Experimental evidence to understand mechanical causes of retinal detachment following blunt trauma.

PURPOSE: This study aimed to perform an in vitro experiment to simulate retinal detachment caused by blunt impact, and provide experimental evidence to understand mechanical causes of traumatic retinal detachment. METHODS: The experiment was conducted on twenty-two fresh porcine eyes using a bespoke pendulum testing device at two energy levels (0.1J for low energy and 1.0J for high energy). We examined dynamic forces and mechanical responses to the impact, including global deformations, intraocular pressure changes and the energy absorption. Another set of twenty-two eyes underwent pathological examination immediately after being subjected to blunt impact. Twelve additional intact eyes were examined as controls. All pathological sections were scored to indicate whether retinal detachment had occurred. RESULTS: A dynamic variation in intraocular pressure was detected following impact and exhibited an approximate sinusoidal oscillation-attenuation profile. The peaks of impact force were 12.9 ± 1.9 N at low-energy level and 34.8 ± 9.8 N at high-energy level, showing a significant difference (p < 0.001). The positive and negative peaks of intraocular pressure were 149.4 ± 18.9 kPa and -10.9 ± 7.2 kPa at low-energy level, and 274.5 ± 55.2 kPa and -35.7 ± 23.7 kPa at high-energy level, showing significant differences (p < 0.001 for both levels). Retinal detachments were observed in damaged eyes while few detachments were found in control eyes. The occurrence rate of retinal detachment differed significantly (p < 0.05) between the high- and low-energy impact groups. CONCLUSIONS: This study provided experimental evidence that shockwaves produced by blunt trauma break the force equilibrium and lead to the oscillation and negative pressure, which mainly contribute to traumatic retinal detachment.

YTHDF2 in dentate gyrus is the m6A reader mediating m6A modification in hippocampus-dependent learning and memory.

N6-methyladenosine (m6A) has been demonstrated to regulate learning and memory in mice. To investigate the mechanism by which m6A modification exerts its function through its reader proteins in the hippocampus, as well as to unveil the specific subregions of the hippocampus that are crucial for memory formation, we generated dentate gyrus (DG)-, CA3-, and CA1-specific Ythdf1 and Ythdf2 conditional knockout (cKO) mice, respectively. Surprisingly, we found that only the DG-specific Ythdf2 cKO mice displayed impaired memory formation, which is inconsistent with the previous report showing that YTHDF1 was involved in this process. YTHDF2 controls the stability of its target transcripts which encode proteins that regulate the elongation of mossy fibers (MF), the axons of DG granule cells. DG-specific Ythdf2 ablation caused MF overgrowth and impairment of the MF-CA3 excitatory synapse development and transmission in the stratum lucidum. Thus, this study identifies the m6A reader YTHDF2 in dentate gyrus as the only regulator that mediates m6A modification in hippocampus-dependent learning and memory.

Immunomodulatory effects of vinegar-egg juice: Potential pharmacological effects of a traditional Chinese food remedy?

Thousands of years of historical practice have proven that the ancient Chinese food, vinegar-egg juice, has immune-boosting effects with the presence of many nutritional factors. However, its mechanism of action in the body remains unclear. In this research project, vinegar-egg juice was chosen to analyze its immune-enhancing effects on mice. The immune enhancing effects of egg, vinegar and vinegar egg juice on lymphocytes of mouse spleen were compared. The effects on immune function of mice were analyzed by studying the organ index, natural killer(NK) cell activity, lymphocyte transformation function and cytokine changes in immune organs after treatment with vinegar-egg juice. The mechanism of immune enhancement was speculated by analyzing the changes of total IKKα/ß/IκBα/NF-κB and its phosphorylated protein kinase by Western blot. Experiments have shown that vinegar and eggs have less immune regulation than vinegar-egg juice. Vinegar-egg juice can regulate the cellular and humoral immunity of spleen lymphocytes, increase the phosphorylated kinases of IKKα/ß, reduce the total protein expression of IκBα, and activate the signaling pathway of IKK/IκB/NF-κB. In addition, compared with the control group, vinegar-egg juice reduced the Firmicutes/Bacteroidetes ratio and increased the relative abundance of beneficial bacteria. Furthermore, vinegar-egg juice can raise phosphatidylserine (PS) and serotonin (5-HT) levels in the body. The results showed that the vinegar-egg juice had obvious immunomodulatory activity. It was speculated that the intake of vinegar-egg juice can increase the activity of NK cells, T lymphocytes and B lymphocytes by increasing 5-HT levels, ultimately enhancing the body's immune function. PRACTICAL APPLICATIONS: In this work, we evaluated the immune regulation of vinegar, egg and vinegar-egg juice in mice. In addition, we investigated the effects of vinegar-egg juice on gut microbiota. And combined with the composition of the vinegar-egg juice, it was found that the intake of vinegar-egg juice could increase the activity of NK cells, T lymphocytes and B lymphocytes by increasing 5-HT levels, ultimately enhancing the body's immune function. On the basis of the results of this study, we recommend vinegar-egg juice can be a potential health food to resist the epidemic and improve autoimmunity in special times of the novel coronavirus outbreak.

The function of VAMP2 in mediating membrane fusion: An overview.

Vesicle-associated membrane protein 2 (VAMP2, also known as synaptobrevin-2), encoded by VAMP2 in humans, is a key component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. VAMP2 combined with syntaxin-1A (SYX-1A) and synaptosome-associated protein 25 (SNAP-25) produces a force that induces the formation of fusion pores, thereby mediating the fusion of synaptic vesicles and the release of neurotransmitters. VAMP2 is largely unstructured in the absence of interaction partners. Upon interaction with other SNAREs, the structure of VAMP2 stabilizes, resulting in the formation of four structural domains. In this review, we highlight the current knowledge of the roles of the VAMP2 domains and the interaction between VAMP2 and various fusion-related proteins in the presynaptic cytoplasm during the fusion process. Our summary will contribute to a better understanding of the roles of the VAMP2 protein in membrane fusion.

A simple indentation technique for identifying localized liquefaction of the vitreous body.

Identification of vitreous liquefaction (VL) is important for investigating some eye pathologies related to changes in the mechanical properties of the vitreous, such as posterior vitreous detachment or retinal detachment. However, because of the extremely high-water content, characterization of the structural and mechanical properties of the vitreous remains a challenge. In the current study, a simple indentation test was performed on the fresh vitreous, partially liquefied vitreous and water, using a mechanical testing machine with a high-precision load cell. Pressure loads on the indenter changing with time for different samples were obtained to characterize their mechanical properties. VL identification was achieved based on a comparison of relative differences in some typical mechanical parameters (e.g. the pressure at the moment of the insertion (P0), the pressure at the steady mechanical state (P∞) and the time when the pressure on the indenter declined to one half the initial value (t1/2)) between 1) partially liquefied vitreous and fresh vitreous samples and 2) partially liquefied vitreous and water samples. The results indicated that P0 of the partially liquefied vitreous was almost half that of fresh vitreous (p < 0.05) and approximately 1.5 times that of water (p < 0.05). t1/2 of the partially liquefied vitreous was approximately 1.4 times higher than that of fresh vitreous (p < 0.05) and approximately 80% of that of water (p < 0.05). It is concluded that P0 and t1/2 can be used as indicators to identify localized liquefaction of the vitreous.

Structure feature and antidepressant-like activity of a novel exopolysaccharide isolated from Marasmius androsaceus fermentation broth.

The structure and antidepressant like activity of MEPS2 extracted from Marasmius androsaceus subjected to submerged fermentation was systematically studied. MEPS2 is a pyranoid polysaccharide composed of glucose and arabinose, which have a molar ratio of 0.56:0.08. The molecular weight was 85,944 Da. The NMR spectrum suggested the extracted MEPS2 contained uronic acid, and the glucosyl linkage was in α form, in accordance with the analysis of FT-IR spectrum. MEPS2 can considerably enhance the levels of noradrenalin (NE) and dopamine (DA) by ELISA. In addition, western blotting results indicated that MEPS2 can enhance the expression levels of TH, D2DR, and CAMKII. Furthermore, we found that AMPT, raclopride, and prazosin blocked the immobility and time-reducing effect of MEPS2. Overall, the antidepressant-like effect of MEPS2 may be involved in catecholamine synthesis and release, and TH, D2DR and CAMKII play an important role in this process.

Mechanical Evaluation of Retinal Damage Associated With Blunt Craniomaxillofacial Trauma: A Simulation Analysis.

PURPOSE: To evaluate retinal damage as the result of craniomaxillofacial trauma and explain its pathogenic mechanism using finite element (FE) simulation. METHODS: Computed tomography (CT) images of an adult man were obtained to construct a FE skull model. A FE skin model was built to cover the outer surface of the skull model. A previously validated FE right eye model was symmetrically copied to create a FE left eye model, and both eye models were assembled to the skull model. An orbital fat model was developed to fill the space between the eye models and the skull model. Simulations of a ball-shaped object striking the frontal bone, temporal bone, brow, and cheekbones were performed, and the resulting absorption of the impact energy, intraocular pressure (IOP), and strains on the macula and ora serrata were analyzed to evaluate retinal injuries. RESULTS: Strain was concentrated in the macular regions (0.18 in average) of both eyes when the frontal bone was struck. The peak strain on the macula of the struck-side eye was higher than that of the other eye (>100%) when the temporal bone was struck, whereas there was little difference (<10%) between the two eyes when the brow and cheekbones were struck. Correlation analysis showed that the retinal strain time histories were highly correlated with the IOP time histories (r > 0.8 and P = 0.000 in all simulation cases). CONCLUSIONS: The risk of retinal damage is variable in craniomaxillofacial trauma depending on the struck region, and the damage is highly related to IOP variation caused by indirect blunt eye trauma. TRANSLATIONAL RELEVANCE: This finite element eye model allows us to evaluate and understand the indirect ocular injury mechanisms in craniomaxillofacial trauma for better clinical diagnosis and treatment.

Roles of afadin in functional differentiations of hippocampal mossy fiber synapse.

A hippocampal mossy fiber synapse has a complex structure and is implicated in learning and memory. In this synapse, the mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions and wrap around a multiply-branched spine, forming synaptic junctions. We have recently shown using transmission electron microscopy, immunoelectron microscopy and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities and the density of synaptic vesicles docked to active zones are decreased in the afadin-deficient synapse. We investigated here the roles of afadin in the functional differentiations of the mossy fiber synapse using the afadin-deficient mice. The electrophysiological studies showed that both the release probability of glutamate and the postsynaptic responsiveness to glutamate were markedly reduced, but not completely lost, in the afadin-deficient mossy fiber synapse, whereas neither long-term potentiation nor long-term depression was affected. These results indicate that afadin plays roles in the functional differentiations of the presynapse and the postsynapse of the hippocampal mossy fiber synapse.

[A simulation study with finite element model on the unequal loss of peripheral vision caused by acceleration].

An unequal loss of peripheral vision may happen with high sustaining multi-axis acceleration, leading to a great potential flight safety hazard. In the present research, finite element method was used to study the mechanism of unequal loss of peripheral vision. Firstly, a 3D geometric model of skull was developed based on the adult computer tomography (CT) images. The model of double eyes was created by mirroring with the previous right eye model. Then, the double-eye model was matched to the skull model, and fat was filled between eyeballs and skull. Acceleration loads of head-to-foot (G z), right-to-left (G y), chest-to-back (G x) and multi-axis directions were applied to the current model to simulate dynamic response of retina by explicit dynamics solution. The results showed that the relative strain of double eyes was 25.7% under multi-axis acceleration load. Moreover, the strain distributions showed a significant difference among acceleration loaded in different directions. It indicated that a finite element model of double eyes was an effective means to study the mechanism of an unequal loss of peripheral vision at sustaining high multi-axis acceleration.

Regulatory role of the cell adhesion molecule nectin-1 in GABAergic inhibitory synaptic transmission in the CA3 region of mouse hippocampus.

Proper operation of a neural circuit relies on both excitatory and inhibitory synapses. We previously showed that cell adhesion molecules nectin-1 and nectin-3 are localized at puncta adherentia junctions of the hippocampal mossy fiber glutamatergic excitatory synapses and that they do not regulate the excitatory synaptic transmission onto the CA3 pyramidal cells. We studied here the roles of these nectins in the GABAergic inhibitory synaptic transmission onto the CA3 pyramidal cells using nectin-1-deficient and nectin-3-deficient cultured mouse hippocampal slices. In these mutant slices, the amplitudes and frequencies of miniature excitatory postsynaptic currents were indistinguishable from those in the control slices. In the nectin-1-deficient slices, but not in the nectin-3-deficient slices, however, the amplitude of miniature inhibitory postsynaptic currents (mIPSCs) was larger than that in the control slices, although the frequency of the mIPSCs was not different between these two groups of slices. In the dissociated culture of hippocampal neurons from the nectin-1-deficient mice, the amplitude and frequency of mIPSCs were indistinguishable from those in the control neurons. Nectin-1 was not localized at or near the GABAergic inhibitory synapses. These results indicate that nectin-1 regulates the neuronal activities in the CA3 region of the hippocampus by suppressing the GABAergic inhibitory synaptic transmission.

Monosynaptic excitatory transmission from the hippocampal CA1 region to the subiculum.

The subiculum is a major output region of the hippocampus, receiving inputs from the CA1 region. We obtained paired patch-clamp recordings from synaptically coupled pairs of CA1 pyramidal cells (CA1PCs) and subicular principal cells (SubPCs), using rat hippocampal organotypic slice cultures. A single action potential in a presynaptic CA1PC evoked a unitary excitatory postsynaptic current in a SubPC (EPSCCA1→Sub). The failure rate of the monosynaptic transmission was remarkably low (0.08). Paired-pulse depression in SubPCs was apparent when an interval of presynaptic action potentials was shorter than 50ms. When trains of action potentials were induced in a CA1PC, EPSCCA1→Sub was significantly depressed with increasing spike frequency (20-100Hz). Thus the unitary monosynaptic transmission from a CA1PC to a SubPC is reliable, and depressed in response to frequent inputs, suggesting that the subiculum may function as a low pass filter to provide the downstream brain regions with appropriate information.