Impact of Online Video Game-Based Dichoptic Training on Binocular Vision Rehabilitation in Post-surgical Patients with Intermittent Exotropia.

INTRODUCTION: Dichoptic training has emerged as a promising rehabilitation approach for improving binocular visual function in patients with strabismus. A prospective observational study design was employed to assess the effectiveness of online video game-based dichoptic training in rehabilitating binocular visual function in patients who had undergone an operation for intermittent exotropia. METHODS: A total of 64 patients who had undergone an operation for intermittent exotropia were recruited and divided into the training group and the control group based on whether they would receive the dichoptic training. The dichoptic training was conducted for 3 months in the training group and the control group would not accept any form of orthoptic therapy. Assessments of binocular visual functions and deviation were conducted at baseline, 3-month and 6-month follow-up. RESULTS: Twenty-nine participants in the training group (mean 9.69 ± 2.66 years old) and 26 participants in the control group (mean 8.41 ± 2.64 years old) completed follow-up. At both 3- and 6-month follow-ups, the training group showed superior distance stereopsis compared to the control group, with near stereopsis only showing significant difference at the 6-month follow-up. Additionally, the training group exhibited significantly less distance exo-deviation drift than the control group at these times, and no significant difference was observed in near exo-deviation drift between the groups. The control group had a significantly higher rate of suboptimal surgical outcomes at both the 3- and 6-month follow-up. However, no significant differences were observed in simultaneous perception and fusion functions between the two groups. CONCLUSIONS: Online video game-based dichoptic training has the potential to become a novel postoperative rehabilitation strategy for patients with intermittent exotropia.

Novel Quantitative Contrast Sensitivity Function Enhances the Prediction of Treatment Outcome and Recurrence in Amblyopia.

Purpose: Although effective amblyopia treatments are available, treatment outcome is unpredictable, and the condition recurs in up to 25% of the patients. We aimed to evaluate whether a large-scale quantitative contrast sensitivity function (CSF) data source, coupled with machine learning (ML) algorithms, can predict amblyopia treatment response and recurrence in individuals. Methods: Visual function measures from traditional chart vision acuity (VA) and novel CSF assessments were used as the main predictive variables in the models. Information from 58 potential predictors was extracted to predict treatment response and recurrence. Six ML methods were applied to construct models. The SHapley Additive exPlanations was used to explain the predictions. Results: A total of 2559 consecutive records of 643 patients with amblyopia were eligible for modeling. Combining variables from VA and CSF assessments gave the highest accuracy for treatment response prediction, with the area under the receiver operating characteristic curve (AUC) of 0.863 and 0.815 for outcome predictions after 3 and 6 months, respectively. Variables from the VA assessment alone predicted the treatment response, with AUC values of 0.723 and 0.675 after 3 and 6 months, respectively. Variables from the CSF assessment gave rise to an AUC of 0.909 for recurrence prediction compared to 0.539 for VA assessment alone, and adding VA variables did not improve predictive performance. The interocular differences in CSF features are significant contributors to recurrence risk. Conclusions: Our models showed CSF data could enhance treatment response prediction and accurately predict amblyopia recurrence, which has the potential to guide amblyopia management by enabling patient-tailored decision making.

Effects of the Taste Substances and Metal Cations in Green Tea Infusion on the Turbidity of EGCG-Mucin Mixtures.

Astringency has an important impact on the taste quality of tea infusion, a process which occurs when polyphenols complex with salivary proteins to form an impermeable membrane. (-)-Epigallocatechin gallate (EGCG) is the main astringent compound found in green tea and mucin is the main protein present in saliva. Determining the turbidity of EGCG-mucin mixtures is an effective method to quantify the astringency intensity of EGCG solutions. In this study, the effects of taste-related, substances present during green tea infusion, on the turbidity of EGCG-mucin mixtures was investigated under the reacting conditions of a pH value of 5.0, at 37 °C, and for 30 min. The results showed that epicatechins, caffeic acid, chlorogenic acid, and gallic acid reduced the turbidity of EGCG-mucin mixtures, while rutin increased turbidity. Metal ions increased the turbidity of EGCG-mucin mixtures. These can be arranged by effectiveness as Al3+ > K+ > Mg2+ > Ca2+. Caffeine, theanine, and sodium glutamate all decreased the turbidity values of EGCG-mucin mixtures, but sucrose had a weak effect. Further experiments confirmed that the turbidity of green tea infusion-mucin mixture indicated the astringent intensity of green tea infusion, and that the turbidity was significantly correlated with the contents of tea polyphenols and EGCG.

Associations between the cause of amblyopia and pre-treatment contrast sensitivity, stereoacuity, fixation, and nystagmus.

Purpose: To explore the association between the cause of amblyopia and pre-treatment contrast sensitivity, stereoacuity, fixation and nystagmus. Design: Retrospective cohort study. Methods: A retrospective review was conducted for 3408 patients with amblyopia who had not yet started amblyopia treatment utilizing a large amblyopia patient database maintained at Zhongshan Ophthalmic Centre. Six amblyogenic factor subtypes were identified: anisometropia, isoametropia, strabismus, anisometropia and strabismus, monocular visual deprivation, and binocular visual deprivation amblyopia. Monocular best corrected visual acuity (BCVA), the contrast sensitivity function (CSF), fixation, and stereopsis were compared between the subtypes before and after propensity score matching (PSM) for age and sex. Results: The two deprivation groups had poorer BCVA and CSF than the other groups. There were no systematic differences in CSF between the non-deprivation groups. Nystagmus was more common in the bilateral amblyopia groups compared to the monocular amblyopia groups. Eccentric fixation was uncommon with the exception of the anisometropia and strabismus group which had an eccentric fixation rate of 20%. Distance stereoacuity measured without monocular cues was absent for almost all patients. The results were consistent when analyzed using PSM. Conclusion: Visual deprivation causes more severe amblyopia than other amblyogenic factors. For non-deprivation amblyopia subtypes, individual differences such as variation in the severity of the amblyogenic factor might be more important in determining pre-treatment vision than whether amblyopia was caused by refractive error, strabismus or both.

Selecting Monoclonal Cell Lineages from Somatic Reprogramming Using Robotic-Based Spatial-Restricting Structured Flow.

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

DWSSA: Alleviating over-smoothness for deep Graph Neural Networks.

Graph Neural Networks (GNNs) have demonstrated great potential in achieving outstanding performance in various graph-related tasks, e.g., graph classification and link prediction. However, most of them suffer from the following issue: shallow networks capture very limited knowledge. Prior works design deep GNNs with more layers to solve the issue, which however introduces a new challenge, i.e., the infamous over-smoothness. Graph representation over emphasizes node features but only considers the static graph structure with a uniform weight are the key reasons for the over-smoothness issue. To alleviate the issue, this paper proposes a Dynamic Weighting Strategy (DWS) for addressing over-smoothness. We first employ Fuzzy C-Means (FCM) to cluster all nodes into several groups and get each node's fuzzy assignment, based on which a novel metric function is devised for dynamically adjusting the aggregation weights. This dynamic weighting strategy not only enables the intra-cluster interactions, but also inter-cluster aggregations, which well addresses undifferentiated aggregation caused by uniform weights. Based on DWS, we further design a Structure Augmentation (SA) step for addressing the issue of underutilizing the graph structure, where some potentially meaningful connections (i.e., edges) are added to the original graph structure via a parallelable KNN algorithm. In general, the optimized Dynamic Weighting Strategy with Structure Augmentation (DWSSA) alleviates over-smoothness by reducing noisy aggregations and utilizing topological knowledge. Extensive experiments on eleven homophilous or heterophilous graph benchmarks demonstrate the effectiveness of our proposed method DWSSA in alleviating over-smoothness and enhancing deep GNNs performance.

METTL14-mediated m6A epitranscriptomic modification contributes to chemotherapy-induced neuropathic pain by stabilizing GluN2A expression via IGF2BP2.

Epigenetics is a biological process that modifies and regulates gene expression, affects neuronal function, and contributes to pain. However, the mechanism by which epigenetics facilitates and maintains chronic pain is poorly understood. We aimed to determine whether N6-methyladenosine (m6A) specifically modified by methyltransferase-like 14 (METTL14) alters neuronal activity and governs pain by sensitizing the GluN2A subunit of the N-methyl-d-aspartate receptor (NMDAR) in the dorsal root ganglion (DRG) neurons in a model of chemotherapy-induced neuropathic pain (CINP). Using dot blotting, immunofluorescence, gain/loss-of-function, and behavioral assays, we found that m6A levels were upregulated in L4-L6 DRG neurons in CINP in a DBP/METTL14-dependent manner, which was also confirmed in human DRGs. Blocking METTL14 reduced m6A methylation and attenuated pain hypersensitivity. Mechanistically, METTL14-mediated m6A modification facilitated the synaptic plasticity of DRG neurons by enhancing the GluN2A subunit of NMDAR, and inhibiting METTL14 blocked this effect. In contrast, overexpression of METTL14 upregulated m6A modifications, enhanced presynaptic NMDAR activity in DRG neurons, and facilitated pain sensation. Our findings reveal a previously unrecognized mechanism of METTL14-mediated m6A modification in DRG neurons to maintain neuropathic pain. Targeting these molecules may provide a new strategy for pain treatment.

Edaravone Maintains AQP4 Polarity Via OS/MMP9/ß-DG Pathway in an Experimental Intracerebral Hemorrhage Mouse Model.

Oxidative stress (OS) is the main cause of secondary damage following intracerebral hemorrhage (ICH). The polarity expression of aquaporin-4 (AQP4) has been shown to be important in maintaining the homeostasis of water transport and preventing post-injury brain edema in various neurological disorders. This study primarily aimed to investigate the effect of the oxygen free radical scavenger, edaravone, on AQP4 polarity expression in an ICH mouse model and determine whether it involves in AQP4 polarity expression via the OS/MMP9/ß-dystroglycan (ß-DG) pathway. The ICH mouse model was established by autologous blood injection into the basal nucleus. Edaravone or the specific inhibitor of matrix metalloproteinase 9 (MMP9), MMP9-IN-1, called MMP9-inh was administered 10 min after ICH via intraperitoneal injection. ELISA detection, neurobehavioral tests, dihydroethidium staining (DHE staining), intracisternal tracer infusion, hematoxylin and eosin (HE) staining, immunofluorescence staining, western blotting, Evans blue (EB) permeability assay, and brain water content test were performed. The results showed that OS was exacerbated, AQP4 polarity was lost, drainage function of brain fluids was damaged, brain injury was aggravated, expression of AQP4, MMP9, and GFAP increased, while the expression of ß-DG decreased after ICH. Edaravone reduced OS, restored brain drainage function, reduced brain injury, and downregulated the expression of AQP4, MMP9. Both edaravone and MMP9-inh alleviated brain edema, maintained blood-brain barrier (BBB) integrity, mitigated the loss of AQP4 polarity, downregulated GFAP expression, and upregulated ß-DG expression. The current study suggests that edaravone can maintain AQP4 polarity expression by inhibiting the OS /MMP9/ß-DG pathway after ICH.

Perceptual Learning Based on the Lateral Masking Paradigm in Anisometropic Amblyopia With or Without a Patching History.

Purpose: Perceptual learning (PL) has shown promising performance in restoring visual function in adolescent amblyopes. We retrospectively compared the effect of a well-accepted PL paradigm on patients with anisometropic amblyopia with or without a patching therapy history (patching therapy [PT] group versus no patching therapy [NPT] group). Methods: Eighteen PT and 13 NPT patients with anisometropic amblyopia underwent monocular PL for 3 months. During training, patients practiced a Gabor detection task following the lateral masking paradigm by applying a temporal two-alternative forced choice procedure with the amblyopic eye. Monocular contrast sensitivity functions (CSF), visual acuity, interocular differences in visual function metrics, and stereoacuity were compared before and after training. Results: PL improved the visual acuity of the amblyopia eyes by 0.5 lines on average in the PT group and 1.5 lines in the NPT group. A significant reduction in the interocular difference in visual acuity was observed in the NPT group (P < 0.01) but not in the PT group (P = 0.05). Regarding CSF metrics, the area under the log CSF and cutoff in the amblyopic eyes of the NPT groups increased after training (P < 0.05). In addition, the interocular differences of the CSF metrics (P < 0.05) in the NPT group were significantly reduced. However, in the PT group, all the CSF metrics were unchanged after training. A total of 27 of 31 patients in both groups had no measurable stereopsis pretraining, and recovery after training was not significant. Conclusions: PL based on a lateral masking training paradigm improved visual function in anisometropic amblyopia. Patients without a patching history achieved greater benefits. Translational Relevance: PL based on a lateral masking training paradigm could be a new treatment for amblyopia.

J24335 exerts neuroprotective effects against 6-hydroxydopamine-induced lesions in PC12 cells and mice.

Parkinson's disease is the second most prevalent age-related neurodegenerative disease and disrupts the lives of people aged >60 years. Meanwhile, single-target drugs becoming inapplicable as PD pathogenesis diversifies. Mitochondrial dysfunction and neurotoxicity have been shown to be relevant to the pathogenesis of PD. The novel synthetic compound J24335 (11-Hydroxy-1-(8-methoxy-5-(trifluoromethyl)quinolin-2-yl)undecan-1-one oxime), which has been researched similarly to J2326, has the potential to be a multi-targeted drug and alleviate these lesions. Therefore, we investigated the mechanism of action and potential neuroprotective function of J24335 against 6-OHDA-induced neurotoxicity in mice, and in PC12 cell models. The key target of action of J24335 was also screened. MTT assay, LDH assay, flow cytometry, RT-PCR, LC-MS, OCR and ECAR detection, and Western Blot analysis were performed to characterize the neuroprotective effects of J24335 on PC12 cells and its potential mechanism. Behavioral tests and immunohistochemistry were used to evaluate behavioral changes and brain lesions in mice. Moreover, bioinformatics was employed to assess the drug-likeness of J24335 and screen its potential targets. J24335 attenuated the degradation of mitochondrial membrane potential and enhanced glucose metabolism and mitochondrial biosynthesis to ameliorate 6-OHDA-induced mitochondrial dysfunction. Animal behavioral tests demonstrated that J24335 markedly improved motor function and loss of TH-positive neurons and dopaminergic nerve fibers, and contributed to an increase in the levels of dopamine and its metabolites in brain tissue. The activation of both the CREB/PGC-1α/NRF-1/TFAM and PKA/Akt/GSK-3ß pathways was a major contributor to the neuroprotective effects of J24335. Furthermore, bioinformatics predictions revealed that J24335 is a low toxicity and highly BBB permeable compound targeting 8 key genes (SRC, EGFR, ERBB2, SYK, MAPK14, LYN, NTRK1 and PTPN1). Molecular docking suggested a strong and stable binding between J24335 and the 8 core targets. Taken together, our results indicated that J24335, as a multi-targeted neuroprotective agent with promising therapeutic potential for PD, could protect against 6-OHDA-induced neurotoxicity via two potential pathways in mice and PC12 cells.

Binocular Summation With Quantitative Contrast Sensitivity Function: A Novel Parameter to Evaluate Binocular Function in Intermittent Exotropia.

Purpose: Intermittent exotropia (IXT) is the most common form of strabismus. Surgery can potentially improve binocular function in patients with IXT. We aimed to evaluate binocular function using a novel parameter-binocular summation ratio (BSR), measured using quantitative contrast sensitivity function (CSF) in patients with IXT before and after surgery. Methods: Prospective study of 63 patients with IXT and 41 healthy controls were consecutively enrolled and underwent quantitative CSF testing binocularly and monocularly. BSR was calculated by dividing the CSF of the binocular value by the better monocular value. Forty-eight patients with IXT underwent strabismus surgery. BSR, stereoacuity, fusion ability, and strabismus questionnaires were assessed pre-operatively and 2 months postoperatively. Results: Sixty-three patients with IXT (median age = 9 years) compared with 41 healthy controls showed a worse mean BSR based on all CSF metrics at baseline (the area under the log CSF [AULCSF], spatial frequency [SF] cutoff, and contrast sensitivity at 1.0-18.0 cpd SF). All 48 patients with IXT showed successful alignment after surgery, and there were significant improvements in BSR based on the AULCSF, SF cutoff, and contrast sensitivity at 6.0, 12.0, and 18.0 cpd SF, respectively. The distance stereoacuity and fusion ability also improved after surgery, and a better BSR was associated with better stereoacuity and fusion. For strabismus questionnaires, the psychosocial subscale scores improved postoperatively, whereas the functional subscale scores did not change. Conclusions: BSR based on quantitative CSF can characterize binocular function across a range of spatial frequencies and can be used as a supplemental measurement for monitoring binocularity in patients with IXT in clinical settings.

Desflurane improves electrical activity of neurons and alleviates oxygen-glucose deprivation-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Several volatile anesthetics have presented neuroprotective functions in ischemic injury. This study investigates the effect of desflurane (Des) on neurons following oxygen-glucose deprivation (OGD) challenge and explores the underpinning mechanism. Mouse neurons HT22 were subjected to OGD, which significantly reduced cell viability, increased lactate dehydrogenase release, and promoted cell apoptosis. In addition, the OGD condition increased oxidative stress in HT22 cells, as manifested by increased ROS and MDA contents, decreased SOD activity and GSH/GSSG ratio, and reduced nuclear protein level of Nrf2. Notably, the oxidative stress and neuronal apoptosis were substantially blocked by Des treatment. Bioinformatics suggested potassium voltage-gated channel subfamily A member 1 (Kcna1) as a target of Des. Indeed, the Kcna1 expression in HT22 cells was decreased by OGD but restored by Des treatment. Artificial knockdown of Kcna1 negated the neuroprotective effects of Des. By upregulating Kcna1, Des activated the Kv1.1 channel, therefore enhancing K+ currents and inducing neuronal repolarization. Pharmacological inhibition of the Kv1.1 channel reversed the protective effects of Des against OGD-induced injury. Collectively, this study demonstrates that Des improves electrical activity of neurons and alleviates OGD-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Inferior displacement of the lateral rectus muscle insertion in exotropia with mild V-pattern or vertical deviation.

BACKGROUND: To describe clinical features and intraoperative findings of the patients with exotropia who presented mild V-pattern or vertical deviation, and to investigate the surgical outcomes of anatomical relocation of inferiorly displaced lateral rectus (LR) muscle insertion. METHODS: Detailed ophthalmological evaluations were obtained in 42 consecutive patients, and the horizontal rectus muscle insertions were detected intraoperatively. The displaced insertion of LR muscle was corrected accompanied with classic recession-resection procedure. RESULTS: The inferiorly displaced LR muscle insertions were detected in 19 patients (Group A), while the remaining 23 patients (Group B) had normal insertions. The mean distance of displaced insertion from the normal position was 2.92 ± 1.05 mm (range: 1.0-4.0). Mild V-pattern was more common in Group A (78.9%, 15/19) than Group B (47.8%, 11/23), and the magnitude of V-pattern in Group A (6.16 ± 3.91 PD) was also greater than Group B (3.43 ± 3.92 PD). The fundus extorsions of the affected eyes (9.68 ± 4.77 °) were greater than the contralateral eyes (5.91 ± 5.82 °) in Group A. At the 2 months follow-up, mild V-pattern and mild vertical deviation were corrected by upward transposition. The significant correlations were identified between the pre-operative misalignments and the amounts of misalignments correction. CONCLUSIONS: Nearly half of the cases with mild V-pattern or vertical deviation resulted from the inferiorly displaced LR muscle insertion, so the intraoperative exploration of the LR muscle insertion is strongly suggested. Upward transposition may effectively correct both the mild V-pattern and vertical deviation.

Comparing the impact of three-dimensional digital visualization technology versus traditional microscopy on microsurgeons in microsurgery: a prospective self-controlled study.

BACKGROUND: Emerging three-dimensional digital visualization technology (DVT) provides more advantages than traditional microscopy in microsurgery; however, its impact on microsurgeons' visual and nervous systems and delicate microsurgery is still unclear, which hinders the wider implementation of DVT in digital visualization for microsurgery. METHODS AND MATERIAL: Forty-two microsurgeons from the Zhongshan Ophthalmic Center were enrolled in this prospective self-controlled study. Each microsurgeon consecutively performed 30 min conjunctival sutures using a three-dimensional digital display and a microscope, respectively. Visual function, autonomic nerve activity, and subjective symptoms were evaluated before and immediately after the operation. Visual functions, including accommodative lag, accommodative amplitude, near point of convergence and contrast sensitivity function (CSF), were measured by an expert optometrist. Heart rate variability was recorded by a wearable device for monitoring autonomic nervous activity. Subjective symptoms were evaluated by questionnaires. Microsurgical performance was assessed by the video-based Objective Structured Assessment of Technical Skill (OSATS) tool. RESULTS: Accommodative lag decreased from 0.63 (0.18) diopters (D) to 0.55 (0.16) D ( P =0.014), area under the log contrast sensitivity function increased from 1.49 (0.15) to 1.52 (0.14) ( P =0.037), and heart rate variability decreased from 36.00 (13.54) milliseconds (ms) to 32.26 (12.35) ms ( P =0.004) after using the DVT, but the changes showed no differences compared to traditional microscopy ( P >0.05). No statistical significance was observed for global OSATS scores between the two rounds of operations [mean difference, 0.05 (95% CI: -1.17 to 1.08) points; P =0.95]. Subjective symptoms were quite mild after using both techniques. CONCLUSIONS: The impact of DVT-based procedures on microsurgeons includes enhanced accommodation and sympathetic activity, but the changes and surgical performance are not significantly different from those of microscopy-based microsurgery. Our findings indicate that short-term use of DVT is reliable for microsurgery and the long-term effect of using DVT deserve more consideration.

CircDYM attenuates microglial apoptosis via CEBPB/ZC3H4 axis in LPS-induced mouse model of depression.

Major depressive disorder (MDD) is a highly prevalent condition and one of the most common psychiatric disorders worldwide. Circular RNA (circRNA) has been increasingly implicated in MDD. However, a comprehensive understanding of circRNA and microglial apoptosis in depression is incomplete. Here, we show that circDYM inhibits microglial apoptosis induced by LPS via CEBPB/ZC3H4 axis. CircDYM prevents the translocation of CEBPB from cytoplasm to the nucleus by binding with CEBPB. Moreover, LPS-induced CEBPB nuclear entry downregulates the expression of ZC3H4, in which promotes autophagy and apoptosis in microglia. Taken together, our findings provide new insights into the relationship between circDYM and microglial apoptosis and shed new light on the function of this novel mechanism in depression-associated complex changes in the brain.

Laser Direct Writing of Flexible Thermal Flow Sensors.

Thin film-based thermal flow sensors afford applications in healthcare and industries owing to their merits in preserving initial flow distributions. However, traditional thermal flow sensors are primarily applied to track flow intensities based on hot-wire or hot-film sensing mechanisms due to their relatively facile device configurations and fabrication strategies. Herein, a calorimetric thermal flow sensor is proposed based on laser direct writing to form laser-induced graphene as heaters and temperature sensors, resulting in monitoring both flow intensities and orientations. Via homogeneously surrounding spiral heaters with multiple temperature sensors, the device exhibits high sensitivity (∼162 K·s/m) at small flows with an extended flow detection range (∼25 m/s). Integrating the device with a data-acquisition board and a dual-mode graphical user interface enables wirelessly and dynamically monitoring respiration and the motion of robotic arms. This versatile flow sensor with facile manufacturing affords potentials in health inspection, remote monitoring, and studying hydrodynamics.

Antagonizing pathological α-synuclein-mediated neurodegeneration by J24335 via the activation of immunoproteasome.

The aggregation of misfolded proteins, such as α-synuclein in Parkinson's disease (PD), occurs intracellularly or extracellularly in the majority of neurodegenerative diseases. The immunoproteasome has more potent chymotrypsin-like activity than normal proteasome. Thus, degradation of α-synuclein aggregation via immunoproteasome is an attractive approach for PD drug development. Herein, we aimed to determine if novel compound, 11-Hydroxy-1-(8-methoxy-5-(trifluoromethyl)quinolin-2-yl)undecan-1-one oxime (named as J24335), is a promising candidate for disease-modifying therapy to prevent the pathological progression of neurodegenerative diseases, such as PD. The effects of J24335 on inducible PC12/A53T-α-syn cell viability and cytotoxicity were evaluated by MTT assay and LDH assay, respectively. Evaluation of various proteasome activities was done by measuring the luminescence of enzymatic activity after the addition of different amounts of aminoluciferin. Immunoblotting and real-time PCR were employed to detect the expression of various proteins and genes, respectively. We also used a transgenic mouse model for behavioral testing and immunochemical analysis, to assess the neuroprotective effects of J24335. J24335 inhibited wild-type and mutant α-synuclein aggregation without affecting the growth or death of neuronal cells. The inhibition of α-synuclein aggregation by J24335 was caused by activation of immunoproteasome, as mediated by upregulation of LMP7, and increased cellular chymotrypsin-like activity in 20S proteasome. J24335-enhanced immunoproteasome activity was mediated by PKA/Akt/mTOR pathway activation. Moreover, animal studies revealed that J24335 treatment markedly mitigated both the loss of tyrosine hydroxylase-positive (TH-) neurons and impaired motor skill development. This is the first report to use J24335 as an immunoproteasome enhancing agent to antagonize pathological α-synuclein-mediated neurodegeneration.

Fabrication of Superhydrophobic Porous Brass by Chemical Dealloying for Efficient Emulsion Separation.

By taking advantage of typical dealloying and subsequent aging methods, a novel homogeneous porous brass with a micro/nano hierarchical structure was prepared without any chemical modification. The treatment of commercial brass with hot concentrated HCl solution caused preferential etching of Zn from Cu62Zn38 alloy foil, leaving a microporous skeleton with an average tortuous channel size of 1.6 µm for liquid transfer. After storage in the atmosphere for 7 days, the wettability of the dealloyed brass changed from superhydrophilic to superhydrophobic with a contact angle > 156° and sliding angle < 7°. The aging treatment enhanced the hydrophobicity of the brass by the formation of Cu2O on the surface. By virtue of the opposite wettability to water and oil, the aged brass separated surfactant-stabilized water-in-oil emulsions with separation efficiency of over 99.4% and permeate flux of about 851 L·m-2·h-1 even after recycling for 60 times. After 10 times of tape peeling or sandpaper abrasion, the aged brass maintained its superhydrophobicity, indicating its excellent mechanical stability. Moreover, the aged brass still retained its superhydrophobicity after exposure to high temperatures or corrosive solutions, displaying high resistance to extreme environments. The reason may be that the bicontinuous porous structure throughout the whole foil endows stable mechanical properties to tolerate extreme environments. This method should have a promising future in expanding the applications of alloys.

Identifying circRNA-miRNA-mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long non-coding RNAs, and 86 differentially expressed messenger RNAs (mRNAs) were identified utilizing RNA sequencing. CircRNA-targeted microRNAs (miRNAs) were predicted using miRanda, and miRNA-targeted mRNAs were predicted using TargetScan and miRDB. The intersection of sequencing and mRNA prediction results was selected to establish the circRNA-miRNA-mRNA networks, which include 15 circRNAs, 18 miRNAs, and 11 mRNAs. Functional enrichment pathway analyses and immune infiltration analyses revealed that differentially expressed mRNAs were enriched in the immune system, especially in T cells, monocytes, and macrophages. Cdh1, Satb2, Fas, P2ry2, and Zfhx2 were further identified as hub genes and validated by RT-qPCR, correlating with macrophages, plasmacytoid dendritic cells, and central memory CD4 T cells in CIPN. Additionally, we predicted the associated diseases, 36 potential transcription factors (TFs), and 30 putative drugs for hub genes using the DisGeNET, TRRUST, and DGIdb databases, respectively. Our results indicated the crucial role of circRNAs, and the immune microenvironment played in CIPN, providing novel insights for further research.