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The gut microbial metabolite trimethylamine N-oxide (TMAO) is regarded as a novel risk factor for hypertension. Berberine (BBR) exerts cardiovascular protective effects by regulating the gut microbiota-metabolite production pathway. However, whether and how BBR alleviates TMAO-induced vascular dysfunction in hypertension remains unclear. In the present study, we observed that plasma TMAO and related bacterial abundance were significantly elevated and negatively correlated with vascular function in 86 hypertensive patients compared with 46 normotensive controls. TMAO activated endoplasmic reticulum stress (ERS) signaling pathway to promote endothelial cell dysfunction and apoptosis in vitro. BBR (100, 200â¯mg⯷â¯kg-1 ·d-1) for 4 weeks ameliorates TMAO-induced vascular dysfunction and ERS activation in a choline-angiotensin II hypertensive mouse model. We found that plasma TMAO levels in 15 hypertensive patients treated with BBR (0.4â¯g, tid) were reduced by 8.8â¯% and 16.7â¯% at months 1 and 3, respectively, compared with pretreatment baseline. The oral BBR treatment also improved vascular function and lowered blood pressure. Faecal 16â¯S rDNA showed that BBR altered the gut bacterial composition and reduced the abundance of CutC/D bacteria in hypertensive mice and patients. In vitro bacterial cultures and enzyme reaction systems indicated that BBR inhibited the biosynthesis of TMAO precursor in the gut microbiota by binding to and inhibiting the activity of CutC/D enzyme. Our results indicate that BBR improve vascular dysfunction at least partially by decreasing TMAO via regulation of the gut microbiota in hypertension.
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Low-cost sodium-ion batteries have demonstrated great prospects in energy storage, among which layered transition metal oxides hold great potential as a cathode material. However, the notorious phase transition in layered cathode materials has greatly hampered their cycle life due to large volume changes upon desodiation/sodiation. In this study, by adopting an O3-type NaNi1/3Fe1/3Mn1/3O2 (NFM) with controlled synthesis temperatures, we have revealed that the grain size is closely related to its phase transition behaviors. The layered material with a smaller grain size and more distorted lattice tends to experience a shorter plateau of the O3-P3-O3 phase transitions during the charge/discharge process. Despite having a lower nominal discharge capacity without the phase transition plateau, its cycling stability increases from 77.4% to 96.2% after 100 cycles with greatly reduced intragranular cracks. The smaller grain size and lattice distortion act as a barrier that prevents the smooth layer from gliding upon sodium intercalation and deintercalation. This study focuses on the influence of grain size on battery cycle stability and provides a basis for future analysis of the structural instability of layered materials.
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Inorganic solid-state electrolytes (SSEs) play a vital role in high-energy all-solid-state batteries (ASSBs). However, the current method of SSE preparation usually involves high-energy mechanical ball milling and/or a high-temperature annealing process, which is not suitable for practical application. Here, a facile strategy is developed to realize the scalable synthesis of cost-effective aluminum-based oxyhalide SSEs, which involves a self-propagating method by the exothermic reaction of the raw materials. This strategy enables the synthesis of various aluminum-based oxyhalide SSEs with tunable components and high ionic conductivities (over 10-3â S cm-1 at 25 °C) for different cations (Li+, Na+, Ag+). It is elucidated that the amorphous matrix, which mainly consists of various oxidized chloroaluminate species that provide numerous sites for smooth ion migration, is actually the key factor for the achieved high conductivities. Benefit from their easy synthesis, low cost, and low weight, the aluminum-based oxyhalide SSEs synthesized by our approach could further promote practical application of high-energy-density ASSBs.
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BACKGROUND: Identifying breast cancer (BC) patients with germline breast cancer susceptibility gene (gBRCA) mutation is important. The current criteria for germline testing for BC remain controversial. This study aimed to develop a nomogram incorporating ultrasound radiomic features and clinicopathological factors to predict gBRCA mutations in patients with BC. MATERIALS AND METHODS: In this retrospective study, 497 women with BC who underwent gBRCA genetic testing from March 2013 to May 2022 were included, including 348 for training (84 with and 264 without a gBRCA mutation) and 149 for validation(36 patients with and 113 without a gBRCA mutation). Factors associated with gBRCA mutations were identified to establish a clinicopathological model. Radiomics features were extracted from the intratumoral and peritumoral regions (3 mm and 5 mm) of each image. The least absolute shrinkage and selection operator regression algorithm was used to select the features and logistic regression analysis was used to construct three imaging models. Finally, a nomogram that combined clinicopathological and radiomics features was developed. The models were evaluated based on the area under the receiver operating characteristic curve (AUC), calibration, and clinical usefulness. RESULTS: Age at diagnosis, family history of BC, personal history of other BRCA-related cancers, and human epidermal growth factor receptor 2 status were independent predictors of the clinicopathological model. The AUC of the imaging radiomics model combining intratumoral and peritumoral 3 mm areas in the validation set was 0.783 (95% confidence interval [CI]: 0.702-0.862), which showed the best performance among three imaging models. The nomogram yielded better performance than the clinicopathological model in validation sets (AUC: 0.824 [0.755-0.894] versus 0.659 [0.563-0.755], p = 0.007). CONCLUSION: The nomogram based on ultrasound images and clinicopathological factors performs well in predicting gBRCA mutations in BC patients and may help to improve clinical decisions about genetic testing.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genética , Radiómica , Estudios Retrospectivos , Mutación , Células GerminativasRESUMEN
Halide solid electrolytes (SEs) have attracted significant attention due to their competitive ionic conductivity and good electrochemical stability. Among typical halide SEs (chlorides, bromides, and iodides), substantial efforts have been dedicated to chlorides or bromides, with iodide SEs receiving less attention. Nevertheless, compared with chlorides or bromides, iodides have both a softer Li sublattice and lower reduction limit, which enable iodides to possess potentially high ionic conductivity and intrinsic anti-reduction stability, respectively. Herein, we report a new series of iodide SEs: Lix YI3+x (x=2, 3, 4, or 9). Through synchrotron X-ray/neutron diffraction characterizations and theoretical calculations, we revealed that the Lix YI3+x SEs belong to the high-symmetry cubic structure, and can accommodate abundant vacancies. By manipulating the defects in the iodide structure, balanced Li-ion concentration and generated vacancies enables an optimized ionic conductivity of 1.04 × 10-3 â S cm-1 at 25 °C for Li4 YI7 . Additionally, the promising Li-metal compatibility of Li4 YI7 is demonstrated via electrochemical characterizations (particularly all-solid-state Li-S batteries) combined with interface molecular dynamics simulations. Our study on iodide SEs provides deep insights into the relation between high-symmetry halide structures and ionic conduction, which can inspire future efforts to revitalize halide SEs.
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Metal halide solid-state electrolytes have gained widespread attention due to their high ionic conductivities, wide electrochemical stability windows, and good compatibility with oxide cathode materials. The exploration of highly ionic conductive halide electrolytes is actively ongoing. Thus, understanding the relationship between composition and crystal structure can be a critical guide for designing better halide electrolytes, which still remains obscure for reliable prediction. Here we show that the cationic polarization factor, which describes the geometric and ionic conditions, is effective in predicting the stacking structure of halide electrolytes formation. By supplementing this principle with rational design and preparation of more than 10 lithium halide electrolytes with high conductivity over 10-3 S cm-1 at 25 °C, we establish that there should be a variety of promising halide electrolytes that have yet to be discovered and developed. This methodology may enable the systematic screening of various potential halide electrolytes and demonstrate an approach to the design of halide electrolytes with superionic conductivity beyond the structure and stability predictions.
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The development of solid-state sodium-ion batteries (SSSBs) heavily hinges on the development of an superionic Na+ conductor (SSC) that features high conductivity, (electro)chemical stability, and deformability. The construction of heterogeneous structures offers a promising approach to comprehensively enhancing these properties in a way that differs from traditional structural optimization. Here, this work exploits the structural variance between high- and low-coordination halide frameworks to develop a new class of halide heterogeneous structure electrolytes (HSEs). The halide HSEs incorporating a UCl3 -type high-coordination framework and amorphous low-coordination phase achieves the highest Na+ conductivity (2.7 mS cm-1 at room temperature, RT) among halide SSCs so far. By discerning the individual contribution of the crystalline bulk, amorphous region, and interface, this work unravels the synergistic ion conduction within halide HSEs and provides a comprehensive explanation of the amorphization effect. More importantly, the excellent deformability, high-voltage stability, and expandability of HSEs enable effective SSSB integration. Using a cold-pressed cathode electrode composite of uncoated Na0.85 Mn0.5 Ni0.4 Fe0.1 O2 and HSEs, the SSSBs present stable cycle performance with a capacity retention of 91.0% after 100 cycles at 0.2 C.
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ConspectusSulfur-based cathode materials have become a research hot spot as one of the most promising candidates for next-generation, high-energy lithium batteries. However, the insulating nature of elemental sulfur or organosulfides has become the biggest challenge that leads to dramatic degradation and hinders their practical application. The disadvantage is more obvious for all-solid-state battery systems, which require both high electronic and ionic migration at the same sites to realize a complete electrochemical reaction. In addition to adding conductive components into the cathode composites, another effective way to realize high-reversibility sulfur-based cathodes is by optimizing the inherent nature of sulfur-based materials to make them "conductive". Inorganic polysulfide materials including polysulfide molecules, selenium-sulfur solid solutions, and (lithium) metal polysulfides are promising, as they have different structures that can make them intrinsically conductive or becoming conductive during lithiation. They all contain at least one -S-S- bridged bond, which is the intrinsic structural characteristic and the source of the chemical properties of these polysulfide compounds. For example, by balancing the conductivity and reversible capacity, researchers in the US National Aeronautics and Space Administration (NASA) have shown that 500 Wh/kg solid-state Li-Se/S batteries can power cars and even electric aircraft.We have long been focusing on the inorganic polysulfide component, reported the selenium-sulfur solid solutions, the first sulfur-rich phosphorus polysulfide molecules, and followed the research of metal polysulfide components. The proposed Account summarizes our current knowledge of the fundamental aspects of inorganic polysulfides in energy storage systems based on state-of-the-art publications on this topic. Both fast electron and ion migrations within the electrode materials are vital to achieving high-energy batteries. We begin by illustrating effective approaches to enhance the electronic/ionic conductivity of sulfur-based electrode materials. We then present some basic observations and properties (especially the intrinsic high conductivities) of the inorganic polysulfide electrode materials. The key chemical and structural factors dictating their conductive and electrochemical behaviors will be discussed. Finally, we show the advantages and broad applications of inorganic polysulfides in energy storage areas. The proposed Account will provide an insightful perspective on the current knowledge of inorganic polysulfide materials, as well as their future research directions and development potential, serving as a keynote reference for researchers in the field of energy storage.
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Hypoxia-induced endothelial cell death and impaired angiogenesis are the main pathophysiological features of critical limb ischemia. Mechanistically, proprotein convertase subtilisin/kexin type 9 (PCSK9) promoted Smac translocation from mitochondria to the cytoplasm. Inhibition of Smac release into the cytoplasm attenuated PCSK9-mediated hypoxia-induced pyroptosis. Functionally, PCSK9 overexpression impaired angiogenesis in vitro and reduced blood perfusion in mice with lower limb ischemia, but the effect was reversed by PCSK9 inhibition. This study demonstrates that PCSK9 aggravates pyroptosis by regulating Smac mitochondrion-cytoplasm translocation in the vascular endothelium, providing novel insights into PCSK9 as a potential therapeutic target in critical limb ischemia.
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As exciting candidates for next-generation energy storage, all-solid-state lithium batteries (ASSLBs) are highly dependent on advanced solid-state electrolytes (SSEs). Here, using cost-effective LaCl3 and CeCl3 lattice (UCl3 -type structure) as the host and further combined with a multiple-cation mixed strategy, we report a series of UCl3 -type SSEs with high room-temperature ionic conductivities over 10-3 â S cm-1 and good compatibility with high-voltage oxide cathodes. The intrinsic large-size hexagonal one-dimensional channels and highly disordered amorphous phase induced by multi-metal cation species are believed to trigger fast multiple ionic conductions of Li+ , Na+ , K+ , Cu+ , and Ag+ . The UCl3 -type SSEs enable a stable prototype ASSLB capable of over 3000â cycles and high reversibility at -30 °C. Further exploration of the brand-new multiple-cation mixed chlorides is likely to lead to the development of advanced halide SSEs suitable for ASSLBs with high energy density.
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PURPOSE: This study aimed to construct a mortality model for the risk stratification of intensive care unit (ICU) patients with sepsis by applying a machine learning algorithm. METHODS: Adult patients who were diagnosed with sepsis during admission to ICU were extracted from MIMIC-III, MIMIC-IV, eICU, and Zigong databases. MIMIC-III was used for model development and internal validation. The other three databases were used for external validation. Our proposed model was developed based on the Extreme Gradient Boosting (XGBoost) algorithm. The generalizability, discrimination, and validation of our model were evaluated. The Shapley Additive Explanation values were used to interpret our model and analyze the contribution of individual features. RESULTS: A total of 16,741, 15,532, 22,617, and 1,198 sepsis patients were extracted from the MIMIC-III, MIMIC-IV, eICU, and Zigong databases, respectively. The proposed model had an area under the receiver operating characteristic curve (AUROC) of 0.84 in the internal validation, which outperformed all the traditional scoring systems. In the external validations, the AUROC was 0.87 in the MIMIC-IV database, better than all the traditional scoring systems; the AUROC was 0.83 in the eICU database, higher than the Simplified Acute Physiology Score III and Sequential Organ Failure Assessment (SOFA),equal to 0.83 of the Acute Physiology and Chronic Health Evaluation IV (APACHE-IV), and the AUROC was 0.68 in the Zigong database, higher than those from the systemic inflammatory response syndrome and SOFA. Furthermore, the proposed model showed the best discriminatory and calibrated capabilities and had the best net benefit in each validation. CONCLUSIONS: The proposed algorithm based on XGBoost and SHAP-value feature selection had high performance in predicting the mortality of sepsis patients within 24 h of ICU admission.
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Sepsis , Adulto , Humanos , Sepsis/diagnóstico , Unidades de Cuidados Intensivos , Cuidados Críticos , Algoritmos , Medición de RiesgoRESUMEN
Solid electrolyte is vital to ensure all-solid-state batteries with improved safety, long cyclability, and feasibility at different temperatures. Herein, we report a new family of amorphous solid electrolytes, xLi2O-MCly (M = Ta or Hf, 0.8 ≤ x ≤ 2, y = 5 or 4). xLi2O-MCly amorphous solid electrolytes can achieve desirable ionic conductivities up to 6.6 × 10-3 S cm-1 at 25 °C, which is one of the highest values among all the reported amorphous solid electrolytes and comparable to those of the popular crystalline ones. The mixed-anion structural models of xLi2O-MCly amorphous SEs are well established and correlated to the ionic conductivities. It is found that the oxygen-jointed anion networks with abundant terminal chlorines in xLi2O-MCly amorphous solid electrolytes play an important role for the fast Li-ion conduction. More importantly, all-solid-state batteries using the amorphous solid electrolytes show excellent electrochemical performance at both 25 °C and -10 °C. Long cycle life (more than 2400 times of charging and discharging) can be achieved for all-solid-state batteries using the xLi2O-TaCl5 amorphous solid electrolyte at 400 mA g-1, demonstrating vast application prospects of the oxychloride amorphous solid electrolytes.
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Líquidos Corporales , Litio , Electrólitos , Cloruros , CloroRESUMEN
Inorganic solid-state electrolytes (SSEs) have gained significant attention for their potential use in high-energy solid-state batteries. However, there is a lack of understanding of the underlying mechanisms of fast ion conduction in SSEs. Here, we clarify the critical parameters that influence ion conductivity in SSEs through a combined analysis approach that examines several representative SSEs (Li3YCl6, Li3HoCl6, and Li6PS5Cl), which are further verified in the xLiCl-InCl3 system. The scaling analysis on conductivity spectra allowed the decoupled influences of mobile carrier concentration and hopping rate on ionic conductivity. Although the carrier concentration varied with temperature, the change alone cannot lead to the several orders of magnitude difference in conductivity. Instead, the hopping rate and the ionic conductivity present the same trend with the temperature change. Migration entropy, which arises from lattice vibrations of the jumping atoms from the initial sites to the saddle sites, is also proven to play a significant role in fast Li+ migration. The findings suggest that the multiple dependent variables such as the Li+ hopping frequency and migration energy are also responsible for the ionic conduction behavior within SSEs.
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Objective: This study aimed to investigate the therapeutic effect of enhanced external counterpulsation (EECP) on radial artery occlusion (RAO) through the oscillatory shear (OS) and pulsatile shear (PS) models of human umbilical vein endothelial cells (HUVECs) and RAO dog models. Methods: We used high-throughput sequencing data GSE92506 in GEO database to conduct time-series analysis of functional molecules on OS intervened HUVECs, and then compared the different molecules and their functions between PS and OS. Additionally, we studied the effect of EECP on the radial artery hemodynamics in Labrador dogs through multi-channel physiological monitor. Finally, we studied the therapeutic effect of EECP on RAO at the histological level through Hematoxylin-Eosin staining, Masson staining, ATPase staining and immunofluorescence in nine Labrador dogs. Results: With the extension of OS intervention, the cell cycle decreased, blood vessel endothelial cell proliferation and angiogenesis responses of HUVECs were down-regulated. By contrast, the inflammation and oxidative stress responses and the related pathways of anaerobic metabolism of HUVECs were up-regulated. Additionally, we found that compared with OS, PS can significantly up-regulate muscle synthesis, angiogenesis, and NO production related molecules. Meanwhile, PS can significantly down-regulate inflammation and oxidative stress related molecules. The invasive arterial pressure monitoring showed that 30Kpa EECP treatment could significantly increase the radial artery peak pressure (p = 0.030, 95%CI, 7.236-82.524). Masson staining showed that RAO significantly increased muscle interstitial fibrosis (p = 0.002, 95%CI, 0.748-2.128), and EECP treatment can reduce this change (p = 0.011, 95%CI, -1.676 to -0.296). ATPase staining showed that RAO significantly increased the area of type II muscle fibers (p = 0.004, 95%CI, 7.181-25.326), and EECP treatment could reduce this change (p = 0.001, 95%CI, -29.213 to -11.069). In addition, immunofluorescence showed that EECP increased angiogenesis in muscle tissue (p = 0.035, 95%CI, 0.024-0.528). Conclusion: EECP improves interstitial fibrosis and hypoxia, and increases angiogenesis of muscle tissue around radial artery induced by RAO.
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The expression abundance of transcripts in nondiseased breast tissue varies among individuals. The association study of genotypes and imaging phenotypes may help us to understand this individual variation. Since existing reports mainly focus on tumors or lesion areas, the heterogeneity of pathological image features and their correlations with RNA expression profiles for nondiseased tissue are not clear. The aim of this study is to discover the association between the nucleus features and the transcriptome-wide RNAs. We analyzed both microscopic histology images and RNA-sequencing data of 456 breast tissues from the Genotype-Tissue Expression (GTEx) project and constructed an automatic computational framework. We classified all samples into four clusters based on their nucleus morphological features and discovered feature-specific gene sets. The biological pathway analysis was performed on each gene set. The proposed framework evaluates the morphological characteristics of the cell nucleus quantitatively and identifies the associated genes. We found image features that capture population variation in breast tissue associated with RNA expressions, suggesting that the variation in expression pattern affects population variation in the morphological traits of breast tissue. This study provides a comprehensive transcriptome-wide view of imaging-feature-specific RNA expression for healthy breast tissue. Such a framework could also be used for understanding the connection between RNA expression and morphology in other tissues and organs. Pathway analysis indicated that the gene sets we identified were involved in specific biological processes, such as immune processes.
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Neoplasias de la Mama , Transcriptoma , Humanos , Femenino , Transcriptoma/genética , ARN/genética , Análisis de Secuencia de ARN , Genotipo , Fenotipo , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genéticaRESUMEN
Insertion-type compounds based on oxides and sulfides have been widely identified and well-studied as cathode materials in lithium-ion batteries. However, halides have rarely been used due to their high solubility in organic liquid electrolytes. Here, we reveal the insertion electrochemistry of VX3 (X=Cl, Br, I) by introducing a compatible halide solid-state electrolyte with a wide electrochemical stability window. X-ray absorption near-edge structure analyses reveal a two-step lithiation process and the structural transition of typical VCl3 . Fast Li+ insertion/extraction in the layered VX3 active materials and favorable interface guaranteed by the compatible electrode-electrolyte design enables high rate capability and stable operation of all-solid-state Li-VX3 batteries. The findings from this study will contribute to developing intercalation insertion electrochemistry of halide materials and exploring novel electrode materials in viable energy storage systems.
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High-energy Ni-rich layered oxide cathode materials such as LiNi0.8Mn0.1Co0.1O2 (NMC811) suffer from detrimental side reactions and interfacial structural instability when coupled with sulfide solid-state electrolytes in all-solid-state lithium-based batteries. To circumvent this issue, here we propose a gradient coating of the NMC811 particles with lithium oxy-thiophosphate (Li3P1+xO4S4x). Via atomic layer deposition of Li3PO4 and subsequent in situ formation of a gradient Li3P1+xO4S4x coating, a precise and conformal covering for NMC811 particles is obtained. The tailored surface structure and chemistry of NMC811 hinder the structural degradation associated with the layered-to-spinel transformation in the grain boundaries and effectively stabilize the cathode|solid electrolyte interface during cycling. Indeed, when tested in combination with an indium metal negative electrode and a Li10GeP2S12 solid electrolyte, the gradient oxy-thiophosphate-coated NCM811-based positive electrode enables the delivery of a specific discharge capacity of 128 mAh/g after almost 250 cycles at 0.178 mA/cm2 and 25 °C.
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Employing lithium-rich layered oxide (LLO) as the cathode of all-solid-state batteries (ASSBs) is highly desired for realizing high energy density. However, the poor kinetics of LLO, caused by its low electronic conductivity and significant oxygen-redox-induced structural degradation, has impeded its application in ASSBs. Here, the charge transfer kinetics of LLO is enhanced by constructing high-efficiency electron transport networks within solid-state electrodes, which considerably minimizes electron transfer resistance. In addition, an infusion-plus-coating strategy is introduced to stabilize the lattice oxygen of LLO, successfully suppressing the interfacial oxidation of solid electrolyte (Li3 InCl6 ) and structural degradation of LLO. As a result, LLO-based ASSBs exhibit a high discharge capacity of 230.7 mAh g-1 at 0.1 C and ultra-long cycle stability over 400 cycles. This work provides an in-depth understanding of the kinetics of LLO in solid-state electrodes, and affords a practically feasible strategy to obtain high-energy-density ASSBs.
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The cerebellum is ontogenetically one of the first structures to develop in the central nervous system; nevertheless, it has been only recently reconsidered for its significant neurobiological, functional, and clinical relevance in humans. Thus, it has been a relatively under-studied compared to the cerebrum. Currently, non-invasive imaging modalities can barely reach the necessary resolution to unfold its entire, convoluted surface, while only histological analyses can reveal local information at the micrometer scale. Herein, we used the BigBrain dataset to generate area and point-wise thickness measurements for all layers of the cerebellar cortex and for each lobule in particular. We found that the overall surface area of the cerebellar granular layer (including Purkinje cells) was 1,732 cm2 and the molecular layer was 1,945 cm2. The average thickness of the granular layer is 0.88 mm (± 0.83) and that of the molecular layer is 0.32 mm (± 0.08). The cerebellum (both granular and molecular layers) is thicker at the depth of the sulci and thinner at the crowns of the gyri. Globally, the granular layer is thicker in the lateral-posterior-inferior region than the medial-superior regions. The characterization of individual layers in the cerebellum achieved herein represents a stepping-stone for investigations interrelating structural and functional connectivity with cerebellar architectonics using neuroimaging, which is a matter of considerable relevance in basic and clinical neuroscience. Furthermore, these data provide templates for the construction of cerebellar topographic maps and the precise localization of structural and functional alterations in diseases affecting the cerebellum.