A multi-classifier system integrated by clinico-histology-genomic analysis for predicting recurrence of papillary renal cell carcinoma.

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.

Influence of Ultrafine Fly Ash and Slag Powder on Microstructure and Properties of Magnesium Potassium Phosphate Cement Paste.

This study investigated the influences of ultrafine fly ash (UFA) and ultrafine slag powder (USL) on the compressive strengths, autogenous shrinkage, phase assemblage, and microstructure of magnesium potassium phosphate cement (MKPC). The findings indicate that the aluminosilicate fractions present in both ultrafine fly ash and ultrafine slag participate in the acid-base reaction of the MKPC system, resulting in a preferential formation of irregularly crystalline struvite-K incorporating Al and Si elements or amorphous aluminosilicate phosphate products. UFA addition mitigates early age autogenous shrinkage in MKPC-based materials, whereas USL exacerbates this shrinkage. In terms of the sustained mechanical strength development of the MKPC system, ultrafine fly ash is preferred over ultrafine slag powder. MKPC pastes with ultrafine fly ash show greater compressive strength compared to those with ultrafine slag powder at 180 days due to denser interfaces between the ultrafine fly ash particles and hydration products like struvite-K. The incorporation of 30 wt% ultrafine fly ash enhances compressive strengths across all testing ages.

Characterizing medaka visual features using a high-throughput optomotor response assay.

Medaka fish (Oryzias latipes) is a powerful model to study genetics underlying the developmental and functional traits of the vertebrate visual system. We established a simple and high-throughput optomotor response (OMR) assay utilizing medaka larvae to study visual functions including visual acuity and contrast sensitivity. Our assay presents multiple adjustable stripes in motion to individual fish in a linear arena. For that the OMR assay employs a tablet display and the Fish Stripes software to adjust speed, width, color, and contrast of the stripes. Our results demonstrated that optomotor responses were robustly induced by black and white stripes presented from below in the linear-pool-arena. We detected robust strain specific differences in the OMR when comparing long established medaka inbred strains. We observed an interesting training effect upon the initial exposure of larvae to thick stripes, which allowed them to better respond to narrower stripes. The OMR setup and protocol presented here provide an efficient tool for quantitative phenotype mapping, addressing visual acuity, trainability of cortical neurons, color sensitivity, locomotor response, retinal regeneration and others. Our open-source setup presented here provides a crucial prerequisite for ultimately addressing the genetic basis of those processes.

Exploring and clinical validation of prognostic significance and therapeutic implications of copper homeostasis-related gene dysregulation in acute myeloid leukemia.

The patterns and biological functions of copper homeostasis-related genes (CHRGs) in acute myeloid leukemia (AML) remain unclear. We explored the patterns and biological functions of CHRGs in AML. Using independent cohorts, including TCGA-GTEx, GSE114868, GSE37642, and clinical samples, we identified 826 common differentially expressed genes. Specifically, 12 cuproptosis-related genes (e.g., ATP7A, ATP7B) were upregulated, while 17 cuproplasia-associated genes (e.g., ATOX1, ATP7A) were downregulated in AML. We used LASSO-Cox, Kaplan-Meier, and Nomogram analyses to establish prognostic risk models, effectively stratifying patients with AML into high- and low-risk groups. Subgroup analysis revealed that high-risk patients exhibited poorer overall survival and involvement in fatty acid metabolism, apoptosis, and glycolysis. Immune infiltration analysis indicated differences in immune cell composition, with notable increases in B cells, cytotoxic T cells, and memory T cells in the low-risk group, and increased monocytes and neutrophils in the high-risk group. Single-cell sequencing analysis corroborated the expression characteristics of critical CHRGs, such as MAPK1 and ATOX1, associated with the function of T, B, and NK cells. Drug sensitivity analysis suggested potential therapeutic agents targeting copper homeostasis, including Bicalutamide and Sorafenib. PCR validation confirmed the differential expression of 4 cuproptosis-related genes (LIPT1, SLC31A1, GCSH, and PDHA1) and 9 cuproplasia-associated genes (ATOX1, CCS, CP, MAPK1, SOD1, COA6, PDK1, DBH, and PDE3B) in AML cell line. Importantly, these genes serve as potential biomarkers for patient stratification and treatment. In conclusion, we shed light on the expression patterns and biological functions of CHRGs in AML. The developed risk models provided prognostic implications for patient survival, offering valuable information on the regulatory characteristics of CHRGs and potential avenues for personalized treatment in AML.

Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop.

BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. CONCLUSION: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.

Postoperative follow-up of 221 patients with infective endocarditis from Gaoligong mountain area of Yunnan in China: a retrospective, single-center, observational cohort study.

Background: Despite improvements in management, infective endocarditis (IE) is still associated with high mortality and morbidity. The outcome of patients with IE remains unclear in high-altitude areas of China. To characterize the epidemiological features and surgical outcomes, a retrospective analysis was conducted to 221 patients diagnosed with IE from a single center. In addition, to assess the prognosis of patients, a multivariate logistic regression model was performed to analyze the affecting risk factors. Methods: A retrospective analysis was conducted on the clinical data of 221 patients with IE who underwent surgical treatment at the Department of Cardiac Surgery of Yan'an Hospital Affiliated to Kunming Medical University from January 2013 to December 2019. The analysis evaluated patient demographics, pathogenic bacterial composition, echocardiography results, and surgical treatment outcomes. After a 1-year follow-up period, the mortality rate was statistically analyzed. The patients were divided into two groups based on their survival status: those who survived and those who did not. Relevant factors were compared between the two groups, and a multivariate logistic regression model was used to analyze the risk factors that affect the prognosis of patients with IE. Results: Out of the 221 patients diagnosed with IE, 164 were male and 57 were female, with an average age of 39.25±14.36 years. The most common underlying heart diseases were bicuspid aortic valve disease (24.9%), congenital heart disease (19.5%), rupture of aortic sinus aneurysm (5.0%) and rheumatic valvular disease (2.3%). The blood culture had a positive rate of 48.42% (107/221), with Streptococcus viridans (29.9%) and Streptococcus haematoides (13.1%) being the main specifically pathogenic bacteria identified. Transthoracic echocardiography produced positive results in 89.6% (198/221) of cases. The findings included vegetation formation (100%), valve perforation or tear (21.7%), and perivalvular abscess formation (5.6%). Out of the patients, 174 underwent elective surgery, 47 received emergency surgery, and 11 died within 1 year after surgery, resulting in a mortality rate of 5.0%. However, the death group had longer operation time, cardiopulmonary bypass (CPB) time and higher EuroSCORE II compared to the non-death group (P<0.05). Logistic regression analysis identified preoperative hematocrit decrease, prolonged operation time and CPB time, high New York Heart Association (NYHA) cardiac function grade, and liver diseases as risk factors for 1-year mortality in patients with IE (OR =1.003, 0.000, 1.006, 1.026, 1.624 and 4.746). Conclusions: IE primarily affects young and middle-aged men with rheumatic heart valvular disease as the main underlying heart disease and Streptococcus viridans as the main pathogen. Surgical intervention significantly reduces early mortality in IE patients. To improve postoperative prognosis, clinicians should remain vigilant, especially in high-risk groups with preoperative hematocrit, prolonged operation time, and CPB time, high NYHA cardiac function grade, EuroSCORE II, and vegetation formation.

Exposed Embolic Coils Observed in a 64-Year-Old Male With Head and Neck Cancer Following Transarterial Embolization for Carotid Blowout Syndrome.

Background: Delayed migration and exposure of embolic coils is a rare complication of endovascular therapy for carotid blowout syndrome. Methods: A 64-year-old man with recurrent tongue cancer noticed the presence of foreign body in the malignant wound on the right side of his neck. He had undergone transarterial embolization on his right vertebral artery, right common carotid artery (CCA), and internal carotid artery (ICA) for carotid blowout syndrome 1 month prior. On physical examination, exposed spring-like metallic coils were observed, covered in brownish granulation tissue, at the bottom of the malignant wound. Neck radiograph and computed tomography confirmed the extrusion and migration of the embolic coils. Results: In this case, the patient was managed by transection of the exposed coils at the wound surface with close monitoring. Conclusions: Computed tomography angiography is essential for assessing the condition of the remaining embolic coils. In cases with thrombosed parent arteries, a conservative approach, like the transection of exposed coils, can be employed as part of the management strategy.

Use of Dixon in magnetic resonance breast contrast-enhanced T1 weighted high-resolution imaging for mastectomy patients at 3T: A prospective study in single center.

BACKGROUND: For patients with complete breast resection, conventional contrast-enhanced T1-weighted imaging (CE-T1WI) with frequency-selective spectral attenuated inversion recovery (SPAIR) provides limited fat suppression on the postoperative side due to the uneven skin surface, inhomogeneous tissue environment, and frequency-selective feature of the SPAIR scheme, leading to difficulties in precise diagnosis. This study aimed to investigate the image quality and performance of the Dixon method compared with SPAIR in breast high-resolution CE-T1WI for mastectomy patients. MATERIALS AND METHODS: Sixty female patients who had not performed any breast surgeries were randomly selected retrospectively as the control group. Postmastectomy female patients were enrolled to undergone high-resolution CE-T1WI with SPAIR and Dixon breast scans. Subjective scores were rated using a 5-point scale. Objective parameters, including contrast-to-noise ratio (CNR), edge sharpness, and signal uniformity were measured and calculated. The Wilcoxon rank-sum test and Kappa statistic were used. RESULTS: A total of 114 consecutive postmastectomy patients were included. Subjective scores of T1WI-SPAIR in the control group were all significantly better than those with SPAIR on the postoperative side of mastectomy patients (P < 0.01). Dixon outperformed SPAIR with significantly better subjective scores in regards to uniformity and degree of fat-suppression, anatomical structures depiction, lesion conspicuity, and axillary visibility (p < 0.05) in both post- and non-operative sides and bilateral axillary areas through the paired comparison. The objective parameters of Dixon were significantly better than those of SPAIR. CONCLUSION: The Dixon method provided better image uniformity and higher fat suppression efficiency, and showed significant advantages in delineating the anatomical structures, with better axillary and lesion visibilities, especially on the completely removed breast side.

Establishing national reference materials for genetic testing of cytochrome P450.

OBJECTIVES: Reference materials for in-vitro diagnostic reagents play a critical role in determining the quality of reagents and ensuring the accuracy of clinical test results. This study aimed to establish a national reference material (NRM) for detecting cytochrome P450 (CYP) genes related to drug metabolism by screening databases on the Chinese population to identify CYP gene polymorphism characteristics. METHODS: To prepare the NRM, we used DNA extracted from healthy human immortalized B lymphoblastoid cell lines as the raw material. Samples of these cell lines were obtained from the Chinese Population PGx Gene Polymorphism Biobank. Further, we used Sanger sequencing, next-generation sequencing, and commercial assay kits to validate the polymorphic genotypes. RESULTS: Among the CYP superfamily genes, we confirmed 24 riboswitch loci related to drug metabolism, with evidence levels of 1A, 2A, 3, and 4. We confirmed the polymorphic loci and validated their genotypes using various sequencing techniques. Our results were consistent with the polymorphism information of samples obtained from the biobank, thus demonstrating high precision and stability of the established NRM. CONCLUSION: An NRM (360 056-202 201) for CYP genetic testing covering 24 loci related to drug metabolism was established and approved to assess in-vitro diagnostic reagents containing CYP family gene polymorphisms and perform clinical inter-room quality evaluations.

Teaching Strategies in Psychiatric Nursing Based on Bloom's Taxonomy of Educational Objectives.

Bloom's Taxonomy of Educational Objective (BTEO), as a classic method for categorizing educational objectives, provides a clear and specific framework for formulating teaching goals in the global education field. Psychiatric nursing, as a highly specialized discipline, demands high requirements for students in both theoretical knowledge and practical skills. However, traditional teaching methods often focus excessively on knowledge impartation, neglecting the cultivation of students' practical abilities and emotional attitudes. Therefore, the purpose of this study was to Improve the existing psychiatric nursing curriculum by combining Bloom's educational goals theory, which emphasizes the comprehensive development of cognitive, affective, and psychomotor skills, providing new perspectives and methods for psychiatric nursing education. By applying BTEO, specific teaching goals at different levels can be defined more clearly, and corresponding teaching strategies and methods can be employed to achieve these goals. Furthermore, the application of BTEO requires effective interaction between teachers and students. Teachers need to monitor students' learning progress, adjust teaching strategies promptly, and ensure that students comprehensively grasp knowledge and skills. Thus, the application of this teaching strategy contributes to improving the quality of psychiatric nursing education and cultivating outstanding psychiatric nursing professionals. We hope to cultivate students' theoretical knowledge and practical skills in mental care by helping them develop their overall skills.

[Correlation of miR-155 Expression with Drug Sensitivity of FLT3-ITD+ Acute Myeloid Leukemia Cell Line and Its Mechanism].

OBJECTIVE: To investigate the correlation of miR-155 expression with drug sensitivity of FLT3-ITD+ acute myeloid leukemia (AML) cell line and its potential regulatory mechanism. METHODS: By knocking out miR-155 gene in FLT3-ITD+ AML cell line MV411 through CRISPR/Cas9 gene-editing technology, monoclonal cells were screened. The genotype of these monoclonal cells was validated by PCR and Sanger sequencing. The expression of mature miRNA was measured by RT-qPCR. The treatment response of doxorubicin, quizartinib and midostaurin were measured by MTT assay and IC50 of these drugs were calculated to identify the sensitivity. Transcriptome sequencing was used to analyze change of mRNA level in MV411 cells after miR-155 knockout, gene set enrichment analysis to analyze change of signaling pathway, and Western blot to verify expressions of key molecules in signaling pathway. RESULTS: Four heterozygotes with gene knockout and one heterozygote with gene insertion were obtained through PCR screening and Sanger sequencing. RT-qPCR results showed that the expression of mature miR-155 in the monoclonal cells was significantly lower than wild-type clones. MTT results showed that the sensitivity of MV411 cells to various anti FLT3-ITD+ AML drugs increased significantly after miR-155 knockout compared with wild-type clones. RNA sequencing showed that the mTOR signaling pathway and Wnt signaling pathway were inhibited after miR-155 knockout. Western blot showed that the expressions of key molecules p-mTOR, Wnt5α and ß-catenin in signaling pathway were down-regulated. CONCLUSION: Drug sensitivity of MV411 cells to doxorubicin, quizartinib and midostaurin can be enhanced significantly after miR-155 knockout, which is related to the inhibition of multiple signaling pathways including mTOR and Wnt signaling pathways.

Radiofrequency radiation reshapes tumor immune microenvironment into antitumor phenotype in pulmonary metastatic melanoma by inducing active transformation of tumor-infiltrating CD8+ T and NK cells.

Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7 W/kg for 1 h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.

Organocatalytic enantioselective decarboxylative protonation of α-alkyl-α-aryl malonate monoesters.

In contrast to the well-established enzymatic enantioselective decarboxylative protonation (EDP), the corresponding chemocatalytic reactions of acyclic malonic acid derivatives remain challenging. Herein, we developed a biomimetic EDP of α-alkyl-α-aryl malonate monoesters using a chiral 1,2-trans-diaminocyclohexane-based N-sulfonamide as an organocatalyst. The method demonstrates excellent chemical yields, good enantioselectivity, mild reaction conditions, and the generation of only CO2 as waste.

Observation of Nonlinear Exceptional Points with a Complete Basis in Dynamics.

The exotic physics associated with exceptional points (EPs) is always under the scrutiny of theoretical and experimental science. Recently, considerable effort has been invested in the combination of nonlinearity and non-Hermiticity. The concept of nonlinear EPs (NEPs) has been introduced, which can avoid the loss of completeness of the eigenbasis in dynamics while retaining the key features of linear EPs. Here, we present the first direct experimental demonstration of a NEP based on two non-Hermition coupled circuit resonators combined with a nonlinear saturable gain. At the NEP, the response of the eigenfrequency to perturbations demonstrates a third-order root law and the eigenbasis of the Hamiltonian governing the system dynamics is still complete. Our results bring this counterintuitive aspect of the NEP to light and possibly open new avenues for applications.

Proof of concept in utilizing the peptidoglycan skeleton of pathogenic bacteria as antigen delivery platform for enhanced immune response.

Subunit vaccines are becoming increasingly important because of their safety and effectiveness. However, subunit vaccines often exhibit limited immunogenicity, necessitating the use of suitable adjuvants to elicit robust immune responses. In this study, we demonstrated for the first time that pathogenic bacteria can be prepared into a purified peptidoglycan skeleton without nucleic acids and proteins, presenting bacterium-like particles (pBLP). Our results showed that the peptidoglycan skeletons screened from four pathogens could activate Toll-like receptor1/2 receptors better than bacterium-like particles from Lactococcus lactis in macrophages. We observed that pBLP was safe in mouse models of multiple ages. Furthermore, pBLP improved the performance of two commercial vaccines in vivo. We confirmed that pBLP successfully loaded antigens onto the surface and proved to be an effective antigen delivery platform with enhanced antibody titers, antibody avidity, balanced subclass distribution, and mucosal immunity. These results indicate that the peptidoglycan skeleton of pathogenic bacteria represents a new strategy for developing subunit vaccine delivery systems.

Designing Ultratough Single-Network Hydrogels with Centimeter-Scale Fractocohesive Lengths via Inelastic Crack Blunting.

Fractocohesive length, defined as the ratio of fracture toughness to work of fracture, measures the sensitivity of materials to fracture in the presence of flaws. The larger the fractocohesive length, the more flaw-tolerant and crack-resistant the hydrogel. For synthetic soft materials, the fractocohesive length is short, often on the scale of 1 mm. Here, highly flaw-insensitive (HFI) single-network hydrogels containing an entangled inhomogeneous polymer network of widely distributed chain lengths are designed. The HFI hydrogels demonstrate a centimeter-scale fractocohesive length of 2.21 cm, which is the highest ever recorded for synthetic hydrogels, and an unprecedented fracture toughness of ≈13 300 J m-2. The uncommon flaw insensitivity results from the inelastic crack blunting inherent to the highly inhomogeneous network. When the HFI hydrogel is stretched, a large number of short chains break while coiled long chains can disentangle, unwind, and straighten, producing large inelastic deformation that substantially blunts the crack tip in a plastic manner, thereby deconcentrating crack-tip stresses and blocking crack extension. The flaw-insensitive design strategy is applicable to various hydrogels such as polyacrylamide and poly(N,N-dimethylacrylamide) hydrogels and enables the development of HFI soft composites.

Study on blasting fragmentation mechanism of burnt rock in open-pit coal mine.

A large number of burnt rocks in some open-pit mines in Xinjiang, Inner Mongolia and Ningxia have a great influence on the blasting effect. For this kind of rock, through the analysis of physical and chemical changes, combined with ANSYS/LS-DYNA and PFC 2D numerical simulation software, a burnt rock model with multiple joint cracks and irregular distribution is constructed to simulate the blasting process of burnt rock under the combined action of stress wave and detonation gas. The results show that the fracture of rock mass affects the propagation of blasting cracks in the fracture area, resulting in stress concentration and stress hindrance. The action time of stress wave is reduced, and the energy of blasting gas is partially absorbed by the fracture, resulting in uneven stress on the burnt rock bench and seriously affecting the bench blasting effect.

Tooth-Supported Overdentures Revisited.

The goal of prosthodontics is to provide a functional prosthesis to restore aesthetics, functions, and masticatory efficiencies. Tooth-supported overdentures are one of the treatment options for removable dentures. This article aims to discuss the advantages and disadvantages of tooth-supported overdentures and the principles of using various overdenture attachments, including non-attachment overdentures. The common treatment options in preparing the overdenture abutment are either with or without abutment coping with or without attachment systems, which were discussed and illustrated. A range of tooth-supported overdenture systems were addressed, from low to high financial implications and treatment complexities. The clinician can choose a system that best fits the patient's condition and expectations. This allows clinicians to decide and consider tooth-supported overdentures as a treatment option before full edentulism. A well-executed tooth-supported overdenture ensures the preservation of alveolar bone, optimizes patient satisfaction in denture treatment, and eventually improves the patient's adaptation when transitioning to complete dentures.

The haplotype-resolved genome assembly of autotetraploid rhubarb Rheum officinale provides insights into its genome evolution and massive accumulation of anthraquinones.

Rheum officinale, a member of the Polygonaceae family, is an important medicinal plant that is widely used in traditional Chinese medicine. Here, we report a 7.68-Gb chromosome-scale assembly of R. officinale with a contig N50 of 3.47 Mb, which was clustered into 44 chromosomes across four homologous groups. Comparative genomics analysis revealed that transposable elements have made a significant contribution to its genome evolution, gene copy number variation, and gene regulation and expression, particularly of genes involved in metabolite biosynthesis, stress resistance, and root development. We placed the recent autotetraploidization of R. officinale at ∼0.58 mya and analyzed the genomic features of its homologous chromosomes. Although no dominant monoploid genomes were observed at the overall expression level, numerous allele-differentially-expressed genes were identified, mainly with different transposable element insertions in their regulatory regions, suggesting that they functionally diverged after polyploidization. Combining genomics, transcriptomics, and metabolomics, we explored the contributions of gene family amplification and tetraploidization to the abundant anthraquinone production of R. officinale, as well as gene expression patterns and differences in anthraquinone content among tissues. Our report offers unprecedented genomic resources for fundamental research on the autopolyploid herb R. officinale and guidance for polyploid breeding of herbs.

Aldosteronism is associated with more severe cerebral small vessel disease in hypertensive intracerebral hemorrhage.

Primary aldosteronism is associated with various types of cardiovascular and cerebrovascular damage independently of hypertension. Although chronic hypertension and related cerebral arteriosclerosis are the main risk factors for intracerebral hemorrhage, the effects of aldosteronism remain poorly understood. We enrolled 90 survivors of hypertensive intracerebral hemorrhage, 21 of them with aldosteronism and 69 with essential hypertension as controls in this study. Clinical parameters and neuroimaging markers of cerebral small vessel disease were recorded, and its correlations with aldosteronism were investigated. Our results showed that the aldosteronism group (55.2 ± 9.7 years, male 47.6%) had similar hypertension severity but exhibited a higher cerebral microbleed count (interquartile range) (8.5 [2.0‒25.8] vs 3 [1.0‒6.0], P = 0.005) and higher severity of dilated perivascular space in the basal ganglia (severe perivascular space [number >20], 52.4% vs. 24.6%, P = 0.029; large perivascular space [>3 mm], 52.4% vs. 20.3%, P = 0.010), compared to those with essential hypertension (53.8 ± 11.7 years, male 73.9%). In multivariate models, aldosteronism remained an independent predictor of a higher (>10) microbleed count (odds ratio = 8.60, P = 0.004), severe perivascular space (odds ratio = 4.00, P = 0.038); the aldosterone-to-renin ratio was associated with dilated perivascular space (P = 0.043) and large perivascular space (P = 0.008). In conclusions, survivors of intracerebral hemorrhage with aldosteronism showed a tendency towards more severe hypertensive arteriopathy than the essential hypertension counterparts independently of blood pressure; aldosteronism may contribute to dilated perivascular space around the deep perforating arteries. Aldosteronism is associated with more severe cerebral small vessel disease in hypertensive intracerebral hemorrhage.