Search Results (1,731)

Activation of cGAS, a receptor recognizing cytosolic DNA, in macrophages might be associated with rabies (an RNA virus) through mitochondrial damage. A similar mortality rate was observed between cGAS-deficient (cGAS-/-) and wild-type (WT) mice post-CVS-11 strain injection. However, 2 out of 12 cGAS-/- mice (but not WT) survived for 15 days post-injection. At 7 days post-infection, less severe brain inflammation in cGAS-/- mice was demonstrated by the viral abundance in the hippocampus, the expression of proinflammatory genes (TNF-α and IL-1β), and the Evans blue dye assay (blood–brain barrier defect) with the presence of higher anti-inflammatory genes (TGF-β and arginase-1). Fecal Proteobacteria was more prominent in the infected WT mice, while serum cytokines (TNF-α and IL-1β) were similar in both mouse strains. There were less prominent responses against the rabies virus in cGAS-/- macrophages than in WT cells, as indicated by supernatant IL-6 and the gene expression of TLR-3, RIG-1, MDA-5, and iNOS. On the other hand, mitochondrial injury and cGAS activation were more prominent in WT macrophages over cGAS-/- cells, as indicated by cGAS expression, supernatant cGAMP (a secondary messenger of cGAS), and mitochondrial oxidative stress (MitoSox) together with a decrease in mitochondrial DNA and maximal respiration (extracellular flux analysis). In conclusion, (i) rabies-damaged mitochondria led to cGAS activation that was less severe in cGAS-/- than in WT, (ii) rabies-induced dysbiosis was demonstrated, and (iii) cGAS manipulation and gut–brain axis-associated inflammation warrants further investigation. Full article

Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application of therapeutic fever to ALS using Computerized Brain-Guided Intelligent Thermofebrile Therapy (CBIT²). This fully noninvasive treatment, delivered through an FDA-approved computerized platform, digitally reengineers the 1927 Nobel Prize-recognized malarial fever therapy into a modern treatment guided by the Brain–Eyelid Thermoregulatory Tunnel. CBIT² induces therapeutic fever through synchronized hypothalamic feedback, activating heat shock proteins, which are known to restore proteostasis and neuronal function. Case presentation: A 56-year-old woman was diagnosed with progressive ALS at the Mayo Clinic, with electromyography (EMG) demonstrating fibrillation and fasciculation indicative of denervation corroborated by neurological and MRI findings; the patient was informed that she had an expected survival of three to five years. A neurologist from Northwestern University confirmed the diagnosis and thus maintained the patient on FDA-approved ALS drugs (riluzole and edaravone). Her condition rapidly worsened despite pharmacological treatment, and she underwent CBIT², resulting in (i) electrophysiological reversal with complete disappearance of denervation; (ii) biomarker correction, including reductions in neurofilament and homocysteine, IL-10 normalization (previously linked to mortality), and robust HSP70 induction; (iii) restoration of gait, swallowing, respiration, speech, and cognition; (iv) reconstitution of tongue structure; and (v) return to complex motor tasks, including golf, pickleball, and swimming. Discussion: This case provides the first documented evidence that ALS can be reversed through digitally reengineered fever therapy aligned with thermoregulation, which induces heat shock response and upregulates heat shock proteins, resulting in the patient no longer meeting diagnostic criteria for ALS and discontinuation of ALS-specific medications. Beyond ALS, shared protein-misfolding pathology suggests that CBIT² may extend to Alzheimer’s, Parkinson’s, and related disorders. By modernizing this Nobel Prize-recognized therapeutic principle with computerized precision, CBIT² establishes a framework for large-scale clinical trials. A century after fever therapy restored lost brain function and so decisively reversed dementia paralytica such that it earned the 1927 Nobel Prize in Medicine, CBIT² now safely harnesses the therapeutic power of fever through noninvasive, intelligent, brain-guided thermal modulation. Amid a global brain health crisis, fever-based therapies may offer a path to preserve thought, memory, movement, and independence for the more than one-third of humanity currently affected by neurological disorders. Full article

Background/Objectives: Numerous studies have demonstrated that dietary plant-derived polyphenols suppress signaling and metabolic pathways in various malignancies, including neuroblastoma. In the present study, we compared the inhibitory activities of selected polyphenols and their combinations on key metabolic and signaling pathways in two human neuroblastoma cell lines and two noncancerous cell lines—mesenchymal stem cells (MSCs). Methods: The influence of polyphenols on neuroblastoma cells and MSCs were studied via an MTT-assay, cell cycle analysis, and an apoptosis assay (flow cytometry). Chou-Talalay algorithms were used to quantify drug interactions. SeaHorse energy profiling was applied to study energy metabolism. The influence of the compounds on metabolic enzymes and signaling pathways was examined using immunoblotting. Total protein biosynthesis was assessed using o-propargyl-puromycin labeling (flow cytometry). Results: While most of the studied polyphenols displayed a more significant inhibitory effect on neuroblastoma cells than on mesenchymal stem cells (MSCs), we found that the combinations of curcumin and quercetin (CQ) and curcumin, quercetin, and resveratrol (CQR) were significantly superior to the individual compounds. These combinations displayed synergistic effects and inhibited the cell cycle while inducing apoptosis. The CQ and CQR combinations effectively suppressed metabolic reprogramming by downregulating key enzymes of glycolysis, respiration, one-carbon metabolism, glutaminolysis, and fatty acid biosynthesis, as well as N-Myc and c-Myc, which are master regulators of metabolic processes. Furthermore, CQ and CQR inhibited AKT/mTOR, MAPK/ERK, and WNT/β-catenin signaling pathways and total protein biosynthesis and sensitized malignant cells to doxorubicin. Conclusions: Polyphenol combinations exert multifaceted inhibitory effects on metabolic rewiring and signaling networks in neuroblastoma cells. Full article

In eutrophic shallow lakes, dissolved oxygen (DO) exhibits significant temporal variations, regulated by the combined effects of photosynthesis and water temperature (WT). High-frequency monitoring enables a detailed capture of DO diel cycles, providing a more comprehensive understanding of the dynamic changes within lake ecosystems. This study involved high-frequency (10 min intervals) in situ monitoring of DO over a three-year period (2020–2022) in the littoral zone of Taihu Lake, China. Random forest regression analysis identified WT, photosynthetically active radiation (PAR), and relative humidity (RH) as the three most influential variables governing DO dynamics. The relative importance of these factors varied seasonally (0.117–0.392), with PAR dominating in summer (0.383), whereas WT had the highest importance in other seasons (0.312–0.392). Cusum analysis further revealed that the DO-WT relationship changed from a dome-shaped pattern in spring, autumn, and winter to a bowl-shaped pattern in summer, indicating that thermal stratification intensified oxygen gradients. In addition, the majority of DO recovery occurred in the late afternoon during summer, suggesting that severe oxygen consumption delayed the daytime accumulation of DO. Our findings emphasize the critical roles of photosynthesis, respiration, and abiotic factors in shaping DO dynamics. This research enhances our understanding of DO fluctuations in eutrophic shallow lakes and provides valuable insights for ecosystem management, supporting the development of effective strategies to prevent and mitigate hypoxia. Full article

The synergistic effects of stratospheric ozone depletion and climate change are intensifying surface ultraviolet-B (UVB) radiation, posing a severe threat to amphibians—one of the most endangered vertebrate groups globally. Xenopus laevis, with its cutaneous respiration and limited photoprotective mechanisms, exhibits high sensitivity to UVB, making it a suitable model for ecotoxicological studies. While UVB is known to cause DNA damage, immune suppression, and microbial dysbiosis, its mechanisms in multi-organ interactions, dose–response thresholds, and host–microbiome regulatory networks remain poorly understood. This study employed a gradient UVB exposure regime integrated with histopathology, oxidative stress assays, and 16S rRNA sequencing to systematically evaluate the effects of UVB on (1) cascade damage across skin, liver, and intestinal barriers; (2) immune cell distribution; (3) redox dynamics; and (4) microbial community structure and function. Our findings demonstrate that low-dose UVB activated compensatory antioxidant defenses without structural disruption, whereas exposure beyond a critical threshold induced nonlinear redox collapse, microbial dysbiosis, and multi-organ barrier failure, collectively exacerbating ecological adaptation risks. These results reveal a cross-scale mechanism by which UVB impairs amphibian health via disruption of host–microbe homeostasis, providing a conceptual and empirical framework for assessing species vulnerability under ongoing climate change. Full article

Tuberculosis continues to represent a major occupational risk in healthcare environments, particularly for healthcare workers who have persistent contact with patients who may be infectious. Despite the high occupational burden of tuberculosis among healthcare workers, there remains a lack of focused reviews that comprehensively evaluate preventive interventions across all levels of prevention within healthcare settings. In this literature review, effective preventive interventions relevant to tuberculosis transmission have been examined. Primary preventive interventions seek to diminish exposure through protective interventions such as respirators, improvements in ventilation systems, and implementation of educational programs regarding infection control protocols. Secondary preventive interventions target early diagnosis and routine screening with efforts to detect cases and latent infections early, before they progress to active disease. Enhancements in diagnostic technology have improved both the accuracy and speed of detection, further aiding the efforts of controlling nosocomial transmission. Tertiary preventive interventions target enhancing compliance with treatment protocols, managing complications of active infection, and controlling resistant strains through individualized follow-up and interventions. Barriers like stigma and lack of resources, however, often impede such interventions’ effectiveness in many cases. This narrative literature review highlights the imperative for strengthened workplace policies, an expansion of educational programs, and continued research in new and emerging interventions like new vaccine and diagnostics technology development. All these factors aim to optimize intervention effectiveness for tuberculosis and protect the health and welfare of workers in the medical field. Full article

Maintaining an effective facial seal is critical for the performance of tight-fitting industrial respirators used in high-risk sectors such as mining, manufacturing, and construction. Traditional fit verification methods—Qualitative Fit Testing (QLFT) and Quantitative Fit Testing (QNFT)—are limited to periodic assessments and cannot detect fit degradation during active use. This study presents a real-time fit detection system based on embedded breath sensors and machine learning algorithms. A compact sensor module inside the respirator continuously measures pressure, temperature, and humidity, transmitting data via Bluetooth Low Energy (BLE) to a smartphone for on-device inference. This system functions as a multimodal biosensor: intra-mask pressure tracks flow-driven mechanical dynamics, while temperature and humidity capture the thermal–hygrometric signature of exhaled breath. Their cycle-synchronous patterns provide an indirect yet reliable readout of respirator–face sealing in real time. Data were collected from 20 healthy volunteers under fit and misfit conditions using OSHA-standardized procedures, generating over 10,000 labeled breathing cycles. Statistical features extracted from segmented signals were used to train Random Forest, Support Vector Machine (SVM), and XGBoost classifiers. Model development and validation were conducted using variable-size sliding windows depending on the person’s breathing cycles, k-fold cross-validation, and leave-one-subject-out (LOSO) evaluation. The best-performing models achieved F1 scores approaching or exceeding 95%. This approach enables continuous, non-invasive fit monitoring and real-time alerts during work shifts. Unlike conventional techniques, the system relies on internal physiological signals rather than external particle measurements, providing a scalable, cost-effective, and field-deployable solution to enhance occupational safety and regulatory compliance. Full article

The use of copper nanoparticles (CuNPs) seems to be an alternative therapeutic strategy for cancer therapy due to low-cost synthesis and anticancer activity. In this work, CuNPs’ effects were tested in various concentrations on two types of cells: mesenchymal stem cells (MSCs) and a breast cancer cell line, SKBR3. The concentrations (0.25 mM, 0.5 mM, 1 mM and 2 mM) were first tested on an impedance-based cytotoxicity assay and then used in further cellular metabolic assays. Next, several techniques were applied to test the chosen concentrations: assessment of apoptosis, intracellular reactive oxygen species (ROS) levels, oxidative stress-related gene expression, assessment of mitochondrial respiration and fatty acid methyl ester (FAME) profile evaluation. The higher CuNP concentrations tested on the SKBR3 cell line showed a dose-dependent decrease in the cell index. SKBR3 cells displayed increased CAT and SOD expression, revealed by strong dose-dependent fluorescence. Annexin/PI staining confirmed increased SKBR3 cell death induced by the higher doses of CuNPs. SKBR3 revealed higher baseline respiratory capacity compared to MSCs. Fatty acid methyl esters (FAMEs) are in higher abundance in MSCs compared to the SKBR3 cell line. The different metabolic response in the tested cells to the CuNPs’ presence could help establish a future personalized treatment for breast cancer patients. Full article

Efficient composting is essential for sustainable organic waste management, yet conventional monitoring approaches are limited by single-parameter measurements and delayed response. This study presents an integrated sensor–AI framework designed to capture the interaction between thermal, chemical, and environmental factors governing composting. A distributed in-pile sensor network continuously measured temperature, moisture, and pH, while ambient parameters and gaseous emissions (O₂, CO₂, CH₄) were recorded to validate process dynamics. Statistical analyses, including correlation and regression modeling, were applied to quantify parameter interdependencies and the influence of external conditions. Results showed strong positive associations between temperature, moisture, and CO₂, and an inverse relationship with O₂, indicating active microbial respiration and accelerated decomposition. The validated sensors maintained high accuracy (±0.5 °C, ±3%, ±0.1 pH units) and supported real-time feedback control, leading to improved nutrient enrichment (notably N, P, and K) in the final compost. The framework demonstrates a transition from static measurement to intelligent, feedback-driven management, providing a scalable and reliable platform for optimizing compost quality and advancing sustainable waste-to-resource applications. Full article

Background: Point mutations in mitochondrial DNA (mtDNA) cause a range of neurometabolic disorders that currently have no curative treatments. The m.8993T>G mutation in the Homo sapiens MT-ATP6 gene leads to neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) when heteroplasmy exceeds approximately 70%. Methods: We engineered a split DddA-derived cytosine base editor (DdCBE), each half fused to programmable TALE DNA-binding domains and a mitochondrial targeting sequence, to correct the m.8993T>G mutation in patient-derived induced pluripotent stem cells (iPSCs). Seven days after plasmid delivery, deep amplicon sequencing showed 35 ± 3% on-target C•G→T•A conversion at position 8993, reducing mutant heteroplasmy from 80 ± 2% to 45 ± 3% with less than 0.5% editing at ten predicted off-target loci. Results: Edited cells exhibited a 25% increase in basal oxygen consumption rate, a 50% improvement in ATP-linked respiration, and a 2.3-fold restoration of ATP synthase activity. Directed neural differentiation yielded 85 ± 2% Nestin-positive progenitors compared to 60 ± 2% in unedited controls. Conclusions: Edits remained stable over 30 days in culture. These results establish mitochondrial base editing as a precise and durable strategy to ameliorate biochemical and cellular defects in NARP patient cells. Full article

Diabetic retinopathy (DR), a major complication of diabetes, is driven by chronic inflammation in which retinal microglial cells play a central role. The Hippo pathway kinases NDR1/2 regulate macrophage function, but their role in microglia and DR remain unknown. This study investigates the function of the NDR2 kinase in microglial cells under high-glucose (HG) conditions. Using CRISPR-Cas9, we partially knocked out the Ndr2/Stk38l gene in BV-2 mouse microglial cells and analyzed metabolic activity, phagocytosis, migration, and cytokine release. We confirmed NDR2 expression in microglia and observed increased levels under HG, suggesting a role in hyperglycemia-induced stress. Ndr2/Stk38l (hereafter referred to as Ndr2) downregulation impaired mitochondrial respiration and reduced metabolic flexibility, indicating defective stress adaptation. Functionally, microglia with a partial downregulation of Ndr2 displayed reduced phagocytic and migratory capacity—both dependent on cytoskeletal dynamics. Moreover, Ndr2 downregulation altered the secretory profile, elevating pro-inflammatory cytokines (IL-6, TNF, IL-17, IL-12p70) even under normal glucose levels. These findings identify NDR2 protein kinase as a key regulator of microglial metabolism and inflammatory behavior under diabetic conditions. By modulating immune and metabolic responses, NDR2 may contribute to the neuroinflammatory processes underlying DR. Targeting NDR2 function in microglia may offer novel therapeutic strategies to mitigate retinal inflammation and progression of DR. Full article

Monitoring electrocardiogram (ECG) and respiration continuously and non-invasively is essential for managing cardiopulmonary health. An effective wearable device can be used to regularly monitor key vitals, reducing the need for clinical visits. In this work, we propose a custom device for real-time continuous ECG by inkjet printed (IJP) dry electrodes and respiration monitoring by using a novel single 6-axis inertial measurement unit (IMU). The proposed system can extract the heart rate (HR) and respiration rate (RR) during static and dynamic postures. The respiration process implements a quaternion-based update and multiple filtering stages to estimate the signal. The custom device uses Bluetooth protocol to send the raw and processed data to a mobile application. The RR is investigated in stationary, i.e., sitting and standing, and dynamic, i.e., walking, running, and cycling, postures. The proposed device is evaluated with commercial Go Direct^® respiration belt from Vernier^® for RR and offers an overall accuracy of 99.3% and 98.6% for static and dynamic conditions, respectively. The wearable also offers 98.9% and 97.9% accuracy for HR measurements, respectively, in static and active postures when compared with the Kardia^® device. Furthermore, the device is assessed in an ambulatory monitoring setup in both indoor and outdoor environments. The low-power wearable consumes an average of only 7.4 mA of current during data processing. The device performs effectively and efficiently in both stationary and active states, offering a low complexity, portable solution for real-time monitoring. The proposed system can benefit from the continuous monitoring and early detection of pulmonary and cardio-respiratory health issues. Full article

Diabetes remains a global health challenge, characterized by persistent hyperglycemia and gradual depletion or impairment of pancreatic β-cells. Current treatments focus on managing glycemic control, but do not mitigate β-cell mass. Verapamil, an FDA-approved calcium channel blocker for hypertension, has shown potential therapeutic action towards β-cells in the context of diabetes. In this study, we investigated the cytoprotective and metabolic efficacy of verapamil on mouse-derived MIN6 β-cells under metabolic and diabetogenic stressors like high glucose, toxins, and an inflammatory cytokine cocktail, as well as investigated a zebrafish model. At safe, non-toxic doses, verapamil elevated the levels of cholecystokinin (CCK), an incretin associated with β-cell preservation and enhanced mitochondrial respiration. Notably, pretreatment and co-treatment of verapamil in the presence of stressors offered substantial protection and preserved mitochondrial function, whereas post-treatment effects were moderate and model dependent. In the zebrafish model, verapamil promoted β-cell recovery and regeneration before, during, and after targeted ablation. The drug seemed to work in several ways: inducing proliferation, reducing stress on β cells, boosting their energy production, and activating survival signals. Together, our data aligned with earlier human clinical trials showing that verapamil administration preserved β-cell mass and function in patients with recent-onset type 1 diabetes. The high efficacy, affordability, and broad mechanisms of action make verapamil a desirable therapeutic candidate for diabetes. Nevertheless, further mechanistic studies and long-term clinical trials are warranted to establish its utility in diabetes management. Full article

Peach trees (Prunus persica L. Batsch) produce climacteric fruits that are prone to senescence and softening after harvesting, and they are susceptible to external pathogens that cause rot and deterioration. This study investigated the effects of 1-methylcyclopropene (1-MCP) treatment combined with laser microporous film (LMF) packaging on the preservation of firm-fleshed honey peaches (‘Xiahui No. 8’ variety) during refrigerated storage at 5 ± 1 °C. The combined 1-MCP + LMF treatment significantly reduced respiration and rot rates and preserved the levels of reducing sugar and titratable acid after 35 days more effectively compared to the control and LMF groups. The 1-MCP + LMF packaging suppressed cell-wall-degrading enzymes (polygalacturonase, β-glucosidase, and cellulase) and maintained high contents of original pectin, cellulose, and hemicellulose. The treatment also reduced the accumulation of superoxide anions and malondialdehyde, maintained cell-wall structural integrity and fruit hardness, and delayed fruit browning by inhibiting polyphenol oxidase and peroxidase activity. Together, our results demonstrate that the combination of 1-MCP treatment and LMF packaging effectively preserved the hardness and quality of firm-fleshed honey peaches during refrigerated storage, extending their shelf life to 28 days while maintaining good sensory and nutritional qualities. Full article

Agriculture significantly contributes to greenhouse gas (GHG) emissions, yet fluxes from irrigated semi-arid systems remain poorly quantified. This study investigates CO₂, CH₄, N₂O, and NH₃ fluxes in a short-term lettuce experiment under semi-arid conditions. The objective was to quantify flux variability and identify key environmental and management drivers. High-frequency soil gas flux measurements were conducted under three treatments: irrigated soil (I), irrigated soil with plants (IP), and irrigated soil with plants plus NH₄NO₃ fertilizer (IPF). Environmental factors, including solar radiation, soil temperature, water-filled pore space, and relative projected leaf area, were monitored. A Random Forest model identified main flux determinants. Fluxes varied with plant function, growth, and fertilization. IP exhibited net CO₂ uptake through photosynthesis, whereas I and IPF showed net CO₂ emissions from soil respiration and fertilizer-induced disruption of plant function, respectively. CH₄ uptake occurred across treatments but decreased with plant presence. Fertilization in IPF triggered episodic N₂O (EF = 0.1%) and NH₃ emissions (EF = 0.97%) linked to nitrogen input. Vegetated semi-arid soils can act as CO₂ sinks when nitrogen is optimally managed. Excess or poorly timed nitrogen delays CO₂ uptake and increases reactive nitrogen losses. Methanotrophic activity drives CH₄ dynamics and is influenced by plants and fertilization. Maintaining crop vigor and applying precision nitrogen management are essential to optimize productivity while mitigating GHG and NH₃ emissions in semi-arid lettuce cultivation. Full article