25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model.

Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.

A new polymodal gating model of the proton-activated chloride channel.

The proton-activated chloride (PAC) channel plays critical roles in ischemic neuron death, but its activation mechanisms remain elusive. Here, we investigated the gating of PAC channels using its novel bifunctional modulator C77304. C77304 acted as a weak activator of the PAC channel, causing moderate activation by acting on its proton gating. However, at higher concentrations, C77304 acted as a weak inhibitor, suppressing channel activity. This dual function was achieved by interacting with 2 modulatory sites of the channel, each with different affinities and dependencies on the channel's state. Moreover, we discovered a protonation-independent voltage activation of the PAC channel that appears to operate through an ion-flux gating mechanism. Through scanning-mutagenesis and molecular dynamics simulation, we confirmed that E181, E257, and E261 in the human PAC channel serve as primary proton sensors, as their alanine mutations eliminated the channel's proton gating while sparing the voltage-dependent gating. This proton-sensing mechanism was conserved among orthologous PAC channels from different species. Collectively, our data unveils the polymodal gating and proton-sensing mechanisms in the PAC channel that may inspire potential drug development.

Decoding the development of the human hippocampus.

The hippocampus is an important part of the limbic system in the human brain that has essential roles in spatial navigation and the consolidation of information from short-term memory to long-term memory1,2. Here we use single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis to illustrate the cell types, cell linage, molecular features and transcriptional regulation of the developing human hippocampus. Using the transcriptomes of 30,416 cells from the human hippocampus at gestational weeks 16-27, we identify 47 cell subtypes and their developmental trajectories. We also identify the migrating paths and cell lineages of PAX6+ and HOPX+ hippocampal progenitors, and regional markers of CA1, CA3 and dentate gyrus neurons. Multiomic data have uncovered transcriptional regulatory networks of the dentate gyrus marker PROX1. We also illustrate spatially specific gene expression in the developing human prefrontal cortex and hippocampus. The molecular features of the human hippocampus at gestational weeks 16-20 are similar to those of the mouse at postnatal days 0-5 and reveal gene expression differences between the two species. Transient expression of the primate-specific gene NBPF1 leads to a marked increase in PROX1+ cells in the mouse hippocampus. These data provides a blueprint for understanding human hippocampal development and a tool for investigating related diseases.

Trends in social mobility in postrevolution China.

In this paper, we study long-term trends in social mobility in the People's Republic of China since its inception in 1949, with two operationalizations: 1) intergenerational occupational mobility and 2) intergenerational educational mobility. We draw on an accumulation of administrative and survey data and provide comparable estimates of these measures for birth cohorts born after 1945. To help interpret the results, we compare trends in China to those in the United States for the same birth cohorts. We find an increase in intergenerational occupational mobility in China due to its rapid industrialization in recent decades. Net of industrialization, however, intergenerational occupational mobility has been declining for recent cohorts. Intergenerational educational mobility in China shows a similar declining trend. In addition, mobility patterns have differed greatly by gender, with women in earlier cohorts and from a rural origin particularly disadvantaged. We attribute the general decline in social mobility to market forces that have taken hold since China's economic reform that began in 1978. In contrast, social mobility by both measures has been relatively stable in the United States. However, while social mobility in China has trended downward, it is still higher than that in the United States, except for women's educational mobility.

Large-Area Near-Infrared Emission Enhancement on Single Upconversion Nanoparticles by Metal Nanohole Array.

Single lanthanide (Ln) ion doped upconversion nanoparticles (UCNPs) exhibit great potential for biomolecule sensing and counting. Plasmonic structures can improve the emission efficiency of single UCNPs by modulating the energy transferring process. Yet, achieving robust and large-area single UCNP emission modulation remains a challenge, which obstructs investigation and application of single UCNPs. Here, we present a strategy using metal nanohole arrays (NHAs) to achieve energy-transfer modulation on single UCNPs simultaneously within large-area plasmonic structures. By coupling surface plasmon polaritons (SPPs) with higher-intermediate state (1D2 → 3F3, 1D2 → 3H4) transitions, we achieved a remarkable up to 10-fold enhancement in 800 nm emission, surpassing the conventional approach of coupling SPPs with an intermediate ground state (3H4 → 3H6). We numerically simulate the electrical field distribution and reveal that luminescent enhancement is robust and insensitive to the exact location of particles. It is anticipated that the strategy provides a platform for widely exploring applications in single-particle quantitative biosensing.

Computation-Driven Rational Design of Self-Assembled Short Peptides for Catalytic Hydrogen Production.

Self-assembling peptides represent a captivating area of study in nanotechnology and biomaterials. This interest is largely driven by their unique properties and the vast application potential across various fields such as catalytic functions. However, design complexities, including high-dimensional sequence space and structural diversity, pose significant challenges in the study of such systems. In this work, we explored the possibility of self-assembled peptides to catalyze the hydrolysis of hydrosilane for hydrogen production using ab initio calculations and carried out wet-lab experiments to confirm the feasibility of these catalytic reactions under ambient conditions. Further, we delved into the nuanced interplay between sequence, structural conformation, and catalytic activity by combining modeling with experimental techniques such as transmission electron microscopy and nuclear magnetic resonance and proposed a dual mode of the microstructure of the catalytic center. Our results reveal that although research in this area is still at an early stage, the development of self-assembled peptide catalysts for hydrogen production has the potential to provide a more sustainable and efficient alternative to conventional hydrogen production methods. In addition, this work also demonstrates that a computation-driven rational design supplemented by experimental validation is an effective protocol for conducting research on functional self-assembled peptides.

Enhanced Broadband Manipulation of Acoustic Vortex Beams Using 3-bit Coding Metasurfaces through Topological Optimization.

The acoustic coding metasurfaces (ACMs) have the ability to manipulate complex acoustic behavior by reconstructing the coding sequence. In particular, the design of broadband coding enhances the versatility of ACMs. ACMs offer significant advantages over traditional metasurfaces, including a limited number of units and flexible wave control performance. The unit quantity is determined by 2n, with 1-bit utilizing 2 units, 2-bit using 4 units, and 3-bit employing 8 units. Utilizing multiple bits allows for precise control over the phase of sound waves and enables the realization of more intricate acoustic functions. To address the requirements of broadband multi-bit applications, this paper presents the development of novel 3-bit broadband reflected acoustic coding metasurfaces (BACMs) with eight coding units. These metasurfaces are systematically designed using the bottom-up topology optimization method. A constant phase difference of 45° can be achieved across all eight coding units within a broad frequency range. Additionally, the spiral distribution of phase differences enables the construction of an acoustic vortex metasurface. Moreover, by combining the convolution method, the strategies are outlined for constructing vortex-focusing metasurfaces and vortex beam manipulation metasurfaces. These 3-bit coding metasurfaces possess significant potential in the fields of acoustic particle suspension and acoustic communication.

Acidified Nitrogen Self-Doped Porous Carbon with Superprotonic Conduction for Applications in Solid-State Proton Battery.

Solid proton electrolytes play a crucial role in various electrochemical energy storage and conversion devices. However, the development of fast proton conducting solid proton electrolytes at ambient conditions remains a significant challenge. In this study, a novel acidified nitrogen self-doped porous carbon material is presented that demonstrates exceptional superprotonic conduction for applications in solid-state proton battery. The material, designated as MSA@ZIF-8-C, is synthesized through the acidification of nitrogen-doped porous carbon, specifically by integrating methanesulfonic acid (MSA) into zeolitic imidazolate framework-derived nitrogen self-doped porous carbons (ZIF-8-C). This study reveals that MSA@ZIF-8-C achieves a record-high proton conductivity beyond 10-2  S cm-1 at ambient condition, along with good long-term stability, positioning it as a cutting-edge alternative solid proton electrolyte to the default aqueous H2 SO4 electrolyte in proton batteries.

Warmer is better for evolutionary rescue, driving a warm-to-cold bias in habitat colonization dynamics.

Evolutionary rescue occurs when populations survive lethal environmental stresses through the rising and fixation of tolerant genotypes. Temperature has long been believed to determine the evolutionary speed of populations and species. Here, we suggest that warmer temperatures can facilitate evolutionary rescue. Moreover, with dispersal among habitats, the advantage in evolutionary rescue for warmer populations may cause a bias in habitat colonization dynamics towards the warm-to-cold direction. We experimentally tested these hypotheses with a model microbial system. Our first experiment showed that bacterial populations at warmer temperatures had a greater chance to evolve resistance and escape the fate of extinction under an antibiotic treatment. In the second experiment, metapopulations that consisted of warm and cold habitats were exposed to the antibiotic stress; local populations that went extinct might be recolonized, and such recolonization events were biased to the warm-to-cold direction. We also examined possible mechanisms underlying the temperature effect on the rapid evolution of resistance in our study system. Our results may help to understand the mechanisms of maintenance of biodiversity and patterns of gene flow among climatic regions, particularly in pest species subject to chemical control treatments.

Influence of NH3 flow rate on the photoelectric properties of high Al content p-AlGaN.

High Al content (60%) p-AlGaN with different NH3 flow rates was grown using metal-organic chemical vapor deposition (MOCVD), and changes in its photoelectric properties were studied using the Hall effect tester (Hall) and cathodoluminescence (CL) spectrometer. The results show that the film resistivity increases from 3.8â€…Ω·cm to 46.5â€…Ω·cm with increasing NH3 flow rate. The impurity peak intensity of p-AlGaN grown under high NH3 flow conditions is particularly high, indicating numerous point defects. The results of high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) show a large number of Ga interstitial atoms (Gai) at the interface. As Gai acts as a donor, this may be the main reason for the increase in resistivity. And under high NH3 flow conditions, a lattice distortion and a high density of dislocation occur between p-AlGaN and p-GaN, which can lead to enhanced carrier scattering and decreased mobility. Additional validation via LED growth experiments indicates that the luminescence intensity of samples with low ammonia concentration increased by more than 13000 times.

Long-term prognosis and risk factors associated with post-ERCP pneumobilia in patients with common bile duct stones.

BACKGROUND AND AIMS: Post-ERCP pneumobilia is not uncommon; however, studies focusing on the long-term prognosis of patients with post-ERCP pneumobilia are limited. This study aimed to explore long-term prognosis and risk factors associated with post-ERCP pneumobilia in patients with common bile duct stones (CBDSs). METHODS: We conducted a retrospective analysis of 1380 patients who underwent ERCP for CBDSs at our hospital from January 2010 to December 2017. Patients were selected based on inclusion and exclusion criteria and divided into pneumobilia and nonpneumobilia groups, followed by propensity score matching. The matched groups were then compared in terms of incidence rates of both single and multiple recurrences of CBDSs, acute cholangitis, and acute cholecystitis. Multivariate logistic regression analysis was used to explore risk factors associated with pneumobilia. RESULTS: After propensity matching, there was no significant difference in the rate of single recurrence of CBDSs (22.5% vs 30%; P = .446) between the pneumobilia and nonpneumobilia groups. However, the incidences of multiple recurrences of CBDSs (32.5% vs 12.5%; P = .032) and acute cholangitis without stone recurrence (32.5% vs 2.5%; P = <.001) were significantly higher in the pneumobilia group. Based on multivariate logistic regression analysis, in addition to a dilated CBD (diameter of >1 cm) (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.03-3.76; P = .043), endoscopic sphincterotomy with moderate incision (OR, 5.38; 95% CI, 1.14-25.47; P = .034) and with large incision (OR, 8.7; 95% CI, 1.83-41.46; P = .007) were identified as independent risk factors for pneumobilia after initial ERCP. CONCLUSIONS: Patients with post-ERCP pneumobilia have increased risk of multiple recurrences of CBDSs and acute cholangitis without stone recurrence. Independent risk factors for pneumobilia include peripapillary diverticulum, a dilated CBD (>1 cm), and endoscopic sphincterotomy with moderate and large incisions. A normal-sized CBD appears to serve as a secondary barrier against enterobiliary reflux, necessitating further research for confirmation.

UNC13D inhibits STING signaling by attenuating its oligomerization on the endoplasmic reticulum.

Stimulator of interferon genes (STING) is an essential signaling protein that is located on the endoplasmic reticulum (ER) and triggers the production of type I interferons (IFN) and proinflammatory cytokines in response to pathogenic DNA. Aberrant activation of STING is linked to autoimmune diseases. The mechanisms underlying homeostatic regulation of STING are unclear. Here, we report that UNC13D, which is associated with familial hemophagocytic lymphohistiocytosis (FHL3), is a negative regulator of the STING-mediated innate immune response. UNC13D colocalizes with STING on the ER and inhibits STING oligomerization. Cellular knockdown and knockout of UNC13D promote the production of interferon-ß (IFN-ß) induced by DNA viruses, but not RNA viruses. Moreover, UNC13D deficiency also increases the basal level of proinflammatory cytokines. These effects are diminished by an inhibitor of STING signaling. Furthermore, the domains involved in the UNC13D/STING interaction on both proteins are mapped. Our findings provide insight into the regulatory mechanism of STING, the previously unknown cellular function of UNC13D and the potential pathogenesis of FHL3.

Genetic switch selectively kills hepatocellular carcinoma cell based on microRNA and tissue-specific promoter.

The clinical treatment of hepatocellular carcinoma (HCC) is still a heavy burden worldwide. Intracellular microRNAs (miRNAs) commonly express abnormally in cancers, thus they are potential therapeutic targets for cancer treatment. miR-21 is upregulated in HCC whereas miR-122 is enriched in normal hepatocyte but downregulated in HCC. In our study, we first generated a reporter genetic switch compromising of miR-21 and miR-122 sponges as sensor, green fluorescent protein (GFP) as reporter gene and L7Ae:K-turn as regulatory element. The reporter expression was turned up in miR-21 enriched environment while turned down in miR-122 enriched environment, indicating that the reporter switch is able to respond distinctly to different miRNA environment. Furthermore, an AAT promoter, which is hepatocyte-specific, is applied to increase the specificity to hepatocyte. A killing switch with AAT promoter and an apoptosis-inducing element, Bax, in addition to miR-21 and miR-122 significantly inhibited cell viability in Huh-7 by 70 % and in HepG2 by 60 %. By contrast, cell viability was not affected in five non-HCC cells. Thus, we provide a novel feasible strategy to improve the safety of miRNA-based therapeutic agent to cancer.

Ethylene Glycol (EG)-Derived Chlorine-Resistant Cu0/TiO2-x for Efficient Photocatalytic Degradation of Nitrate to N2 without Sacrificial Agents at Near-Neutral pH Conditions: The Synergistic Effects of Cu0 and EG Radicals.

The selective photoreduction of nitrate to nontoxic nitrogen gas has emerged as an energy-efficient and environmentally friendly route for nitrate removal. However, the coexisting high-concentration chloride ions in wastewater can exert a significant influence on nitrate reduction due to the competitive adsorption and corrosion of Cl- on photocatalysts. Herein, we prepared ethylene glycol-Cu/TiO2-x (EG-Cu/TiO2-x) through a solvothermal reaction of Cu-doped TiO2 in an EG solution. The photodegradation of nitrate using EG-Cu/TiO2-x without adding sacrificial agents can efficiently occur in near-neutral pH solutions containing 50 mM Cl- with 95.26% of NO3- removal and 76.52% of N2 selectivity. Moreover, the photocatalyst performance remained at a high level after 8 cycles. In this work, NO3- was first converted to NH4+ by Cu0 and Ti3+, followed by the NH4+-to-N2 conversion by photogenerated chlorine free radicals. Compared to HO•, Cl•, and Cl2•-, ClO• is proved to play the predominant role in transforming NH4+ to N2. The EG radicals produced by UV light impede Cl- adsorption on Cu, protecting Cu0 from being corroded. What's more, photoelectrons can reduce Ti4+ to Ti3+ and protect Cu0 from being oxidized, enabling the stability of reactive sites. This work provides novel insights and understanding on designing photocatalysts for NO3- removal in solutions containing chloride ions, highlighting the significance of eliminating Cl- by EG radicals and adjusting the conversion process of NO3- for the efficient removal of NO3-.

Loss of function of OsL1 gene cause early flowering in rice under short-day conditions.

Heading date is one of the important agronomic traits that affects rice yield. In this study, we cloned a new rice B3 family gene, OsL1, which regulates rice heading date. Importantly, osl1-1 and osl1-2, two different types of mutants of OsL1 were created using the gene editing technology CRISPR/Cas9 system and exhibited 4 days earlier heading date than that of the wild type under short-day conditions. Subsequently, the plants overexpressing OsL1, OE-OsL1, showed a 2-day later heading date than the wild type in Changsha and a 5-day later heading date in Lingshui, but there was no significant difference in other yield traits. Moreover, the results of subcellular localization study indicated that OsL1 protein was located in the nucleus and the expression pattern analysis showed that OsL1 gene was expressed in rice roots, stems, leaves, and panicles, and the expression level was higher at the root and weak green panicle. In addition, the OsL1 gene was mainly expressed at night time under short-light conditions. The transcriptomic analysis indicated that OsL1 might be involved in the Hd1-Hd3a pathway function. Together, our results revealed that the cloning and functional analysis of OsL1 can provide new strategy for molecular design breeding of rice with suitable fertility period. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01444-1.

Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.

BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.

Tau aggravates stress-induced anxiety by inhibiting adult ventral hippocampal neurogenesis in mice.

Ventral adult hippocampal neurogenesis may be a key factor in determining individual levels of vulnerability to stress and related psychiatric disorders. However, the underlying mechanism remains unclear. Here, we show that the expression of Tau and Tau isoforms is markedly increased in the ventral dentate gyrus (vDG) after social defeat stress in young adult mice. Furthermore, glycogen synthase kinase-3ß and calcium/calmodulin-dependent protein kinase II-α activity and calcium/calmodulin-dependent protein kinase II-ß upregulation substantially promote Tau phosphorylation, which disrupts the dendritic structural plasticity of granule cells in the vDG of the hippocampus, and this action is necessary and sufficient for the stress response. In addition, Tau substantially inhibits the proliferation of newborn neurons in the vDG by regulating the PI3K-AKT signaling pathway in a mouse model of social defeat stress. Taken together, our findings reveal a novel mechanism by which Tau exacerbates stress responses and anxiety-related behavior by inhibiting the proliferation and maturation of hippocampal vDG neurons, providing a potential molecular target for the treatment of anxiety-like behavior induced by stress.

Fibrin sealant for closure of mucosal penetration at the oesophagus or cardia during submucosal tunnelling endoscopic resection for gastrointestinal submucosal tumours.

BACKGROUND AND STUDY AIM: To assess the efficacy and safety of a fibrin sealant for the prevention of leak resulting from mucosal penetration at the esophagus or cardia during a STER procedure to remove gastrointestinal submucosal tumors (SMTs). PATIENTS AND METHODS: Between April 2014 and October 2022, a total of 290 patients with oesophageal or cardiac SMTs underwent STER at our centre. We retrospectively identified patients with oesophageal or cardia SMTs who underwent STER and experienced mucosal penetration of the cardia or oesophagus during the procedure. A total of 31 mucosal penetrations in 30 procedures were included. Of the 31 mucosal penetrations, 12 occurred in the cardia, and the other 19 occurred in the oesophagus. All 31 sites received the fibrin sealant to close the mucosal penetration. Clinical characteristics, procedure-related parameters, detailed data of the mucosal penetrations, and treatment outcomes using the fibrin sealant were reviewed for all 30 patients to assess the efficacy and safety of the fibrin sealant for closure of mucosal penetration at the cardia or oesophagus. RESULTS: For the 31 mucosal penetrations, the mean size was 0.08 ± 0.06 cm2 (range 0.01-0.25 cm2). Mucosal closure using the fibrin sealant was performed successfully in all 31 mucosal penetrations. Of the 31 mucosal penetrations, clips were used in 13 cases. All 30 patients were discharged after a median of 7 days (range 4-20 day) postoperatively. During a mean 62 months (range 6-107 months) follow-up, all 31 mucosal penetrations successfully healed without the occurrence of infection, ulcer, oesophagitis, chest infection or abdominal infection. CONCLUSION: For the closure of mucosal penetration during STER at the cardia or oesophagus, a fibrin sealant is both safe and efficacious. It is necessary to conduct more research on the viability, effectiveness, and safety of using a fibrin sealant to close wider mucosal penetrations.

Neuroprotective Effects of Intermittent Fasting in the Aging Brain.

BACKGROUND: A major risk factor for neurodegenerative disorders is old age. Nutritional interventions that delay aging, such as calorie restriction (CR) and intermittent fasting (IF), as well as pharmaceuticals that affect the pathways linking nutrition and aging processes, have been developed in recent decades and have been shown to alleviate the effects of aging on the brain. SUMMARY: CR is accomplished by alternating periods of ad libitum feeding and fasting. In animal models, IF has been shown to increase lifespan and slow the progression and severity of age-related pathologies such as cardiovascular and neurodegenerative diseases and cancer. According to recent research, dietary changes can help older people with dementia retain brain function. However, the mechanisms underlying the neuroprotective effect of IF on the aging brain and related questions in this area of study (i.e., the potential of IF to treat neurodegenerative disorders) remain to be examined. KEY MESSAGES: This review addresses the hypothesis that IF may have translational potential in protecting the aged brain while summarizing the research supporting the putative neuroprotective mechanisms of IF in animal models. Additionally, given the emerging understanding of the connection between aging and dementia, our investigations may offer a fresh perspective on the use of dietary interventions for enhancing brain function and preventing dementia in elderly individuals. Finally, the absence of guidelines regarding the application of IF in patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge of the long-term effects of IF on dementia before it can be widely prescribed. In conclusion, IF may be an ancillary intervention for preserving memory and cognition in elderly individuals.

Shifting gradients of macroscale cortical organization mark the transition from childhood to adolescence.

The transition from childhood to adolescence is marked by pronounced shifts in brain structure and function that coincide with the development of physical, cognitive, and social abilities. Prior work in adult populations has characterized the topographical organization of the cortex, revealing macroscale functional gradients that extend from unimodal (somatosensory/motor and visual) regions through the cortical association areas that underpin complex cognition in humans. However, the presence of these core functional gradients across development as well as their maturational course have yet to be established. Here, leveraging 378 resting-state functional MRI scans from 190 healthy individuals aged 6 to 17 y old, we demonstrate that the transition from childhood to adolescence is reflected in the gradual maturation of gradient patterns across the cortical sheet. In children, the overarching organizational gradient is anchored within the unimodal cortex, between somatosensory/motor and visual territories. Conversely, in adolescence, the principal gradient of connectivity transitions into an adult-like spatial framework, with the default network at the opposite end of a spectrum from primary sensory and motor regions. The observed gradient transitions are gradually refined with age, reaching a sharp inflection point in 13 and 14 y olds. Functional maturation was nonuniformly distributed across cortical networks. Unimodal networks reached their mature positions early in development, while association regions, in particular the medial prefrontal cortex, reached a later peak during adolescence. These data reveal age-dependent changes in the macroscale organization of the cortex and suggest the scheduled maturation of functional gradient patterns may be critically important for understanding how cognitive and behavioral capabilities are refined across development.