Hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

BACKGROUND: Postoperative Cognitive Dysfunction (POCD) has attracted increased attention, but its precise mechanism remains to be explored. This study aimed to figure out whether HDAC6 could regulate NLRP3-induced pyroptosis by modulating the functions of HSP70 and HSP90 in microglia to participate in postoperative cognitive dysfunction in aged mice. METHODS: Animal models of postoperative cognitive dysfunction in aged mice were established by splenectomy under sevoflurane anesthesia. Morris water maze was used to examine the cognitive function and motor ability. Sixteen-months-old C57BL/6 male mice were randomly divided into six groups: control group (C group), sham surgery group (SA group), splenectomy group (S group), splenectomy + HDAC6 inhibitor ACY-1215 group (ACY group), splenectomy + HDAC6 inhibitor ACY-1215 + HSP70 inhibitor Apoptozole group (AP group), splenectomy + solvent control group (SC group). The serum and hippocampus of mice were taken after mice were executed. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, cleaved-Caspase-1 (P20), IL-1ß were detected by western blotting. Serum IL-1ß, IL-6 and S100ß were measured using ELISA assay, and cell localization of HDAC6 was detected by immunofluorescence. In vitro experiments, BV2 cells were used to validate whether this mechanism worked in microglia. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, P20, IL-1ß were detected by western blotting and the content of IL-1ß in the supernatant was measured using ELISA assay. The degree of acetylation of HSP90, the interaction of HSP70, HSP90 and NLRP3 were analyzed by coimmunoprecipitation assay. RESULTS: Splenectomy under sevoflurane anesthesia in aged mice could prolong the escape latency, reduce the number of crossing platforms, increase the expression of HDAC6 and activate the NLRP3 inflammasome to induce pyroptosis in hippocampus microglia. Using ACY-1215 could reduce the activation of NLRP3 inflammasome, the pyroptosis of microglia and the degree of spatial memory impairment. Apoptozole could inhibit the binding of HSP70 to NLRP3, reduce the degradation of NLRP3 and reverse the protective effect of HDAC6 inhibitors. The results acquired in vitro experiments closely resembled those in vivo, LPS stimulation led to the pyroptosis of BV2 microglia cells and the release of IL-1ß due to the activation of the NLRP3 inflammasome, ACY-1215 showed the anti-inflammatory effect and Apoptozole exerted the opposite effect. CONCLUSIONS: Our findings suggest that hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

A prediction model of elderly hip fracture mortality including preoperative red cell distribution width constructed based on the random survival forest (RSF) and Cox risk ratio regression.

An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients. With further research, a treatment algorithm can be developed to potentially identify patients at high risk of preoperative mortality. INTRODUCTION: Red blood cell distribution width (RDW) is an independent predictor of various disease states in elderly individuals, but its association with the prognosis of elderly hip fracture patients is controversial. This study aimed to evaluate the prognostic value of RDW in such patients, construct a prediction model containing RDW using random survival forest (RSF) and Cox regression analysis, and compare RDW in patients with and without anemia. METHODS: We retrospectively analyzed the data of elderly patients who underwent hip fracture surgery, selected the best variables using RSF, stratified the independent variables by Cox regression analysis, constructed a 1-year mortality prediction model of elderly hip fracture with RDW, and conducted internal validation and external validation. RESULTS: Two thousand one hundred six patients were included in this study. The RSF algorithm selects 12 important influencing factors, and Cox regression analysis showed that eight variables including preoperative RDW (pre-RDW) were independent risk factors for death within 1-year after hip fracture surgery in elderly patients. Stratified analysis showed that pre-RDW was still independently associated with 1-year mortality in the non-anemia group and not in the anemia group. The nomogram prediction model had high differentiation and fit, and the prediction model constructed by the total cohort of patients was also used for validation of patients in the anemia patients and obtained good clinical benefits. CONCLUSION: An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients.

Multi-Wavelength Selective and Broadband Near-Infrared Plasmonic Switches in Anisotropic Plasmonic Metasurfaces.

Anisotropic plasmonic metasurfaces have attracted broad research interest since they possess novel optical properties superior to natural materials and their tremendous design flexibility. However, the realization of multi-wavelength selective plasmonic metasurfaces that have emerged as promising candidates to uncover multichannel optical devices remains a challenge associated with weak modulation depths and narrow operation bandwidth. Herein, we propose and numerically demonstrate near-infrared multi-wavelength selective passive plasmonic switching (PPS) that encompasses high ON/OFF ratios and strong modulation depths via multiple Fano resonances (FRs) in anisotropic plasmonic metasurfaces. Specifically, the double FRs can be fulfilled and dedicated to establishing tailorable near-infrared dual-wavelength PPS. The multiple FRs mediated by in-plane mirror asymmetries cause the emergence of triple-wavelength PPS, whereas the multiple FRs governed by in-plane rotational asymmetries avail the implementation of the quasi-bound states in the continuum-endowed multi-wavelength PPS with the ability to unfold a tunable broad bandwidth. In addition, the strong polarization effects with in-plane anisotropic properties further validate the existence of the polarization-resolved multi-wavelength PPS. Our results provide an alternative approach to foster the achievement of multifunctional meta-devices in optical communication and information processing.

Young Sca-1+ bone marrow stem cell-derived exosomes preserve visual function via the miR-150-5p/MEKK3/JNK/c-Jun pathway to reduce M1 microglial polarization.

BACKGROUND: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. METHODS: Exosomes were enriched from young Sca-1+ or Sca-1- cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. RESULTS: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1-, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1- exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. CONCLUSION: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.

Plasmonic Sensing and Switches Enriched by Tailorable Multiple Fano Resonances in Rotational Misalignment Metasurfaces.

Fano resonances that feature strong field enhancement in the narrowband range have motivated extensive studies of light-matter interactions in plasmonic nanomaterials. Optical metasurfaces that are subject to different mirror symmetries have been dedicated to achieving nanoscale light manipulation via plasmonic Fano resonances, thus enabling advantages for high-sensitivity optical sensing and optical switches. Here, we investigate the plasmonic sensing and switches enriched by tailorable multiple Fano resonances that undergo in-plane mirror symmetry or asymmetry in a hybrid rotational misalignment metasurface, which consists of periodic metallic arrays with concentric C-shaped- and circular-ring-aperture unit cells. We found that the plasmonic double Fano resonances can be realized by undergoing mirror symmetry along the X-axis. The plasmonic multiple Fano resonances can be tailored by adjusting the level of the mirror asymmetry along the Z-axis. Moreover, the Fano-resonance-based plasmonic sensing that suffer from mirror symmetry or asymmetry can be implemented by changing the related structural parameters of the unit cells. The passive dual-wavelength plasmonic switches of specific polarization can be achieved within mirror symmetry and asymmetry. These results could entail benefits for metasurface-based devices, which are also used in sensing, beam-splitter, and optical communication systems.

Ti3 C2 Tx MXene Composite 3D Hydrogel Potentiates mTOR Signaling to Promote the Generation of Functional Hair Cells in Cochlea Organoids.

Organoids have certain cellular composition and physiological features in common with real organs, making them promising models of organ formation, function, and diseases. However, Matrigel, the commonly used animal-derived matrices in which they are developed, has limitations in mechanical adjustability and providing complex physicochemical signals. Here, the incorporation of Ti3 C2 Tx MXene nanomaterial into Matrigel regulates the properties of Matrigel and exhibits satisfactory biocompatibility. The Ti3 C2 Tx MXene Matrigel composites (MXene-Matrigel) regulate the development of Cochlear Organoids (Cochlea-Orgs), particularly in promoting the formation and maturation of organoid hair cells. Additionally, regenerated hair cells in MXene-Matrigel are functional and exhibit better electrophysiological properties compared to hair cells in Matrigel. MXene-Matrigel potentiates the amycin (mTOR) signaling pathway to promote hair cell differentiation, and mTOR signaling inhibition restrains hair cell differentiation. Moreover, MXene-Matrigel facilitates innervation establishment between regenerated hair cells and spiral ganglion neurons (SGNs) growing from the Cochlea modiolus in a co-culture system, as well as promotes synapse formation efficiency. The approach overcomes some limitations of the Matrigel-dependent culture system and greatly accelerates the application of nanomaterials in organoid development and research on therapies for hearing loss.

Near-infrared plasmonic sensing and digital metasurface via double Fano resonances.

Plasmonic sensing that enables the detection of minute events, when the incident light field interacts with the nanostructure interface, has been widely applied to optical and biological detection. Implementation of the controllable plasmonic double Fano resonances (DFRs) offers a flexible and efficient way for plasmonic sensing. However, plasmonic sensing and digital metasurface induced by tailorable plasmonic DFRs require further study. In this work, we numerically and theoretically investigate the near-infrared plasmonic DFRs for plasmonic sensing and digital metasurface in a hybrid metasurface with concentric ϕ-shaped-hole and circular-ring-aperture unit cells. We show that a plasmonic Fano resonance, resulting from the interaction between a narrow and a wide effective dipolar modes, can be realized in the ϕ-shaped hybrid metasurface. In particular, we demonstrate that the tailoring plasmonic DFRs with distinct mechanisms of actions can be accomplished in three different ϕ-shaped hybrid metasurfaces. Moreover, the resonance mode-broadening and mode-shifting plasmonic sensing can be fulfilled by modulating the polarization orientation and the related geometric parameters of the unit cells in the near-infrared waveband, respectively. In addition, the plasmonic switch with a high ON/OFF ratio can not only be achieved but also be exploited to establish a single-bit digital metasurface, even empower to implement two- and three-bit digital metasurface characterized by the plasmonic DFRs in the telecom L-band. Our results offer a new perspective toward realizing polarization-sensitive optical sensing, passive optical switches, and programmable metasurface devices, which also broaden the landscape of subwavelength nanostructures for biosensors and optical communications.

Cerebellar artery infarction with sudden hearing loss and vertigo as initial symptoms: A case report.

BACKGROUND: Sudden hearing loss (SHL) is associated with serious systematic conditions such as neoplasms, vascular events, autoimmune diseases, infections, and iatrogenic injury. Some authors report that SHL can be an early warning sign of impending vertebrobasilar ischemic stroke. It is important to distinguish stroke from benign disease. CASE SUMMARY: A 48-year-old male patient presented with SHL and vertigo as first symptoms. Diffusion-weighted imaging revealed high signal intensity in the left posterior inferior cerebellar artery territory of the cerebellar hemisphere and high signal intensity in the right pons and bridge cerebellar arm, confirming that the patient had cerebral infarction. Treatment with antiplatelet drugs, steroid anti-inflammatory drugs, and neurotrophic nerve therapy promoted blood circulation and removed blood stasis, and the symptoms of the patient were significantly improved. CONCLUSION: SHL and vertigo could be the initial symptoms of vertebrobasilar ischemic stroke.