a personalized treatment approach for ITP after first-line treatment (corticosteroids, intravenous immunoglobulin, anti-D therapy) based on targeting underlying disease mechanisms with immunomodulatory and bone marrow-supportive therapies (fostamatinib, rituximab, and thrombopoietin receptor agonists [TPO-RAs]) prior to proceeding to later-line therapies. Clinical evidence of monotherapy and real-world studies of combination therapy are reviewed to support mechanism-based treatment selection, focusing on the complementary actions of fostamatinib (to target platelet destruction) and TPO-RAs (to stimulate platelet production). In prior studies, fostamatinib with or without TPO-RAs demonstrated durable platelet responses and manageable safety as second-line or later ITP treatment. The proposed treatment framework augments guidelines by recommending fostamatinib, rituximab, or TPO-RAs as second-line therapy options based on patient-specific disease characteristics and risks. Patients with inadequate response to fostamatinib or TPO-RA monotherapy may combine these therapies to address both platelet destruction and platelet production deficits. This novel framework tailors therapy to patient-specific pathophysiology by preferentially targeting both impaired platelet production and increased platelet destruction to support individualized care. Full article

The X-Men are a superhero team published by Marvel Comics. Initially marketed as a team of teenage superheroes, the franchise eventually began emphasizing the “mutant metaphor” as a narrative device that differentiated it from other comic books. This pivot towards highlighting the empathy displayed by the X-Men towards others and the intolerance their foes have for anyone who is different became defining characteristics of the franchise that have carried forward for decades. As the X-Men moved from a somewhat generic franchise to one that framed its heroes as symbolic outsiders, a wider and deeper fanbase embraced the series. Through complex storylines, symbolic metaphors, and nuanced character development, the series implicitly and often explicitly encourages empathy. With a thematic focus on concepts such as marginalization and otherness, the X-Men franchise promotes tolerance as heroic and condemns prejudice as villainous. The message for readers is that empathy, not optic blasts or the ability to control the weather, is what makes the X-Men heroic. Full article

Background: Alcohol is associated with increased mortality and morbidity globally. Pulmonary infections with opportunistic pathogens can occur in healthy humans; however, binge alcohol intoxication (≥0.08% BAC) is a major risk factor. We have previously shown that a single dose of alcohol comparable to binge alcohol intoxication increases infection by reducing alveolar macrophage function in vivo. Sulforaphane (SFN), a phytonutrient, is a potent inducer of antioxidant production through the induction of nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibition of the nuclear factor kappa-light-chain-enhancer (NF-kB) pathway. The aim of this study was to test the therapeutic potential of SFN given as a pretreatment to prevent alcohol-induced phagocytic dysfunction. Methods: Intracellular phagocytic killing was measured via colony-forming units (CFU) and cytokine expression via ELISA. G. mellonella survival was used to determine the therapeutic potential of SFN in vivo. Results: Dose–response curves indicated that SFN concentrations of less than 20 µM were not cytotoxic in either MH-S (murine) or THP-1 (human) cells. Live infection assay results showed that MH-S and THP-1 cells pretreated with SFN (5 µM) and challenged with 0.2% (v/v) alcohol for 3 or 8 h prior to live B. thailandensis or S. epidermidis infection improved intracellular pathogen killing between 12- and 20-fold compared to macrophages treated with alcohol alone. ELISA analysis indicated that SFN significantly reduced levels of Tumor necrosis factor-alpha (TNF-α) expression at 3 and 8 h compared to controls. Additionally, a Galleria mellonella larvae model demonstrated greater survivability in the prophylaxis group compared to larvae exposed to either Gram-positive or Gram-negative pathogens, as well as in groups that received alcohol prior to pathogen inoculation. Conclusions: Taken together, SFN-induced cytoprotection was extended beyond in vitro cell culture to include an in vivo G. mellonella model demonstrating protection against Gram-positive and negative opportunistic pathogens. These data demonstrate that SFN may be an effective pretreatment option to prevent alcohol-mediated innate immune dysfunction and restore macrophage phagocytic killing. Full article

Since children spend a significant portion of their developmental years in educational settings, the environmental quality of these institutions—specifically, the extent to which they expose their occupants to green space and heat stress—is a critical determinant of well-being and academic performance. This study assesses the green environmental quality of 121 educational institutions (kindergartens, and elementary and secondary schools) in Debrecen, Hungary. The main objective of the research is to identify educational institutions that require immediate intervention to address their lack of green spaces, improve the green environment, and mitigate the urban heat island (UHI) effect. A further aim of the study is to understand how different urban planning practices over the past century have led to the current situation. Therefore, we utilized high-resolution geospatial data (specifically, WorldView-2 imagery) to classify schoolyard vegetation; Landsat data to derive Land Surface Temperature (LST); and the Hoover index to quantify institutions’ spatial concentration. We developed a composite indicator to categorize green environmental quality and heat stress exposure. Our results reveal deep spatial and institutional inequalities. 47.5% of students attend institutions with low environmental quality. While kindergartens typically offer green-rich environments, secondary schools with significant student populations—which are primarily concentrated in the dense historical downtown—are trapped in “grey” zones possessing poor environmental quality. Furthermore, we identify a “green paradox” in socialist housing estates: despite abundant surrounding greenery, schools here record high LST values due to the heat-trapping morphology of vertical concrete structures. The study also highlights institutional maladaptation, such as converting schoolyards into parking lots and using rubber pavements for safety reasons, which contributes to the deterioration of environmental quality. We conclude that current urban planning and school architecture must shift paradigms, treating schoolyards as integral components of the public green infrastructure network through climate-adaptive design. In addition, stakeholders should develop the green environment of educational institutions comprehensively, taking into account both on-site and surrounding green spaces. Full article

Background/Objectives: Beta-hydroxybutyrate (BHB) exists as two enantiomers with potentially distinct biological activities. While D-BHB is the physiological form produced during ketogenesis, L-BHB is present in equal amounts in racemic supplements, yet its biological effects remain poorly understood. Additionally, the ketone precursor 1,3-butanediol (BD) is used in some formulations despite limited safety data. Methods: We investigated acute (single gavage, 2-h time course) and short-term (daily gavage for 8 days) hepatic effects of D-BHB, L-BHB, and 1,3-butanediol compared to a vehicle control in male C57BL/6 mice. Acute studies assessed hepatic ATP dynamics and lipid peroxidation (MDA) at multiple timepoints. Eight-day protocols evaluated mitochondrial function (oxygen consumption, Complex II activity, SDH activity), lipid accumulation (triglycerides), and inflammatory markers (IL-1β, TNF-α, CRP). Results: Acute ATP responses differed markedly among treatments. Compared to the baseline and the control, L- and D-BHB elicited significant increases in ATP, while BD caused sustained ATP depletion. Over this same time, oxidative stress markers remained stable in the control and both BHB groups but increased dramatically with BD. After 8 days, the mitochondrial effects of BD were more apparent with a significant reduction in complex II-supported respiration and activity. Both forms of BHB maintained control levels of inflammation and BD showed significant effects on all inflammatory markers. Hepatic triglycerides increased only with BD treatment. Conclusions: This study reveals striking hepatic effects of various ketone supplements. In contrast to the positive or inert effects of BHB enantiomers, 1,3-butanediol induces significant hepatic stress. These findings have implications for ketone supplement formulation and highlight the therapeutic potential of D- and L-BHB. Full article

Screening for spinal muscular atrophy (SMA) was adopted by all US state newborn screening programs between 2018 and 2024; by the end of 2022, 48 states were screening for SMA. We assessed trends in health insurance records of SMA diagnoses to quantify improvements in the timeliness of SMA identification following the adoption of screening. We used nationally representative Medicaid claims data for approximately half of US births covered by public insurance and a convenience sample of employer-sponsored health plans. We analyzed records for birth cohorts with at least 1 full year of follow-up (i.e., through the end of the following calendar year). For 2017 births, 1.3 per 100,000 infants had SMA codes first recorded by 1 month of age; this increased to 6.6 per 100,000 among publicly insured newborns born in 2022. The rollout of SMA newborn screening across US states was also followed by improvements in the timely detection of SMA. The proportion of infants with SMA detected by 1 month increased from 18% in 2017 to 61% in 2021 and is projected to reach 75% in 2022. Growth in timely detection was even greater in the employer-insured sample. Timely diagnosis of SMA can enable the initiation of treatment prior to the irreversible loss of motor function. Full article

The limited ductility of the VW63K rare-earth magnesium alloy fabricated via cold metal transfer wire arc additive manufacturing (CMT-WAAM) was targeted in this work. An integrated approach that combines first-principles calculations with experimental characterization was employed to achieve this goal. This approach was used to systematically investigate how Ag doping alters the microstructure and mechanical properties of the alloy. First-principles calculations performed on the primary precipitate phase Mg₂₄(Gd,Y)₅ demonstrated that Ag atoms preferentially occupy the Mg lattice sites and form pronounced orbital hybridization with neighboring rare-earth atoms. These interactions were found to enhance critical mechanical parameters, including the Cauchy pressure, B/G ratio, and Poisson’s ratio, which are indicative of enhanced ductility and toughness of the phase. Experimental results indicate that the fracture strain of the VW63K-Ag alloy was increased from approximately 4% to above 12% following Ag doping. This resulted in a significant improvement in ductility. The ultimate tensile strength (UTS) underwent only a moderate reduction. Using a closed-loop approach integrating theoretical prediction and experimental validation, the microstructural modification and strengthening mechanisms of Ag in the VW63K alloy fabricated via CMT-WAAM were clarified. These findings offer a theoretical foundation and experimental evidence for compositional design and optimizing additive manufacturing (AM) processes for rare-earth magnesium alloys. Full article

Cognitive impairment is a major comorbidity in temporal lobe epilepsy (TLE), yet its underlying pathophysiology remains poorly understood and current therapies provide minimal benefit. While oxidative stress has traditionally been viewed as a precursor to cell death-mediated cognitive decline, cell death is absent in many patients and preclinical models with memory impairment. Here, we tested whether excessive mitochondrial reactive oxygen species (ROS) actively contribute to memory impairment through mechanisms distinct from cell death. Using Kv1.1 knockout (KO) mice, a TLE model with mitochondrial respiratory chain complex I (MRCI) impairment, we found elevated hippocampal mitochondrial superoxide, impaired recognition memory, deficits in synaptic plasticity, and abnormal sharp wave–ripple oscillations. Applying the MRCI inhibitor rotenone to wild-type hippocampal slices caused increased superoxide and mirrored electrophysiology deficits. Both acute and sub-chronic treatment with the mitochondria-targeted antioxidant mitoquinone (MitoQ) reduced superoxide levels, rescued synaptic plasticity, restored network activity, and normalized memory performance in KO mice—without altering seizure frequency, severity, or neuronal excitability. Our results identify mitochondrial superoxide as a reversible driver of hippocampal dysfunction in epilepsy and demonstrate that mitochondria-targeted antioxidant therapy can restore cognition despite persistent seizures. This study provides proof-of-concept for novel treatments improving cognitive comorbidities in TLE beyond seizure control. Full article

Background/Objectives: Antimicrobial resistance (AMR) continues to expand under sustained exposure to conventional antibiotics, contributing to the emergence of multidrug- and pan-resistant bacterial pathogens. There remains a critical need for antimicrobial agents that maintain activity during prolonged selective pressure while minimizing the potential for resistance development. This study aimed to evaluate EVQ-218, a non-ionic silver-based antimicrobial, against World Health Organization-designated ESKAPE pathogens. Methods: EVQ-218 was assessed using extended serial passage experiments performed under both sub- and supra-minimum inhibitory concentration (MIC) conditions. Comparative resistance selection experiments were conducted in parallel using tobramycin and ciprofloxacin, and susceptibility was evaluated through MIC determination and phenotypic analysis. Results: Across extended serial passage experiments, EVQ-218 did not exhibit measurable increases in MIC or phenotypic indicators of adaptive resistance. In contrast, parallel exposure to tobramycin and ciprofloxacin resulted in rapid and sustained MIC elevation. Notably, isolates that acquired resistance to either comparator antibiotic retained susceptibility to EVQ-218, indicating a lack of cross-resistance. Mechanistic analyses were consistent with a non-lytic, intracellular mode of antibacterial activity involving disruption of sulfur-associated biomolecular processes, suggestive of a multi-site mechanism distinct from classical antibiotics. Conclusions: These findings support EVQ-218 as a promising broad-spectrum antimicrobial candidate with resistance-resilient activity and warrant further investigation of its potential role in addressing unmet needs in AMR therapeutics. Full article

Newborn bloodspot screening (NBS) began in Guthrie’s laboratory in 1961 for phenylketonuria. A federal study the following year formed the basis for expanding NBS as a public health function. Diseases detectable through NBS gradually expanded, eventually including sickle cell anemia, which was included in the screening panel in New York in 1975. Universal inclusion of full population screening for sickle cell anemia was included in all US NBS programs by 2006. Through the years, NBS for sickle cell anemia has expanded to include other clinically significant hemoglobin disorders (both hemoglobinopathies and thalassemias). While NBS programs exist in most high-income countries, their implementation in low- and middle-income settings has been slow, with the inclusion of hemoglobin disorders occurring even more slowly. It is particularly noteworthy that the low-resource settings with the highest incidences of sickle cell diseases (Sub-Saharan Africa, the Caribbean Islands, and India) and therefore the greatest potential for benefitting from NBS, continue to struggle with its implementation. Recent advances in curative treatments further emphasize the importance of NBS in early disease identification. This report reviews some of the history of newborn screening for hemoglobinopathies and thalassemias and provides an update of related activities currently ongoing globally. Full article

The Bahamas is an ideal location for studying the calcium carbonate sedimentation of Holocene strandplains in relation to seaward progradation. We use ground-penetrating radar (GPR) to image and interpret the fine-scale stratigraphy of three carbonate strandplains on Crooked Island, The Bahamas. GPR has been extensively used to analyse the interiors of clastic strandplain deposits worldwide, while tropical carbonate settings have received less attention. Due to the lack of outcrops in our study area on Crooked Island, we validate the interpretation of the 2D profiles by comparing them with a 3D GPR data volume collected adjacent to and over a Pleistocene aeolianite outcrop on San Salvador Island, where porosity layering can be directly observed. Data processing employed state-of-the-art techniques adapted from the petroleum industry to enhance the visualisation of reflection amplitude on the GPR images. Our data support a model in which the progradation of carbonate sediment preserved in strandplains was deposited through a combination of storm processes and gradual sediment progradation. Full article

“Rotten” sea ice, ice in an advanced stage of melt, represents an important but understudied habitat in the rapidly changing Arctic. As Arctic warming accelerates, this late-season ice type will become more prevalent, yet little is known about its microbial inhabitants or their roles in Arctic marine biogeochemical cycles. We examined microbial communities (prokaryote and algal abundance, 16S and 18S rRNA gene and transcript sequencing) and biogeochemical properties of rotten sea ice and earlier-season ice near Utqiaġvik, Alaska, USA. Rotten ice was comparatively warm, isothermal, and largely drained of brine, with extensive, interconnected pore networks linked to melt ponds above and seawater below. Unlike earlier-season ice, fluids saturating rotten ice were vertically homogeneous in pH, dissolved inorganic carbon, prokaryote and phytoplankton abundance, and microbial community composition. However, particulate carbon and nitrogen exhibited strong vertical gradients, with the highest concentrations near the surface. Microbial communities in rotten ice were significantly different from those in earlier-season ice and varied between individual floes. These findings indicate that rotten ice constitutes a distinct microbial habitat and may serve as an important source of nutrient-rich particulate matter in the future Arctic Ocean during the summer melt season. Full article