Mfn2 regulates mitochondria and mitochondria-associated endoplasmic reticulum membrane function in neurodegeneration induced by repeated sevoflurane exposure.

Repeated sevoflurane exposure in neonatal mice can leads to neuronal apoptosis and mitochondrial dysfunction. The mitochondria are responsible for energy production to maintain homeostasis in the central nervous system. The mitochondria-associated endoplasmic reticulum membrane (MAM) is located between the mitochondria and endoplasmic reticulum (ER), and it is critical for mitochondrial function and cell survival. MAM malfunction contributes to neurodegeneration, however, whether it is involved in sevoflurane-induced neurotoxicity remains unknown. Our study demonstrated that repeated sevoflurane exposure induced mitochondrial dysfunction and dampened the MAM structure. The upregulated ER-mitochondria tethering enhanced Ca2+ transition from the cytosol to the mitochondria. Overload of mitochondrial Ca2+ contributed to opening of the mitochondrial permeability transition pore (mPTP), which caused neuronal apoptosis. Mitofusin 2(Mfn2), a key regulator of ER-mitochondria contacts, was found to be suppressed after repeated sevoflurane exposure, while restoration of Mfn2 expression alleviated cognitive dysfunction due to repeated sevoflurane exposure in the adult mice. These evidences suggest that sevoflurane-induced MAM malfunction is vulnerable to Mfn2 suppression, and the enhanced ER-mitochondria contacts promotes mitochondrial Ca2+ overload, contributing to mPTP opening and neuronal apoptosis. This paper sheds light on a novel mechanism of sevoflurane-induced neurotoxicity. Furthermore, targeting Mfn2-mediated regulation of the MAM structure and mitochondrial function may provide a therapeutic advantage in sevoflurane-induced neurodegeneration.

Gram-negative bacteria recognition and photodynamic elimination by Zn-DPA based sensitizers.

The abuse and overuse of antibiotics let drug-resistant bacteria emerges. Antibacterial photodynamic therapy (APDT) has shown outstanding merits to eliminate the drug-resistant bacteria via cytotoxic reactive oxygen species produced by irradiating photosensitizer. However, most of photosensitizers are not effective for Gram-negative bacteria elimination. Herein conjugates of NBS, a photosensitizer, linked with one (NBS-DPA-Zn) or two (NBS-2DPA-Zn) equivalents of zinc-dipicolylamine (Zn-DPA) have been designed to achieve the functional recognition of different bacteria. Due to the cationic character of NBS and metal transfer channel effect of Zn-DPA, NBS-DPA-Zn exhibited the first regent to distinguish P. aeruginosa from other Gram-negative bacteria. Whereas NBS-2DPA-Zn showed broad-spectrum antibacterial effect because the two arm of double Zn-DPA enhanced interactions with anionic membranes of bacteria, led the bacteria aggregation and thus provided the efficacy of APDT to bacteria and corresponding biofilm. In combination with a hydrogel of Pluronic, NBS-2DPA-Zn@gel shows promising clinical application in mixed bacterial diabetic mouse model infection. This might propose a new method that can realize functional identification and elimination of bacteria through intelligent regulation of Zn-DPA, and shows excellent potential for antibacterial application.

Choroidal Vascularity Index and Choroidal Structural Changes in Children With Nephrotic Syndrome.

Purpose: To investigate the choroidal vascularity index (CVI) and choroidal structural changes in children with nephrotic syndrome. Methods: This was a cross-sectional study involving 45 children with primary nephrotic syndrome and 40 normal controls. All participants underwent enhanced depth imaging-optical coherence tomography examinations. An automatic segmentation method based on deep learning was used to segment the choroidal vessels and stroma, and the choroidal volume (CV), vascular volume (VV), and CVI within a 4.5 mm diameter circular area centered around the macular fovea were obtained. Clinical data, including blood lipids, serum proteins, renal function, and renal injury indicators, were collected from the patients. Results: Compared with normal controls, children with nephrotic syndrome had a significant increase in CV (nephrotic syndrome: 4.132 ± 0.464 vs. normal controls: 3.873 ± 0.574; P = 0.024); no significant change in VV (nephrotic syndrome: 1.276 ± 0.173 vs. normal controls: 1.277 ± 0.165; P = 0.971); and a significant decrease in the CVI (nephrotic syndrome: 0.308 [range, 0.270-0.386] vs. normal controls: 0.330 [range, 0.288-0.387]; P < 0.001). In the correlation analysis, the CVI was positively correlated with serum total protein, serum albumin, serum prealbumin, ratio of serum albumin to globulin, and 24-hour urine volume and was negatively correlated with total cholesterol, low-density lipoprotein cholesterol, urinary protein concentration, and ratio of urinary transferrin to creatinine (all P < 0.05). Conclusions: The CVI is significantly reduced in children with nephrotic syndrome, and the decrease in the CVI parallels the severity of kidney disease, indicating choroidal involvement in the process of nephrotic syndrome. Translational Relevance: Our findings contribute to a deeper understanding of how nephrotic syndrome affects the choroid.

An ER-targeted, Viscosity-sensitive Hemicyanine Dye for the Diagnosis of Nonalcoholic Fatty Liver and Photodynamic Cancer Therapy by Activating Pyroptosis Pathway.

The concept of molecular design, integrating diagnostic and therapeutic functions, aligns with the general trend of modern medical advancement. Herein, we rationally designed the smart molecule ER-ZS for endoplasmic reticulum (ER)-targeted diagnosis and treatment in cell and animal models by combining hemicyanine dyes with ER-targeted functional groups (p-toluenesulfonamide). Owing to its ability to target the ER with a highly specific response to viscosity, ER-ZS demonstrated substantial fluorescence turn-on only after binding to the ER, independent of other physiological environments. In addition, ER-ZS, being a small molecule, allows for the diagnosis of nonalcoholic fatty liver disease (NAFLD) via liver imaging based on high ER stress. Importantly, ER-ZS is a type I photosensitizer, producing O2 ⋅- and ⋅OH under light irradiation. Thus, after irradiating for a certain period, the photodynamic therapy inflicted severe oxidative damage to the ER of tumor cells in hypoxic (2 % O2 ) conditions and activated the unique pyroptosis pathway, demonstrating excellent antitumor capacity in xenograft tumor models. Hence, the proposed strategy will likely shed new light on integrating molecular optics for NAFLD diagnosis and cancer therapy.

Simultaneous detection of SO2 and viscosity in drug-induced inflammation in live cells and zebrafish.

The viscosity within cells is a crucial microenvironmental factor, and sulfur dioxide (SO2 ) has essential functions in regulating cellular apoptosis and inflammation. Some evidence has been confirmed that changes in viscosity and overexposure of SO2 within the cell may cause detrimental effects including, but not limited to, respiratory and cardiovascular illnesses, inflammation, fatty liver, and various types of cancer. Therefore, precise monitoring of SO2 and viscosity in biological entities holds immense practical importance. Therefore, in this research, we developed a versatile fluorescent TCF-Cou that enables the dual detection of SO2 and viscosity in the living system. Probe TCF-Cou possessed a response to viscosity and SO2 through red and green emissions. The alteration of SO2 and viscosity levels in live cells and zebrafish were also monitored using probe TCF-Cou. We hope that this fluorescent probe could be a potential tool for revealing the related pathological and physiological processes through monitoring the changes in SO2 and viscosity.

The Effect of Perceived Environmental Uncertainty on University Students' Anxiety, Academic Engagement, and Prosocial Behavior.

Uncertainty, as the predominant characteristic of the contemporary landscape, poses significant challenges and exerts profound influence on individual decision making and behaviors; however, there remains a limited understanding of its impact on university student behavior. Building upon the uncertainty management theory, this study presents a conceptual framework to investigate the impact of perceived environmental uncertainty on university students' anxiety levels and behaviors, including academic engagement and prosocial behavior. Additionally, our model proposes that the intolerance of uncertainty moderates a mediating effect on anxiety. These hypotheses are empirically tested using a sample of 221 Chinese university students. The results reveal a positive relationship between perceived environmental uncertainty and anxiety among university students; subsequently, anxiety exerts a negative influence on both academic engagement and prosocial behavior. Furthermore, we find that anxiety serves as a psychological mediator between perceived environmental uncertainty and both academic engagement and prosocial behavior. This research also underscores the significance of the intolerance of uncertainty in shaping university students' involvement in academic pursuits when confronted with anxiety stemming from perceived environmental uncertainty. Consequently, these findings have practical implications for facilitating university students' adaptive coping strategies in uncertain contexts and mitigating the negative effects of anxiety on their behavioral responses.

Infrared Thermography: Clinical Value for Diagnosing Persistent Somatoform Pain Disorders?

BACKGROUND: Patients with persistent somatoform pain disorder (PSPD) are not uncommon. Still, the disease diagnosis relies primarily on structured interviews, with no objective indicators yet available to aid in the diagnosis. This has led to low diagnostic rates and overconsumption of health care resources for the disorder. Although there is a large body of research to improve the diagnosis of the condition, there are currently no objective indicators available for diagnosis. OBJECTIVES: The aim of this study is to investigate the clinical value of infrared thermography (IRT) for diagnosing PSPD. STUDY DESIGN: This is a retrospective study. SETTING: A single academic hospital, outpatient setting. METHODS: The clinical data of patients diagnosed with PSPD in the Pain Department of the First Affiliated Hospital of the Army Medical University from September 2020 to September 2022 were analyzed. The differences in IR thermograms between PSPD patients and healthy controls were analyzed, as well as the relationship between the Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index (PSQI) score, Patient Health Questionnaire-15, and Symptom Check List-90 and the differences in IR thermograms of PSPD patients. RESULTS: The mean squared error, structural similarity measure, different hash, contrast, entropy, inverse variance, and correlation values of the IR thermogram helped to determine PSPD with statistically significant differences (P < 0.05). Inverse variance values were weakly negatively correlated with PSQI scores of PSPD patients (r -0.4721, P < 0.05). LIMITATIONS: This study was limited by its sample size and retrospective observational design. CONCLUSIONS: IRT analysis is a useful objective method in diagnosis of PSPD, which also provides a new line of thought for studying the pathogenesis of PSPD. KEY WORDS: Persistent somatoform pain disorder, PSPD, thermal imaging, infrared thermography, IRT, image texture characteristics, psychometric variables, image analysis.

Fluorescent dyes based on rhodamine derivatives for bioimaging and therapeutics: recent progress, challenges, and prospects.

Since their inception, rhodamine dyes have been extensively applied in biotechnology as fluorescent markers or for the detection of biomolecules owing to their good optical physical properties. Accordingly, they have emerged as a powerful tool for the visualization of living systems. In addition to fluorescence bioimaging, the molecular design of rhodamine derivatives with disease therapeutic functions (e.g., cancer and bacterial infection) has recently attracted increased research attention, which is significantly important for the construction of molecular libraries for diagnostic and therapeutic integration. However, reviews focusing on integrated design strategies for rhodamine dye-based diagnosis and treatment and their wide application in disease treatment are extremely rare. In this review, first, a brief history of the development of rhodamine fluorescent dyes, the transformation of rhodamine fluorescent dyes from bioimaging to disease therapy, and the concept of optics-based diagnosis and treatment integration and its significance to human development are presented. Next, a systematic review of several excellent rhodamine-based derivatives for bioimaging, as well as for disease diagnosis and treatment, is presented. Finally, the challenges in practical integration of rhodamine-based diagnostic and treatment dyes and the future outlook of clinical translation are also discussed.

General anesthetic action profile on the human prefrontal cortex cells through comprehensive single-cell RNA-seq analysis.

The cellular and molecular actions of general anesthetics to induce anesthesia state and also cellular signaling changes for subsequent potential "long term" effects remain largely elusive. General anesthetics were reported to act on voltage-gated ion channels and ligand-gated ion channels. Here we used single-cell RNA-sequencing complemented with whole-cell patch clamp and calcium transient techniques to examine the gene transcriptome and ion channels profiling of sevoflurane and propofol, both commonly used clinically, on the human fetal prefrontal cortex (PFC) mixed cell cultures. Both propofol and sevoflurane at clinically relevant dose/concentration promoted "microgliosis" but only sevoflurane decreased microglia transcriptional similarity. Propofol and sevoflurane each extensively but transiently (<2 h) altered transcriptome profiling across microglia, excitatory neurons, interneurons, astrocytes and oligodendrocyte progenitor cells. Utilizing scRNA-seq as a robust and high-through put tool, our work may provide a comprehensive blueprint for future mechanistic studies of general anesthetics in clinically relevant settings.

Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapy.

Pyroptosis, a unique lytic programmed cell death, inspired tempting implications as potent anti-tumor strategy in pertinent to its potentials in stimulating anti-tumor immunity for eradication of primary tumors and metastasis. Nonetheless, rare therapeutics have been reported to successfully stimulate pyroptosis. In view of the intimate participation of reactive oxygen species (ROS) in stimulating pyroptosis, we attempted to devise a spectrum of well-defined subcellular organelle (including mitochondria, lysosomes and endoplasmic reticulum)-targeting photosensitizers with the aim of precisely localizing ROS (produced from photosensitizers) at the subcellular compartments and explore their potentials in urging pyroptosis and immunogenic cell death (ICD). The subsequent investigations revealed varied degrees of pyroptosis upon photodynamic therapy (PDT) towards cancerous cells, as supported by not only observation of the distinctive morphological and mechanistic characteristics of pyroptosis, but for the first-time explicit validation from comprehensive RNA-Seq analysis. Furthermore, in vivo anti-tumor PDT could exert eradication of the primary tumors, more importantly suppressed the distant tumor and metastatic tumor growth through an abscopal effect, approving the acquirement of specific anti-tumor immunity as a consequence of pyroptosis. Hence, pyroptosis was concluded unprecedently by our proposed organelles-targeting PDT strategy and explicitly delineated with molecular insights into its occurrence and the consequent ICD.

Bicuculline and Bumetanide Attenuate Sevoflurane-Induced Impairment of Myelination and Cognition in Young Mice.

Sevoflurane (Sevo) is one of the most commonly used general anesthetics for infants and young children. We investigated whether Sevo impairs neurological functions, myelination, and cognition via the γ-aminobutyric acid A receptor (GABAAR) and Na+-K+-2Cl- cotransporter (NKCC1) in neonatal mice. On postnatal days 5-7, mice were exposed to 3% Sevo for 2 h. On postnatal day 14, mouse brains were dissected, and oligodendrocyte precursor cell line level lentivirus knockdown of GABRB3, immunofluorescence, and transwell migration assays were performed. Finally, behavioral tests were conducted. Multiple Sevo exposure groups exhibited increased neuronal apoptosis levels and decreased neurofilament protein levels in the mouse cortex compared with the control group. Sevo exposure inhibited the proliferation, differentiation, and migration of the oligodendrocyte precursor cells, thereby affecting their maturation process. Electron microscopy revealed that Sevo exposure reduced myelin sheath thickness. The behavioral tests showed that multiple Sevo exposures induced cognitive impairment. GABAAR and NKCC1 inhibition provided protection against Sevo-induced neurotoxicity and cognitive dysfunction. Thus, bicuculline and bumetanide can protect against Sevo-induced neuronal injury, myelination impairment, and cognitive dysfunction in neonatal mice. Furthermore, GABAAR and NKCC1 may be mediators of Sevo-induced myelination impairment and cognitive dysfunction.

Observing hydrogen sulfide in the endoplasmic reticulum of cancer cells and zebrafish by using an activity-based fluorescent probe.

A crucial endogenous signaling chemical, hydrogen sulfide, is involved in many physiological actions. In this work, we created the fluorescent probe ER-Nap-NBD using a naphthalimide fluorophore as the signal reporter, a 7-nitro-1,2,3-benzoxadiazole amine as the responsive moiety, and a sulfonamide part for endoplasmic reticulum targeting. ER-Nap-NBD could be detected the H2S levels in solution and in living systems (cells and zebrafish).

Association between vitamin D concentration and delirium in hospitalized patients: A meta-analysis.

BACKGROUND: Now the occurrence of delirium is more concerning to clinicians and psychiatrists. It has been reported that vitamin D deficiency may be a relevant factor in the development of delirium in hospitalized patients. STUDY OBJECTIVE: To investigate the association between vitamin D concentration and delirium in hospitalized patients. DESIGN: Meta-analysis. METHODS: A systematic literature search was conducted using PubMed, EMBASE, and the Cochrane Library. The primary outcome was the occurrence of delirium in the inpatient setting. Odds ratios (OR) were calculated with random or fixed effects models. RESULTS: In this article, we define the normal range of vitamin D concentrations as greater than 75 nmol / L, 50-75 nmol / L as vitamin D insufficiency, 25-50 nmol / L as vitamin D deficiency, and less than 25 nmol / L as vitamin D severe deficiency. The Results showed that severe vitamin D deficiency (OR: 1.98 [1.41-2.79], P<0.001) and vitamin D deficiency (OR: 1.50 [1.12-2.00], P = 0.006) were more likely to develop delirium than normal vitamin D levels. Subgroup analysis also revealed that low vitamin D concentrations were associated with a higher incidence of delirium, whether the cutoff point was 25 nmol/L (OR: 1.52 [1.40-1.64], P<0.001), 50 nmol/L (OR: 1.47 [1.19-1.82], P<0.001), or 75 nmol/L (OR: 1.54 [1.21-1.96], P<0.001). The included studies scored medium and high on the Newcastle-Ottawa quality assessment scale. CONCLUSION: Compared with normal vitamin D levels, severe vitamin D deficiency and vitamin D deficiency, but not vitamin D insufficiency, are associated with a higher incidence of delirium in hospitalized patients. TRIAL REGISTRATION: This review was registered in the PROSPERO database under identifier CRD42021271347. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021271347.

Prospects of coupled iron-based nanostructures in preclinical antibacterial therapy.

Bacterial infections can threaten human health. Drug-resistant bacteria have become a challenge because of the excessive use of drugs. We summarize the current metallic antibacterial materials, especially Fe-based materials, for efficiently killing bacteria. The possible antibacterial mechanisms of metallic antibacterial agents are classified into interactions with bacterial proteins, iron metabolism, catalytic activity, and combinations of magnetic, photodynamic, and photothermal effects. This review will inspire the development of novel Fe-based antibacterial agents for clinical settings.

Comparison of surgical complications after curative surgery in patients with oral cavity squamous cell carcinoma and sarcopenia.

BACKGROUND: The study aims to clarify the association of sarcopenia with perioperative and postoperative complications in oral cavity squamous cell carcinoma (OCSCC) patients undergoing curative surgery and to understand the reasons causing the poor oncologic outcomes for OCSCC. METHODS: We conducted a propensity score matching study to investigate the association of perioperative and postoperative outcomes in OCSCC patients with sarcopenia and without sarcopenia. A retrospective analysis of a large national data set from the Taiwan Cancer Registry Database was conducted. At least two claims for patients with a principal diagnosis of sarcopenia within the 12-month preoperative period were defined as the criteria for sarcopenia diagnosis (ICD-10-CM code M62.84). Sarcopenia was diagnosed through the measurement of low muscle strength and low muscle mass by any one of the patient's attending orthopaedic physician, rehabilitation physician, family medicine specialist or geriatrician. A multivariate logistic regression model was used to calculate the perioperative, and postoperative major complications. RESULTS: Our final cohort included 16 293 patients with OCSCC (10 862 and 5 431 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for further analysis. The sarcopenia group was 10.40% female and 89.60% male, and the nonsarcopenia group was 9.74% female and 90.26% male. The mean age ± standard deviation (SD) were 56.44 ± 11.14 and 56.22 ± 11.29 for sarcopenia and nonsarcopenia groups. OCSCC patients with sarcopenia undergoing curative surgery had a significantly higher blood transfusion rate and volume; longer intensive care unit (ICU) stay, and hospital stay; higher postoperative 30-day mortality (adjusted odds ratio [aOR]: 1.12, 95% confidence interval [CI] [1.07, 1.56]) and rates of pneumonia (aOR: 1.34, 95% CI [1.20, 1.50]), acute renal failure (aOR: 1.45, 95% CI [1.12, 1.87]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]); higher postoperative first-year mortality (aOR: 1.18, 95% CI [1.13, 1.51]) and rates of pneumonia (aOR: 1.43, 95% CI [1.30, 1.56]), acute myocardial infarction (aOR: 1.52, 95% CI [1.06, 2.18]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]). CONCLUSIONS: OCSCC patients with sarcopenia might exhibit more perioperative and surgical complications than those without sarcopenia.

Development and characterization of reference materials for EGFR, KRAS, NRAS, BRAF, PIK3CA, ALK, and MET genetic testing.

BACKGROUND: Along with the dramatic development of molecular diagnostic testing for the detection of oncogene variations, reference materials (RMs) have become increasingly important in performance evaluation of genetic testing. OBJECTIVE: In this study, we built a set of RMs for genetic testing based on next-generation sequencing (NGS). METHOD: Solid tumor tissues were selected as the samples of RMs for preparation. NGS was used to determine and validate the variants and the mutation frequency in DNA samples. Digital PCR was used to determine the copy numbers of RNA samples. The performance of the RMs was validated by six laboratories. RESULTS: Thirty common genetic alterations were designed based on these RMs. RMs consisted of a positive reference, a limit of detection reference, and a negative reference. The validation results confirmed the performance of the RMs. CONCLUSION: These RMs may be an attractive tool for the development, validation, and quality monitoring of molecular genetic testing.

Identification and Validation of Ferroptosis-Related Genes in Sevoflurane-Induced Hippocampal Neurotoxicity.

Background: Sevoflurane is one of the most popular inhalational anesthetics during perioperative period but presenting neurotoxicity among pediatric and aged populations. Recent experiments in vivo and in vitro have indicated that ferroptosis may contribute to the neurotoxicity of sevoflurane anesthesia. However, the exact mechanism is still unclear. Methods: In current study, we explored the differential expressed genes (DEGs) in HT-22 mouse hippocampal neuronal cells after sevoflurane anesthesia using RNA-seq. Differential expressed ferroptosis-related genes (DEFRGs) were screened and analyzed by Gene Ontology (GO) and pathway enrichment analysis. Protein-to-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes (STRING). Significant modules and the hub genes were identified by using Cytoscape. The Connectivity Map (cMAP) was used for screening drug candidates targeting the identified DEFRGs. Potential TF-gene network and drug-gene pairs were established towards the hub genes. In final, we validated these results in experiments. Results: A total of 37 ferroptosis-related genes (18 upregulated and 19 downregulated) after sevoflurane exposure in hippocampal neuronal cells were finally identified. These differentially expressed genes were mainly involved into the biological processes of cellular response to oxidative stress. Pathway analysis indicated that these genes were involved in ferroptosis, mTOR signaling pathway, and longevity-regulating pathway. PPI network was constructed. 10 hub genes including Prkaa2, Chac1, Arntl, Tfrc, Slc7a11, Atf4, Mgst1, Lpin1, Atf3, and Sesn2 were found. Top 10 drug candidates, gene-drug networks, and TFs targeting these genes were finally identified. These results were validated in experiments. Conclusion: Our results suggested that ferroptosis-related genes play roles in sevoflurane anesthesia-related hippocampal neuron injury and offered the hub genes and potential therapeutic agents for investigating and treatment of this neurotoxicity after sevoflurane exposure. Finally, therapeutic effect of these drug candidates and function of potential ferroptosis targets should be further investigated for treatment and clarifying mechanisms of sevoflurane anesthesia-induced neuron injury in future research.

Sevoflurane exposure induces neurotoxicity by regulating mitochondrial function of microglia due to NAD insufficiency.

Developmental neurons received with sevoflurane, the commonly used inhalational anesthetic agent in clinical surgery, several times tend to be destroyed. Microglia, the resident immune cells of the central nervous system (CNS), are activated after sevoflurane exposure, accompanied by releasing proinflammatory cytokines that damage developing neurons. The sevoflurane-induced neurotoxicity could be attributed to activated microglia presenting proinflammatory and anti-inflammatory functions. Proinflammatory microglia release cytokines to impair the CNS, while anti-inflammatory microglia engulf damaged neurons to maintain CNS homeostasis. Sevoflurane exposure promotes the secretion of proinflammatory cytokines by microglia, inhibiting the microglial phagocytic function. Microglia with poor phagocytic function cannot engulf damaged neurons, leading to the accumulation of damaged neurons. The mechanism underlying poor phagocytic function may be attributed to mitochondrial dysfunction of microglia induced by sevoflurane exposure, in which affected mitochondria cannot generate adequate ATP and NAD to satisfy the energy demand. We discovered that sevoflurane treatment impaired the mitochondrial metabolism of microglia, which resulted in NAD deficiency and couldn't produce sufficient energy to clear damaged neurons to maintain CNS development. Our findings provide an explanation of a new mechanism underlying sevoflurane-induced neurotoxicity.

Carbon Nanostructures for Ocular Tissue Reinforcement.

Purpose: The purpose of this study was to improve the biomechanical properties of the cornea through the incorporation of carbon nanostructures. Methods: Healthy Japanese rabbits were used to evaluate the effect of carbon nanostructures' incorporation in the cornea. Rabbits were divided in two groups A and B. In each of these groups, the corneas were divided in (i) corneas not submitted to any treatment (the control group), (ii) corneas modified either with carbon nanostructures (group A), or with the traditional cross-linking technology (group B). After modification, rabbits were euthanized at different time intervals. The biomechanical properties of the treated corneas were evaluated using the inflation method. Results: Biomechanical tests based on the inflation method show that the incorporation of carbon nanostructures to the cornea and their proper distribution within it gives rise to a large improvement in the mechanical properties and tangential elastic modulus (up to 155%). These results anticipate that this novel and easy approach based on nanotechnology is able to compete with the actual cross-linking technology applied in clinical ophthalmology using a photosensitive molecule, such as riboflavin and unpleasant UV-A radiation. Conclusions: The incorporation of carbon nanostructures (single-walled carbon nanotubes and graphene) in corneal stroma is proposed as a promising alternative to improve the mechanical properties in the treated eyes. The proper dispersion of the carbon nanostructures a few days after implementation (down to 60 micrometers depth) explains the successful results achieved. Translational Relevance: Nanotechnology applied to the eye constitutes a promising approach for ocular tissue reinforcement.