Integrating AlphaFold and deep learning for atomistic interpretation of cryo-EM maps.

Interpretation of cryo-electron microscopy (cryo-EM) maps requires building and fitting 3D atomic models of biological molecules. AlphaFold-predicted models generate initial 3D coordinates; however, model inaccuracy and conformational heterogeneity often necessitate labor-intensive manual model building and fitting into cryo-EM maps. In this work, we designed a protein model-building workflow, which combines a deep-learning cryo-EM map feature enhancement tool, CryoFEM (Cryo-EM Feature Enhancement Model) and AlphaFold. A benchmark test using 36 cryo-EM maps shows that CryoFEM achieves state-of-the-art performance in optimizing the Fourier Shell Correlations between the maps and the ground truth models. Furthermore, in a subset of 17 datasets where the initial AlphaFold predictions are less accurate, the workflow significantly improves their model accuracy. Our work demonstrates that the integration of modern deep learning image enhancement and AlphaFold may lead to automated model building and fitting for the atomistic interpretation of cryo-EM maps.

Resolving length-scale-dependent transient disorder through an ultrafast phase transition.

Material functionality can be strongly determined by structure extending only over nanoscale distances. The pair distribution function presents an opportunity for structural studies beyond idealized crystal models and to investigate structure over varying length scales. Applying this method with ultrafast time resolution has the potential to similarly disrupt the study of structural dynamics and phase transitions. Here we demonstrate such a measurement of CuIr2S4 optically pumped from its low-temperature Ir-dimerized phase. Dimers are optically suppressed without spatial correlation, generating a structure whose level of disorder strongly depends on the length scale. The redevelopment of structural ordering over tens of picoseconds is directly tracked over both space and time as a transient state is approached. This measurement demonstrates the crucial role of local structure and disorder in non-equilibrium processes as well as the feasibility of accessing this information with state-of-the-art XFEL facilities.

Exosomes derived from bone marrow mesenchymal stem cells alleviate biliary ischemia reperfusion injury in fatty liver transplantation by inhibiting ferroptosis.

Fatty liver grafts are susceptible to ischemia reperfusion injury (IRI), increasing the risk of biliary complications after liver transplantation (LT). Ferroptosis, a newly recognized programmed cell death, is expected to be a novel therapeutic target for IRI. We investigated whether exosomes derived from heme oxygenase 1-modified bone marrow mesenchymal stem cells (HExos) relieve ferroptosis and protect biliary tracts from IRI in a rat fatty liver transplantation model. Rats were fed with a methionine choline deficient (MCD) diet for 2 weeks to induce severe hepatic steatosis. Steatotic grafts were implanted and HExos were administered after liver transplantation. A series of functional assays and pathological analysis were performed to assess ferroptosis and biliary IRI. The HExos attenuated IRI following liver transplantation, as demonstrated by less ferroptosis, improved liver function, less Kupffer and T cell activation, and less long-term biliary fibrosis. MicroRNA (miR)-204-5p delivered by HExos negatively regulated ferroptosis by targeting a key pro-ferroptosis enzyme, ACSL4. Ferroptosis contributes to biliary IRI in fatty liver transplantation. HExos protect steatotic grafts by inhibiting ferroptosis, and may become a promising strategy to prevent biliary IRI and expand the donor pool.

A nomogram predicting the histologic activity of lupus nephritis from clinical parameters.

BACKGROUND: The 2021 clinical guidelines of the Kidney Disease: Improving Global Outcomes emphasize the importance of the histological activity index (AI) in the management of lupus nephritis (LN). Patients with LN and a high AI have poor renal outcomes and high rates of nephritic relapse. In this study we constructed prediction models for the AI in LN. METHODS: The study population comprised 337 patients diagnosed with LN using kidney biopsy. The participants were randomly divided into training and testing cohorts. They were further divided into high-activity (AI >2) and low-activity (AI ≤2) groups. This study developed two clinical prediction models using logistic regression and least absolute shrinkage and selection operator (LASSO) analyses with laboratory test results collected at the time of kidney biopsy. The performance of models was assessed using 5-fold cross-validation and validated in the testing cohort. A nomogram for individual assessment was constructed based on the preferable model. RESULTS: Multivariate analysis showed that higher mean arterial pressure, lower estimated glomerular filtration rate, lower complement 3 level, higher urinary erythrocytes count and anti-double-stranded DNA seropositivity were independent risk factors for high histologic activity in LN. Both models performed well in the testing cohort regarding the discriminatory ability to identify patients with an AI >2. The average area under the curve of 5-fold cross-validation was 0.855 in the logistic model and 0.896 in the LASSO model. A webtool based on the LASSO model was created for clinicians to enter baseline clinical parameters to produce a probability score of an AI >2. CONCLUSIONS: The established nomogram provides a quantitative auxiliary tool for distinguishing LN patients with a high AI and helps physicians make clinical decisions in their comprehensive assessment.

miR-124-3p delivered by exosomes from heme oxygenase-1 modified bone marrow mesenchymal stem cells inhibits ferroptosis to attenuate ischemia-reperfusion injury in steatotic grafts.

BACKGROUND: Steatotic livers tolerate ischemia-reperfusion injury (IRI) poorly, increasing the risk of organ dysfunction. Ferroptosis is considered the initiating factor of organ IRI. Heme oxygenase oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) (HO-1/BMMSCs) can reduce hepatic IRI; however, the role of ferroptosis in IRI of steatotic grafts and the effect of HO-1/BMMSCs-derived exosomes (HM-exos) on ferroptosis remain unknown. METHODS: A model of rat liver transplantation (LT) with a severe steatotic donor liver and a model of hypoxia and reoxygenation (H/R) of steatotic hepatocytes were established. Exosomes were obtained by differential centrifugation, and the differentially expressed genes (DEGs) in liver after HM-exo treatment were detected using RNA sequencing. The expression of ferroptosis markers was analyzed. microRNA (miRNA) sequencing was used to analyze the miRNA profiles in HM-exos. RESULTS: We verified the effect of a candidate miRNA on ferroptosis of H/R treated hepatocytes, and observed the effect of exosomes knockout of the candidate miRNA on hepatocytes ferroptosis. In vitro, HM-exo treatment reduced the IRI in steatotic grafts, and enrichment analysis of DEGs suggested that HM-exos were involved in the regulation of the ferroptosis pathway. In vitro, inhibition of ferroptosis by HM-exos reduced hepatocyte injury. HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis. CONCLUSION: Ferroptosis is involved in the IRI during LT with a severe steatotic donor liver. miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft IRI, which might be a promising strategy to treat IRI in steatotic grafts.

Real Space Imaging of Spin Stripe Domain Fluctuations in a Complex Oxide.

Understanding the formation and dynamics of charge and spin-ordered states in low-dimensional transition metal oxide materials is crucial to understanding unconventional high-temperature superconductivity. La_{2-x}Sr_{x}NiO_{4+δ} (LSNO) has attracted much attention due to its interesting spin dynamics. Recent x-ray photon correlation spectroscopy studies have revealed slow dynamics of the spin order (SO) stripes in LSNO. Here, we applied resonant soft x-ray ptychography to map the spatial distribution of the SO stripe domain inhomogeneity in real space. The reconstructed images show the SO domains are spatially anisotropic, in agreement with previous diffraction studies. For the SO stripe domains, it is found that the correlation lengths along different directions are strongly coupled in space. Surprisingly, fluctuations were observed in the real space amplitude signal, rather than the phase or position. We attribute the observed slow dynamics of the stripe domains in LSNO to thermal fluctuations of the SO domain boundaries.

Kaempferol, the melanogenic component of Sanguisorba officinalis, enhances dendricity and melanosome maturation/transport in melanocytes.

Kaempferol, a representative flavonoid constituent of Sanguisorba officinalis, promotes melanogenesis, but the underlying mechanisms remain unknown. Here, we evaluated the effects of kaempferol on melanocytes morphology and behavior and determined the mechanisms regulating kaempferol-induced pigmentation. We observed that kaempferol increased melanin contents and dendritic length and stimulated melanocyte migration both in vitro and vivo. It significantly enhanced the expression of microphthalmia-associated transcription factor (MITF) and downstream enzymes of melanin biosynthesis-tyrosinase (TYR), tyrosinase-related protein (TRP-1), and dopachrome tautomerase (DCT). It also induced melanosome maturation (increased stage III and IV melanosomes) and melanin transfer to dendritic tips; this was evidenced as follows: kaempferol-treated melanocytes exhibited the perimembranous accumulation of HMB45-positive melanosomes and increased the expression of Rab27A, RhoA, and Cdc42, which improved melanosome transport to perimembranous actin filaments. These results jointly indicated that kaempferol promotes melanogenesis and melanocyte growth. Additionally, kaempferol stimulated the phosphorylation of P38/ERK MAPK and downregulated p-PI3K, p-AKT, and p-P70s6K expression. Pre-incubation with P38 (SB203580) and ERK (PD98059) signaling inhibitors reversed the melanogenic and dendritic effects and MITF expression. PI3K/AKT inhibitor augmented kaempferol-induced melanin content and dendrite length. In summary, kaempferol regulated melanocytes' dendritic growth and melanosome quantity, maturation, and transport via P38/ERK MAPK and PI3K/AKT signaling pathways.

Protective Effects of Bone Marrow Mesenchymal Stem Cells (BMMSCS) Combined with Normothermic Machine Perfusion on Liver Grafts Donated After Circulatory Death via Reducing the Ferroptosis of Hepatocytes.

BACKGROUND To improve the quality of liver grafts from extended-criteria donors donated after circulatory death (DCD), this study explored whether bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP) have protective effects on DCD donor livers and the effects of ferroptosis in this procedure. MATERIAL AND METHODS Twenty-four male rat DCD donor livers were randomly and averagely divided into normal, static cold storage (SCS), NMP, and NMP combined with BMMSCs groups. Liver function, bile secretion, and pathological features of DCD donor livers were detected to evaluate the protective effects of NMP and BMMSCs on DCD donor livers. Hydrogen peroxide was used to induce an oxidative stress model of hepatocyte IAR-20 cells to evaluate the protective effects of BMMSCs in vitro. RESULTS Livers treated with NMP combined with BMMSCs showed better liver function, relieved histopathological damage, reduced oxidative stress injury and ferroptosis, and the mechanism of reduction was associated with downregulation of intracellular reactive oxygen species (ROS) and free Fe²âº levels. BMMSCs showed significant protective effects on the ultrastructure of DCD donor livers and ROS-induced injury to IAR-20 cells under electron microscopy. BMMSCs also significantly improved the expression level of microtubule-associated protein 1 light chain 3 (LC3)-II in both DCD donor livers and ROS-induced injured IAR-20 cells, including upregulating the expression of ferritin. CONCLUSIONS BMMSCs combined with NMP could reduce the level of ROS and free Fe²âº in oxidative stress damaged rat DCD donor livers, potentially reduce the ferroptosis in hepatocytes, and repair both morphology and function of DCD donor livers.

Laboratory markers associated with COVID-19 progression in patients with or without comorbidity: A retrospective study.

OBJECTIVES: To investigate laboratory markers for COVID-19 progression in patients with different medical conditions. METHODS: We performed a multicenter retrospective study of 836 cases in Hubei. To avoid the collinearity among the indicators, principal component analysis (PCA) followed by partial least squares discriminant analysis (PLS-DA) was performed to obtain an overview of laboratory assessments. Multivariable logistic regression analysis and multivariable Cox proportional hazards regression analysis were respectively used to explore risk factors associated with disease severity and mortality. Survival analysis was performed in patients with the most common comorbidities. RESULTS: Lactate dehydrogenase (LDH) and prealbumin were associated with disease severity in patients with or without comorbidities, indicated by both PCA/PLS-DA and multivariable logistic regression analysis. The mortality risk was associated with age, LDH, C-reactive protein (CRP), D-dimer, and lymphopenia in patients with comorbidities. CRP was a risk factor associated with short-term mortality in patients with hypertension, but not liver diseases; additionally, D-dimer was a risk factor for death in patients with liver diseases. CONCLUSIONS: Lactate dehydrogenase was a reliable predictor associated with COVID-19 severity and mortality in patients with different medical conditions. Laboratory biomarkers for mortality risk were not identical in patients with comorbidities, suggesting multiple pathophysiological mechanisms following COVID-19 infection.

Precise Fabrication of De Novo Nanoparticle Lattices on Dynamic 2D Protein Crystalline Lattices.

The science of protein self-assembly has experienced significant development, from discrete building blocks of self-assembled nanoarchitectures to advanced nanostructures with adaptive functionalities. Despite the prominent achievements in the field, the desire of designing de novo protein-nanoparticle (NP) complexes and constructing dynamic NP systems remains highly challenging. In previous works, l-rhamnulose-1-phosphate aldolase (C98RhuA) tetramers were self-assembled into two-dimensional (2D) lattices via disulfide bond interactions. These interactions provided 2D lattices with high structural quality and a sophisticated assembly mode. In this study, we devised a rational design for RhuA building blocks to fabricate 2D functionalized protein lattices. More importantly, the lattices were used to direct the precise assembly of NPs into highly ordered and diverse nanoarchitectures. These structures can be employed as an excellent tool to adequately verify the self-assembly mode and structural quality of the designed RhuA crystals. The subsequent redesign of RhuA building blocks enabled us to predictably produce a novel protein lattice whose conformational dynamics can be controllably regulated. Thus, a dynamic system of AuNP lattices was achieved. Transmission electron microscopy and small-angle X-ray scattering indicated the presence of these diverse NP lattices. This contribution enables the fabrication of future NP structures in a more programmable manner with more expected properties for potential applications in nanoelectronics and other fields.

Abscisic acid mediated proline biosynthesis and antioxidant ability in roots of two different rice genotypes under hypoxic stress.

BACKGROUND: Abscisic acid (ABA) and proline play important roles in rice acclimation to different stress conditions. To study whether cross-talk exists between ABA and proline, their roles in rice acclimation to hypoxia, rice growth, root oxidative damage and endogenous ABA and proline accumulation were investigated in two different rice genotypes ('Nipponbare' (Nip) and 'Upland 502' (U502)). RESULTS: Compared with U502 seedlings, Nip seedlings were highly tolerant to hypoxic stress, with increased plant biomass and leaf photosynthesis and decreased root oxidative damage. Hypoxia significantly stimulated the accumulation of proline and ABA in the roots of both cultivars, with a higher ABA level observed in Nip than in U502, whereas the proline levels showed no significant difference in the two cultivars. The time course variation showed that the root ABA and proline contents under hypoxia increased 1.5- and 1.2-fold in Nip, and 2.2- and 0.7-fold in U502, respectively, within the 1 d of hypoxic stress, but peak ABA production (1 d) occurred before proline accumulation (5 d) in both cultivars. Treatment with an ABA synthesis inhibitor (norflurazon, Norf) inhibited proline synthesis and simultaneously aggravated hypoxia-induced oxidative damage in the roots of both cultivars, but these effects were reversed by exogenous ABA application. Hypoxia plus Norf treatment also induced an increase in glutamate (the main precursor of proline). This indicates that proline accumulation is regulated by ABA-dependent signals under hypoxic stress. Moreover, genes involved in proline metabolism were differentially expressed between the two genotypes, with expression mediated by ABA under hypoxic stress. In Nip, hypoxia-induced proline accumulation in roots was attributed to the upregulation of OsP5CS2 and downregulation of OsProDH, whereas upregulation of OsP5CS1 combined with downregulation of OsProDH enhanced the proline level in U502. CONCLUSION: These results suggest that the high tolerance of the Nip cultivar is related to the high ABA level and ABA-mediated antioxidant capacity in roots. ABA acts upstream of proline accumulation by regulating the expression of genes encoding the key enzymes in proline biosynthesis, which also partly improves rice acclimation to hypoxic stress. However, other signaling pathways enhancing tolerance to hypoxia in the Nip cultivar still need to be elucidated.

Dynamic Crystallization and Phase Transition in Evaporating Colloidal Droplets.

Evaporating colloidal droplets are an omnipresent phenomenon in nature and engage in many scientific and commercial technologies. Despite their apparent importance, many of the fundamental aspects remain unknown, particularly the relationships between evaporation kinetics, volume fraction, crystallization, and phase transition. Here, we follow the structural evolution and drying dynamics across the liquid-to-solid transition of evaporating colloidal droplets containing polystyrene nanospheres with both spatial and temporal resolutions through the in situ small-angle X-ray scattering and ex situ electron microscopy techniques. We find the unconventional evaporation-driven heterogeneous crystallization and the sequential stacking of face-centered cubic (fcc), random hexagonal close-packed (rhcp), and random close-packed (rcp) superlattice structures. The crystallization and phase transition processes are further elucidated and coordinated with the real-time volume fraction variation, which constitutes a rich and dynamic picture of the self-assembly process. Starting with the Onsager principle, we provide quantitative analysis to the evaporation kinetics, including concentration gradient, gelation, and cavitation. Our findings impart a new mechanism of dynamic nucleation and crystallization and reveal the intimate link between structural heterogeneity and evaporation kinetics.

Real-Time Probing of Nanowire Assembly Kinetics at the Air-Water Interface by In†Situ Synchrotron X-Ray Scattering.

Although many assembly strategies have been used to successfully construct well-aligned nanowire (NW) assemblies, the understanding of their assembly kinetics has remained elusive, which restricts the development of NW-based device and circuit fabrication. Now a versatile strategy that combines interfacial assembly and synchrotron-based grazing-incidence small-angle X-ray scattering (GISAXS) is presented to track the assembly evolution of the NWs in real time. During the interface assembly process, the randomly dispersed NWs gradually aggregate to form small ordered NW-blocks and finally are constructed into well-defined NW monolayer driven by the conformation entropy. The NW assembly mechanism can be well revealed by the thermodynamic analysis and large-scale molecular dynamics theoretical evaluation. These findings point to new opportunities for understanding NW assembly kinetics and manipulating NW assembled structures by bottom-up strategy.

Wide-angle polarization-free plasmon-enhanced light absorption in perovskite films using silver nanowires.

Since the successful implementation of organic-inorganic hybrid perovskites as light-absorbing materials, stunning progresses have been made towards the efficiency boost of perovskite solar cells. To build upon these successes, further impetus may derive from revisits to the intrinsic properties of perovskites, such as their optical properties. Herein, we introduce periodic Ag nanowire (AgNW) structures into perovskite films to optimize their solar absorption efficiency through plasmonic interactions. Numerical simulations show a remarkable integrated solar absorption enhancement of 25.9% attained by incorporating properly tailored AgNW arrays into perovskite films. The AgNW crosses are further introduced to achieve polarization-independent light harvesting capability. The omnidirectional light absorption enhancement ability of the AgNW embedded perovskite films is also demonstrated.

Diseleno[2,3-b:3',2'-d]selenophene and Diseleno[2,3-b:3',2'-d] thiophene: Building Blocks for the Construction of [7]Helicenes.

New building blocks, 2,5-di(trimethylsilanyl)diseleno[2,3-b:3',2'-d]selenophene ((TMS)2-DSS) and 2,5-di(trimethylsilanyl)diseleno[2,3-b:3',2'-d]thiophene ((TMS)2-DST), for helicenes were obtained from selenophene with total yields of 54 and 61%. From (TMS)2-DSS and (TMS)2-DST, selenophene-based hetero[7]helicenes, 5,5'-di(trimethylsilanyl)benzo[1,2-b:3,4-b']bis(diseleno[2,3-b:3',2'-d]thiophene) (rac-1), and 5,5'-di(trimethylsilanyl)benzo[1,2-b:3,4-b']bis(diseleno[2,3-b:3',2'-d]selenophene) (rac-2) were prepared. The overall yields from selenophene were approximately 6.5 and 6.1%, respectively. Intermolecular interactions such as C-Se, C-S, and Se-Se were observed in the crystal packings of rac-1 and rac-2. In addition, the absorption behaviors of rac-1 and rac-2 were investigated.

Two-Dimensional Organic-Inorganic Hybrid Perovskite Photonic Films.

Organic-inorganic hybrid perovskites have created enormous expectations for low-cost and high-performance optoelectronic devices. In prospect, future advancements may derive from reaping novel electrical and optical properties beyond pristine perovskites through microscopic structure design and engineering. Herein, we report the successful preparation of two-dimensional inverse-opal perovskite (IOP) photonic films, featuring unique nanostructures and vivid colors. Further compositional and structural managements promise optical property and energy level tunability of the IOP films. They are further functionalized in solar cells, resulting in colorful devices with respectable power conversion efficiency. Such concept has not been previously applied for perovskite-based solar cells, which could open a route for more versatile optoelectronic devices.

Silicon Spiro Double Helicene-like Compounds Based on Dithieno[2,3-b:3',2'-d]thiophene: Syntheses and Crystal Structures.

Silicon spiro carbon-sulfur double helicene-like compounds 1 and rac-2 were synthesized from 2,5-bis-trimethylsilanyldithieno[2,3-b:3',2'-d]thiophene, with total yields of 17% and 7%, respectively. (1)H and (13)C NMR spectra and X-ray crystallographic analysis showed the predicted 4-fold symmetry for 1 and rac-2 and confirmed their spiro double helicene-like spatial configurations. The absorption behavior of compounds 1 and rac-2 was also investigated.

Veronica linariifolia subsp. dilatata ameliorates LPS-induced acute lung injury by attenuating endothelial cell barrier dysfunction via EGFR/Akt/ZO-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried aerial parts of Veronica linariifolia subsp. dilatata (Nakai & Kitag.) D.Y.Hong named Shui Man Jing (SMJ) is a traditional Chinese medicine with a long history of clinical use in the treatment of chronic bronchitis and coughing up blood, however, its role on acute lung injury (ALI) has not been revealed yet. AIM OF THE STUDY: To assess the efficiency of SMJ on ALI and to investigate whether it inhibited endothelial barrier dysfunction by regulating the EGFR/Akt/ZO-1 pathway to alleviate ALI in vivo and in vitro based on the result of network pharmacology. MATERIALS AND METHODS: An in vivo model of ALI was established using inhalation of atomized lipopolysaccharide (LPS), and the effects of SMJ on ALI were evaluated through histopathological examination and inflammatory cytokines, lung histology and edema, vascular and alveolar barrier disruption. Network pharmacology was applied to predict the mechanism of SMJ in the treatment of ALI. The crucial targets were validated by RT-PCR, Western Blotting, molecular docking, immunohistochemistry and immunofluorescence methods in vivo and in virto. RESULTS: Administration of SMJ protected mice against LPS-induced ALI, including ameliorating the histological alterations in the lung tissues, and decreasing lung edema, protein content of bronchoalveolar lavage fluid, infiltration of inflammatory cell and secretion of cytokines. SMJ exerted protective effects in ALI by inhibiting endothelial barrier dysfunction in mice and bEnd.3 cell. SMJ relieved endothelial barrier dysfunction induced by LPS through upregulating the EGFR expression. SMJ also increased the phosphorylation of Akt, and ZO-1 expression both in vivo and in vitro. CONCLUSION: SMJ attenuates vascular endothelial barrier dysfunction for LPS-induced ALI via EGFR/Akt/ZO-1 pathway, and is a promising novel therapeutic candidate for ALI.

Crescent calculator: A webtool enabling objective decision-making for assessment of IgA nephropathy immune activity throughout the disease course.

IgA nephropathy (IgAN) is an immune-mediated glomerulonephritis, posing a challenge for the long-term management. It is crucial to monitor the disease's activity over the disease course. Crescent lesions have been known as an active lesion associated with immune activity. We aimed to develop the Crescent Calculator to aid clinicians in making timely and well-informed decisions throughout the long-term disease course, such as renal biopsies and immunosuppressive therapy. 1,761 patients with biopsy-proven IgAN were recruited from four medical centers in Zhejiang Province, China. 16.9% presented crescent lesions. UPCR, URBC, eGFR and C4 were independently associated with the crescent lesions. By incorporating these variables, the Crescent Calculator was constructed to estimate the likelihood of crescent lesions. The predictor achieved AUC values of over 0.82 in two independent testing datasets. In addition, to fulfill varied clinical needs, multiple classification modes were established. The Crescent Calculator was developed to estimate the risk of crescent lesions for patients with IgAN, assisting clinicians in making timely, objective, and well-informed decisions regarding the need for renal biopsies and more appropriate use of immunosuppressive therapy in patients with IgAN.