Copper-Nanoparticle-Induced Neurotoxic Effect and Oxidative Stress in the Early Developmental Stage of Zebrafish (Danio rerio).

Copper nanoparticles (CuNPs) are extensively used in electronics, cosmetics, fungicides, and various other fields due to their distinctive qualities. However, this widespread usage can contribute to environmental contamination and heightened health risks for living organisms. Despite their prevalent use, the ecological impacts and biosafety of CuNPs remain inadequately understood. The present study aims to delve into the potential toxic effects of CuNPs on zebrafish (Danio rerio) embryos, focusing on multiple indexes such as embryonic development, neurotoxicity, oxidative stress, and inflammatory response. The results revealed a notable increase in the death rate and deformity rate, alongside varying degrees of decrease in hatching rate and heart rate following CuNPs exposure. Particularly, the frequency of spontaneous tail coiling significantly declined under exposure to CuNPs at concentrations of 500 µg/L. Furthermore, CuNPs exposure induced alterations in the transcriptional expression of GABA signaling pathway-related genes (gabra1, gad, abat, and gat1), indicating potential impacts on GABA synthesis, release, catabolism, recovery, and receptor binding. Additionally, CuNPs triggered oxidative stress, evidenced by disruption in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, along with elevated malondialdehyde (MDA) levels. This oxidative stress subsequently led to a proinflammatory cascade, as demonstrated by the increased transcriptional expression of inflammatory markers (il-1ß, tnf-α, il-6, and il-8). Comparative analysis with copper ion (provided as CuCl2) exposure highlighted more significant changes in most indexes with CuCl2, indicating greater toxicity compared to CuNPs at equivalent concentrations. In conclusion, these findings provide valuable insights into the toxic effects of CuNPs on zebrafish embryo development and neurotransmitter conduction. Furthermore, they present technical methodologies for assessing environmental and health risks associated with CuNPs, contributing to a better understanding of their biosafety and ecological impact.

Evaluation of a new Q-switched Nd:YAG laser on premacular hemorrhage.

BACKGROUND: Premacular hemorrhage is among the causes of sudden deterioration of visual acuity. This study aimed to investigate the therapeutic outcomes of a new Q-switched Nd:YAG laser on premacular hemorrhage. METHODS: Retrospective, case series study of 16 eyes from 16 patients diagnosed with premacular hemorrhage, including 3 cases of Valsalva retinopathy, 8 cases of retinal macroaneurysm, 3 cases of diabetic retinopathy, 1 case of trauma-related hemorrhage and 1 case with leukemia. A 1064nm Q-switched Nd:YAG laser was performed to puncture the posterior hyaloid and inner limiting membrane to drain the hemorrhage. RESULTS: The success rate of 16 patients with premacular hemorrhage drainage was 100% in this study. Improved visual acuity was observed in each patient. CONCLUSIONS: In this case series of 16 patients, the new Q-switched Nd:YAG laser was successful in draining premacular hemorrhage with no serious complications.

Clemastine Enhances Myelination, Delays Axonal Loss and Promotes Functional Recovery in Spinal Cord Injury.

Recent evidence has shown that demyelination occurs along with axonal degeneration in spinal cord injury (SCI) during the secondary injury phase. Oligodendrocyte precursor cells (OPC) are present in the lesions but fail to differentiate into mature oligodendrocytes and form new myelin. Given the limited recovery of neuronal functions after SCI in adults without effective treatment available so far, it remains unknown whether enhancing OPC differentiation and myelination could benefit the recovery of SCI. To show the significance of myelin regeneration after SCI, the injury was treated with clemastine in the rat model. Clemastine is an FDA-approved drug that is potent in promoting oligodendrocyte differentiation and myelination in vivo, for four weeks following SCI. Motor function was assessed using sloping boards and grid walking tests and scored according to the Basso, Beattie, and Bresnahan protocol. The myelin integrity and protein expression were evaluated using transmission electron microscopy and immunofluorescence, respectively. The results indicated that clemastine treatment preserves myelin integrity, decreases loss of axons and improves functional recovery in the rat SCI model. The presented data suggest that myelination-enhancing strategies may serve as a potential therapeutic approach for the functional recovery in SCI.

Functional acute acquired comitant esotropia: clinical characteristics and efficacy of single Botulinum toxin type A injection.

BACKGROUND: To examine the clinical features of acute acquired comitant esotropia (AACE) and to evaluate the clinical effectiveness of a single injection of botulinum toxin type A (BTXA) on binocular visual function (BVF). METHODS: This retrospective, observational case series study enrolled patients with AACE examined from October 2018-May 2019. BTXA was injected into the both medial rectus muscles. The refractive error, best-corrected visual acuity (BCVA), stereoacuity, vergence, accommodation, the horizontal angle of deviation, and the gradient accommodative convergence/accommodation (AC/A) ratio were measured pre- and post-BTXA injection. Data pre- and postinjection were compared by the Wilcoxon signed-rank test. A Spearman correlation coefficient was calculated to explore the relationships between demographic characteristics and BVF. RESULTS: Twenty-two AACE cases were included. Compared with preinjection deviation, the postinjection deviation in the primary position was smaller for near (p < 0.001) and distance (p < 0.001) fixation at 3 months after injection (BTXA). Furthermore, convergence was better for near (p = 0.003) and distance (p < 0.001) fixation, divergence was better for near (p = 0.021) and distance (p < 0.001) fixation, accommodation was better in the right (p = 0.011) and left (p = 0.004) eyes, and the gradient AC/A ratio was better at the third month after injection (p = 0.001). Stereoacuity was improved in 11 (50%), unchanged in 5 (22.73%) and decreased in 6 (27.27%) patients. The preinjection stereoacuity (p = 0.013, r = 0.522) and preinjection deviation for near (p = 0.015 r, = - 0.512) and distance (p = 0.009, r = - 0.541) were significantly associated with patient age. CONCLUSIONS: AACE is characterized by a high AC/A ratio and low accommodation. A single injection of BTXA is effective for AACE. Deviation, stereoacuity, and the therapeutic effect of BTXA may be correlated with patient age.

ISRIB improves white matter injury following TBI by inhibiting NCOA4-mediated ferritinophagy.

Traumatic brain injury (TBI) often results in persistent neurological dysfunction, which is closely associated with white matter injury. The mechanisms underlying white matter injury after TBI remain unclear. Ferritinophagy is a selective autophagic process that degrades ferritin and releases free iron, which may cause ferroptosis. Although ferroptosis has been demonstrated to be involved in TBI, it is unclear whether ferritinophagy triggers ferroptosis in TBI. Integrated stress response inhibitor (ISRIB) has neuroprotective properties. However, the effect of ISRIB on white matter after TBI remains uncertain. We aimed to investigate whether ferritinophagy was involved in white matter injury following TBI and whether ISRIB can mitigate white matter injury after TBI by inhibiting ferritinophagy. In this study, controlled cortical impact (CCI) was performed on rats to establish the TBI model. Ferritinophagy was measured by assessing the levels of nuclear receptor coactivator 4 (NCOA4), which regulates ferritinophagy, ferritin heavy chain 1(FTH1), LC3, ATG5, and FTH1 colocalization with LC3 in the white matter. Increased NCOA4 and decreased FTH1 were detected in our study. FTH1 colocalization with LC3 enhanced in the white matter after TBI, indicating that ferritinophagy was activated. Immunofluorescence co-localization results also suggested that ferritinophagy occurred in neurons and oligodendrocytes after TBI. Furthermore, ferroptosis was assessed by determining free iron content, MDA content, GSH content, and Perl's staining. The results showed that ferroptosis was suppressed by NCOA4 knockdown via shNCOA4 lentivirus infection, indicating that ferroptosis in TBI is triggered by ferritinophagy. Besides, NCOA4 deletion notably improved white matter injury following TBI, implying that ferritinophagy contributed to white matter injury. ISRIB treatment reduced the occurrence of ferritinophagy in neurons and oligodendrocytes, attenuated ferritinophagy-induced ferroptosis, and alleviated white matter injury. These findings suggest that NCOA4-mediated ferritinophagy is a critical mechanism underlying white matter injury after TBI. ISRIB holds promise as a therapeutic agent for this condition.

The efficacy of botulinum toxin type A treatment and surgery for acute acquired comitant esotropia.

Aim: To compare the long-term efficiency of botulinum toxin type A (BTXA) injection and surgery on acute acquired comitant esotropia (AACE). Methods: This retrospective study enrolled patients with AACE from January 2020 to August 2022. The horizontal angle of deviation pre- and post-treatment was measured. Deviations in BTXA and surgical treatment were compared. The BTXA group was divided into adequate treatment (AT) and inadequate treatment (inAT) subgroup based on the deviation of no more than 4 prism diopters (at near and distance) or temporary exotropia at the 2 week follow-up. The two subgroups were compared to determine the long-term efficacy of BTXA treatment. Results: Ninety-two patients with AACE were included. Follow-up was 6 months. The deviations of the surgery and BTXA group were significantly smaller at the 6 month follow-up than at pre-treatment (p < 0.001). The deviation before treatment in the surgery group was larger than in the BTXA groups (p < 0.001) but smaller at the 6 month follow-up (p < 0.001). The deviation was similar in the AT-BTXA and inAT-BTXA subgroups before treatment (p = 0.322 for distance and p = 0.051 for near) but smaller in the AT-BTXA subgroup at 6 month follow-up (p < 0.001 for near and distance). Conclusion: Surgery and BTXA successfully treat AACE. Surgery has a more precise and lasting therapeutic effect than BTXA. AACE patients adequately treated with BTXA and with deviations of no more than 4 prism diopters at 2 weeks follow-up had better outcomes.

Reduced Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients With Essential Hypertension and Subclinical Carotid Atherosclerosis.

BACKGROUND: It has long been hypothesized that the abnormal immune responses contribute to the essential hypertension (EH) and its subclinical target organ damage (STOD). However, the mechanism is unclear. This study aimed at exploring the potential association with abnormal T-cell responses and EH, STOD, and early atherosclerosis in patients with EH. METHODS: This cross-sectional study included 146 patients with EH and 73 age-matched normotensive individuals. The expressed peripheral TCR (T-cell receptor) ß repertoire was analyzed by high through-put sequencing. RESULTS: The TCRß repertoires of the patients with EH were significantly different, with significantly elevated certain TCR beta variable (TRBV) and joint (TRBJ) gene usages, significantly reduced TCRß diversity indexes (diversity 50s) and numbers of total TCRß clonal types, significantly elevated percentages of the biggest TCRß clones and numbers of clones accounting >0.1% sequences, compared with those in the normotensive controls. Decreased diversity 50s and increased biggest TCRß clone percentages were independently correlated with carotid intima-media thickness and subclinical carotid atherosclerosis (SCA) in the patients with EH. Moreover, the diversity 50s were further significantly reduced and the biggest TCRß clone percentages were significantly increased in the patients with EH with SCA (n=89) comparing to the patients with EH/patients without SCA (n=57), and in patients with EH/SCA with carotid plaque (n=22) comparing to patients with EH/SCA/patients without carotid plaque (n=67). Importantly, specific TCRß clones were identified in different subgroups of the patients with EH. CONCLUSIONS: These results reveal that abnormal T-cell responses may play important roles in the progression of EH and its SCA, especially the formation of carotid plaque. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100054414.

Case Report: Exacerbation and Spontaneous Separation of the Epiretinal Membrane Following Laser Photocoagulation of a Vasoproliferative Tumor of the Retina.

The present report concerns a rare vasoproliferative tumor of the retina (VPTR) combined with a severe case of secondary epiretinal membrane (ERM). A 56-year-old male patient was diagnosed with VPTR and secondary ERM of the left eye. The patient underwent two rounds of laser photocoagulation (LP) of the tumor. The exacerbation of the ERM was observed after the first round of LP, while spontaneous separation over the five-month follow-up period was noted after the second round of LP. Thus, LP may represent a viable alternative treatment approach for VPTR combined with severe ERM.

Clemastine Promotes Differentiation of Oligodendrocyte Progenitor Cells Through the Activation of ERK1/2 via Muscarinic Receptors After Spinal Cord Injury.

The recovery of spinal cord injury (SCI) is closely associated with the obstruction of oligodendrocyte progenitor cell (OPC) differentiation, which ultimately induces the inability to generate newly formed myelin. To address the concern, drug-based methods may be the most practical and feasible way, possibly applying to clinical therapies for patients with SCI. In our previous study, we found that clemastine treatment preserves myelin integrity, decreases the loss of axons, and improves functional recovery in the SCI model. Clemastine acts as an antagonist of the muscarinic acetylcholine receptor (muscarinic receptor, MR) identified from a string of anti-muscarinic drugs that can enhance oligodendrocyte differentiation and myelin wrapping. However, the effects of clemastine on OPC differentiation through MRs in SCI and the underlying mechanism remain unclear. To explore the possibility, a rat model of SCI was established. To investigate if clemastine could promote the differentiation of OPCs in SCI via MR, the expressions of OPC and mature OL were detected at 7 days post injury (dpi) or at 14 dpi. The significant effect of clemastine on encouraging OPC differentiation was revealed at 14 dpi rather than 7 dpi. Under pre-treatment with the MR agonist cevimeline, the positive role of clemastine on OPC differentiation was partially disrupted. Further studies indicated that clemastine increased the phosphorylation level of extracellular signal-regulated kinase 1/2 (p-ERK1/2) and the expressions of transcription factors, Myrf and Olig2. To determine the relationship among clemastine, ERK1/2 signaling, specified transcription factors, and OPC differentiation, the ERK1/2 signaling was disturbed by U0126. The inhibition of ERK1/2 in SCI rats treated with clemastine decreased the expressions of p-ERK 1/2, Myrf, Olig2, and mature OLs, suggesting that ERK1/2 is required for clemastine on promoting OPC differentiation and that specified transcription factors may be affected by the activity of ERK1/2. Moreover, the impact of clemastine on modulating the level of p-ERK 1/2 was restricted following cevimeline pre-injecting, which provides further evidence that the role of clemastine was mediated by MRs. Altogether, our data demonstrated that clemastine, mediated by MRs, promotes OPC differentiation under the enhancement of Myrf and Olig2 by activating ERK1/2 signaling and suggests a novel therapeutic prospect for SCI recovery.

Subconjunctival Thelazia in a Chinese Woman Aged 49 Years.

This case report describes a diagnosis of subconjunctival Thelazia callipaeda in a 49-year-old Chinese woman who presented with pruritis and a crawling sensation of the left eye for 1 week.