Resolution Phase Research Articles

Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis.

Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway. Depletion of TAZ in tumor-associated macrophages promoted tumor growth by suppressing the recruitment of tumor-infiltrating lymphocytes. Moreover, in a diet-induced metabolic dysfunction-associated steatohepatitis model, macrophage-specific deletion of TAZ ameliorated liver inflammation and hepatic fibrosis. Thus, targeted therapies being developed against YAP/TAZ-TEAD are ineffective in macrophages. Together, our results introduce Golgi-associated TAZ as a potential molecular target for therapeutic intervention to treat tumor progression and chronic inflammatory diseases.

Breathing chimera states in nonlocally coupled type-I excitable phase oscillators

Breathing chimera states in nonlocally coupled type-I excitable phase oscillators

Field-Programmable Gate Array (FPGA)-Based Lock-In Amplifier System with Signal Enhancement: A Comprehensive Review on the Design for Advanced Measurement Applications.

Lock-in amplifiers (LIAs) are critical tools in precision measurement, particularly for applications involving weak signals obscured by noise. Advances in signal processing algorithms and hardware synthesis have enabled accurate signal extraction, even in extremely noisy environments, making LIAs indispensable in sensor applications for healthcare, industry, and other services. For instance, the electrical impedance measurement of the human body, organs, tissues, and cells, known as bioelectrical impedance, is commonly used in biomedical and healthcare applications because it is non-invasive and relatively inexpensive. Also, due to its portability and miniaturization capabilities, it has great potential for the development of new point-of-care and portable testing devices. In this document, we highlight existing techniques for high-frequency resolution and precise phase detection in LIA reference signals from field-programmable gate array (FPGA) designs. A comprehensive review is presented under the key requirements and techniques for single- and dual-phase digital LIA architectures, where relevant insights are provided to address the LIAs' digital precision in measurement system configurations. Furthermore, the document highlights a novel method to enhance the spurious-free dynamic range (SFDR), thereby advancing the precision and effectiveness of LIAs in complex measurement environments. Finally, we summarize the diverse applications of impedance measurement, highlighting the wide range of fields that can benefit from the design of high performance in modern measurement technologies.

The Changes in ICD-11 Related to Sexual Health and Dysfunction and Their Implication for Clinical Practice.

The classification of sexual health-related conditions was reformulated in 11th revision of International Classification of Diseases (ICD-11) following current evidence, best practice, and taking human rights into consideration, which is expected to reflect and provide guidance for more integrative clinical approaches. Overcoming the artificial, yet historical, distinction between "organic" and "non-organic" conditions, sexual dysfunctions classified in the "Mental and Behavioral Disorders" and "Disorders of Genitourinary System" in ICD-10 were listed in a new chapter called "Conditions Related to Sexual Health." In practice, this approach has been consistently recommended. However, diagnostical clasification was not congruent with the recommendation. Dysfunctions, defined with a non-normative but individual-based threshold, are categorized according to different stages of the sexual response cycle, similar to ICD-10 and Diagnostic and Statistical Manual of Mental Disorders 5th version (DSM-5). However, similarities and distinctions in the clinical presentation of the dysfunction in men and women were also considered, resulting in differences from the DSM-5 approach. Gender Incongruence is classified in this newly formed "Conditions Related to Sexual Health" chapter, not with mental disorders as in the earlier version, reflecting the current non-pathologizing understanding of gender diversity. Furthermore, the criteria for these conditions were revised to embrace the variability in the experience of gender identity. In addition, the residuals of sexual orientation-related diagnostic categories were removed. Paraphilic disorders categories replaced "Disorders of sexual preference" in ICD-10, with significant modifications in conceptualization and classification.

The Immune System: An Arrow to the Heart and Principles of Cardioimmunology as an Emerging Branch of Medicine.

Cardioimmunology is an emerging branch of medicine whose development has been facilitated by more sophisticated diagnostic procedures. Recent studies have mainly focused on the immune response during myocardial infarction (MI), and there is evidence that both resident and external immune cells participate in acute inflammatory disease, as well as tissue remodeling. Cardiac Innate Immune Cells: Following MI, macrophages, dendritic cells (DCs) and mast cells (MCs) are the main players in the heart. Under steady-state conditions, cardiac resident macrophages (CRMs) protect the heart against stress and infectious events, being involved in cell and matrix turnover, as well as phagocytosis of apoptotic cells. Moreover, CRMs contribute to the resolution of inflammation via release of interleukin (IL)-10, and efferocytosis of dying cells. Conversely, CCR2+ monocyte-derived macrophages promote inflammation in the acute phase of myocardial damage, with the release of pro-inflammatory cytokines. Conventional (c) DCs possess enhanced capacity to present antigens to T lymphocytes. In MI patient autopsies, massive infiltration of T helper (Th) cells and CDs has been detected in the myocardium. Cardiac MCs play a dual role during MI, with the production of cytokines for early inflammatory response, and the release of anti-inflammatory cytokines, IL10 and IL-13 during the resolution phase. Adaptive Immune Response: In experimental coronary artery ligation, the myocardium is infiltrated with Th1, Th2, Th17, and T regulatory (TREG) cells, which participate in the acute inflammation. In cardiac repair, T cell reparative response is mediated by TREG cells, with improved ventricular remodeling and function post-ischemia. In this review, emphasis will be placed on the innate and adaptive immune response during and post-MI. At the same time, immunotherapy-based cardiac failure following chimeric antigen receptor T-cell and immune checkpoint inhibitory therapy will be pointed out.

Oscillatory Transcranial ElectricalStimulation and the Amplitude-Modulated Frequency Dictate the Quantitative Features of Phosphenes.

Previous research demonstrated that transcranial alternating current stimulation (tACS) can induce phosphene perception. However, tACS involves rhythmic changes in the electric field and alternating polarity (excitatory vs. inhibitory phases), leaving the precise mechanism behind phosphene perception unclear. To disentangle the effects of rhythmic changes from those of alternating polarity, this study employs oscillatory transcranial direct current stimulation (otDCS), in which the current oscillation remains confined to either a positive or negative polarity, thereby eliminating the influence of polarity switching. We applied scalp electrical stimulations using both polarity-switching (tACS) and non-polarity-switching (otDCS) methods, with anodal or cathodal polarities, targeting the occipital lobe. All stimulations were performed using sinusoidal or amplitude modulation (AM)waveforms at threshold or suprathreshold intensities. Our results show that tACS results in faster response times compared to cathodal otDCS, but not anodal otDCS, while anodal otDCS elicits greater brightness perception than both cathodal otDCS and tACS. Additionally, AM frequency induced a higher threshold than the sinusoidal frequency, and response times were slower in the AM condition across all positive, negative, and polarity-switching stimulations. However, stimulation intensity in the anodal AM condition could influence speed ratings, unlike in cathodal or tACS conditions. Our findings reveal that both tACS and otDCS induce phosphenes, with significant differences between polarities and current oscillation types, indicating that both mechanisms are critical in phosphene induction. This study provides evidence linking phosphene occurrence to oscillatory current activity and highlights the robustness and impact of AM coding in visual perception.

A microphysiological system of sterile injury demonstrates neutrophil reverse migration via macrophage-derived extracellular vesicle crosstalk.

Persistent neutrophilic inflammation can lead to tissue damage and chronic inflammation, contributing to non-healing wounds. The resolution phase of neutrophilic inflammation is critical to preventing tissue damage, as observed in diseases characterized by influx of neutrophils such as atherosclerosis and non-healing wounds. Animal models have provided insight into resolution of neutrophilic inflammation via efferocytosis and reverse migration (rM); however, species-specific differences and complexity of innate immune responses make translation to humans challenging. Thus, there is a need for in vitro systems that can elucidate mechanisms of resolution of human neutrophilic inflammation. Here, we developed a human microphysiological system (MPS) to mimic an inflammatory sterile injury (SI) microenvironment to study the role of macrophage derived extracellular vesicles (M-EVs) in determining the resolution of inflammation via neutrophil rM. The MPS integrates a human umbilical vein endothelial cell (HUVEC) lined lumen, injury site spheroid, human neutrophils, macrophages and macrophage derived EVs to investigate the role of M-EVs in neutrophil rM in vitro . The key features of the MPS enabled us to demonstrate that EVs derived from macrophage subsets modulate migratory behavior in primary neutrophils differently in specific inflammatory microenvironments. Importantly, we identified a new mechanism underlying neutrophil rM via M-EV, where neutrophils exposed to M2-EV-derived IL-8 migrate away from the SI site upon reaching the site, using the SI MPS. Overall, our SI MPS system demonstrates a reverse migratory pattern in human primary neutrophils, advancing the study of the resolution of inflammation via M-EVs.

ULTRASTRUCTURAL CHANGES IN THE KIDNEYS OF RATS DURING THE EARLY AND LATE STAGES OF ACUTE RESPIRATORY DISTRESS SYNDROME

Introduction. Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia and activation of the inflammatory cascade, which leads to multi-organ failure. Kidneys are one of the organs commonly affected by ARDS. However, the extent of ultrastructural changes in the parenchyma and stroma of the kidneys at different stages of ARDS progression remains unclear. The aim of this study was to use transmission electron microscopy to study the main components of the kidneys in rats at the early and late stages of experimentally induced ARDS. Materials and methods. The study included 24 healthy, sexually mature male rats weighing 200–220 g, divided into three groups: intact animals, 24 hours post-ARDS induction, and 14 days after the start of the experiment. ARDS was modeled by intranasal administration of lipopolysaccharide (5 mg/kg body weight) under anesthesia with ketamine at a dose of 50 mg/kg. Terminal anesthesia was performed using sodium thiopental at a dose of 150 mg/kg. Results: Submicroscopic examination of the kidneys from intact rats revealed no species-specific structural abnormalities. In the early stage of ARDS (24 hours post-modeling), renal corpuscles showed signs of vascular endothelial damage, fragmentation of the glomerular basement membrane, and degeneration of organelles and nuclear components in tubular epithelial cells. By day 14 of ARDS progression, signs of damage to the filtration barrier persisted, resulting in podocyte swelling. However, partial restoration of the tubular epithelial cell structure was observed, indicating the onset of the resolution phase of ARDS, as evidenced by the gradual recovery of the kidney ultrastructure. Conclusions. During the early stage of modeled ARDS, kidney damage manifests through destructive changes in the glomerular apparatus and renal tubular epithelial cells. In the late stage, although glomerular damage remains, partial restoration of the renal tubular epithelial cell structure is still evident.

Review of methodology and re-analysis of lipidomic data focusing on specialised pro-resolution lipid mediators (SPMs) in a human model of resolving inflammation.

Using a model of UV-killed E. coli driven dermal inflammation in healthy human volunteers, we originally reported that following inflammatory resolution there was infiltration of macrophages, which, through prostanoids including prostaglandin (PG) E2, imprints long-term tissue immunity. In addition to the prostanoids, data on levels of Specialised Pro-Resolution Lipid Mediators (SPMs) throughout inflammatory onset, resolution and post-resolution phases of this model were presented, but as illustrations rather than as primary data. Therefore, in response to a request for increased transparency, a subset of the original data from our human UV-killed E. coli model was re-analysed by two experts from an independent laboratory alongside a review of the methodology used. The prostanoids were detected robustly following re-analysis but the areas of the chromatographic peaks of the SPM lipid mediators were too small to yield amounts that could be reliably detected and/or quantified using community standards. Importantly, with prostanoids including PGE2 being robustly detected, this re-analysis does not alter the original report that post-resolution PGs imprint tissue immunity. Here we show the outcome of this re-analysis and review the biology surrounding SPMs as a result.

Cross-Attention-Based High Spatial-Temporal Resolution Fusion of Sentinel-2 and Sentinel-3 Data for Ocean Water Quality Assessment

Current marine research that leverages remote sensing data urgently requires gridded data of high spatial and temporal resolution. However, such high-quality data is often lacking due to the inherent physical and technical constraints of sensors. A necessary trade-off therefore exists between spatial, temporal, and spectral resolution in satellite remote sensing technology: increasing spatial resolution often reduces the coverage area, thereby diminishing temporal resolution. This manuscript introduces an innovative remote sensing image fusion algorithm that combines Sentinel-2 (high spatial resolution) and Sentinel-3 (relatively high spectral and temporal resolution) satellite data. The algorithm, based on a cross-attention mechanism and referred to as the Cross-Attention Spatio-Temporal Spectral Fusion (CASTSF) model, accounts for variations in spectral channels, spatial resolution, and temporal phase among different sensor images. The proposed method enables the fusion of atmospherically corrected ocean remote sensing reflectance products (Level 2 OSR), yielding high-resolution spatial data at 10 m resolution with a temporal frequency of 1–2 days. Subsequently, the algorithm generates chlorophyll-a concentration remote sensing products characterized by enhanced spatial and temporal fidelity. A comparative analysis against existing chlorophyll-a concentration products demonstrates the robustness and effectiveness of the proposed approach, highlighting its potential for advancing remote sensing applications.

TLR7 Promotes Acute Inflammatory-Driven Lung Dysfunction in Influenza-Infected Mice but Prevents Late Airway Hyperresponsiveness.

Severe lower respiratory tract disease following influenza A virus (IAV) infection is characterized by excessive inflammation and lung tissue damage, and this can impair lung function. The effect of toll-like receptor 7 (TLR7), which detects viral RNA to initiate antiviral and proinflammatory responses to IAV, on lung function during peak infection and in the resolution phase is not fully understood. Using wild-type (WT) C57BL/6 and TLR7 knockout (TLR7 KO) mice, we found that IAV infection induced airway dysfunction in both genotypes, although in TLR7 KO mice, this dysfunction manifested later, did not affect lung tissue elastance and damping, and was associated with a different immune phenotype. A positive correlation was found between lung dysfunction and the infiltration of neutrophils and Ly6Clo patrolling monocytes at day 7 post-infection. Conversely, in TLR7 KO mice, eosinophil and CD8+ cytotoxic T cells were associated with airway hyperactivity at day 14. IL-5 expression was higher in the airways of IAV-infected TLR7 KO mice, suggesting an enhanced Th2 response due to TLR7 deficiency. This study highlights an underappreciated duality of TLR7 in IAV disease: promoting inflammation-driven lung dysfunction during the acute infection but suppressing eosinophilic and CD8+ T cell-dependent hyperresponsiveness during disease resolution.

Near-isotropic sub-Ångstrom 3d resolution phase contrast imaging achieved by end-to-end ptychographic electron tomography

Abstract Three-dimensional atomic resolution imaging using transmission electron microscopes is a unique capability that requires challenging experiments. Linear electron tomography methods are limited by the missing wedge effect, requiring a high tilt range. Multislice ptychography can achieve deep sub-Ångstrom resolution in the transverse direction, but depth resolution is limited to 2 to 3 nanometers. In this paper, we propose and demonstrate an end-to-end approach to reconstructing the electrostatic potential volume of the sample directly from the 4D-STEM datasets. End-to-end multislice ptychographic tomography recovers several slices at each tomography tilt angle and compensates for the missing wedge effect. The algorithm is initially tested in simulation with a Pt@Al2O3 core–shell nanoparticle, where both heavy and light atoms are recovered in 3D from an unaligned 4D-STEM tilt series with a restricted tilt range of 90 degrees. We also demonstrate the algorithm experimentally, recovering a Te nanoparticle with sub-Ångstrom resolution.

Improved Thermal Resolution and Macroscale Phase Transformation Modeling of the Semi-Crystalline Polymer Polyamide-12 during Laser Powder Bed Fusion

Improved Thermal Resolution and Macroscale Phase Transformation Modeling of the Semi-Crystalline Polymer Polyamide-12 during Laser Powder Bed Fusion

Optical and Band Gap Study of Violet-Blue Broadband Emitting Dy3+ Codoped Y2SiO5:Ce3+ Phosphor for nUV White Light-Emitting Diodes.

Y2SiO5:Ce3+, Y2SiO5:Dy3+, and Y2SiO5:Ce3+ and Dy3+ phosphors were successfully synthesized using the oxalate wet chemical method. Phase purity, emission and excitation spectra, FTIR, and the chromaticity coordinate were adopted to represent the performance of the samples. The photoluminescence (PL) spectrum Y2SiO5:Ce3+ and Dy3+ phosphor shows a broadband in violet-blue region with a bandwidth of nearly 75 nm due to combine effect of Ce3+-Dy3+ ions with another emission peaks of Dy3+ ions peaking at 574 nm. It has been discussed how the Ce3+-Dy3+ ion pair enhances the PL intensity of violet-blue light through efficient energy transfer (ET). The chromaticity coordinate of Y2SiO5:Ce3+ (1 mol%), Dy3+ (0.3 mol%) phosphors is 𝑥 = 0.167 and 𝑦 = 0.034. The CCT value is used to find color temperatures. The energy band gap and refractive index of Y2SiO5:Dy3+ are determined using the bonding parameter and Tauc's plot. Prepared phosphors might be an excellent choice for lighting applications based on all of the findings.

Low‐Profile Beam‐Steering Metasurface Lens Antenna Utilizing Defocused Array Feed Without Amplitude–Phase Network

ABSTRACTThe present study introduces a low‐profile beam‐steering metasurface lens antenna (MLA) that is excited by a defocused array antenna (DAA), eliminating the need for amplitude and phase excitation modulation. First, we modify an ultrathin Huygens' unit cell to provide greater angular stability, which is intended for use in beam‐steering lens antennas. Subsequently, we analyze the effect of the focal–diameter ratio (F/D) on the beam‐steering performance of the lens. Further, a one‐dimensional (1D) MLA equipped with a DAA is modeled. Based on this model, we investigate the influence of DAA distance from the lens, DAA diameter, and F/D on radiation directivity and scanning capability. By adjusting the distance between the DAA and the lens, sub‐arrays located in different regions of the DAA can be excited with uniform amplitude and phase, enabling dual‐polarized single‐beam scanning radiation. This excitation technique eliminates the need for amplitude and phase modulation networks, thereby reducing beam‐steering costs and the complexity of the feed network. Finally, a 1010 MLA prototype excited by a 52‐unit dual‐polarized DAA is simulated and fabricated. The simulation and measurement results demonstrate that the proposed MLA achieves a scanning range of ± 15°/± 16° in the E/H‐plane at 10.3 GHz, with a gain fluctuation of less than 2.35/2.25 dB.

The response of droplet cloud decomposition to the gas phase excitation

The response of droplet cloud decomposition to the gas phase excitation

22. SEXUAL PROBLEMS AMONG OLDER ADULTS IN ASIA AND AFRICA: A REVIEW

The aim of this review was to explore the prevalence of sexual problems among older adults in Asia and Africa; and to analyze how difficult it was for them to seek help. Sexual problems are characterized by diminished or absent of sexual interests and by disturbances in the physiological or psychosocial patterns associated with sexual response cycle. Male sexual dysfunction (ED) and female sexual dysfunction increase with age. Studies show that about 33% of the elderly population has at least one complaint with their sexual functioning. Old people face shame and hesitancy when consulting health-care professionals for sexual problems due to the taboos surrounding sex, compounded by a lack of knowledge of older sexuality and ageism in healthcare. The General Practitioners (GP) on the other hand, tend to ignore older adult’s complaints due to lack of training, or just perceiving sexual problems is a norm at old age. However, GP should always give their clients’ opportunity to voice out their concerns with sexual function and offer them various health care regimen and alternatives for evaluation and treatments.

Psychological and sociodemographic factors associated with hypoactive sexual desire in Ecuadorian women.

Human sexuality is a multifaceted process, and sexual desire plays a central role in the triphasic model of the sexual response cycle, as proposed by Helen Singer Kaplan. In this cross-sectional correlational study, we examined the relationship between various sociodemographic factors, such as age and motherhood, and sexual variables, including erotophobia, erotophilia, homophobia, and unconventional sex, with hypoactive sexual desire in women from Quito, Ecuador. The study sample comprised 421 women between the ages of 18 and 50, who were administered the Revised Sexual Opinion Survey and the Inhibited Sexual Desire Scale to assess their sexual attitudes and levels of desire. The findings revealed that age (F = 7.13, p < 0.001) and motherhood (F = 13.72, p < 0.001) had a significant impact on inhibited sexual desire. Furthermore, significant correlations were observed between inhibited sexual desire and age (r = 0.16, p < 0.001), motherhood (r = 0.18, p < 0.001), erotophobia (r = 0.19, p < 0.001), erotophilia (r = -0.21, p < 0.001), and homophobia (r = -0.18, p < 0.001). These results suggest that women who are older, mothers, or have higher levels of erotophobia are more likely to experience hypoactive sexual desire. In contrast, higher levels of erotophilia and homophobia were inversely related to hypoactive sexual desire. This contributes to a deeper understanding of how different personal and sexual attitudes influence sexual desire in Ecuadorian women.

A potent proresolving mediator 17R-resolvin D2 from human macrophages, monocytes, and saliva.

Production of specialized proresolving mediators (SPMs) during the resolution phase in the acute inflammatory response is key to orchestrating complete resolution. Here, we uncovered a trihydroxy resolvin in fresh human saliva. We identified and determined its complete stereochemistry as 7S,16R,17R-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid (17R-RvD2) using total organic synthesis and matching of physical properties. The 17R-RvD2 was produced by activated human M2-like macrophages, M1-like macrophages, and human peripheral blood monocytes. 17R-RvD2 displayed potent proresolving functions (picomolar to nanomolar). Topical application of 17R-RvD2 on mouse ear skin reduced neutrophilic infiltration (~50%). 17R-RvD2 increased M2 markers CD206 and CD163 on human monocyte-derived macrophages and enhanced efferocytosis of senescent red blood cells by M2-like macrophages (EC50 ~ 2.6 × 10-14 M). In addition, 17R-RvD2 activated the RvD2 receptor and was equipotent to its epimer RvD2. 17R-RvD2 also significantly increased phagocytosis of Escherichia coli by human neutrophils. Together, these results establish the complete stereochemistry and potent proresolving functions of the previously unknown 17R-RvD2.

Photoinduced hydrogen dissociation in thymine predicted by coupled cluster theory

The fate of thymine upon excitation by ultraviolet radiation has been the subject of intense debate. Today, it is widely believed that its ultrafast excited state gas phase decay stems from a radiationless transition from the bright ππ* state to a dark nπ* state. However, conflicting theoretical predictions have made the experimental data difficult to interpret. Here we simulate the early gas phase ultrafast dynamics in thymine at the highest level of theory to date. This is made possible by performing wavepacket dynamics with a recently developed coupled cluster method. Our simulation confirms an ultrafast ππ* to nπ* transition (τ = 41 ± 14 fs). Furthermore, the predicted oxygen-edge X-ray absorption spectra agree quantitatively with experiment. We also predict an as-yet uncharacterized πσ* channel that leads to hydrogen dissociation at one of the two N-H bonds. Similar behavior has been identified in other heteroaromatic compounds, including adenine, and several authors have speculated that a similar pathway may exist in thymine. However, this was never confirmed theoretically or experimentally. This prediction calls for renewed efforts to experimentally identify or exclude the presence of this channel.