Developmental Causes of Focal Segmental Glomerulosclerosis.

Background: Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular damage that includes idiopathic conditions as well as genetic and non-genetic forms. Among these various etiologies, different phenotypes within the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) have been associated with FSGS. Summary: Until recently, the main pathomechanism of how congenital kidney and urinary tract defects lead to FSGS was attributed to a reduced number of nephrons, resulting in biomechanical stress on the remaining glomeruli, detachment of podocytes, and subsequent inability to maintain normal glomerular architecture. The discovery of deleterious single-nucleotide variants in PAX2, a transcription factor crucial in normal kidney development and a known cause of papillorenal syndrome, in individuals with adult-onset FSGS without congenital kidney defects has shed new light on developmental defects that become evident during podocyte injury. Key Message: In this mini-review, we challenge the assumption that FSGS in CAKUT is caused by glomerular hyperfiltration alone and hypothesize a multifactorial pathogenesis that includes overlapping cellular mechanisms that are activated in both damaged podocytes as well as nephron progenitor cells.

Flexible males, reactive females: faecal glucocorticoid metabolites indicate increased stress in the colonist population, damping with time in males but not in females.

Individuals colonizing new areas at expanding ranges encounter numerous and unpredictable stressors. Exposure to unfamiliar environments suggests that colonists would differ in stress levels from residents living in familiar conditions. Few empirical studies tested this hypothesis and produced mixed results, and the role of stress regulation in colonization remains unclear. Studies relating stress levels to colonization mainly use a geographical analysis comparing established colonist populations with source populations. We used faecal glucocorticoid metabolites (FGMs) to assess both spatial and temporal dynamics of stress levels in an expanding population of midday gerbils (Meriones meridianus). We demonstrated that adult males and females had higher FGM levels in newly emerged colonies, compared with the source population, but differed in the pattern of FGM dynamics post-foundation. In males, FGM levels sharply decreased in the second year after colony establishment. In females, FGM levels did not change with time and remained high despite the decreasing environmental unpredictability, exhibiting among-individual variation. Increased stress levels of colonist males damping with time post-colonization suggest they are flexible in responding to immediate changes in environmental uncertainty. On the contrary, high and stable over generations stress levels uncoupled from the changes in the environmental uncertainty in female colonists imply that they carry a relatively constant phenotype associated with the reactive coping strategy favouring colonization. We link sex differences in consistency and plasticity in stress regulation during colonization to the sex-specific life-history strategies.

Superresolution Expansion Microscopy in Dictyostelium Amoebae.

Expansion microscopy (ExM) is a superresolution technique for fixed specimens that improves resolution of a given microscopy system approximately fourfold. The gain in resolution in ExM is not achieved by improvement of the resolution of the microscope itself but by isotropic expansion of the sample. To achieve this, the sample is cross-linked to an expandable gel matrix that swells approximately fourfold by incubation in water. We have applied the method to Dictyostelium amoebae and discuss the pros and cons of different labeling techniques in combination with pre- and post-expansion staining protocols.

Structurally and mechanically tuned macroporous hydrogels for scalable mesenchymal stem cell-extracellular matrix spheroid production.

Mesenchymal stem cells (MSCs) are essential in regenerative medicine. However, conventional expansion and harvesting methods often fail to maintain the essential extracellular matrix (ECM) components, which are crucial for their functionality and efficacy in therapeutic applications. Here, we introduce a bone marrow-inspired macroporous hydrogel designed for the large-scale production of MSC-ECM spheroids. Through a soft-templating approach leveraging liquid-liquid phase separation, we engineer macroporous hydrogels with customizable features, including pore size, stiffness, bioactive ligand distribution, and enzyme-responsive degradability. These tailored environments are conducive to optimal MSC proliferation and ease of harvesting. We find that soft hydrogels enhance mechanotransduction in MSCs, establishing a standard for hydrogel-based 3D cell culture. Within these hydrogels, MSCs exist as both cohesive spheroids, preserving their innate vitality, and as migrating entities that actively secrete functional ECM proteins. Additionally, we also introduce a gentle, enzymatic harvesting method that breaks down the hydrogels, allowing MSCs and secreted ECM to naturally form MSC-ECM spheroids. These spheroids display heightened stemness and differentiation capacity, mirroring the benefits of a native ECM milieu. Our research underscores the significance of sophisticated materials design in nurturing distinct MSC subpopulations, facilitating the generation of MSC-ECM spheroids with enhanced therapeutic potential.

FreqSNet: a multiaxial integration of frequency and spatial domains for medical image segmentation.

Objective.In recent years, convolutional neural networks, which typically focus on extracting spatial domain features, have shown limitations in learning global contextual information. However, frequency domain can offer a global perspective that spatial domain methods often struggle to capture. To address this limitation, we propose FreqSNet, which leverages both frequency and spatial features for medical image segmentation.Approach.To begin, we propose a Frequency-Space Representation Aggregation Block (FSRAB) to replace conventional convolutions. FSRAB contains three frequency domain branches to capture global frequency information along different axial combinations, while a convolutional branch is designed to interact information across channels in local spatial features. Secondly, the Multiplex Expansion Attention Block (MEAB) extracts long-range dependency information using dilated convolutional blocks, while suppressing irrelevant information via attention mechanisms. Finally, the introduced Feature Integration Block enhances feature representation by integrating semantic features that fuse spatial and channel positional information.Main results.We validated our method on 5 public datasets, including BUSI, CVC-ClinicDB, CVC-ColonDB, ISIC-2018, and Luna16. On these datasets, our method achieved Intersection over Union (IoU) scores of 75.46%, 87.81%, 79.08%, 84.04%, and 96.99%, and Hausdorff Distance (HD) values of 22.22mm, 13.20mm, 13.08mm, 13.51mm, and 5.22mm, respectively. Compared to other state-of-the-art methods, our FreqSNet achieves better segmentation results.Significance.Our method can effectively combine frequency domain information with spatial domain features, enhancing the segmentation performance and generalization capability in medical image segmentation tasks.

Dual Strategy of Morphology Optimization and Interlayer Expansion in VS2 Cathode Toward High-Performance Mg-Li Hybrid Ion Batteries.

Combining the merits of the dendrite-free formation of a Mg anode and the fast kinetics of Li ions, the Mg-Li hybrid ion batteries (MLIBs) are considered an ideal energy storage system. However, the lack of advanced cathode materials limits their further practical application. Herein, we report a dual strategy of morphology optimization and interlayer expansion for the construction of hierarchical flower-like VS2 architecture coated by N-doped amorphous carbon layers. This tailored hierarchical flower-like structure coupled with homogeneous N-doped amorphous carbon layers cooperatively provide more active sites and buffer volume changes, thus realizing the enhancement of capacity and structural stability. Moreover, the enlarged interlayer spacing caused by the cointercalation of polyvinylpyrrolidone and ammonium ions can effectively promote the charge transfer rate and facilitate the rapid ion diffusion, as further demonstrated by electrochemical results and theoretical calculations. These features endow the hierarchical flower-like VS2 cathode with superior specific energy density (644.4 Wh kg-1, average voltage of 1.2 V vs Mg2+/Mg) and excellent rate capability (181.1 mAh g-1 at 2000 mA g-1). Systematic ex situ characterization measurements are employed to reveal the ion storage mechanism, which confirms that Li+ storage plays a leading role in the capacity contribution of MLIBs. Our strategy is in favor of providing useful insights to design and construct MLIBs with high energy density and excellent rate performance.

Biosynthesis of Halogenated Tryptophans for Protein Engineering using Genetic Code Expansion.

Genetic Code Expansion technology offers significant potential in incorporating noncanonical amino acids into proteins at precise locations, allowing for the modulation of protein structures and functions. However, this technology is often limited by the need for costly and challenging-to-synthesize external noncanonical amino acid sources. In this study, we address this limitation by developing autonomous cells capable of biosynthesizing halogenated tryptophan derivatives and introducing them into proteins using Genetic Code Expansion technology. By utilizing inexpensive halide salts and different halogenases, we successfully achieve the selective biosynthesis of 6-chloro-tryptophan, 7-chloro-tryptophan, 6-bromo-tryptophan, and 7-bromo-tryptophan. These derivatives are introduced at specific positions with corresponding bioorthogonal aminoacyl-tRNA synthetase/tRNA pairs in response to the amber codon. Following optimization, we demonstrate the robust expression of proteins containing halogenated tryptophan residues in cells with the ability to biosynthesize these tryptophan derivatives. This study establishes a versatile platform for engineering proteins with various halogenated tryptophans.

Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity.

Signals emanating from the T-cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T-cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T-cell function. Through forward genetic screening in mice, we discover that loss-of-function mutations in LDL receptor-related protein 10 (Lrp10) cause naive and central memory CD8 T cells to accumulate in peripheral lymphoid organs. Lrp10 encodes a conserved cell surface protein of unknown immunological function. T-cell activation induces Lrp10 expression, which post-translationally suppresses IL7 receptor (IL7R) levels. Accordingly, Lrp10 deletion enhances T-cell homeostatic expansion through IL7R signaling. Lrp10-deficient mice are also intrinsically resistant to syngeneic tumors. This phenotype depends on dense tumor infiltration of CD8 T cells, which display increased memory cell characteristics, reduced terminal exhaustion, and augmented responses to immune checkpoint inhibition. Here, we present Lrp10 as a new negative regulator of CD8 T-cell homeostasis and a host factor that controls tumor resistance with implications for immunotherapy.

Evaluation of Mandibular Projection in Class II Division 2 Subjects Following Orthodontic Treatment Using Clear Aligners.

AIM: The purpose of this study was to evaluate the mandibular growth and/or projection following maxillary incisor proclination, overbite correction, and maxillary dentoalveolar expansion without the use of any class II mechanics, in growing class II division 2 patients treated with clear aligners. MATERIALS AND METHODS: Before and after treatment cone-beam computed tomographic (CBCT) generated lateral and posteroanterior cephalograms of thirty-two patients with skeletal class II division 2, 16 in the treatment group and 16 in the untreated group, were reviewed to evaluate treatment-related changes. Upper incisors were proclined and protruded, as well as upper arch expansion and overbite correction were performed as part of their regular treatment. Cephalometric analysis was performed to evaluate skeletal and dental changes. Unpaired statistical t-tests were performed to determine if significant skeletal class II correction was achieved in the treatment group. RESULTS: In the treatment group, after treatment, the upper incisors became more proclined and protruded, and the inter-molar width increased while the overbite was reduced compared to the control group. An increase in skeletal mandibular growth and forward projection was also observed, thus contributing to an improvement of the sagittal skeletal relationship as evidenced by ANB and Wits values compared to the control group. CONCLUSION: A combination of upper incisor proclination, correction of deep overbite, and maxillary dentoalveolar expansion using clear aligners appears to contribute to an improvement of the skeletal class II relationship in growing patients with class II division 2. CLINICAL SIGNIFICANCE: This study shows that unlocking the mandible by correcting a deep overbite, proclining upper incisors, and expanding the upper arch in growing class II division 2 patients can improve skeletal class II using clear aligners. How to cite this article: Mirzasoleiman P, El-Bialy T, Wiltshire WA, et al. Evaluation of Mandibular Projection in Class II Division 2 Subjects Following Orthodontic Treatment Using Clear Aligners. J Contemp Dent Pract 2024;25(4):295-302.

Woody encroachment: social-ecological impacts and sustainable management.

Woody plants are encroaching across terrestrial ecosystems globally, and this has dramatic effects on how these systems function and the livelihoods of producers who rely on the land to support livestock production. Consequently, the removal of woody plants is promoted widely in the belief that it will reinstate former grasslands or open savanna. Despite this popular management approach to encroachment, we still have a relatively poor understanding of the effects of removal on society, and of alternative management practices that could balance the competing needs of pastoral production, biodiversity conservation and cultural values. This information is essential for maintaining both ecological and societal benefits in encroached systems under predicted future climate changes. In this review, we provide a comprehensive synthesis of the social-ecological perspectives of woody encroachment based on recent studies and global meta-analyses by assessing the ecological impacts of encroachment and its effects on sustainable development goals (SDGs) when woody plants are retained and when they are removed. We propose a working definition of woody encroachment based on species- and community-level characteristics; such a definition is needed to evaluate accurately the effects of encroachment. We show that encroachment is a natural process of succession rather than a sign of degradation, with encroachment resulting in an overall 8% increase in ecosystem multifunctionality. Removing woody plants can increase herbaceous plant richness, biomass and cover, but at the expense of biocrust cover. The effectiveness of woody plant removal depends on plant identity, and where, when and how they are removed. Under current management practices, either removal or retention of woody plants can induce trade-offs among ecosystem services, with no management practice maximising all SDGs [e.g. SDG2 (end hunger), SDG13 (climate change), SDG 15 (combat desertification)]. Given that encroachment of woody plants is likely to increase under future predicted hotter and drier climates, alternative management options such as carbon farming and ecotourism could be effective land uses for areas affected by encroachment.

Tuned exchange imaging: Can the filter exchange imaging pulse sequence be adapted for applications with thin slices and restricted diffusion?

Filter exchange imaging (FEXI) is a double diffusion-encoding (DDE) sequence that is specifically sensitive to exchange between sites with different apparent diffusivities. FEXI uses a diffusion-encoding filtering block followed by a detection block at varying mixing times to map the exchange rate. Long mixing times enhance the sensitivity to exchange, but they pose challenges for imaging applications that require a stimulated echo sequence with crusher gradients. Thin imaging slices require strong crushers, which can introduce significant diffusion weighting and bias exchange rate estimates. Here, we treat the crushers as an additional encoding block and consider FEXI as a triple diffusion-encoding sequence. This allows the bias to be corrected in the case of multi-Gaussian diffusion, but not easily in the presence of restricted diffusion. Our approach addresses challenges in the presence of restricted diffusion and relies on the ability to independently gauge sensitivities to exchange and restricted diffusion for arbitrary gradient waveforms. It follows two principles: (i) the effects of crushers are included in the forward model using signal cumulant expansion; and (ii) timing parameters of diffusion gradients in filter and detection blocks are adjusted to maintain the same level of restriction encoding regardless of the mixing time. This results in the tuned exchange imaging (TEXI) protocol. The accuracy of exchange mapping with TEXI was assessed through Monte Carlo simulations in spheres of identical sizes and gamma-distributed sizes, and in parallel hexagonally packed cylinders. The simulations demonstrate that TEXI provides consistent exchange rates regardless of slice thickness and restriction size, even with strong crushers. However, the accuracy depends on b-values, mixing times, and restriction geometry. The constraints and limitations of TEXI are discussed, including suggestions for protocol adaptations. Further studies are needed to optimize the precision of TEXI and assess the approach experimentally in realistic, heterogeneous substrates.

Scalp-Split Technique: A concept of bone splitting and expansion for thin alveolar ridges to place dental implants.

BACKGROUND: Bone expansion is where the existing bone at the implant site is split and separated to create a gap to widen it. This article introduces a novel concept of bone expansion for the ultra-thin alveolar ridges to place dental implants with zero wastage of existing natural bone in long-term edentulous arches. Instead of using twist drills and piezo surgery kits, the bone is split with a surgical scalpel blade to prevent natural bone wastage. METHODS: The split will help to expand the bone horizontally by using expanders to accommodate the smaller diameter implants. This technique was applied to 12 individuals to rehabilitate their atrophic edentulous mandibles to facilitate the implant-supported overdentures, and it revealed that all the cases achieved successful osseointegration after placing implants following this method. CONCLUSIONS: The "Scalp-Spilt Technique" is a promising technique for providing implant- retained or implant-supported prostheses over ultra-thin edentulous alveolar ridges.

Leakage sign is a reliable predictor of hematoma expansion in acute epidural hematoma.

BACKGROUND: Hematoma expansion in small/medium-sized acute epidural hematoma (AEDH) cases upon emergency admission is critical. Predicting hematoma expansion can lead to early surgical interventions, improving outcomes and eliminating the need to check for expansion via computed tomography (CT). This study aimed to identify the most reliable predictors of AEDH expansion. METHODS: We retrospectively collected data from patients with pure AEDH not requiring surgical treatment upon emergency admission from 2012-2022. We assessed clinical and laboratory data, time from injury to the first CT, and time to follow-up CT. Factors predictive of hematoma expansion on the second follow-up CT, including the leakage sign (LS), were analyzed. RESULTS: A total of 23 patients with pure AEDH without surgery at admission were included, and LS was positive in 18. Thirteen patients showed hematoma expansion. The hematoma expansion group showed a significantly higher rate of positive LS and lower mean platelet count than the group without hematoma expansion. LS's predictive value for AEDH expansion showed 100% sensitivity and 50% specificity. All patients with negative LS and normal platelet counts showed no hematoma expansion. Analyzing the time from injury to the first CT suggested that LS (+) within 120 min strongly predicted hematoma expansion. Reconstructed three-dimensional images of the leakage point on the skull revealed multiple mottled bleeding points on the dural surface. CONCLUSION: LS can predict hematoma expansion in patients with pure AEDH for whom emergency surgery is unnecessary at admission. The time from injury and platelet counts must also be considered.

Isolation of Human Hematopoietic Stem Cells from an Apheresis Sample.

The hematopoietic system constantly produces new blood cells through hematopoiesis, and maintaining this balance is vital for human health. This balance is maintained by self-renewing hematopoietic stem cells (HSCs) and various progenitor cells. Under typical circumstances, HSCs are not abundantly found in peripheral blood; hence, their mobilization from the bone marrow is vital. Hematopoietic growth factors achieve this effectively, enabling mobilization and thus allowing blood sample and thus HSC collection via apheresis. Securing a sufficient supply of HSCs is vital for successful hematopoietic reconstitution and the rapid integration of committed cells. Thus, isolation and expansion of HSCs are crucial for convenient extraction, production of transplantable quantities, genetic modifications for enhanced therapeutic efficacy, and as a source of increased/expanded/synthesized blood cells in vitro. In conclusion, the isolation and expansion of HSCs play pivotal roles in both regenerative medicine and hematology. This protocol describes the isolation of human HSCs by providing an overview of the primary method for isolating human hematopoietic stem cells from apheresis blood samples and sheds light on human HSC studies and developments in research and medicine.

Tremor-associated short tandem repeat intermediate and pathogenic expansions in familial essential tremor.

There is an obvious clinical-pathological overlap between essential tremor and some known tremor-associated short tandem repeat expansion disorders. The aim is to analyse whether these short tandem repeat genes, including ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATXN8OS, ATXN10, PPP2R2B, TBP, BEAN1, NOP56, DAB1, ATN1, SADM12 and FMR1, are associated with familial essential tremor patients. Genetic analysis of repeat sizes in tremor-associated short tandem repeat expansions was performed in a large cohort of 515 familial essential tremor probands and 300 controls. The demographic and clinical features among carriers of pathogenic expansions, intermediate repeats and non-carriers were compared. A total of 18 out of 515 (18/515, 3.7%) patients were found to have repeats expansions, including 12 cases (12/515, 2.5%) with intermediate repeat expansions (one ATXN1, eight TBP, two FMR1, one ATN1), and six cases (6/515, 1.2%) with pathogenic expansions (one ATXN1, one ATXN2, one ATXN8OS, one PPP2R2B, one FMR1, one SAMD12). There were no statistically significant differences in intermediate repeats compared to healthy controls. Furthermore, there were no significant differences in demographics and clinical features among individuals with pathogenic expansions, intermediate repeat expansions carriers and non-carriers. Our study indicates that the intermediate repeat expansion in tremor-associated short tandem repeat expansions does not pose an increased risk for essential tremor, and rare pathogenic expansion carriers have been found in the familial essential tremor cohort. The diagnosis of essential tremor based solely on clinical symptoms remains a challenge in distinguishing it from known short tandem repeat expansions diseases with overlapping clinical-pathological features.

Lung volume recruitment and airway clearance for children at home in France.

BACKGROUND: Airway clearance (ACT) and lung volume recruitment (LVR) techniques are used to manage bronchial secretions, increase cough efficiency and lung/chest wall recruitment, to prevent and treat respiratory tract infections. The aim of the study was to review the prescription of ACT/LVR techniques for home use in children in France. METHODS: All the centers of the national pediatric noninvasive ventilation (NIV) network were invited to fill in an anonymous questionnaire for every child aged ≤20 years who started a treatment with an ACT/LVR device between 2022 and 2023. The devices comprised mechanical in-exsufflation (MI-E), intermittent positive pressure breathing (IPPB), intrapulmonary percussive ventilation (IPV), and/or invasive mechanical ventilation (IMV)/NIV for ACT/LVR. RESULTS: One hundred and thirty-nine patients were included by 13 centers. IPPB was started in 83 (60 %) patients, MI-E in 43 (31 %) and IPV in 30 (22 %). No patient used IMV/NIV for ACT/LVR. The devices were prescribed mainly by pediatric pulmonologists (103, 74 %). Mean age at initiation was 8.9 ± 5.6 (0.4-18.5) years old. The ACT/LVR devices were prescribed mainly in patients with neuromuscular disorders (n = 66, 47 %) and neurodisability (n = 37, 27 %). The main initiation criteria were cough assistance (81 %) and airway clearance (60 %) for MI-E, thoracic mobilization (63 %) and vital capacity (47 %) for IPPB, and airway clearance (73 %) and repeated respiratory exacerbations (57 %) for IPV. The parents were the main carers performing the treatment at home. CONCLUSIONS: IPPB was the most prescribed technique. Diseases and initiation criteria are heterogeneous, underlining the need for studies validating the indications and settings of these techniques.

Characteristics of deformation and damage of surrounding rock along the top roadway in the working face of an isolated island and its evolution law.

This study investigates the deformation and damage characteristics of the surrounding rock along the top return mining roadway of an isolated island working face at different stages and reveals its damage mechanism and evolution law. Utilizing a mine in Yangquan City, Shanxi Province, China, as the engineering background, this research employs FLAC 3D numerical simulation and on-site measurements. The findings suggest that the evolution of the plastic zone along the top roadway of the 15,106 island face is largely similar during both the excavation and mining periods. The plastic zones on either side of the roadway are expanding asymmetrically and gradually merging into the plastic zone of the coal pillar. In the destructive stage, the sub-gangs of the roadway are penetrated, indicating the progression into the plastic zone. The investigation points to extensive damage on the larger side of the roadway, the development of fissures, and the significant depth of damage as primary causes of roadway deformation. Moreover, the extent of the plastic zones on both sides of the roadway correlates positively with their relative distance. Continuous monitoring reveals an ongoing increase in roadway displacement, consistent with general observations in coal mining. The results provide valuable insights for optimizing support structures in similar mining environments.

Optical Genome Mapping for Applications in Repeat Expansion Disorders.

Short tandem repeat (STR) expansions are associated with more than 60 genetic disorders. The size and stability of these expansions correlate with the severity and age of onset of the disease. Therefore, being able to accurately detect the absolute length of STRs is important. Current diagnostic assays include laborious lab experiments, including repeat-primed PCR and Southern blotting, that still cannot precisely determine the exact length of very long repeat expansions. Optical genome mapping (OGM) is a cost-effective and easy-to-use alternative to traditional cytogenetic techniques and allows the comprehensive detection of chromosomal aberrations and structural variants >500 bp in length, including insertions, deletions, duplications, inversions, translocations, and copy number variants. Here, we provide methodological guidance for preparing samples and performing OGM as well as running the analysis pipelines and using the specific repeat expansion workflows to determine the exact repeat length of repeat expansions expanded beyond 500 bp. Together these protocols provide all details needed to analyze the length and stability of any repeat expansion with an expected repeat size difference from the expected wild-type allele of >500 bp. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Genomic ultra-high-molecular-weight DNA isolation, labeling, and staining Basic Protocol 2: Data generation and genome mapping using the Bionano Saphyr® System Basic Protocol 3: Manual De Novo Assembly workflow Basic Protocol 4: Local guided assembly workflow Basic Protocol 5: EnFocus Fragile X workflow Basic Protocol 6: Molecule distance script workflow.

Coaching ribosome biogenesis from the nuclear periphery.

Severe invagination of the nuclear envelope is a hallmark of cancers, aging, neurodegeneration, and infections. However, the outcomes of nuclear invagination remain unclear. This work identified a new function of nuclear invagination: regulating ribosome biogenesis. With expansion microscopy, we observed frequent physical contact between nuclear invaginations and nucleoli. Surprisingly, the higher the invagination curvature, the more ribosomal RNA and pre-ribosomes are made in the contacted nucleolus. By growing cells on nanopillars that generate nuclear invaginations with desired curvatures, we can increase and decrease ribosome biogenesis. Based on this causation, we repressed the ribosome levels in breast cancer and progeria cells by growing cells on low-curvature nanopillars, indicating that overactivated ribosome biogenesis can be rescued by reshaping nuclei. Mechanistically, high-curvature nuclear invaginations reduce heterochromatin and enrich nuclear pore complexes, which promote ribosome biogenesis. We anticipate that our findings will serve as a foundation for further studies on nuclear deformation.