Inhibition of autophagosome-lysosome fusion contributes to TDCIPP-induced Aß1-42 production in N2a-APPswe cells.

Alzheimer's disease is the most common form of dementia and is characterized by cognitive impairment. The disruption of autophagosome-lysosome function has been linked to the pathogenesis of Alzheimer's disease. Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphorus flame retardant that has the potential to cause neuronal damage. We found that TDCIPP significantly increased the expression of ß-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), presenilin-1 (PS1) and Aß42. Proteomic studies with TMT labeling revealed changes in the profiles of N2a-APPswe cells after exposure to TDCIPP. Proteomic and bioinformatics analyses revealed that lysosomal proteins were dysregulated in N2a-APPswe cells after treatment with TDCIPP. The LC3, P62, CTSD, and LAMP1 levels were increased after TDCIPP exposure, and dysregulated protein expression was validated by Western blotting. The exposure to TDCIPP led to the accumulation of autophagosomes, and this phenomenon was enhanced in the presence of chloroquine (CQ). Our results revealed for the first time that TDCIPP could be a potential environmental risk factor for AD development. The inhibition of autophagosome-lysosome fusion may have a significant impact on the generation of Aß1-42 in response to TDCIPP.

Causal association between air pollution and autoimmune diseases: a two-sample Mendelian randomization study.

Background: In recent years, an increasing number of observational studies have reported the impact of air pollution on autoimmune diseases (ADs). However, no Mendelian randomization (MR) studies have been conducted to investigate the causal relationships. To enhance our understanding of causality, we examined the causal relationships between particulate matter (PM) and nitrogen oxides (NOx) and ADs. Methods: We utilized genome-wide association study (GWAS) data on PM and NOx from the UK Biobank in European and East Asian populations. We also extracted integrated GWAS data from the Finnish consortium and the Japanese Biobank for two-sample MR analysis. We employed inverse variance weighted (IVW) analysis to assess the causal relationship between PM and NOx exposure and ADs. Additionally, we conducted supplementary analyses using four methods, including IVW (fixed effects), weighted median, weighted mode, and simple mode, to further investigate this relationship. Results: In the European population, the results of MR analysis suggested a statistically significant association between PM2.5 and psoriasis only (OR = 3.86; 95% CI: 1.89-7.88; PIVW < 0.00625), while a potential association exists between PM2.5-10 and vitiligo (OR = 7.42; 95% CI: 1.02-53.94; PIVW < 0.05), as well as between PM2.5 and systemic lupus erythematosus (OR = 68.17; 95% CI: 2.17-2.1e+03; PIVW < 0.05). In East Asian populations, no causal relationship was found between air pollutants and the risk of systemic lupus erythematosus and rheumatoid arthritis (PIVW > 0.025). There was no pleiotropy in the results. Conclusion: Our results suggest a causal association between PM2.5 and psoriasis in European populations. With the help of air pollution prevention and control, the harmful progression of psoriasis may be slowed.

Integrating machine learning and nontargeted plasma lipidomics to explore lipid characteristics of premetabolic syndrome and metabolic syndrome.

Objective: To identify plasma lipid characteristics associated with premetabolic syndrome (pre-MetS) and metabolic syndrome (MetS) and provide biomarkers through machine learning methods. Methods: Plasma lipidomics profiling was conducted using samples from healthy individuals, pre-MetS patients, and MetS patients. Orthogonal partial least squares-discriminant analysis (OPLS-DA) models were employed to identify dysregulated lipids in the comparative groups. Biomarkers were selected using support vector machine recursive feature elimination (SVM-RFE), random forest (rf), and least absolute shrinkage and selection operator (LASSO) regression, and the performance of two biomarker panels was compared across five machine learning models. Results: In the OPLS-DA models, 50 and 89 lipid metabolites were associated with pre-MetS and MetS patients, respectively. Further machine learning identified two sets of plasma metabolites composed of PS(38:3), DG(16:0/18:1), and TG(16:0/14:1/22:6), TG(16:0/18:2/20:4), and TG(14:0/18:2/18:3), which were used as biomarkers for the pre-MetS and MetS discrimination models in this study. Conclusion: In the initial lipidomics analysis of pre-MetS and MetS, we identified relevant lipid features primarily linked to insulin resistance in key biochemical pathways. Biomarker panels composed of lipidomics components can reflect metabolic changes across different stages of MetS, offering valuable insights for the differential diagnosis of pre-MetS and MetS.

Evaluating the risk of developing hyperuricemia in patients with type 2 diabetes mellitus using least absolute shrinkage and selection operator regression and machine learning algorithm.

Background: Hyperuricemia is a common complication of type 2 diabetes mellitus and can lead to serious consequences such as gout and kidney disease. Methods: Patients with type 2 diabetes mellitus from six different communities in Fuzhou were recruited from June to December 2022. Questionnaires, physical examinations, and laboratory tests were conducted to collect data on various variables. Variable screening steps were performed using univariate and multivariate stepwise regression, least absolute shrinkage and selection operator (LASSO) regression, and Boruta feature selection. The dataset was divided into a training-testing set (80%) and an independent validation set (20%). Six machine learning models were built and validated. Results: A total of 8243 patients with type 2 diabetes mellitus were included in this study. According to Occam's razor method, the LASSO regression algorithm was determined to be the optimal risk factors selection method, and nine variables were identified as parameters for the risk assessment model. The absence of diabetes medication and elevated fasting blood glucose levels exhibited a negative correlation with the risk of hyperuricemia. Conversely, seven other variables demonstrated a positive association with the risk of hyperuricemia among patients diagnosed with type 2 diabetes mellitus. Among the six machine learning models, the artificial neural network (ANN) model demonstrated the highest performance. It achieved an areas under curve of 0.736, accuracy of 68.3%, sensitivity of 65.0%, specificity of 72.2%, precision of 73.6% and F1-score of 69.0%. Conclusions: We developed an ANN model to better evaluate the risk of hyperuricemia in the type 2 diabetes population. In the type 2 diabetes population, women should pay particular attention to their uric acid levels, and type 2 diabetics should not neglect their obesity level, blood pressure, kidney function and lipid profile during their regular medical check-ups, in order to do their best to avoid the risks associated with the combination of type 2 diabetes and hyperuricemia.

Exhaustive exercise decreases tau phosphorylation and modifies biological processes associated with the protein translation and electron transport chain in P301L tau transgenic mice.

Stress response is a fundamental mechanism for cell survival, providing protection under unfavorable conditions. Mitochondrial stress, in particular, can trigger mitophagy, a process that restores cellular health. Exhaustive exercise (EE) is a form of acute mitochondrial stress. The objective of this current study is to investigate the impact of EE on tau pathology in pR5 mice, as well as the potential underlying mechanisms. To evaluate this, we examined the levels of total and phosphorylated tau in the hippocampus of pR5 mice, both with and without EE treatment. Furthermore, the application of weighted correlation network analysis (WGCNA) was employed to identify protein modules associated with the phenotype following the proteomic experiment. The findings of our study demonstrated a significant decrease in tau phosphorylation levels upon EE treatment, in comparison to the pR5 group. Moreover, the proteomic analysis provided additional insights, revealing that the mitigation of tau pathology was primarily attributed to the modulation of various pathways, such as translation factors and oxidative phosphorylation. Additionally, the analysis of heatmaps revealed a significant impact of EE treatment on the translation process and electron transport chain in pR5 mice. Furthermore, biochemical analysis provided further confirmation that EE treatment effectively modulated the ATP level in pR5 mice. In conclusion, our study suggests that the observed decrease in tau phosphorylation resulting from EE treatment may primarily be attributed to its regulation of the translation process and enhancement of mitochondrial function.

Hierarchical porous carbon aerogels as a versatile electrode material for high-stability supercapacitors.

Supercapacitors (SCs), as new energy storage devices with low cost and high performance, urgently require an electrode material with good pore structure and developed graphitization. Herein, we report a 3D hierarchical porous structured carbon aerogel (CA) obtained via dissolving-gelling and a subsequent carbonizing process. The gelling process was realized by using different types of anti-solvents. The carbon aerogel-acetic acid (CA-AA) has a specific surface area of 616.97 m2 g-1 and a specific capacitance of 138 F g-1 which is superior to cellulose-based active carbon. The CA was assembled into a SC, which showed excellent cycle stability. After charging and discharging 5000 times at the current density of 1 A g-1, the capacitance retention ratio of CA-AA reaches 102%. In addition, CA-AA has an energy density of 10.06 W h kg-1 when the power density is 181.06 W kg-1. It provides a choice for non-activation to effectively regulate the porous structure of biomass carbon materials.

An artificial neural network model for evaluating the risk of hyperuricaemia in type 2 diabetes mellitus.

Type 2 diabetes with hyperuricaemia may lead to gout, kidney damage, hypertension, coronary heart disease, etc., further aggravating the condition of diabetes as well as adding to the medical and financial burden. To construct a risk model for hyperuricaemia in patients with type 2 diabetes mellitus based on artificial neural network, and to evaluate the effectiveness of the risk model to provide directions for the prevention and control of the disease in this population. From June to December 2022, 8243 patients with type 2 diabetes were recruited from six community service centers for questionnaire and physical examination. Secondly, the collected data were used to select suitable variables and based on the comparison results, logistic regression was used to screen the variable characteristics. Finally, three risk models for evaluating the risk of hyperuricaemia in type 2 diabetes mellitus were developed using an artificial neural network algorithm and evaluated for performance. A total of eleven factors affecting the development of hyperuricaemia in patients with type 2 diabetes mellitus in this study, including gender, waist circumference, diabetes medication use, diastolic blood pressure, γ-glutamyl transferase, blood urea nitrogen, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting glucose and estimated glomerular filtration rate. Among the generated models, baseline & biochemical risk model had the best performance with cutoff, area under the curve, accuracy, recall, specificity, positive likelihood ratio, negative likelihood ratio, precision, negative predictive value, KAPPA and F1-score were 0.488, 0.744, 0.689, 0.625, 0.749, 2.489, 0.501, 0.697, 0.684, 0.375 and 0.659. In addition, its Brier score was 0.169 and the calibration curve also showed good agreement between fitting and observation. The constructed artificial neural network model has better efficacy and facilitates the reduction of the harm caused by type 2 diabetes mellitus combined with hyperuricaemia.

A quantitative proteomic study reveals oxidative stress and synapse-related proteins contributed to TDCIPP exposure induced neurotoxicity.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been consistently identified in various environmental media and biological specimens. Current understanding of the in vivo toxicities of TDCIPP is limited, especially for potential for neurotoxic and cognitive impairment effects. To better evaluate the potential adverse effect of the chemical on learning and memory, Sprague Dawley (SD) rats were administered TDCIPP via gavage at doses of 40, 120, and 360 mg/kg/day for a period of 90 days. Quantitative proteomic analysis, immunohistochemistry, and Western blotting were employed to assess alterations in proteins following exposure to TDCIPP. An open field test and the Morris Water Maze were used to assess anxiety and spatial learning memory capacity. Administration of TDCIPP induced anxiety and cognitive impairments in rats. Additionally, a noteworthy decrease in the number of neurons was observed in the hippocampal CA3 and dentate gyrus (DG) regions. Proteomic and bioinformatic analyses revealed dysregulation of numerous hippocampal proteins, particularly those associated with synapses (PKN1) or oxidative stress (GSTM4, NQO1, and BMAL1), which was further confirmed by Western blot analysis. In sum, the cognitive impairment of rats caused by TDCIPP exposure was associated with dysregulation of synaptic and oxidative stress-related proteins.

Long non-coding HOXA-AS3 contributes to osteosarcoma progression through the miR-1286/TEAD1 axis.

Long non-coding RNA (lncRNA) HOXA cluster antisense RNA 3 (HOXA-AS3) regulates the progression of several types of human malignancy. However, the role and potential mechanism of HOXA-AS3 in osteosarcoma (OS) remain unknown. In this study, upregulation of HOXA-AS3 was observed in OS tissues and cell lines and associated with poor clinical outcomes. Silencing of HOXA-AS3 significantly inhibited the proliferation, migration and invasion of OS cells in vitro and suppressed the tumorigenesis of OS cells in vivo. Furthermore, knockdown of HOXA-AS3 inhibited the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and epithelial-to-mesenchymal transition (EMT) in OS. Further investigation of this mechanism revealed that HOXA-AS3 could directly upregulate the expression of TEAD1 via its competing endogenous RNA (ceRNA) activity on miR-1286. This study clarified the oncogenic roles of the HOXA-AS3/miR-1286/TEAD1 axis in OS progression, suggesting a novel therapeutic target for OS.

SET-mediated epigenetic dysregulation of p53 impairs trichloroethylene-induced DNA damage response.

Trichloroethylene (TCE) was a widely used industrial solvent, and now has become a major environmental pollutant. Exposure to TCE has been found to result in significant damage to the liver, leading to hepatic toxicity. In our previous study, we discovered that a histone chaperon called SET plays a crucial role in mediating the DNA damage and apoptosis caused by TCE in hepatic cells. However, the precise function of SET in the response to DNA damage is still not fully understood. In this study, we evaluated TCE-induced DNA damage of hepatic L-02 cells with SET-knockdown, then analyzed alterations of H3K79me3 and p53 in hepatic cells and carcinogenic mice livers. Results suggested that SET interferes with DNA response via mediating down-regulation of p53 and partially suppressing H3K79me3 under treatment of TCE. To further verify the regulatory cascade, H3K79me3 was reduced and p53 was knocked down in L-02 cells respectively, and extent of DNA damage was evaluated. Reduced H3K79me3 was found leading to down-regulation of p53 which further exacerbated TCE-induced DNA injury. These findings demonstrated that SET-H3K79me3-p53 served as an epigenetic regulatory axis involved in TCE-induced DNA damage response.

Low-dose Cu exposure enhanced α-synuclein accumulation associates with mitochondrial impairments in mice model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that mainly affects the elder population, and its etiology is enigmatic. Both environmental risks and genetics may influence the development of PD. Excess copper causes neurotoxicity and accelerates the progression of neurodegenerative diseases. However, the underlying mechanisms of copper-induced neurotoxicity remain controversial. In this study, A53T transgenic α-synuclein (A53T) mice and their matching wild-type (WT) mice were treated with a low dose of copper (0.13 ppm copper chlorinated drinking water, equivalent to the copper exposure of human daily copper intake dose) for 4 months, and copper poisoning was performed on human A53T mutant SHSY5Y cells overexpressed with α-synuclein (dose of 1/4 IC50), to test the effects of copper exposure on the body. The results of the open field test showed that the moto function of Cu-treated mice was impaired. Proteomics revealed changes in neurodevelopment, transport function, and mitochondrial membrane-related function in Cu-treated WT mice, which were associated with reduced expression of mitochondrial complex (NDUFA10, ATP5A), dopamine neurons (TH), and dopamine transporter (DAT). Mitochondrial function, nervous system development, synaptic function, and immune response were altered in Cu-treated A53T mice. These changes were associated with increased mitochondrial splitting protein (Drp1), decreased mitochondrial fusion protein (OPA1, Mfn1), abnormalities in mitochondrial autophagy protein (LC3BII/I, P62), decreased dopamine neuron (TH) expression, increased α-synuclein expression, inflammatory factors (IL-6, IL-1ß, and TNF-α) release and microglia (Iba1) activation. In addition, we found that Cu2+ (30 µM) induced excessive ROS production and reduced mitochondrial ATP production in human A53T mutant α-synuclein overexpressing SHSY5Y cells by in vitro experiments. In conclusion, low-dose copper treatment altered critical proteins involved in mitochondrial, neurodevelopmental, and inflammatory responses and affected mitochondria's ROS and ATP production levels.

Degradation performance of methylene blue in metal nanoparticle modified 3D mesoporous wood microchannels.

Wood has a rich three-dimensional pore structure and many bottom-up nanochannels. However, the structure of wood itself has limited ability to adsorb dyes, so the effective combination of the unique structure of wood and Pd NPs was studied to achieve efficient degradation of dyes. First, the three-dimensional structure of natural wood is optimized by combining the complex pore structure of wood with Pd NPs to improve the contact process between the dye and Pd NPs. Then, Pd (II) ion can be well reduced to Pd NPs by wood lignin. In addition, Pd NPs can be fixed by hydroxyl groups on cellulose in wood. The flow state inside Pd NPs/wood film and the contact area between catalyst and dye were discussed in detail by hydrodynamic simulation, which filled the gap. It provides reference for composite structure. When Pd NPs/wood membrane was used to treat methylene blue (MB), the degradation efficiency was up to 96.7%, which was 90% higher than that of natural wood. Its TOF value was 1.82 molMB molPd-1min-1, which was higher than that in the previous literature. Therefore, the novelty of this study is that the mechanism of catalytic degradation of MB by Pd nanoparticles/wood composites is reported for the first time. The internal flow mode and contact condition of the new material are understood, which has a good application prospect.

Pankun: A New Generation of Broadband Ocean Bottom Seismograph.

This paper presents a new broadband ocean bottom seismograph (OBS) developed by the SUSTech OBS lab for passive-source seafloor seismic observations. This instrument, called Pankun, has several key features that set it apart from traditional OBS instruments. In addition to the seismometer-separated scheme, these features include a unique shielding structure to minimize current-induced noise, a compact gimbal for accurate leveling, and low power consumption for extended operation on the seafloor. The design and testing of Pankun's primary components are thoroughly described in this paper. The instrument has been successfully tested in the South China Sea, demonstrating its ability to record high-quality seismic data. The anti-current shielding structure of Pankun OBS has the potential to improve low-frequency signals, particularly on the horizontal components, in seafloor seismic data.

Chrysin prevents inflammation-coinciding liver steatosis via AMPK signalling.

OBJECTIVES: We aimed to elucidate the therapeutic potential of Chrysin (CN) against the high-fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) and its mechanism. METHODS: To assess the hypothesis, NAFLD was induced in C57BL/6 mice by feeding a high-fat diet for up to two months, followed by CN administration (for three months). Liver injury/toxicity, lipid deposition, inflammation and fibrosis were detected via molecular and biochemical analysis, including blood chemistry, immunoimaging and immunoblotting. Moreover, we performed proteomic analysis to illuminate Chrysin's therapeutic effects further. KEY FINDINGS: CN treatment significantly reduced liver-fat accumulation and inflammation, ultimately improving obesity and liver injury in NAFLD mice. Proteomic analysis showed that CN modified the protein expression profiles in the liver, particularly improving the expression of proteins related to energy, metabolism and inflammation. Mechanistically, CN treatment increased AMP-activated protein and phosphorylated CoA (P-ACC). Concurrently, it reduced inflammation and inflammation activation by inhibiting NLRP3 expression. CONCLUSIONS: In summary, CN treatment reduced lipid metabolism by AMPK and inflammasome activation by NLRP3 inhibition, ultimately improving NAFLD progression. These findings suggest that CN could be a potential treatment candidate for the NFLAD condition.

Co-exposure to parabens and triclosan and associations with cognitive impairment in an elderly population from Shenzhen, China.

Parabens and triclosan (TCS) have been extensively applied in personal care products (PCPs) as preservatives and antibacterial agents. However, their potentiality to disrupt the neurological system has induced increasing concern. The elderly population is at a higher risk of neurodegenerative disorder, although research on its association with PCP exposure remains scarce. Here, we measured the urinary levels of four parabens, TCS, and an oxidative stress marker among 540 participants from the Shenzhen aging-related disorder cohort during 2017-2018. The Mini-Mental State Examination (MMSE) was used to assess the cognitive status of participants. Their demographic, dietary, and behavioral factors were collected via questionnaire survey. Among the four paraben analogs, the median concentration of methyl parabens (MeP) was the highest (Low-risk group: 1.21 ng/mL, High-risk group: 1.64 ng/mL). TCS and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were detected in more than 90% of the samples. Weighted quantile sum regression and quantile-based g-computation showed that the combined effect of all analytes was positively associated with the level of 8-OHdG. BtP, EtP and MeP were identified as the major contributors to the joint effect. After stratification by gender, females exhibited more pronounced changes in urinary 8-OHdG level than males. However, the positive correlation between co-exposure to parabens and TCS and cognitive impairment was not significant (p > 0.05) in both models, which warrants investigation with the larger sample size.

Correlating metal exposures and dietary habits with hyperuricemia in a large urban elderly cohort by artificial intelligence.

Epidemiological studies using conventional statistical methods have reported an association between individual metal exposure and hyperuricemia (HUA). There is also evidence that diet may influence HUA development, although the available data are inconsistent. We therefore used an elastic net regression (ENR) model to screen the usefulness of various environmental and dietary factors as predictors of HUA in a large sample cohort. This study included 6217 subjects drawn from the Shenzhen Aging Related Disorder Cohort. We obtained information on the subjects' dietary habits via face-to-face interviews and used inductively coupled plasma mass spectrometry (ICP-MS) to measure the urinary concentrations of 24 metals to which elderly persons in large urban areas may be exposed. An elastic net regression (ENR) model was generated to screen the utility of the metals and dietary factors as predictors of HUA, and we demonstrated the superiority of the ENR model by comparing it to a traditional logistic regression model. The identified predictors were used to create a clinically usable nomogram for identifying patients at risk of developing HUA. The area under curve (AUC) value of the final model was 0.692 for the training set and 0.706 for the test set. Important predictors of HUA were Zn, As, V, and Fe as well as consumption of wheat, beans, and rice; the corresponding estimated odds ratios and 95% confidence intervals were 1.091 (0.932,1.251), 1.190 (1.093,1.286), 0.924 (0.793,1.055), 0.704 (0.626,0.781), 0.998 (0.996,1.001), 0.993 (0.989,0.998), and 1.001 (0.998,1.002), respectively. In contrast to previous studies, we found that both urinary metal concentrations and dietary habits are important for predicting HUA risk. Exposure to specific metals and consumption of specific foods were identified as important predictors of HUA, indicating that the incidence of this disease could be reduced by reducing exposure to these metals and promoting improved dietary habits.

Association between organophosphorus flame retardants exposure and cognitive impairment among elderly population in southern China.

The wide application of organophosphorus flame retardants (OPFRs) in consumer products leads to their ubiquitous occurrence. The neurotoxicity of OPFRs has been raised, whereas evidence from the elderly population were rather scarce. Hence, a case-control study was conducted based on the Shenzhen Aging-related Disorder Cohort. A total of 184 cases [Mini-mental State Examination (MMSE) < 24] and 795 participants as controls (MMSE ≥24) were recruited. Eight metabolites of OPFRs (m-OPFRs) in urine samples were measured, including bis(2-butoxyethyl) phosphate (BBOEP), bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), dibutyl phosphate (DBP), di-o-cresyl phosphate (DOCP), di-p-cresyl phosphate (DPCP) and diphenyl phosphate (DPHP). The detection frequencies of m-OPFRs ranged from 88.8 % to 95.4 %. BCEP had the highest median concentration (0.93 µg/L), followed by BCIPP (0.32 µg/L), DPHP (0.27 µg/L) and DBP (0.20 µg/L). Significant correlations were found between all pairs of urinary m-OPFRs with correlation coefficients ranging from 0.22 to 0.71 (p< 0.05). Logistic regression models showed that urinary concentrations of BDCIPP (adjusted odds ratio [OR]: 1.25, 95 % confidential interval [CI]: 1.04-1.50) and DBP (adjusted OR: 1.10, 95 % CI: 1.01-1.20) were positively associated with lower cognitive functions. Furthermore, a nonlinear dose-response relationship was found between urinary BDCIPP concentration and cognitive decline. To our knowledge, this is the first report on OPFR exposure and cognitive impairment among elderly population. Further toxicological tests of BDCIPP and DBP are needed to illustrate these results.

Melanopsin retinal ganglion cells mediate light-promoted brain development.

During development, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) become light sensitive much earlier than rods and cones. IpRGCs project to many subcortical areas, whereas physiological functions of these projections are yet to be fully elucidated. Here, we found that ipRGC-mediated light sensation promotes synaptogenesis of pyramidal neurons in various cortices and the hippocampus. This phenomenon depends on activation of ipRGCs and is mediated by the release of oxytocin from the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) into cerebral-spinal fluid. We further characterized a direct connection between ipRGCs and oxytocin neurons in the SON and mutual projections between oxytocin neurons in the SON and PVN. Moreover, we showed that the lack of ipRGC-mediated, light-promoted early cortical synaptogenesis compromised learning ability in adult mice. Our results highlight the importance of light sensation early in life on the development of learning ability and therefore call attention to suitable light environment for infant care.