Current evidence of synaptic dysfunction after stroke: Cellular and molecular mechanisms.

BACKGROUND: Stroke is an acute cerebrovascular disease in which brain tissue is damaged due to sudden obstruction of blood flow to the brain or the rupture of blood vessels in the brain, which can prompt ischemic or hemorrhagic stroke. After stroke onset, ischemia, hypoxia, infiltration of blood components into the brain parenchyma, and lysed cell fragments, among other factors, invariably increase blood-brain barrier (BBB) permeability, the inflammatory response, and brain edema. These changes lead to neuronal cell death and synaptic dysfunction, the latter of which poses a significant challenge to stroke treatment. RESULTS: Synaptic dysfunction occurs in various ways after stroke and includes the following: damage to neuronal structures, accumulation of pathologic proteins in the cell body, decreased fluidity and release of synaptic vesicles, disruption of mitochondrial transport in synapses, activation of synaptic phagocytosis by microglia/macrophages and astrocytes, and a reduction in synapse formation. CONCLUSIONS: This review summarizes the cellular and molecular mechanisms related to synapses and the protective effects of drugs or compounds and rehabilitation therapy on synapses in stroke according to recent research. Such an exploration will help to elucidate the relationship between stroke and synaptic damage and provide new insights into protecting synapses and restoring neurologic function.

Boosting the Curie temperature of GaN monolayer through van der Waals heterostructures.

The pursuit of van der Waals (vdW) heterostructures with high Curie temperature and strong perpendicular magnetic anisotropy (PMA) is vital to the advancement of next generation spintronic devices. First-principles calculations are used to study the electronic structures and magnetic characteristics of GaN/VS2vdW heterostructure under biaxial strain and electrostatic doping. Our findings show that a ferromagnetic ground state with a remarkable Curie temperature (477 K), much above room temperature, exists in GaN/VS2vdW heterostructure and 100% spin polarization efficiency. Additionally, GaN/VS2vdW heterostructure still maintains PMA under biaxial strain, which is indispensable for high-density information storage. We further explore the electron, magnetic, and transport properties of VS2/GaN/VS2vdW sandwich heterostructure, where the magnetoresistivity can reach as high as 40%. Our research indicates that the heterostructure constructed by combining the ferromagnet VS2and the non-magnetic semiconductor GaN is a promising material for vdW spin valve devices at room temperature.

Packaged structure optimization for enhanced light extraction efficiency and reduced thermal resistance of ultraviolet B LEDs.

Ultraviolet B light-emitting diodes (UVB LEDs) hold promise in medical and agricultural applications. The commonly used sapphire substrate for their epitaxy growth possesses a high refractive index and excellent UV light absorption characteristics. However, this high refractive index can induce total internal reflection (TIR) within the substrate, leading to decreased Light Extraction Efficiency (LEE) due to light absorption within the material. In this study, UVB LED chips were detached from the sub-mount substrate and directly affixed onto an aluminum nitride (AlN) substrate with superior heat dissipation using a eutectic process. This was undertaken to diminish packaged thermal resistance (PTR). Simultaneously, optimization of the UVB LED packaging structure was employed to alleviate LEE losses caused by the TIR phenomenon, with the overarching goal of enhancin external quantum efficiency (EQE). The final experimental findings suggest that optimal LEE is achieved with packaging dimensions, including a length (ELL) of 2 mm, a width (ELW) of 1.62 mm, and a height (ELH) of 0.52 mm. At an input current of 200 mA, the output power reaches 50 mW, resulting in an EQE of 6.3%. Furthermore, the packaged thermal resistance from the chip to the substrate surface can be reduced to 4.615 K/W.

Full-angle chip scale package of mini LEDs with a V-shape packaging structure.

The light distribution of light-emitting diodes (LEDs) generally resembles that of a Lambertian light source. When used as large-area light sources, the light distribution angle of LEDs must be modified through secondary optics design to achieve uniformity and minimize the number of light sources. However, secondary optical components pose several challenges such as demanding alignment accuracy, material aging, detachment, and lower reliability. Therefore, this paper proposes a primary optical design approach to achieve full-angle emission in LEDs without the need for lenses. The design employs a flip-chip as the light source and incorporates a V-shaped packaged structure, including a white wall layer, optical structure layers, and a V-shaped diffuse structure. With this design, the LEDs achieve full-angle emission without relying on lenses. Our experimental results demonstrated a peak intensity angle of 77.7°, a 20.3% decrease in the intensity of the central point ratio, and a full width at half maximum (FWHM) of the light distribution of 175.5°. This design is particularly suitable for thin, large-area, and flexible backlight light sources. Moreover, the absence of secondary optical components allows for a thinner light source module.

A positive feedback inhibition of isocitrate dehydrogenase 3ß on paired-box gene 6 promotes Alzheimer-like pathology.

Impaired brain glucose metabolism is an early indicator of Alzheimer's disease (AD); however, the fundamental mechanism is unknown. In this study, we found a substantial decline in isocitrate dehydrogenase 3ß (IDH3ß) levels, a critical tricarboxylic acid cycle enzyme, in AD patients and AD-transgenic mice's brains. Further investigations demonstrated that the knockdown of IDH3ß induced oxidation-phosphorylation uncoupling, leading to reduced energy metabolism and lactate accumulation. The resulting increased lactate, a source of lactyl, was found to promote histone lactylation, thereby enhancing the expression of paired-box gene 6 (PAX6). As an inhibitory transcription factor of IDH3ß, the elevated PAX6 in turn inhibited the expression of IDH3ß, leading to tau hyperphosphorylation, synapse impairment, and learning and memory deficits resembling those seen in AD. In AD-transgenic mice, upregulating IDH3ß and downregulating PAX6 were found to improve cognitive functioning and reverse AD-like pathologies. Collectively, our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3ß-lactate-PAX6-IDH3ß. Breaking this loop by upregulating IDH3ß or downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

BGP-15 alleviates LPS-induced depression-like behavior by promoting mitophagy.

The high prevalence of major depressive disorder (MDD) frequently imposes severe constraints on psychosocial functioning and detrimentally impacts overall well-being. Despite the growing interest in the hypothesis of mitochondrial dysfunction, the precise mechanistic underpinnings and therapeutic strategies remain unclear and require further investigation. In this study, an MDD model was established in mice using lipopolysaccharide (LPS). Our research findings demonstrated that LPS exposure induced depressive-like behaviors and disrupted mitophagy by diminishing the mitochondrial levels of PINK1/Parkin in the brains of mice. Furthermore, LPS exposure evoked the activation of the NLRP3 inflammasome, accompanied by a notable elevation in the concentrations of pro-inflammatory factors (TNF-α, IL-1ß, and IL-6). Additionally, neuronal apoptosis was stimulated through the JNK/p38 pathway. The administration of BGP-15 effectively nullified the impact of LPS, corresponding to the amelioration of depressive-like phenotypes and restoration of mitophagy, prevention of neuronal injury and inflammation, and suppression of reactive oxygen species (ROS)-mediated NLRP3 inflammasome activation. Furthermore, we elucidated the involvement of mitophagy in BGP-15-attenuated depressive-like behaviors using the inhibitors targeting autophagy (3-MA) and mitophagy (Mdivi-1). Notably, these inhibitors notably counteracted the antidepressant and anti-inflammatory effects exerted by BGP-15. Based on the research findings, it can be inferred that the antidepressant properties of BGP-15 in LPS-induced depressive-like behaviors could potentially be attributed to the involvement of the mitophagy pathway. These findings offer a potential novel therapeutic strategy for managing MDD.

Monolithic Integration of GaN-Based Transistors and Micro-LED.

Micro-LED is considered an emerging display technology with significant potential for high resolution, brightness, and energy efficiency in display applications. However, its decreasing pixel size and complex manufacturing process create challenges for its integration with driving units. Recently, researchers have proposed various methods to achieve highly integrated micro-structures with driving unit. Researchers take advantage of the high performance of the transistors to achieve low power consumption, high current gain, and fast response frequency. This paper gives a review of recent studies on the new integration methods of micro-LEDs with different types of transistors, including the integration with BJT, HEMT, TFT, and MOSFET.

Wide heart-shaped mini-LEDs without a second lens as a large area, ultra-high luminance, and flat light source.

In recent years, the demand for outdoor advertising and industrial display applications has been steadily increasing. Outdoor environments require higher brightness levels, thus requiring a reduction in the thermal resistance of the light source package. However, using secondary optical lenses to decrease the number of light sources is not a suitable solution because it may lead to the issue of lens detachment. Therefore, this paper proposes a packaging structure for wide heart-shaped angular light distribution mini-light emitting diodes (WHS mini-LEDs) with a primary optical design to enhance the light-emitting angle. The chips are directly bonded to an aluminum substrate using the metal eutectic process to minimize thermal resistance in the packaging. The experimental results indicated that the WHS mini-LED package had a total thermal resistance of 6.7 K/W. In a 55-inch backlight module (BLM), only 448 WHS mini-LEDs coupled with a quantum dot (QD) film and a brightness enhancement film (BEF) were required. Each lamp board was operated at 20.5 V and 5.5 A. The average luminance of the liquid crystal module (LCM) can reach 2234.2 cd/m2 with a uniformity of 90% and an NTSC value of 119.3%. This design offers a competitive advantage for outdoor advertising displays and industrial displays that require large areas, high brightness, and high color saturation.

Acetylated tau exacerbates apoptosis by disturbing mitochondrial dynamics in HEK293 cells.

An increase in tau acetylation at K274 and K281 and abnormal mitochondrial dynamics have been observed in the brains of Alzheimer's disease (AD) patients. Here, we constructed three types of tau plasmids, TauKQ (acetylated tau mutant, by mutating its K274/K281 into glutamine to mimic disease-associated lysine acetylation), TauKR (non-acetylated tau mutant, by mutating its K274/K281 into arginine), and TauWT (wild-type human full-length tau). By transfecting these tau plasmids in HEK293 cells, we found that TauWT and TauKR induced mitochondrial fusion by increasing the level of mitochondrial fusion proteins. Conversely, TauKQ induced mitochondrial fission by reducing mitochondrial fusion proteins, exacerbating mitochondrial dysfunction and apoptosis. BGP-15 ameliorated TauKQ-induced mitochondrial dysfunction and apoptosis by improving mitochondrial dynamics. Our findings suggest that acetylation of K274/281 represents an important post-translational modification site regulating mitochondrial dynamics, and that BGP-15 holds potential as a therapeutic agent for mitochondria-associated diseases such as AD.

High-sensitivity flip chip blue Mini-LEDs miniaturized optical instrument for non-invasive glucose detection.

The colorimetric detection of glucose typically involves a peroxidase reaction producing a color, which is then recorded and analyzed. However, enzyme detection has difficulties with purification and storage. In addition, replacing enzyme detection with chemical methods involves time-consuming steps such as centrifugation and purification and the optical instruments used for colorimetric detection are often bulky and not portable. In this study, ammonium metavanadate and sulfuric acid were used to prepare the detection solution instead of peroxidase to produce color. We also analyzed the effect of different concentrations of detection solution on absorbance sensitivity. Finally, a flip chip blue Mini-LEDs miniaturized optical instrument (FC blue Mini-LEDs MOI) was designed for glucose detection using optics fiber, collimating lenses, a miniaturized spectrometer, and an FC Blue Mini-LEDs with a center wavelength of 459 nm. While detecting glucose solutions in the concentration range of 0.1-10 mM by the developed MOI, the regression equation of y = 0.0941x + 0.1341, R2 of 0.9744, the limit of detection was 2.15 mM, and the limit of quantification was 7.163 mM. Furthermore, the preparation of the detection solution only takes 10 min, and the absorbance sensitivity of the optimized detection solution could be increased by 2.3 times. The detection solution remained stable with only a 0.6% decrease in absorbance compared to the original after storing it in a refrigerated environment at 3 °C for 14 days. The method proposed in this study for detecting glucose using FC blue light Mini-LEDs MOI reduces the use of peroxidase. In addition, it has a wide detection range that includes blood as well as non-invasive saliva and tear fluids, providing patients with a miniaturized, highly sensitive, and quantifiable glucose detection system.

Spectral analysis with highly collimated mini-LEDs as light sources for quantitative detection of direct bilirubin.

Because the human eye cannot visually detect the results of direct bilirubin test papers accurately and quantitatively, this study proposes four different highly collimated mini light-emitting diodes (HC mini-LEDs) as light sources for detection. First, different concentrations of bilirubin were oxidized to biliverdin by FeCl3 on the test paper, and pictures were obtained with a smartphone. Next, the red, green, and blue (RGB) channels of the pictures were separated to average grayscale values, and their linear relationship with the direct bilirubin concentration was analyzed to detect bilirubin on the test paper noninvasively and quantitatively. The experimental results showed that when green HC mini-LEDs were used as the light sources and image analysis was performed using the G channel, for a direct bilirubin concentration range of 0.1-2 mg/dL, the G channel determination coefficient (R2) reached 0.9523 and limit of detection was 0.459 mg/dL. The detection method proposed herein has advantages such as rapid analysis, noninvasive detection, and digitization according to RGB grayscale changes in the images of the detection test paper.

Investigation of highly reflective p-electrodes for AlGaN-based deep-ultraviolet light-emitting diodes.

We proposed a "Ni sacrifice" method to fabricate Al-based highly reflective p-electrode in the ultraviolet spectral region for AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs). The "Ni sacrifice" p-electrode could have a high optical reflectivity of around 90% at the DUV spectral region below 300 nm. Compared to Ni/Au, indium tin oxide (ITO), and Pd p-contacts, the "Ni sacrifice" led to a higher resistivity of p-contacts and a slightly higher operated voltage of the DUV-LEDs (within 0.6 V at 20 mA). Although the electrical performance was degraded slightly, the light output power and external quantum efficiency of the DUV-LEDs could be improved by utilizing the "Ni sacrifice" p-electrode. Besides, we introduced a grid of vias in the device mesa and reduced the diameter of the vias to achieve an enhanced peak external quantum efficiency (EQE) up to 1.73%. And the wall-plug efficiency (WPE) of DUV-LEDs with a "Ni sacrifice" p-electrode was higher than that of Ni/Au p-electrode DUV-LEDs at low currents. These results highlight the great potential of the proposed "Ni sacrifice" reflective p-electrode for use in DUV-LEDs.

GaN/Ga2O3 avalanche photodiodes with separate absorption and multiplication structure.

This article proposes a new, to the best of our knowledge, separate absorption and multiplication (SAM) APD based on GaN/ß-Ga2O3 heterojunction with high gains. The proposed APD achieved a high gain of 1.93 × 104. We further optimized the electric field distribution by simulating different doping concentrations and thicknesses of the transition region, resulting in the higher avalanche gain of the device. Furthermore, we designed a GaN/ß-Ga2O3 heterojunction instead of the single Ga2O3 homogeneous layer as the multiplication region. Owing to the higher hole ionization coefficient, the device offers up to a 120% improvement in avalanche gain reach to 4.24 × 104. We subsequently clearly elaborated on the working principle and gain mechanism of GaN/ß-Ga2O3 SAM APD. The proposed structure is anticipated to provide significant guidance for ultraweak ultraviolet light detection.

Deformable Catalytic Material Derived from Mechanical Flexibility for Hydrogen Evolution Reaction.

Deformable catalytic material with excellent flexible structure is a new type of catalyst that has been applied in various chemical reactions, especially electrocatalytic hydrogen evolution reaction (HER). In recent years, deformable catalysts for HER have made great progress and would become a research hotspot. The catalytic activities of deformable catalysts could be adjustable by the strain engineering and surface reconfiguration. The surface curvature of flexible catalytic materials is closely related to the electrocatalytic HER properties. Here, firstly, we systematically summarized self-adaptive catalytic performance of deformable catalysts and various micro-nanostructures evolution in catalytic HER process. Secondly, a series of strategies to design highly active catalysts based on the mechanical flexibility of low-dimensional nanomaterials were summarized. Last but not least, we presented the challenges and prospects of the study of flexible and deformable micro-nanostructures of electrocatalysts, which would further deepen the understanding of catalytic mechanisms of deformable HER catalyst.

Revisiting mitogenome evolution in Medusozoa with eight new mitochondrial genomes.

Mitogenomics has improved our understanding of medusozoan phylogeny. However, sequenced medusozoan mitogenomes remain scarce, and Medusozoa phylogeny studies often analyze mitogenomic sequences without incorporating mitogenome rearrangements. To better understand medusozoan evolution, we analyzed Medusozoa mitogenome phylogeny by sequencing and assembling eight mitogenomes from three classes (Cubozoa, Hydrozoa, and Scyphozoa). We reconstructed the mitogenome phylogeny using these mitogenomes and 84 other existing cnidarian mitogenomes to study mitochondrial gene rearrangements. All reconstructed mitogenomes had 13 mitochondrial protein-coding genes and two ribosomal genes typical for Medusozoa. Non-cubozoan mitogenomes were all linear and had typical gene orders, while arrangement of genes in the fragmented Cubozoa (Morbakka sp.) mitogenome differed from other Cubozoa mitogenomes. Gene order comparisons and ancestral state reconstruction suggest minimal rearrangements within medusozoan classes except for Hydrozoa. Our findings support a staurozoan ancestral medusozoan gene order, expand the pool of available medusozoan mitogenomes, and enhance our understanding of medusozoan phylogenetic relationships.

Cooperative motility, force generation and mechanosensing in a foraging non-photosynthetic diatom.

Diatoms are ancestrally photosynthetic microalgae. However, some underwent a major evolutionary transition, losing photosynthesis to become obligate heterotrophs. The molecular and physiological basis for this transition is unclear. Here, we isolate and characterize new strains of non-photosynthetic diatoms from the coastal waters of Singapore. These diatoms occupy diverse ecological niches and display glucose-mediated catabolite repression, a classical feature of bacterial and fungal heterotrophs. Live-cell imaging reveals deposition of secreted extracellular polymeric substance (EPS). Diatoms moving on pre-existing EPS trails (runners) move faster than those laying new trails (blazers). This leads to cell-to-cell coupling where runners can push blazers to make them move faster. Calibrated micropipettes measure substantial single-cell pushing forces, which are consistent with high-order myosin motor cooperativity. Collisions that impede forward motion induce reversal, revealing navigation-related force sensing. Together, these data identify aspects of metabolism and motility that are likely to promote and underpin diatom heterotrophy.

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Acupuncture and moxibustion therapies are widely used in the field of anti-inflammation, but the dynamic characteristics of inflammatory response with time in the modern biological mechanism research has been ignored to some extent. Therefore, the body surface intervention system represented by acupuncture-moxibustion urgently needs to rebuild the research perspective oriented to the complex immune regulation model, and then to explore the opportunity of acupuncture-moxibustion anti-inflammatory intervention according to the dynamic change process of inflammatory response. Through comparative analysis on the ancient and modern acupuncture-moxibustion immune regulation, and starting from the construction of clinical body surface intervention system, we propose that grasping the appropriate "intervention opportunity" is an important entry point that cannot be ignored to effectively "pry" inflammatory response.

Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson's disease.

Introduction: Early diagnosis of Parkinson's disease (PD) remains challenging. It has been suggested that abnormal brain iron metabolism leads to excessive iron accumulation in PD, although the mechanism of iron deposition is not yet fully understood. Ferritin and transferrin receptor (TfR) are involved in iron metabolism, and the exosome pathway is one mechanism by which ferritin is transported and regulated. While the blood of healthy animals contains a plentiful supply of TfR-positive exosomes, no studies have examined ferritin and TfR in plasma neural-derived exosomes. Methods: Plasma exosomes were obtained from 43 patients with PD and 34 healthy controls. Neural-derived exosomes were isolated with anti-human L1CAM antibody immunoabsorption. Transmission electron microscopy and western blotting were used to identify the exosomes. ELISAs were used to quantify ferritin and TfR levels in plasma neural-derived exosomes of patients with PD and controls. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of ferritin and TfR. Independent predictors of the disease were identified using logistic regression models. Results: Neural-derived exosomes exhibited the typical exosomal morphology and expressed the specific exosome marker CD63. Ferritin and TfR levels in plasma neural-derived exosomes were significantly higher in patients with PD than controls (406.46 ± 241.86 vs. 245.62 ± 165.47 ng/µg, P = 0.001 and 1728.94 ± 766.71 vs. 1153.92 ± 539.30 ng/µg, P < 0.001, respectively). There were significant positive correlations between ferritin and TfR levels in plasma neural-derived exosomes in control group, PD group and all the individuals (rs = 0.744, 0.700, and 0.752, respectively). The level of TfR was independently associated with the disease (adjusted odds ratio 1.002; 95% CI 1.000-1.003). ROC performances of ferritin, TfR, and their combination were moderate (0.730, 0.812, and 0.808, respectively). However, no relationship was found between the biomarkers and disease progression. Conclusion: It is hypothesized that ferritin and TfR in plasma neural-derived exosomes may be potential biomarkers for PD, and that they may participate in the mechanism of excessive iron deposition in PD.

Video Scene Detection Using Transformer Encoding Linker Network (TELNet).

This paper introduces a transformer encoding linker network (TELNet) for automatically identifying scene boundaries in videos without prior knowledge of their structure. Videos consist of sequences of semantically related shots or chapters, and recognizing scene boundaries is crucial for various video processing tasks, including video summarization. TELNet utilizes a rolling window to scan through video shots, encoding their features extracted from a fine-tuned 3D CNN model (transformer encoder). By establishing links between video shots based on these encoded features (linker), TELNet efficiently identifies scene boundaries where consecutive shots lack links. TELNet was trained on multiple video scene detection datasets and demonstrated results comparable to other state-of-the-art models in standard settings. Notably, in cross-dataset evaluations, TELNet demonstrated significantly improved results (F-score). Furthermore, TELNet's computational complexity grows linearly with the number of shots, making it highly efficient in processing long videos.