Vertically Integrated Monolithic Neuromorphic Nanowire Device for Physiological Information Processing.

This study demonstrates the conceptual design and fabrication of a vertically integrated monolithic (VIM) neuromorphic device. The device comprises an n-type SnO2 nanowire bottom channel connected by a shared gate to a p-type P3HT nanowire top channel. This architecture establishes two distinct neural pathways with different response behaviors. The device generates excitatory and inhibitory postsynaptic currents, mimicking the corelease mechanism of bilingual synapses. To enhance the signal processing efficiency, we employed a bipolar spike encoding strategy to convert fluctuating sensory signals to spike trains containing positive and negative pulses. Utilizing the neuromorphic platform for synaptic processing, physiological signals featuring bidirectional fluctuations, including electrocardiogram and breathing signals, can be classified with an accuracy of over 90%. The VIM device holds considerable promise as a solution for developing highly integrated neuromorphic hardware for healthcare and edge intelligence applications.

Comprehensive analysis reveals the prognostic and immunogenic characteristics of DNA methylation regulators in lung adenocarcinoma.

DNA methylation regulators (DMRs) play a key role in DNA methylation, thus mediating tumor occurrence, metastasis, and immunomodulation. However, the effects of DMRs on clinical outcomes and immunotherapy response remain unexplored in lung adenocarcinoma (LUAD). In this study, eight LUAD cohorts and one immunotherapeutic cohort of lung cancer were utilized. We constructed a DNA methylation regulators-related signature (DMRRS) using univariate and multivariate COX regression analysis. The DMRRS-defined low-risk group was preferentially associated with favorable prognosis, tumor-inhibiting microenvironment, more sensitivity to several targeted therapy drugs, and better immune response. Afterward, the prognostic value and predictive potential in immunotherapy response were validated. Collectively, our findings uncovered that the DMRRS was closely associated with the tumor immune microenvironment and could effectively predict the clinical outcome and immune response of LUAD patients.

Multidimensional plasma lipid composition and its causal association with type 2 diabetes mellitus: A Mendelian randomization study.

BACKGROUND AND AIM: Recent research extends our knowledge of plasma lipid species, building on established links between serum lipid levels and Type 2 Diabetes Mellitus (T2DM) risk. Identifying the causal roles of these lipid species is key to improving T2DM risk assessment. METHODS AND RESULTS: This study employs Mendelian randomization (MR) to investigate the causal relationship between 179 lipid species across 13 lipid categories and T2DM. Summary-level data were sourced from genome-wide association studies. The primary analytical methods included the inverse variance weighted (IVW) approach and the Wald ratio, complemented by a series of sensitivity analyses to ensure the robustness of results. The IVW analysis reveals a significant causal association between elevated levels of ceramide (d40:2) (OR = 1.071, 95% CI 1.034-1.109, P = 1.36 × 10-4), sphingomyelin (d38:1) (OR = 1.052, 95% CI 1.028-1.077, P = 1.80 × 10-5), and triacylglycerol (56:8) (OR = 1.174, 95% CI 1.108-1.243, P = 4.65 × 10-8), and an increased risk of T2DM. Conversely, Wald ratio analysis indicates that higher levels of phosphatidylcholine (O-16:1_16:0) (OR = 0.928, 95% CI 0.892-0.966, P = 2.37 × 10-4), phosphatidylcholine (O-16:1_20:4) (OR = 0.932, 95% CI 0.897-0.967, P = 2.37 × 10-4), and phosphatidylcholine (O-18:2_20:4) (OR = 0.872, 95% CI 0.812-0.935, P = 1.24 × 10-4) are significantly associated with a reduced risk of T2DM. Furthermore, suggestive causal evidence for 22 additional lipid species was identified. CONCLUSIONS: This MR study establishes a causal relationship between specific lipid classes in modulating the risk of T2DM. It offers new insights for risk assessment and potential therapeutic targets in T2DM.

Mixed-Dimensional Nanoparticle-Nanowire Channels for Flexible Optoelectronic Artificial Synapse with Enhanced Photoelectric Response and Asymmetric Bidirectional Plasticity.

A mixed-dimensional dual-channel synaptic transistor composed of inorganic nanoparticles and organic nanowires was fabricated to expand the photoelectric gain range. The device can actualize the sensitization features of the nociceptor and shows improved responsiveness to visible light. Under electrical pulses with different polarities, the apparatus exhibits reconfigurable asymmetric bidirectional plasticity. Moreover, the devices demonstrate good operational tolerance and mechanical stability, retaining more than 60% of their maximum responsiveness after 100 consecutive/bidirectional and 1000 flex/flat operations. The improved photoelectric response of the device endows a high image recognition accuracy of greater than 80%. Asymmetric bidirectional plasticity is used as punishment/reward in a psychological experiment to emulate the improvement of learning motivation and enables real-time forward and backward deflection (+7 and -25°) of artificial muscle. The mixed-dimensional optoelectronic artificial synapses with switchable behavior and electron/hole transport type have important prospects for neuromorphic processing and artificial somatosensory nerves.

Effect of red-light therapy on retinal and choroidal blood perfusion in myopic children.

OBJECTIVE: To investigate the effect of repeated low-level red-light therapy (RLRLT) on retinal and choroidal blood perfusion in myopic children. METHODS: Forty-seven myopic children (mean spherical equivalent refractive error [SE]: -2.31 ± 1.26 D; age range: 8.0-11.0 years) were enrolled and received RLRLT (power 2 mW, wavelength 650 nm) for 3 min twice a day, while 20 myopic children (SE: -2.75 ± 0.84 D; age range: 7.0-10.0 years) were included as a control group. All participants wore single-vision distance glasses. Refractive error, axial length (AL) and other biometric parameters were measured at baseline and during follow-up visits in the first, second and fourth weeks after initiation of treatment. Retinal thickness, subfoveal choroidal thickness (SFCT), total choroidal area (TCA), luminal area (LA), stromal area (SA) and choroidal vascularity index (CVI) were obtained using optical coherence tomography (OCT). The percentage retinal vascular density (VD%) and choriocapillaris flow voids (FV%) were measured using en-face OCT angiography. RESULTS: After 4 weeks of treatment, a significant increase in SFCT was observed in the RLRLT group, with an average increase of 14.5 µm (95% confidence interval [CI]: 9.6-19.5 µm), compared with a decrease of -1.7 µm (95% CI: -9.1 to 5.7 µm) in the control group (p < 0.0001). However, no significant changes in retinal thickness or VD% were observed in either group (all p > 0.05). In the OCT images from the RLRLT group, no abnormal retinal morphology related to photodamage was observed. The horizontal scans revealed an increase in TCA, LA and CVI over time (all p < 0.05), while SA and FV% remained unchanged (both p > 0.05). CONCLUSIONS: These findings indicate that RLRLT can enhance choroidal blood perfusion in myopic children, demonstrating a cumulative effect over time.

Associated risk factors of postoperative pain after glaucoma surgery: a prospective study.

PURPOSE: This study aimed to determine degree of postoperative pain and the incidence of serious postoperative pain after glaucoma surgery and further to identify the associated risk factors. METHODS: A total of 194 consecutive patients who were diagnosed with glaucoma and underwent glaucoma surgery were enrolled in this study. The intensity of postoperative pain was evaluated using numerical rating scale (NRS) within 24 h after surgery; NRS ≥ 5 was considered as clinically significant postoperative pain. Risk factors associated with the development of postoperative pain were analyzed by multivariate logistic regression analysis. RESULTS: Clinically significant postoperative pain was experienced at any time after glaucoma surgery in 41.75% of the patients, which peak at 2 h. 27.8% of the patients requested analgesic medication within 24 h after surgery. According to multivariate logistic regression analysis, preoperative anxiety (OR = 4.13 [1.29-13.2], p = 0.017), cyclophotocoagulation (OR = 30.9 [3.47-375.1], p = 0.002), and phacotrabeculectomy combined with or without intraocular lens implantation (OR = 30.0 [2.69-335.6], p = 0.006) were associated with increased clinically significant postoperative pain. Interestingly, patients with diabetes and/or hypertension were associated with less postoperative pain after glaucoma surgery (OR = 0.23 [0.08-0.64], p = 0.005). CONCLUSION: Patients undergoing glaucoma surgery tend to experience postoperative pain in the early postoperative period. Anxiety level and surgery types of cyclophotocoagulation and phacotrabeculectomy are risk factors for postoperative pain. Patients with diabetes and/or hypertension are less likely to develop postoperative pain.

Recent Process of Flexible Transistor-Structured Memory.

Flexible transistor-structured memory (FTSM) has attracted great attention for its important role in flexible electronics. For nonvolatile information storage, FTSMs with floating-gate, charge-trap, and ferroelectric mechanisms have been developed. By introducing an optical sensory module, FTSM can be operated by optical inputs to function as an optical memory transistor. As a special type of FTSM, transistor-structured artificial synapse emulates important functions of a biological synapse to mimic brain-inspired memory behaviors and nervous signal transmissions. This work reviews the recent development of the above mentioned FTSMs, with a focus on working mechanism and materials, and flexibility.

Improved receiver of ICI compensation for a spectral efficient frequency division multiplexing IM/DD system.

Spectral efficient frequency division multiplexing (SEFDM) can greatly increase the spectral efficiency for intensity modulation/direct detection (IM/DD) optical communication systems. The sphere detection algorithm (SD) is the most efficient way to get the maximum likelihood (ML) solution to solve the inter-carrier interference (ICI) induced by the bandwidth compression of SEFDM system. However, SD algorithm is restricted by the numbers of subcarriers for SEFDM system, especially for larger numbers. Therefore, a sorted Gram-Schmidt (SGS) orthogonal decomposition algorithm, which can be applied to any subcarrier numbers, is proposed to overcome this restriction. To the best of our knowledge, the searched paths of FSD are researched for the first time to balance performance and complexity. Based on the analysis, a soft-tree-width sphere detection algorithm (SSD) is proposed and demonstrated by simulation and experiment. The results show that the proposed algorithm can greatly reduce the computational complexity (at least 40%) with the same system performance. The proposed algorithms are a promising candidate for flexible and efficient SEFDM systems. The SEFDM with the proposed detector is significant for the IM/DD optical systems.

TLR2 signaling contributes to the angiogenesis of oxygen-induced retinopathy.

PURPOSE: To evaluate the role of Toll-like receptor 2 (TLR2) signaling in retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). MATERIALS AND METHODS: The OIR model was established in C57BL/6J wild type (WT) mice and TLR2-/- mice. Retinal neovascularization in the OIR model was measured by counting new vascular cell nuclei above the internal limiting membrane and analyzing flat-mounted retinas perfused with fluorescein dextran and immunostained with Griffonia Simplicifolia (GS) isolectin. The expression of TLR2 and VEGF in the retina was detected by immunofluorescence. Expression of TGF- ß1, b-FGF, and IL-6 mRNA in the retina was measured by quantitative real-time PCR. RESULTS: Compared to WT OIR mice, retinal neovascularization was attenuated in TLR2-/- OIR mice. The co-expressions of TLR2 and VEGF were remarkably and consistently increased in WT OIR mice; however, there was no expression of TLR2 and a significant decrease in VEGF expression in TLR2-/- OIR mice. These results suggest that TLR2 plays a central role in OIR model angiogenesis. Expression of TGF- ß1, b-FGF, and IL-6 mRNA were reduced in the TLR2-/- OIR mice, suggesting that the inflammatory response induced by TLR2 relates to angiogenesis. CONCLUSION: TLR2 signaling in the retina is associated with neovascularization in mice. Inflammation contributes to the activation of angiogenesis and is partially mediated through the TLR2-VEGF retinal signaling pathway.

Integrated analyses identify potential prognostic markers for uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, which has a high rate of metastases and can induce vision loss and even death to the patients. To identify suitable prognostic markers of UM for the early detection or prognosis prediction would be an essential step toward successful management of the disease. Herein, we extracted the mRNA expression data along with the clinical information from The Cancer Genome Atlas (TCGA) database. A total of eight co-expression modules were constructed by 5,000 genes based on the weighted gene co-expression network analysis (WGCNA). We found the blue and yellow modules were significantly associated with clinical stage. The Cox regression analyses found the blue, yellow, green and brown modules were significantly associated with overall survival (OS), while the blue, yellow, brown, green and pink modules were significantly associated with recurrence-free survival (RFS). Furthermore, the hallmark pathway enrichment analyses found the genes encompassed in the blue, yellow, and brown modules were significantly enriched in critical pathways involved in tumorigenesis and progression process, such as EMT and KRAS pathways. The hub-genes in these three modules were visualized by Cytoscape software and further validated by an external Gene Expression Omnibus (GEO) dataset. Besides, the OS and RFS predicting signatures were constructed based on the validated hub-genes according to the LASSO Cox regression model. The UM patients were assigned to low-/high-risk population. The survival analyses indicated high-risk patients mostly had bad OS/RFS rate compared with the low-risk population. The receiver operating characteristic (ROC) curve proved the stability and superiority of the two signatures. To sum up, our findings provide a framework of co-expression network of UM and identify a series of biomarkers, which will benefit from improving the prognosis prediction of UM patients.

Metabolic syndrome is independently associated with a mildly reduced estimated glomerular filtration rate: a cross-sectional study.

BACKGROUND: Association between metabolic syndrome (MS) and mildly reduced estimated glomerular filtration rates (eGFRs) remains unclear. Therefore, we aimed to evaluate the association between MS and a mildly reduced eGFR in Chinese adults. METHODS: Anthropometric and biochemical examinations were performed in 2992 individuals. The eGFR was calculated from the creatinine level. MS was defined according to the Adult Treatment Panel III criteria as the presence of three or more risk factors. Mildly reduced eGFR was defined as a value between 60 and 90 mL/min/1.73 m2. Multiple linear regression and multiple logistic regression analysis were used to evaluate association between metabolic syndrome and estimate glomerular filtration rate. RESULTS: After adjusting for several potential confounders, the participants with MS showed a 1.29-fold increased odds ratio for a mildly reduced eGFR compared with those without MS. Additionally, the odds ratios (and 95% confidence intervals (CIs)) for mildly reduced eGFR in participants with elevated triglycerides (TG), decreased high-density lipoprotein (HDL), obesity and elevated fasting blood glucose (FPG) after multivariable adjustment were 1.25 (1.05-1.49), 1.23 (1.03-1.48), 1.22 (1.03-1.45) and 0.64 (0.52-0.78), respectively. The odds ratios (95% CIs) for hyperfiltration in participants with elevated FPG and HbA1c levels after multivariable adjustment were 1.53 (1.30-1.81) and 2.86 (2.00-4.09), respectively. CONCLUSIONS: MS is associated with an increased risk of a mildly reduced eGFR in the Chinese population, and several individual components of MS have different impacts on eGFR levels. MS had dual roles on renal damage. TRIAL REGISTRATION: ChiCTR-TRC- 14005029 . Registered 28 July 2014.

Genetic Insights into the causal relationship between cannabis use and diabetic phenotypes: A genetic correlation and Mendelian randomization study.

BACKGROUND: Previous studies have highlighted the association between cannabis use and diabetes and its complications; however, the causality remains ambiguous. METHODS: Univariate Mendelian randomization (MR), multivariate MR, mediation MR, and linkage disequilibrium score (LDSC) analysis to assess the causal relationship between cannabis use and 12 diabetic phenotypes. Summary statistics for lifetime cannabis use (N = 184,765) and cannabis use disorder (CUD) (N = 374,287) from genome-wide association studies. The primary method used was inverse-variance-weighted (IVW). A range of sensitivity analyses ensured the robustness of the results. RESULTS: LDSC analysis revealed a significant genetic correlation between CUD and T2DM, as well as between lifetime cannabis use and four diabetic phenotypes (P < 0.05). After correction by false discovery rate (FDR), the primary IVW analysis indicates that the genetically predicted CUD is positively associated with the risk of diabetic hypoglycemia (OR = 1.11, 95% CI 1.04-1.20, P = 0.003, PFDR = 0.04) and proliferative diabetic retinopathy (PDR) (OR = 1.12, 95% CI 1.04-1.19, P = 4.89×10-4, PFDR =0.01). Additionally, suggestive evidence links CUD with increased risks of diabetic nephropathy, type 1 diabetes mellitus (T1DM), diabetic retinopathy, and T1DM associated with diabetic ketoacidosis (P < 0.05 & PFDR > 0.05). No causal relationship was detected between lifetime cannabis use and diabetic phenotypes (P > 0.05 & PFDR > 0.05). Multivariable and mediation MR analyses revealed that glycated hemoglobin A1c partially mediates the causal effect of CUD on PDR and diabetic hypoglycemia. CONCLUSION: This MR study suggests that CUD may have a causal role in several diabetic disease phenotypes.

Corrigendum: The influence of adolescents' internet adaptation on internet addiction: the mediating role of internet cultural adaptation.

[This corrects the article DOI: 10.3389/fpsyt.2023.1338343.].

Choriocapillaris flow features in children with myopic anisometropia.

AIMS: To examine differences between the eyes in choriocapillaris perfusion and choroidal thickness in children with myopic anisometropia. METHODS: In this observational and prospective study, 46 children with myopic anisometropia were enrolled. Choriocapillaris perfusion parameters, including the percentage of flow voids, the total number of flow voids and the average flow void area were obtained by optical coherence tomography angiography (OCTA). The OCTA image was divided into a 1 mm-diameter central circle (C1) and a 2.5 mm-diameter annulus (without the inner central 1 mm circle, C1-2.5). Both C1 and C1-2.5 are centred on the foveola. The C1-2.5 was divided into nasal (N1-2.5), temporal (T1-2.5), inferior (I1-2.5) and superior (S1-2.5) areas. Differences in these parameters in different regions between eyes were analysed. RESULTS: There were no significant differences in the percentage of flow voids and the average flow void area between the fellow eyes. The total number of signal voids was significantly higher in the less myopic eyes in C1-2.5 (p=0.032), S1-2.5 (p=0.008) and N1-2.5 (p=0.019). Changes in spherical equivalent refraction and axial length were both correlated with the changes in the total number of flow voids in N1-2.5 (R=-0.431, p=0.03; R=-0.297, p=0.047). CONCLUSIONS: The choroid in the macular region becomes thinner and the total number of flow voids in the nasal macular region decreased with the amplitude of myopia. This suggests that a decrease in total number of flow voids may indicate an early change in myopia.

Body mass index, smoking behavior, and depression mediated the effects of schizophrenia on chronic obstructive pulmonary disease: trans-ethnic Mendelian-randomization analysis.

Background: Previous studies have highlighted the association between schizophrenia (SCZ) and chronic obstructive pulmonary disease (COPD), yet the causal relationship remains unestablished. Methods: Under the genome-wide significance threshold (P<5×10-8), data from individuals of European (EUR) and East Asian (EAS) ancestries with SCZ were selected for analysis. Univariable Mendelian randomization (MR) explored the causal relationship between SCZ and COPD. Linkage disequilibrium score (LDSC) regression was used to calculate genetic correlation, while multivariable and mediation MR further investigated the roles of six confounding factors and their mediating effects. The primary method utilized was inverse-variance weighted (IVW), complemented by a series of sensitivity analyses and false discovery rate (FDR) correction. Results: LDSC analysis revealed a significant genetic correlation between SCZ and COPD within EUR ancestry (rg = 0.141, P = 6.16×10-7), with no such correlation found in EAS ancestry. IVW indicated a significant causal relationship between SCZ and COPD in EUR ancestry (OR = 1.042, 95% CI 1.013-1.071, P = 0.003, PFDR = 0.015). Additionally, replication datasets provide evidence of consistent causal associations(P < 0.05 & PFDR < 0.05). Multivariable and mediation MR analyses identified body mass index (BMI)(Mediation effect: 50.57%, P = 0.02), age of smoking initiation (Mediation effect: 27.42%, P = 0.02), and major depressive disorder (MDD) (Mediation effect: 60.45%, P = 6.98×10-5) as partial mediators of this causal relationship. No causal associations were observed in EAS (OR = 0.971, 95% CI 0.875-1.073, P = 0.571, PFDR = 0.761) ancestry. No causal associations were found in the reverse analysis across the four ancestries (P > 0.05 & PFDR > 0.05). Conclusions: This study confirmed a causal relationship between SCZ and the risk of COPD in EUR ancestry, with BMI, smoking, and MDD serving as key mediators. Future research on a larger scale is necessary to validate the generalizability of these findings across other ancestries.

A neuromorphic device mimicking synaptic plasticity under different body fluid K+ homeostasis for artificial reflex path construction and pattern recognition.

The ionic environment of body fluids influences nervous functions for maintaining homeostasis in organisms and ensures normal perceptual abilities and reflex activities. Neural reflex activities, such as limb movements, are closely associated with potassium ions (K+). In this study, we developed artificial synaptic devices based on ion concentration-adjustable gels for emulating various synaptic plasticities under different K+ concentrations in body fluids. In addition to performing essential synaptic functions, potential applications in information processing and associative learning using short- and long-term plasticity realized using ion concentration-adjustable gels are presented. Artificial synaptic devices can be used for constructing an artificial neural pathway that controls artificial muscle reflex activities and can be used for image pattern recognition. All tests show a strong relationship with ion homeostasis. These devices could be applied to neuromorphic robots and human-machine interfaces.

Visualized in-sensor computing.

In artificial nervous systems, conductivity changes indicate synaptic weight updates, but they provide limited information compared to living organisms. We present the pioneering design and production of an electrochromic neuromorphic transistor employing color updates to represent synaptic weight for in-sensor computing. Here, we engineer a specialized mechanism for adaptively regulating ion doping through an ion-exchange membrane, enabling precise control over color-coded synaptic weight, an unprecedented achievement. The electrochromic neuromorphic transistor not only enhances electrochromatic capabilities for hardware coding but also establishes a visualized pattern-recognition network. Integrating the electrochromic neuromorphic transistor with an artificial whisker, we simulate a bionic reflex system inspired by the longicorn beetle, achieving real-time visualization of signal flow within the reflex arc in response to environmental stimuli. This research holds promise in extending the biomimetic coding paradigm and advancing the development of bio-hybrid interfaces, particularly in incorporating color-based expressions.

Evaluation of corneal changes with accommodation in young and presbyopic populations using Pentacam High Resolution Scheimpflug system.

BACKGROUND: To evaluate the changes occurring in the cornea with accommodation in young and presbyopic people. DESIGN: Prospective study. PARTICIPANTS: Twenty-three young and 15 presbyopic emmetropic volunteers. METHODS: The Pentacam High Resolution system was used to obtain data on the anterior eye segments of emmetropic volunteers in unaccommodated (with an accommodation stimulus of 0.0 D) and accommodated (with an accommodation stimulus of 5.0 D for the young volunteers and 1.0 D for the presbyopic) states. MAIN OUTCOME MEASURES: Anterior and posterior corneal axial curvature, corneal volume, corneal aberration, anterior chamber depth and anterior chamber volume were evaluated. RESULTS: A significant decline in anterior chamber depth and anterior chamber volume was induced by accommodation in both young and presbyopic volunteers. There was a small but statistically significant change in corneal volume within 3.0, 5.0 and 7.0 mm diameters during accommodation in both groups. The changes in the corneal curvature map were significant with accommodation in both groups, although individual variations were found in anterior and posterior corneal axial curvature. Moreover, the decreased higher order aberrations were found in both anterior and entire cornea. In particular, spherical aberration was changed in the young group with 5.0 D accommodation stimulus. CONCLUSION: This study showed that accommodation can influence the corneal shape and curvature, and, especially, decreased corneal high-order aberrations. Although the modification in corneal shape was small, it produced variations in higher order aberrations with accommodation that may be beneficial for visual performance in near vision.