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Molecular Neurodegeneration Jun 2024Aging significantly elevates the risk of developing neurodegenerative diseases. Neuroinflammation is a universal hallmark of neurodegeneration as well as normal brain...
BACKGROUND
Aging significantly elevates the risk of developing neurodegenerative diseases. Neuroinflammation is a universal hallmark of neurodegeneration as well as normal brain aging. Which branches of age-related neuroinflammation, and how they precondition the brain toward pathological progression, remain ill-understood. The presence of elevated type I interferon (IFN-I) has been documented in the aged brain, but its role in promoting degenerative processes, such as the loss of neurons in vulnerable regions, has not been studied in depth.
METHODS
To comprehend the scope of IFN-I activity in the aging brain, we surveyed IFN-I-responsive reporter mice at multiple ages. We also examined 5- and 24-month-old mice harboring selective ablation of Ifnar1 in microglia to observe the effects of manipulating this pathway during the aging process using bulk RNA sequencing and histological parameters.
RESULTS
We detected age-dependent IFN-I signal escalation in multiple brain cell types from various regions, especially in microglia. Selective ablation of Ifnar1 from microglia in aged mice significantly reduced overall brain IFN-I signature, dampened microglial reactivity, lessened neuronal loss, restored expression of key neuronal genes and pathways, and diminished the accumulation of lipofuscin, a core hallmark of cellular aging in the brain.
CONCLUSIONS
Overall, our study demonstrates pervasive IFN-I activity during normal mouse brain aging and reveals a pathogenic, pro-degenerative role played by microglial IFN-I signaling in perpetuating neuroinflammation, neuronal dysfunction, and molecular aggregation. These findings extend the understanding of a principal axis of age-related inflammation in the brain, one likely shared with multiple neurological disorders, and provide a rationale to modulate aberrant immune activation to mitigate neurodegenerative process at all stages.
Topics: Animals; Aging; Interferon Type I; Mice; Brain; Signal Transduction; Microglia; Receptor, Interferon alpha-beta; Neurons
PubMed: 38886816
DOI: 10.1186/s13024-024-00736-6 -
Chemosphere Jun 2024Anaerobic co-digestion (AcoD) of food waste (FW) and landfill leachate has shown promising results in enhancing the methane yield. However, leachate includes toxic and...
Anaerobic co-digestion (AcoD) of food waste (FW) and landfill leachate has shown promising results in enhancing the methane yield. However, leachate includes toxic and refractory compounds that may impact the decomposition process. In this research, co-digested leachate was pretreated using ultrasonication and alkalinization to manipulate its characteristics toward improved synergism with FW. Experimental optimization was conducted through biochemical methane potential (BMP) assays to identify the optimum operating conditions of the pretreatment methods. The study evaluated the synergistic effects of co-digestion with raw and pretreated leachate on enhancing the performance in terms of feedstock solubilization and methane production. The BMP test demonstrated that alkalinization and ultrasonication improved the total methane generation by 35% and 27%, respectively, yielding around 397 and 375 mL CH per g of volatile solids. Moreover, ultrasonication and alkalinization enhanced the synergistic effects by 28% and 36%, respectively, compared to co-digestion with untreated leachate. Optimization by response surface methodology revealed that maximum performance could be achieved with leachate sonication at 212 W for 37.5 min or augmenting 788 g NaOH per kg of volatile solids. Kinetic and statistical models were derived to simulate and assess the impacts of the pretreatment parameters on the AcoD process. The results indicated that the ultrasonication energy had a higher influence on total solubility and methane production than alkaline dosage. Additionally, energy efficiency analyses were performed to examine the overall viability of the examined management approach and found that alkalinization increased the net energy efficiency by 23%, whereas ultrasonication was inefficient within the examined laboratory conditions despite the improved performance. The findings support an integrated organic waste management system where separated FW is co-treated with landfill leachate.
PubMed: 38885770
DOI: 10.1016/j.chemosphere.2024.142634 -
Proceedings of the National Academy of... Jun 2024Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain...
Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain areas without invasive techniques. Here, we introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type-specific, spatially precise, and flexible neuromodulation approach in freely moving mice. AhSonogenetics utilizes wearable ultrasound devices manufactured using 3D-printed Airy-beam holographic metasurfaces. These devices are designed to manipulate neurons genetically engineered to express ultrasound-sensitive ion channels, enabling precise modulation of specific neuronal populations. By dynamically steering the focus of Airy beams through ultrasound frequency tuning, AhSonogenetics is capable of modulating neuronal populations within specific subregions of the striatum. One notable feature of AhSonogenetics is its ability to flexibly stimulate either the left or right striatum in a single mouse. This flexibility is achieved by simply switching the acoustic metasurface in the wearable ultrasound device, eliminating the need for multiple implants or interventions. AhSonogentocs also integrates seamlessly with in vivo calcium recording via fiber photometry, showcasing its compatibility with optical modalities without cross talk. Moreover, AhSonogenetics can generate double foci for bilateral stimulation and alleviate motor deficits in Parkinson's disease mice. This advancement is significant since many neurological disorders, including Parkinson's disease, involve dysfunction in multiple brain regions. By enabling precise and flexible cell type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders.
Topics: Animals; Holography; Mice; Neurons; Wearable Electronic Devices; Ultrasonic Waves; Corpus Striatum; Brain
PubMed: 38885384
DOI: 10.1073/pnas.2402200121 -
Biological Psychiatry Global Open... Jul 2024Clinical anxiety is a generalized state characterized by feelings of apprehensive expectation and is distinct from momentary responses such as fear or stress. In...
BACKGROUND
Clinical anxiety is a generalized state characterized by feelings of apprehensive expectation and is distinct from momentary responses such as fear or stress. In contrast, most laboratory tests of anxiety focus on acute responses to momentary stressors.
METHODS
Apprehensive expectation was induced by subjecting mice (for 18 days) to manipulations in which a running response (experiment 1) or a conditioned stimulus (experiment 2) were unpredictably paired with reward (food) or punishment (footshock). Before this treatment, the mice were tested in an open field and light/dark box to assess momentary responses that are asserted to reflect state anxiety. After treatment, the mice were assessed for state anxiety in an elevated plus maze, social interaction test, startle response test, intrusive object burying test, and stress-induced corticosterone elevations. In experiment 3, we treated mice similarly to experiment 1, but after mixed-valence training, some mice received either no additional training, additional mixed-valence training, or were shifted to consistent (predictable) reinforcement with food.
RESULTS
We consistently observed an increase in anxiety-like behaviors after the experience with mixed-valence unpredictable reinforcement. This generalized anxiety persisted for at least 4 weeks after the mixed-valence training and could be reversed if the mixed-valence training was followed by predictable reinforcement with food.
CONCLUSIONS
Results indicate that experience with unpredictable reward/punishment can induce a chronic state analogous to generalized anxiety that can be mitigated by exposure to stable, predictable conditions. This learned apprehension protocol provides a conceptually valid model for the study of the etiology and treatment of anxiety in laboratory animals.
PubMed: 38883866
DOI: 10.1016/j.bpsgos.2024.100318 -
Journal of Thoracic Disease May 2024Anesthesia remains challenging for bronchoscopic tracheobronchial surgeries (BTS) involving surgical manipulations for central airway obstruction within shared airways....
BACKGROUND
Anesthesia remains challenging for bronchoscopic tracheobronchial surgeries (BTS) involving surgical manipulations for central airway obstruction within shared airways. To provide complete airway use through intervention with spontaneous breathing without endotracheal tubes, monitored non-intubated anesthesia has been successfully applied with electroencephalogram-derived monitored total intravenous anesthesia. This study evaluated the feasibility and the outcomes of BTS with monitored non-intubated anesthesia. The factors associated with desaturation and complications were also analyzed.
METHODS
Data from patients receiving non-intubated BTS performed between October 2019 and August 2022 were retrospectively collected. Intraoperative results and postoperative outcomes were analyzed.
RESULTS
Data of 92 patients were collected. Supraglottic airways devices and high-flow nasal oxygen were used in 68 and 24 patients respectively. Surgery was successfully completed in 87 patients (94.6%), whereas three patients required conversion to intubation because of substantial bleeding. In total, 11% of patients experienced desaturation [oxygen saturation (SpO) <90%] for an average of 9 minutes. Unexpected admission to the intensive care unit (ICU) occurred in 12.2% (5/41) of patients from outpatient department and 7.8% (4/51) of hospitalization settings because of high-grade surgical bleeding. With comparable desaturation incidence, tracheal surgery had significantly longer desaturation times (14.5±6.9 min) than bronchial surgeries (5.8±2.6 min) did.
CONCLUSIONS
Monitored non-intubated anesthesia with spontaneous breathing is feasible for BTS, with high success rate, few complications, and rapid recovery. High-grade bleeding remains the most unpredictable risk for intraoperative desaturation and postoperative ICU admission, especially in tracheal obstruction cases.
PubMed: 38883685
DOI: 10.21037/jtd-23-1935 -
Cureus May 2024Nanotechnology enables precise manipulation of matter at the molecular level, with nanoparticles offering diverse applications in medicine and beyond. Green synthesis...
BACKGROUND
Nanotechnology enables precise manipulation of matter at the molecular level, with nanoparticles offering diverse applications in medicine and beyond. Green synthesis methods, utilizing natural sources like plant extracts, are favored for their eco-friendliness. Zinc oxide (ZnO) nanoparticles are recognized for their ability to combat microbes and reduce inflammation, which holds promise for biomedical applications. , renowned for its medicinal properties, warrants further exploration in oral health management due to its anti-inflammatory and antioxidant attributes.
AIM
The current study aimed to synthesize -mediated ZnO nanoparticles and to evaluate their anti-inflammatory and antioxidant activity.
MATERIALS AND METHODS
powder (1 g) was dissolved in distilled water (100 ml), heated at 60°C for 15-20 minutes, and filtered to obtain 20 ml extract. ZnO nanoparticles were synthesized by adding 0.594 g ZnO powder to 50 ml water, mixed with plant extract, and stirred for 72 hours, and the resulting solution was centrifuged. Nanoparticles were collected and analyzed for Fourier-transform infrared spectroscopy (FTIR) using Bruker's Alpha II FTIR spectrometer (Bruker, Billerica, Massachusetts, United States), antioxidant, and anti-inflammatory activities.
RESULTS
FTIR analysis revealed characteristic peaks indicative of functional groups present in -mediated ZnO nanoparticles, including O-H, N-O, C-O, C=C, and C≡C-H. Anti-inflammatory activity evaluation showed inhibition ranging from 48% to 89%, with the maximum inhibition at 50 μL concentration. Similarly, antioxidant activity ranged from 62% to 88%, with the maximum inhibition also seen at 50 μL concentration.
CONCLUSION
Both assays effectively showcased the superior anti-inflammatory and antioxidant activity of the -incorporated ZnO nanoparticles extract compared to the control. This suggests their potential as a viable therapeutic agent for further evaluation.
PubMed: 38883108
DOI: 10.7759/cureus.60407 -
Stem Cells International 2024Genetically modified intestinal organoids are being explored as potential surrogates of immortalized cell lines and gene-engineered animals. However, genetic...
Genetically modified intestinal organoids are being explored as potential surrogates of immortalized cell lines and gene-engineered animals. However, genetic manipulation of intestinal organoids is time-consuming, and the efficiency is far beyond satisfactory. To ensure the yield of the genetically modified organoids, large quantity of starting materials is required, and the procedure usually takes more than 10 days. Two major obstacles that restrict the genetic delivery efficiency are the three-dimensional culture condition and that the genetic delivery is carried out in cell suspensions. In the present study, we introduce a novel highly efficient strategy for building genetically modified intestinal organoids in which genetic delivery was performed in freshly established monolayer primary intestinal epithelial cells under two-dimensional conditions and subsequentially transformed into three-dimensional organoids. The total procedure can be finished within 10 hr while displaying much higher efficiency than the traditional methods. Furthermore, this strategy allowed for the selection of transgenic cells in monolayer conditions before establishing high-purity genetically modified intestinal organoids.
PubMed: 38882597
DOI: 10.1155/2024/2005845 -
Arthroplasty Today Jun 2024Stiffness is a common complication following total knee arthroplasty. Manipulation under anesthesia (MUA) is an intervention that can potentially improve range of motion...
BACKGROUND
Stiffness is a common complication following total knee arthroplasty. Manipulation under anesthesia (MUA) is an intervention that can potentially improve range of motion (ROM). Continuous passive motion (CPM) therapy has been utilized to enhance post-MUA ROM, but its effectiveness remains debated. This study assesses whether CPM therapy after MUA results in superior ROM outcomes compared to MUA alone.
METHODS
A retrospective analysis included patients undergoing MUA for stiff primary total knee arthroplasty between 2017 and 2022. Demographics and ROM data were collected. Patients were in 2 groups: those who received inpatient CPM post-MUA and those who received day-case MUA alone. Complications and further interventions were noted.
RESULTS
Of 126 patients, 39 underwent MUA only (day-case group), and 87 received CPM and MUA (inpatient group). Mean preoperative ROM was 69.4° (standard deviation [SD]:18.0°) and 73.9° (SD: 18.1°) for inpatient and day-case groups, respectively. Mean post-MUA ROM improved by 39.4° (SD: 17.7°) and 25.5° (SD: 11.1°) inpatient groups and day-case, respectively. The mean percentage of ROM gained at MUA maintained at final follow-up was 63.7% (40.8%) and 67.0% (47.5%) inpatient and day-case groups, respectively.
CONCLUSIONS
This study found no advantage in the routine use of CPM post-MUA for stiff total knee replacement patients, suggesting it may not provide sustained ROM improvements compared to MUA alone. Cost-effectiveness and patient selection merit further investigation.
PubMed: 38882466
DOI: 10.1016/j.artd.2024.101397 -
Journal of Neuroscience Methods Jun 2024Significant research has been devoted to developing noninvasive approaches to neuromonitoring. Clinical validation of such approaches is often limited, with minimal data...
BACKGROUND
Significant research has been devoted to developing noninvasive approaches to neuromonitoring. Clinical validation of such approaches is often limited, with minimal data available in the clinically relevant elevated ICP range.
NEW METHOD
To allow ultrasound-guided placement of an intraventricular catheter and to perform simultaneous long-duration ICP and ultrasound recordings of cerebral blood flow, we developed a large unilateral craniectomy in a swine model. We also used a microprocessor-controlled actuator for intraventricular saline infusion to reliably and reversibly manipulate ICP according to pre-determined profiles.
RESULTS
The model was reproducible, resulting in over 80hours of high-fidelity, multi-parameter physiological waveform recordings in twelve animals, with ICP ranging from 2 to 78mmHg. ICP elevations were reversible and reproducible according to two predetermined profiles: a stepwise elevation up to an ICP of 30 to 35mmHg and return to normotension, and a clinically significant plateau wave. Finally, ICP was elevated to extreme levels of greater than 60mmHg, simulating extreme clinical emergency.
COMPARISON WITH EXISTING METHODS
Existing methods for ICP monitoring in large animals typically relied on burr-hole approaches for catheter placement. Accurate catheter placement can be difficult in pigs, given the thickness of their skull. Additionally, ultrasound is significantly attenuated by the skull. The open cranium model overcomes these limitations.
CONCLUSIONS
The hemicraniectomy model allowed for verified placement of the intraventricular catheter, and reversible and reliable ICP manipulation over a wide range. The large dural window additionally allowed for long-duration recording of cerebral blood flow velocity from the middle cerebral artery.
PubMed: 38880344
DOI: 10.1016/j.jneumeth.2024.110196 -
Neuroscience and Biobehavioral Reviews Jun 2024Accounts of shared representations posit that the experience of pain and pain empathy rely on similar neural mechanisms. Experimental research employing novel analytical... (Review)
Review
Accounts of shared representations posit that the experience of pain and pain empathy rely on similar neural mechanisms. Experimental research employing novel analytical and methodological approaches has made significant advances in both the identification and targeted manipulation of such shared experiences and their neural underpinnings. This revealed that painful experiences can be shared on different representational levels, from pain-specific to domain-general features, such as negative affect and its regulation. In view of direct links between such representations and social behaviors such as prosocial behavior, conditions characterized by aberrant pain processing may come along with heavy impairments in the social domain, depending on the affected representational level. This has wide potential implications in light of the high prevalence of pain-related clinical conditions, their management, and the overuse of pain medication. In this review and opinion paper, we aim to chart the path toward a better understanding of the link between shared affect and prosocial behavior.
PubMed: 38879099
DOI: 10.1016/j.neubiorev.2024.105769