Dynamic Cortical Connectivity During Propofol Sedation in Glioma Patients.

BACKGROUND: The behavioral manifestations and neurophysiological responses to sedation can assist in understanding brain function after neurological damage, and can be described by cortical functional connectivity. Glioma patients may experience neurological deficits that are not clinically detectable before sedation. We hypothesized that patients with gliomas exhibit distinct cortical connectivity patterns compared to non-neurosurgical patients during sedation. METHODS: This is a secondary analysis of a previously published prospective observational study. Patients scheduled for resection of supratentorial glioma (n=21) or a non-neurosurgical procedure (n=21) under general anesthesia were included in this study. Frontal electroencephalography (EEG) signals were recorded at different sedation levels as assessed by the Observer Assessment of Alertness/Sedation (OAA/S) score. Kernel principal component analysis and k-means clustering were used to determine possible temporal dynamics from the weighted phase lag index characteristics. RESULTS: Ten EEG connectivity states were identified by clustering (76% consistency), each with unique properties. At OAA/S 3, the median (Q1, Q3) occurrence rates of state 6 (glioma group, 0.110 [0.083, 0.155] vs. control group, 0.070 [0.030, 0.110]; P=0.008) and state 7 (glioma group, 0.105 [0.083, 0.148] vs. control group: 0.065 [0.038, 0.090]; P=0.001), which are dominated by beta connectivity, were significantly different between the 2 groups, reflecting differential conversion of the beta band between the left and right brain regions. In addition, the temporal dynamics of the brain's functional connectivity was also reflected in the transition relationships between metastable states. CONCLUSIONS: There were differences in EEG functional connectivity, which is dynamic, between the glioma and nonglioma groups during sedation.

Magnetic nanoparticle-mediated enrichment technology combined with microfluidic single cell separation technology: A technology for efficient separation and degradation of functional bacteria in single cell liquid phase.

Although there are many microorganisms in nature, the limitations of isolation and cultivation conditions have restricted the development of artificial enhanced remediation technology using functional microbial communities. In this study, an integrated technology of Magnetic Nanoparticle-mediated Enrichment (MME) and Microfluidic Single Cell separation (MSC) that breaks through the bottleneck of traditional separation and cultivation techniques and can efficiently obtain more in situ functional microorganisms from the environment was developed. MME technology was first used to enrich rapidly growing active bacteria in the environment. Subsequently, MSC technology was applied to isolate and incubate functional bacterial communities in situ and validate the degradation ability of individual bacteria. As a result, this study has changed the order of traditional pure culture methods, which are first selected and then cultured, and provided a new method for obtaining non-culturable functional microorganisms.

Enhancing Protein Solubility via Glycosylation: From Chemical Synthesis to Machine Learning Predictions.

Glycosylation is a valuable tool for modulating protein solubility; however, the lack of reliable research strategies has impeded efficient progress in understanding and applying this modification. This study aimed to bridge this gap by investigating the solubility of a model glycoprotein molecule, the carbohydrate-binding module (CBM), through a two-stage process. In the first stage, an approach involving chemical synthesis, comparative analysis, and molecular dynamics simulations of a library of glycoforms was employed to elucidate the effect of different glycosylation patterns on solubility and the key factors responsible for the effect. In the second stage, a predictive mathematical formula, innovatively harnessing machine learning algorithms, was derived to relate solubility to the identified key factors and accurately predict the solubility of the newly designed glycoforms. Demonstrating feasibility and effectiveness, this two-stage approach offers a valuable strategy for advancing glycosylation research, especially for the discovery of glycoforms with increased solubility.

The m6 RNA methylation regulator KIAA1429 is associated with autophagy-mediated drug resistance in lung cancer.

N6-methyladenosine (m6A) modification plays a crucial role in cancer progression. However, the role of m6A modification-mediated autophagy underlying non-small cell lung cancer (NSCLC) gefitinib resistance remains unknown. Here, we discovered that m6A methyltransferase KIAA1429 was highly expressed in NSCLC gefitinib-resistant cells (PC9-GR) as well as tissues, and KIAA1429 high expression was associated with poor survival. In addition, silent KIAA1429 repressed gefitinib resistance in NSCLC and reduced tumor growth in vivo. Mechanistically, KIAA1429 stabilized WTAP, a significant player in autophagy, by binding to the 3' untranslated regions (3'-UTR) of WTAP. In a word, our findings indicated that KIAA1429 could elevate NSCLC gefitinib resistance, which may provide a promising targeted therapy for NSCLC patients.

In situ carbothermal synthesis of carbonized bacterial cellulose embedded with nano zero-valent iron for removal of Cr(VI).

Carbonized bacterial cellulose embedded with highly dispersed nano zero-valent iron (nZVI), denoted as nZVI@CBC, was prepared through one-step in situ carbothermal treatment of bacterial cellulose adsorbing iron(III) nitrate. The structure characteristics of nZVI@CBC and its performance in removing hexavalent chromium Cr(VI) were investigated. Results showed the formation of nZVI@CBC with a surface area of 409.61 m2/g at 800 °C, with nZVI particles of mean size 28.2 nm well distributed within the fibrous network of CBC. The stability of nZVI was enhanced by its carbon coating, despite some inevitable oxidation of exposed nZVI. Batch experiments demonstrated that nZVI@CBC exhibited superior removal efficiency compared to bare nZVI and CBC. Under optimal conditions, nZVI@CBC exhibited a high Cr(VI) adsorption capacity of up to 372.42 mg/g. Therefore, nZVI@CBC shows promise as an effective adsorbent for remediating Cr(VI) pollution in water.

Wafer Scale Gallium Nitride Integrated Electrode Toward Robust High Temperature Energy Storage.

Gallium Nitride (GaN), as the representative of wide bandgap semiconductors, has great prospects in accomplishing rapid charge delivery under high-temperature environments thanks to excellent structural stability and electron mobility. However, there is still a gap in wafer-scale GaN single-crystal integrated electrodes applied in the energy storage field. Herein, Si-doped GaN nanochannel with gallium oxynitride (GaON) layer on a centimeter scale (denoted by GaN NC) is reported. The Si atoms modulate electronic redistribution to improve conductivity and drive nanochannel formation. Apart from that, the distinctive nanochannel configuration with a GaON layer provides adequate active sites and extraordinary structural stability. The GaN-based supercapacitors are assembled and deliver outstanding charge storage capabilities at 140 °C. Surprisingly, 90% retention is maintained after 50 000 cycles. This study opens the pathway toward wafer-scale GaN single-crystal integrated electrodes with self-powered characteristics that are compatible with various (opto)-electronic devices.

Pyrite Characteristics in Lacustrine Shale and Implications for Organic Matter Enrichment and Shale Oil: A Case Study from the Triassic Yanchang Formation in the Ordos Basin, NW China.

Pyrite is widely distributed in lacustrine shales and has become a research focus in unconventional oil and gas exploration. Pyrite morphology is useful for identifying different types of organic matter and assessing shale oil enrichment in organic-rich shale. Abundant pyrite is developed in the source rocks from the Chang 7 Member of the Yanchang Formation in the Ordos Basin, NW China. However, the relationship between different pyrite types and the differential enrichment of shale oil still needs to be clarified. The organic geochemistry, petrology, and isotopic composition of the Chang 7 Member samples were analyzed. The significance of pyrite types and sulfur isotopic compositions as indicators of depositional environments and shale oil enrichment was emphasized. The Chang 7 shales contain three pyrite morphologies, framboidal pyrite (type A), spherulitic pyrite (type B), and euhedral and anhedral pyrite (type C), and their aggregates. The sulfur isotopic compositions of pyrite (δ34Spy) in Chang 7 shales with different pyrite types exhibited regular patterns. The δ34S values of types A, B, and C pyrites were sequentially positive overall (average values are -2.739, 2.201, and 7.487‰ in sequence), indicating that type A pyrite was formed during the syn-sedimentary to early diagenetic stage and types B and C pyrites were formed during the early to middle diagenetic stage. Types A, B, and C pyrites showed sequentially increasing kerogen type index values and kerogen carbon isotope values (mean values of -31.59, -28.70, and -26.45‰, successively), indicating that the horizons where types A, B, and C pyrites developed correspond to types I, II, and III organic matter, respectively. Strong correlations between the pyrite content and oil components reveal that pyrite indicates shale oil enrichment. Moreover, variations in pyrite type significantly influenced the enrichment behavior of shale oil. Types A and B pyrites contributing to reservoir space showed shale oil enrichment. They promoted saturated hydrocarbon enrichment at >15% pyrite content, whereas type C pyrite did not indicate shale oil enrichment. These findings provide new insights into the differential enrichment of organic matter and shale oil and valuable guidance for the large-scale exploration and development of shale oil resources.

Dual growth factor methacrylic alginate microgels combined with chitosan-based conduits facilitate peripheral nerve repair.

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.

Bone morphogenetic protein-6 suppresses TGF-ß2-induced epithelial-mesenchymal transition in retinal pigment epithelium.

AIM: To evaluate the effect of bone morphogenetic protein-6 (BMP-6) on transforming growth factor (TGF)-ß2-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE). METHODS: Adult retinal pigment epithelial cell line (ARPE-19) were randomly divided into control, TGF-ß2 (5 µg/L), and BMP-6 small interfering RNA (siRNA) group. The cell morphology was observed by microscopy, and the cell migration ability were detected by Transwell chamber. The EMT-related indexes and BMP-6 protein levels were detected by Western blotting. Furthermore, a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group, TGF-ß2+empty plasmid group, BMP-6 overexpression group, and TGF-ß2+BMP-6 overexpression group. The EMT-related indexes and extracellular regulated protein kinases (ERK) protein levels were detected. RESULTS: Compared with the control group, the migration of RPE cells in the TGF-ß2 group was significantly enhanced. TGF-ß2 increased the protein expression levels of α-smooth muscle actin (α-SMA), fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6 (P<0.05) in RPE. Similarly, the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced. BMP-6 siRNA increased the protein expression levels of α-SMA, fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin (P<0.05). Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-ß2 and prevented TGF-ß2 from affecting EMT-related biomarkers (P<0.05). CONCLUSION: BMP-6 prevents the EMT in RPE cells induced by TGF-ß2, which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

Amanitin-induced variable cytotoxicity in various cell lines is mediated by the different expression levels of OATP1B3.

Amanita phalloides is one of the deadliest mushrooms worldwide, causing most fatal cases of mushroom poisoning. Among the poisonous substances of Amanita phalloides, amanitins are the most lethal toxins to humans. Currently, there are no specific antidotes available for managing amanitin poisoning and treatments are lack of efficacy. Amanitin mainly causes severe injuries to specific organs, such as the liver, stomach, and kidney, whereas the lung, heart, and brain are hardly affected. However, the molecular mechanism of this phenomenon remains not understood. To explore the possible mechanism of organ specificity of amanitin-induced toxicity, eight human cell lines derived from different organs were exposed to α, ß, and γ-amanitin at concentrations ranging from 0.3 to 100 µM. We found that the cytotoxicity of amanitin differs greatly in various cell lines, among which liver-derived HepG2, stomach-derived BGC-823, and kidney-derived HEK-293 cells are most sensitive. Further mechanistic study revealed that the variable cytotoxicity is mainly dependent on the different expression levels of the organic anion transporting polypeptide 1B3 (OATP1B3), which facilitates the internalization of amanitin into cells. Besides, knockdown of OATP1B3 in HepG2 cells prevented α-amanitin-induced cytotoxicity. These results indicated that OATP1B3 may be a crucial therapeutic target against amanitin-induced organ failure.

Quantum-Confined-Superfluidics-Enabled Multiresponsive MXene-Based Actuators.

MXene, renowned for its natural "quantum-confined-superfluidic" (QSF) channels, demonstrates superior electrical/thermal conductivity, favorable hydrophilicity, and remarkable mechanical strength, rendering it an ideal candidate for multiresponsive actuators, which are promising for soft electronics and robots. Currently, most MXene-based actuators are mainly prepared by combining an active layer and an inner layer, with only a few utilizing regulated QSF channels. However, tailoring QSF channels for multiresponsive actuators is extremely challenging. Herein, we introduce a multiresponsive graphene oxide (GO)&Fe3O4/MXene actuator that can respond to humidity, light, heat, electricity, and magnetic fields by constructing asymmetric QSF channels. The asymmetric water adsorption, transportation, and desorption behaviors, controlled by the different QSF channels between the GO&Fe3O4 layer and the MXene layer, enable the multiresponsiveness of the actuator. As proof-of-concept demonstrations, several smart devices, such as a bionic crab-like crawler, a transporting flower robot, and a smart gripper, are prepared, holding great potential for advancing future soft robotics.

Syringin alleviates bisphenol A-induced spermatogenic defects and testicular injury by suppressing oxidative stress and inflammation in male zebrafish.

Syringin (SRG) is a bioactive principle possessing extensive activities including scavenging of free radicals, inhibition of apoptosis, and anti-inflammatory properties. However, its effects on spermatogenic defects and testicular injury as well as the underlying mechanisms are still unclear. This study aims to investigate the protective effect of SRG on testis damage in zebrafish and explore its potential molecular events. Zebrafish testicular injury was induced by exposure to bisphenol A (BPA) (3000 µg/L) for two weeks. Fish were treated with intraperitoneal injection of SRG at different doses (5 and 50 mg/kg bodyweight) for two more weeks under BPA induction. Subsequently, the testis and sperm were collected for morphological, histological, biochemical and gene expression examination. It was found that the administration of SRG resulted in a significant protection from BPA-caused impact on sperm concentration, morphology, motility, fertility rate, testosterone level, spermatogenic dysfunction and resulted in increased apoptotic and reactive oxygen species' levels. Furthermore, testicular transcriptional profiling alterations revealed that the regulation of inflammatory response and oxidative stress were generally enriched in differentially expressed genes (DEGs) after SRG treatment. Additionally, it was identified that SRG prevented BPA-induced zebrafish testis injury through upregulation of fn1a, krt17, fabp10a, serpina1l and ctss2. These results indicate that SRG alleviated spermatogenic defects and testicular injury by suppressing oxidative stress and inflammation in male zebrafish.

Achieving Strong Circularly Polarized Luminescence through Cascade Cationic Insertion in Lead-free Hybrid Metal Halides.

Generating circularly polarized luminescence (CPL) with simultaneous high photoluminescence quantum yield (PLQY) and dissymmetry factor (glum) is difficult due to usually unmatched electric transition dipole moment (µ) and magnetic transition dipole moment (m) of materials. Herein we tackle this issue by playing a "cascade cationic insertion" trick to achieve strong CPL (with PLQY of ~100 %) in lead-free metal halides with high glum values reaching -2.3×10-2 without using any chiral inducers. Achiral solvents of hydrochloric acid (HCl) and N, N-dimethylformamide (DMF) infiltrate the crystal lattice via asymmetric hydrogen bonding, distorting the perovskite structure to induce the "intrinsic" chirality. Surprisingly, additional insertion of Cs+ cation to substitute partial (CH3)2NH2 + transforms the chiral space group to achiral but the crystal maintains chiroptical activity. Further doping of Sb3+ stimulates strong photoluminescence as a result of self-trapped excitons (STEs) formation without disturbing the crystal framework. The chiral perovskites of indium-antimony chlorides embedded on LEDs chips demonstrate promising potential as CPL emitters. Our work presents rare cases of chiroptical activity of highly luminescent perovskites from only achiral building blocks via spontaneous resolution as a result of symmetry breaking.

Distribution and associations of anterior lens zonules lengths in patients with cataract.

PURPOSE: To investigate the characteristics and associations of anterior lens zonules lengths in cataract patients via ultrasound biomicroscope (UBM) measurement. METHODS: Patients with age-related cataracts and high myopic cataracts who planned to undergo cataract surgery were included in the study. After routine ophthalmic examinations, the UBM was performed on both eyes to get images of the anterior lens zonules, and Image J software was used to measure the lengths of the lens zonules. Axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and white-to-white (WTW) diameter of both eyes were obtained by IOL Master 700. Univariate and multivariate regression analyses were used to assess associated factors of anterior lens zonules lengths. RESULTS: Forty-nine patients with age-related cataracts and 33 patients with high myopic cataracts were enrolled. High myopic cataract patients were younger and had longer anterior lens zonules. Multivariate regression analysis showed that anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.036, P = 0.029; nasal location: ß = 0.034, P = 0.011; superior location: ß = 0.046, P = 0.002) and ACD (inferior location: ß = 0.305, P = 0.016) in right eyes. In left eyes, anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.028, P = 0.017; inferior location: ß = 0.026, P = 0.016; nasal location: ß = 0.033, P < 0.001) and ACD (inferior location: ß = 0.215, P = 0.030; superior location: ß = 0.290, P = 0.011). CONCLUSIONS: High myopic cataract patients have longer anterior lens zonules. AL and ACD contributed to the lengths of anterior lens zonules. Thus, for patients with long AL and deeper ACD, lens zonules measurement was crucial. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn identifier is ChiCTR2300071397.

Intracellular Delivery of Therapeutic Protein via Ultrathin Layered Double Hydroxide Nanosheets.

The therapeutic application of biofunctional proteins relies on their intracellular delivery, which is hindered by poor cellular uptake and transport from endosomes to cytoplasm. Herein, we constructed a two-dimensional (2D) ultrathin layered double hydroxide (LDH) nanosheet for the intracellular delivery of a cell-impermeable protein, gelonin, towards efficient and specific cancer treatment. The LDH nanosheet was synthesized via a facile method without using exfoliation agents and showed a high loading capacity of proteins (up to 182%). Using 2D and 3D 4T1 breast cancer cell models, LDH-gelonin demonstrated significantly higher cellular uptake efficiency, favorable endosome escape ability, and deep tumor penetration performance, leading to a higher anticancer efficiency, in comparison to free gelonin. This work provides a promising strategy and a generalized nanoplatform to efficiently deliver biofunctional proteins to unlock their therapeutic potential for cancer treatment.

Effects of depth of straw returning on maize yield potential and greenhouse gas emissions.

Appropriate straw incorporation has ample agronomic and environmental benefits, but most studies are limited to straw mulching or application on the soil surface. To determine the effect of depth of straw incorporation on the crop yield, soil organic carbon (SOC), total nitrogen (TN) and greenhouse gas emission, a total of 4 treatments were set up in this study, which comprised no straw returning (CK), straw returning at 15 cm (S15), straw returning at 25 cm (S25) and straw returning at 40 cm (S40). The results showed that straw incorporation significantly increased SOC, TN and C:N ratio. Compared with CK treatments, substantial increases in the grain yield (by 4.17~5.49% for S15 and 6.64~10.06% for S25) were observed under S15 and S25 treatments. S15 and S25 could significantly improve the carbon and nitrogen status of the 0-40 cm soil layer, thereby increased maize yield. The results showed that the maize yield was closely related to the soil carbon and nitrogen index of the 0-40 cm soil layer. In order to further evaluate the environmental benefits of straw returning, this study measured the global warming potential (GWP) and greenhouse gas emission intensity (GHGI). Compared with CK treatments, the GWP of S15, S25 and S40 treatments was increased by 9.35~20.37%, 4.27~7.67% and 0.72~6.14%, respectively, among which the S15 treatment contributed the most to the GWP of farmland. GHGI is an evaluation index of low-carbon agriculture at this stage, which takes into account both crop yield and global warming potential. In this study, GHGI showed a different trend from GWP. Compared with CK treatments, the S25 treatments had no significant difference in 2020, and decreased significantly in 2021 and 2022. This is due to the combined effect of maize yield and cumulative greenhouse gas emissions, indicating that the appropriate straw returning method can not only reduce the intensity of greenhouse gas emissions but also improve soil productivity and enhance the carbon sequestration effect of farmland soil, which is an ideal soil improvement and fertilization measure.

A Senescence-Associated Secretory Phenotype of Bone Marrow Mesenchymal Stem Cells Inhibits the Viability of Breast Cancer Cells.

Breast cancer, the most prevalent malignancy in women, often progresses to bone metastases, especially in older individuals. Dormancy, a critical aspect of bone-metastasized breast cancer cells (BCCs), enables them to evade treatment and recur. This dormant state is regulated by bone marrow mesenchymal stem cells (BMMSCs) through the secretion of various factors, including those associated with senescence. However, the specific mechanisms by which BMMSCs induce dormancy in BCCs remain unclear. To address this gap, a bone-specific senescence-accelerated murine model, SAMP6, was utilized to minimize confounding systemic age-related factors. Confirming senescence-accelerated osteoporosis, distinct BMMSC phenotypes were observed in SAMP6 mice compared to SAMR1 counterparts. Notably, SAMP6-BMMSCs exhibited premature senescence primarily due to telomerase activity loss and activation of the p21 signaling pathway. Furthermore, the effects of conditioned medium (CM) derived from SAMP6-BMMSCs versus SAMR1-BMMSCs on BCC proliferation were examined. Intriguingly, only CM from SAMP6-BMMSCs inhibited BCC proliferation by upregulating p21 expression in both MCF-7 and MDA-MB-231 cells. These findings suggest that the senescence-associated secretory phenotype (SASP) of BMMSCs suppresses BCC viability by inducing p21, a pivotal cell cycle inhibitor and tumor suppressor. This highlights a heightened susceptibility of BCCs to dormancy in a senescent microenvironment, potentially contributing to the increased incidence of breast cancer bone metastasis and recurrence observed with aging.

Effects of three plant growth-promoting bacterial symbiosis with ryegrass for remediation of Cd, Pb, and Zn soil in a mining area.

The quality of soil containing heavy metals (HMs) around nonferrous metal mining areas is often not favorable for plant growth. Three types of plant growth promoting rhizobacteria (PGPR)-assisted ryegrass were examined here to treat Cd, Pb, and Zn contaminated soil collected from a nonferrous metal smelting facility. The effects of PGPR-assisted plants on soil quality, plant growth, and the migration and transformation of HMs were evaluated. Results showed that inter-root inoculation of PGPR to ryegrass increased soil redox potential, urease, sucrase and acid phosphatase activities, microbial calorimetry, and bioavailable P, Si, and K content. Inoculation with PGPR also increased aboveground parts and root length, P, Si, and K contents, and antioxidant enzyme activities. The most significant effect was that the simultaneous inoculation of all three PGPRs increased the ryegrass extraction (%) of Cd (59.04-79.02), Pb (105.56-157.13), and Zn (27.71-40.79), compared to CK control (without fungi). Correspondingly, the inter-root soil contents (%) of total Cd (39.94-57.52), Pb (37.59-42.17), and Zn (34.05-37.28) were decreased compared to the CK1 control (without fungi and plants), whereas their bioavailability was increased. Results suggest that PGPR can improve soil quality in mining areas, promote plant growth, transform the fraction of HMs in soil, and increase the extraction of Cd, Pb, and Zn by ryegrass. PGPR is a promising microbe-assisted phytoremediation strategy that can promote the re-greening of vegetation in the mining area while remediating HMs pollution.

KDM4C promotes mouse hippocampal neural stem cell proliferation through modulating ApoE expression.

KDM4C is implicated in the regulation of cell proliferation, differentiation, and maintenance in various stem cell types. However, its function in neural stem cells (NSCs) remains poorly understood. Therefore, this study aims to investigate the role and regulatory mechanism of KDM4C in NSCs. Primary hippocampal NSCs were isolated from neonatal mice, and both in vivo and in vitro lentivirus-mediated overexpression of KDM4C were induced in these hippocampal NSCs. Staining results revealed a significant increase in BrdU- and Ki-67-positive cells, along with an elevated number of cells in S phases due to KDM4C overexpression. Subsequently, RNA-seq was employed to analyze gene expression changes following KDM4C upregulation. GO enrichment analysis, KEGG analysis, and GSEA highlighted KDM4C-regulated genes associated with development, cell cycle, and neurogenesis. Protein-protein interaction analysis uncovered that ApoE protein interacts with several genes (top 10 upregulated and downregulated) regulated by KDM4C. Notably, knocking down ApoE mitigated the proliferative effect induced by KDM4C overexpression in NSCs. Our study demonstrates that KDM4C overexpression significantly upregulates ApoE expression, ultimately promoting proliferation in mouse hippocampal NSCs. These findings provide valuable insights into the molecular mechanisms governing neurodevelopment, with potential implications for therapeutic strategies in neurological disorders.

Influence of Lens Thickness on Accuracy of Kane, Hill-RBF 3.0, Barrett Universal II, Emmetropia Verifying Optical, and Pearl-DGS Formulas in Eyes with Nonhigh Myopia and High Myopia.

PURPOSE: To investigate the influence of lens thickness (LT) on accuracy of Kane, Hill-RBF 3.0 Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO), and Pearl-DGS formulas in eyes with different axial lengths (AL). METHODS: The prospective cohort study was conducted at Eye and ENT Hospital of Fudan University. Patients who had uneventful cataract surgery between March 2021 and July 2023 were recruited. Manifest refraction was conducted two-month post-surgery. Eyes were divided into 4 groups based on AL: short (<22mm), medium (22-24.5 mm), medium long (24.5-26mm) and very long (≥26mm). In each AL group, eyes were then divided into 3 subgroups based on the LT measured with IOLmaster700: thin (<4.5 mm), medium (4.5-5.0 mm), and thick (≥ 5 mm). The influence of LT on accuracy of Kane, Hill-RBF 3.0, BUII, EVO, and Pearl-DGS formulas were investigated in each AL group. RESULTS: A total of 327 eyes from 327 patients were analyzed, with 64, 102, 73 and 88 eyes in each AL group, respectively. In eyes with AL < 24.5 mm, myopic PE was significantly associated with greater LT using all the 5 formulas (all p < 0.05). Backward stepwise multivariate regression analyses revealed that LT was an important influencing factor for PE in all 5 formulas, particularly in eyes with AL <24.5 mm. In eyes with AL <24.5 mm and LT > 5.0 mm, PE of all 5 formulas calculated with the optional parameter LT were more myopic than those calculated without LT. CONCLUSIONS: Thicker LT was associated with more myopic PE among eyes with AL <24.5 mm when using all 5 formulas. Further optimization of current formulas is necessary, especially for eyes with short AL and thick LT.