First report of Fusarium humuli causing stem spots in Nicotiana tabacum L in China.

Tobacco is one of the most important economic crops in China. Disease is one of the main factors affecting the quality of tobacco production (Cai et al. 2022). Stem spot disease of tobacco was observed in the Planting Demonstration Garden in Chang Ning (26°37N; 112° 31E), Hunan Province of China, from May to June 2023. The disease seriously retarded tobacco growth and the incidence rate was about 30-50% of the plants(Yun Yan 87). Most of infected tobacco had black spots on the stems, and the spots expanded and joined together quickly, while many stems turned black and withered. For pathogen isolation, symptomatic stem samples were collected and disinfected with 75% ethanol for 30 s and 2% sodium hypochlorite for 1 minute, followed by rinsing with sterile distilled water three times. Subsequently, small pieces (5 × 5 mm) of diseased tissues were placed on potato dextrose agar (PDA) and incubated in the dark at 25 °C for 24 h to 36 h. The emerging fungal hyphal tips were transferred to PDA and purified by the single-spore method(Yu et al. 2022). In total, 16 cultures with the same appearance were isolated from 30 disease spots on the stem. Strain coded as hnxryc2 was randomly selected for identification. After culturing in PDA for 7 days, white and dense colonies wereobserved with a mean radial growth rate of 6.4 mm/day. The strain cultured 10 days on SNA. Morphological observations were made on 10-day-old culture on SNA medium, and macroconidia were sickle-shaped and slightly curved, with 3-5 septa (2.32-7.00 µm × 0.53-1.17 µm, n = 50), neither microconidia nor chlamydospores were observed. These morphological characteristics were consistent with the description of Fusarium humuli (Wang et al. 2019, Li et al. 2023). Furthermore, primers ITS1/ITS4, EF728F/EF986R, RPB1-F5/RPB1-R8 and fRPB2-5F2/fRPB2-7cR(Xie et al. 2023) were used to amplify the ITS region, EF-1α, RPB1, and RPB2 from strain hnxryc2, respectively. The sequence alignment of hnxryc2 with the NCBI database and FUSARIOID-ID shows the following results: The sequence of ITS region(GenBank accession number PP543715) was 100% identical to these of Fusarium sp. (MN428026.1), the sequences of EF-1α, RPB1, and RPB2 of strain hnxryc2(GenBank accession numbersOR257586, OR326856 and OR257587 respectively) were 99% to 100% identical to these of F. humuli (GenBank accession numbers MK289578.1, MZ824672.1 and MZ824673.1, respectively). Then a phylogenetic tree based on ITS region, EF-1α, and RPB2 sequences was constructed (Kroon et al. 2004). The strain hnxryc2 was more closely related to F. humuli (CGMCC3.19374 GenBank accession nos. MK280845.1, MK289570.1 and MK289724.1, respectively), with bootstrap values 88%. Pathogenicity tests were performed on detached stems of tobacco and potted plants. Wounded stems were inoculated with conidial suspensions (100 µL, 1×107 spores/mL), and the controls were inoculated with sterile water (Xu et al. 2023). The inoculated detached stems were kept in humid chambers (Zhong et al., 2019), each treatment was given a 12h/12h light/dark cycle at 25°C. Deep black spots were observed for 3 days after inoculation. After 9 days, typical symptoms similar to the original diseased plants in the field were found on all inoculated stems, while the control stems did not exhibit any symptoms. Pathogenicity assays were repeated thrice. The pathogen F. humuli was successfully reisolated from the stem of inoculated samples showing symptoms. To our knowledge, this is the first report of F. humuli inducing stem spot on tobacco in China. Since F. humuli is a common pathogenic fungus that infects different plant species, more attention should be paid to its prevalence in tobacco, and the potential risk of a disease outbreak in other provinces of China.

Comparative genomic and transcriptomic analyses provide new insight into symbiotic host specificity.

Host specificity plays important roles in expanding the host range of rhizobia, while the genetic information responsible for host specificity remains largely unexplored. In this report, the roots of four symbiotic systems with notable different symbiotic phenotypes and the control were studied at four different post-inoculation time points by RNA sequencning (RNA-seq). The differentially expressed genes (DEGs) were divided into "found only in soybean or Lotus," "only expressed in soybean or Lotus," and "expressed in both hosts" according to the comparative genomic analysis. The distributions of enriched function ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways vary significantly in different symbiotic systems. Host specific genes account for the majority of the DEGs involved in response to stimulus, associated with plant-pathogen interaction pathways, and encoding resistance (R) proteins, the symbiotic nitrogen fixation (SNF) proteins and the target proteins in the SNF-related modules. Our findings provided molecular candidates for better understanding the mechanisms of symbiotic host-specificity.

Broadening anticancer spectrum by preprocessing and treatment of T- lymphocytes expressed FcγRI and monoclonal antibodies for refractory cancers.

Background: Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs. Methods: We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods. Results: The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model. Conclusions: This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.

Enhanced electroactive bacteria enrichment and facilitated extracellular electron transfer in microbial fuel cells via polydopamine coated graphene aerogel anode.

The structure and surface physicochemical properties of anode play a crucial role in microbial fuel cells (MFCs). To enhance the enrichment of exoelectrogen and facilitate extracellular electron transfer (EET), a three-dimensional macroporous graphene aerogel with polydopamine coating was successfully introduced to modify carbon brush (PGA/CB). The three-dimensional graphene aerogel (GA) with micrometer pores improved the space utilization efficiency of microorganisms. Polydopamine (PDA) coating enhanced the physicochemical properties of the electrode surface by introducing abundant functional groups and nitrogen-containing active sites. MFCs equipped with PGA/CB anodes (PGA/CB-MFCs) demonstrated superior power generation compared to GA/CB-MFCs and CB-MFCs (MFCs with GA/CB and CB anodes respectively), including a 23.0 % and 30.1 % reduction in start-up time, and an increase in maximum power density by 2.43 and 1.24 times respectively. The higher bioelectrochemical activity exhibited by the biofilm of PGA/CB anode and the promoted riboflavin secretion by PGA modification imply the enhanced EET efficiency. 16S rRNA high-throughput sequence analysis of the biofilms revealed successful enrichment of Geobacter on PGA/CB anodes. These findings not only validate the positive impact of the synergistic effects between GA and PDA in promoting EET and improving MFC performance but also provide valuable insights for electrode design in other bioelectrochemical systems.

Graph-Based Bidirectional Transformer Decision Threshold Adjustment Algorithm for Class-Imbalanced Molecular Data.

Data sets with imbalanced class sizes, often where one class size is much smaller than that of others, occur extremely often in various applications, including those with biological foundations, such as drug discovery and disease diagnosis. Thus, it is extremely important to be able to identify data elements of classes of various sizes, as a failure to detect can result in heavy costs. However, many data classification algorithms do not perform well on imbalanced data sets as they often fail to detect elements belonging to underrepresented classes. In this paper, we propose the BTDT-MBO algorithm, incorporating Merriman-Bence-Osher (MBO) techniques and a bidirectional transformer, as well as distance correlation and decision threshold adjustments, for data classification problems on highly imbalanced molecular data sets, where the sizes of the classes vary greatly. The proposed method not only integrates adjustments in the classification threshold for the MBO algorithm in order to help deal with the class imbalance, but also uses a bidirectional transformer model based on an attention mechanism for self-supervised learning. Additionally, the method implements distance correlation as a weight function for the similarity graph-based framework on which the adjusted MBO algorithm operates. The proposed model is validated using six molecular data sets, and we also provide a thorough comparison to other competing algorithms. The computational experiments show that the proposed method performs better than competing techniques even when the class imbalance ratio is very high.

Catalytic Fast Pyrolysis of Tar-Rich Coal with a Bauxite Residue for Upgrading High-Value Products: Product Distribution and Kinetic Analysis.

Fast pyrolysis technology can reduce the secondary reactions, improve the volatile product yield, and reduce the semicoke yield. Still, the high proportion of heavy tar components affects the development of fast pyrolysis industrialization. Therefore, this paper put forward a catalytic upgrading method of coal based on the solid waste bauxite residue (BR) as a catalyst. This study investigated the impact of varying particle sizes of pulverized coal and the addition of the BR catalyst on the product distribution and kinetics of coal fast pyrolysis. The results found that the tar yield was the highest at 600 °C when the particle size of pulverized coal was 75-150 µm, which was 19.44%. In the range of 550-650 °C, the relative content of benzene and toluene xylene (BTX) in liquid products increased with the temperature. With the increase of the proportion of the BR catalyst, the yield of semicoke in coal pyrolysis products increased, the yield of the gas phase also increased, and the yield of the liquid phase decreased.

Genetic diversity and population structure of wheat landraces in Southern Winter Wheat Region of China.

BACKGROUND: Wheat landraces are considered a valuable source of genetic diversity for breeding programs. It is useful to evaluate the genetic diversity in breeding studies such as marker-assisted selection (MAS), genome-wide association studies (GWAS), and genomic selection. In addition, constructing a core germplasm set that represents the genetic diversity of the entire variety set is of great significance for the efficient conservation and utilization of wheat landrace germplasms. RESULTS: To understand the genetic diversity in wheat landrace, 2,023 accessions in the Jiangsu Provincial Crop Germplasm Resource Bank were used to explore the molecular diversity and population structure using the Illumina 15 K single nucleotide polymorphism (SNP) chip. These accessions were divided into five subpopulations based on population structure, principal coordinate and kinship analysis. A significant variation was found within and among the subpopulations based on the molecular variance analysis (AMOVA). Subpopulation 3 showed more genetic variability based on the different allelic patterns (Na, Ne and I). The M strategy as implemented in MStratv 4.1 software was used to construct the representative core collection. A core collection with a total of 311 accessions (15.37%) was selected from the entire landrace germplasm based on genotype and 12 different phenotypic traits. Compared to the initial landrace collections, the core collection displayed higher gene diversity (0.31) and polymorphism information content (PIC) (0.25), and represented almost all phenotypic variation. CONCLUSIONS: A core collection comprising 311 accessions containing 100% of the genetic variation in the initial population was developed. This collection provides a germplasm base for effective management, conservation, and utilization of the variation in the original set.

The role of LDH and ferritin levels as biomarkers for corticosteroid dosage in children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: This study explored the relationship between inflammatory markers and glucocorticoid dosage upon admission. METHODS: We conducted a retrospective analysis of 206 patients with refractory Mycoplasma pneumoniae pneumonia (RMPP) admitted to a Children's Hospital from November 2017 to January 2022. Patients were categorized into three groups based on their methylprednisolone dosage: low-dose (≤ 2 mg/kg/d), medium-dose (2-10 mg/kg/d), and high-dose (≥ 10 mg/kg/d). We compared demographic data, clinical manifestations, laboratory findings, and radiological outcomes. Spearman's rank correlation coefficient was used to assess relationships between variables. RESULTS: The median age was highest in the low-dose group at 7 years, compared to 5.5 years in the medium-dose group and 6 years in the high-dose group (P < 0.001). The body mass index (BMI) was also highest in the low-dose group at 16.12, followed by 14.86 in the medium-dose group and 14.58 in the high-dose group (P < 0.001). More severe radiographic findings, longer hospital stays, and greater incidence of hypoxia were noted in the high-dose group (P < 0.05). Additionally, significant increases in white blood cells, C-reactive protein, procalcitonin, lactate dehydrogenase (LDH), alanine transaminase, aspartate transaminase, ferritin, erythrocyte sedimentation rate, and D-dimer levels were observed in the high-dose group (P < 0.05). Specifically, LDH and ferritin were markedly higher in the high-dose group, with levels at 660.5 U/L and 475.05 ng/mL, respectively, compared to 450 U/L and 151.4 ng/mL in the medium-dose group, and 316.5 U/L and 120.5 ng/mL in the low-dose group. Correlation analysis indicated that LDH and ferritin levels were significantly and positively correlated with glucocorticoid dose (Spearman ρ = 0.672 and ρ = 0.654, respectively; P < 0.001). CONCLUSIONS: Serum LDH and ferritin levels may be useful biomarkers for determining the appropriate corticosteroid dosage in treating children with RMPP.

Towards rapid formation of electroactive biofilm: insights from thermodynamics and electric field manipulation.

Electroactive biofilm (EAB) has garnered significant attention due to its effectiveness in pollutant remediation, electricity generation, and chemical synthesis. However, achieving precise control over the rapid formation of EAB presents challenges for the practical implementation of bioelectrochemical technology. In this study, we investigated the regulation of EAB formation by manipulating applied electric potential. We developed a modified XDLVO model for the applied electric field and quantitatively assessed the feasibility of existing rapid formation strategies for EAB. Our results revealed that electrostatic (EL) force significantly influenced EAB formation in the presence of the applied electric field, with the potential difference between the electrode and the microbial solution being the primary determinant of EL force. Compared to -0.2 V and 0 V vs.Ag/AgCl, EAB exhibited the highest electrochemical performance at 0.2 V vs.Ag/AgCl, with a maximum current density of 6.044 ± 0.10 A/m2, surpassing that at -0.2 V vs.Ag/AgCl and 0 V vs.Ag/AgCl by 1.73 times and 1.31 times, respectively. Furthermore, EAB demonstrated the highest biomass accumulation, measuring a thickness of 25 ± 2 µm at 0.2 V vs. Ag/AgCl, representing increases of 1.67 and 1.25 times compared to -0.2 V vs.Ag/AgCl and 0 V vs.Ag/AgCl, respectively. The strong electrostatic attraction under the anodic potential promoted the formation of a monolayer of biofilm. Additionally, the hydrophilicity and hydrophobicity of the biofilm were altered following inversion culture. The Lewis acid-base (AB) attraction offset the electrostatic repulsion caused by negative charges, it is beneficial for the formation of biofilms. This study, for the first time, elucidated the difference in the formation of cathode and anode biofilm from a thermodynamic perspective in the context of electric field introduction, laying the theoretical foundation for the directional regulation of the rapid formation of typical electroactive biofilms.

S-Block Metal Mg-Mediated Co─N─C as Efficient Oxygen Electrocatalyst for Durable and Temperature-Adapted Zn-Air Batteries.

In the quest to enhance Zn-air batteries (ZABs) for operating across a wide spectrum of temperatures, synthesizing robust oxygen electrocatalysts is paramount. Conventional strategies focusing on orbital hybridization of d-d and p-d aim to moderate the excessive interaction between the d-band of the transition metal active site and oxygen intermediate, yet often yield suboptimal performance. Herein, an innovative s-block metal modulation is reported to refine the electronic structure and catalytic behavior of Co─NC catalysts. Employing density functional theory (DFT) calculations, it is revealed that incorporating Mg markedly depresses the d-band center of Co sites, thereby fine-tuning the adsorption energy of the oxygen reduction reaction (ORR) intermediate. Consequently, the Mg-modified Co─NC catalyst (MgCo─NC) unveils remarkable intrinsic ORR activity with a significantly reduced activation energy (Ea) of 10.0 kJ mol-1, outstripping the performance of both Co─NC (17.6 kJ mol-1), benchmark Pt/C (15.9 kJ mol-1), and many recent reports. Moreover, ZABs outfitted with the finely tuned Mg0.1Co0.9─NC realize a formidable power density of 157.0 mW cm-2, paired with an extremely long cycle life of 1700 h, and an exceptionally minimal voltage gap decay rate of 0.006 mV h-1. Further, the Mg0.1Co0.9─NC-based flexible ZAB presents a mere 2% specific capacity degradation when the temperature fluctuates from 25 to -20 °C, underscoring its robustness and suitability for practical deployment in diverse environmental conditions.

Discovery of autophagy-tethering compounds as potent NLRP3 degraders for IBD Immunotherapy.

Nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) constitutes an essential inflammasome sensor protein, pivotal in the orchestration of innate immunity. Given its paramount role, NLRP3 has recently emerged as an enticing therapeutic target for disorders associated with inflammation. In this study, we embarked on the design and synthesis of two series of compounds, endowed with the capacity to induce NLRP3 degradation via autophagy-tethering compounds (ATTECs)-an innovative targeted protein degradation technology. Notably, MC-ND-18 emerged as the most potent agent for effectuating NLRP3 degradation through autophagic mechanisms and concurrently exhibited marked anti-inflammatory efficacy in mice model of dextran sulfate sodium (DSS)-induced colitis. Consequently, we have successfully developed a pioneering NLRP3 protein degrader, offering a novel therapeutic avenue for ameliorating NLRP3-associated pathologies.

The roles of metal ions in gallstones formation.

Gallstones (GSs) disease is a common disease worldwide. The mechanisms of their formation are diverse and complex and are related to cholesterol metabolism, gallbladder motility, biliary tract infection, the immune response, and ion metabolism. In recent years, with the application of inductively coupled plasma‒mass spectrometry and other methods, studies have suggested a correlation between the metabolism of metal ions and GSs formation. A literature search on gallstones and metal ions was instituted on PubMed and EMBASE. The specific topics of interest were etiology, formation mechanism, component Analysis and metabolism. References of papers were subsequently searched to obtain older literature. After reading and summarizing a large amount of literature, we found that calcium, iron, and copper can potentially promote the release of inflammatory factors and increase the level of reactive oxygen species, which is positively correlated with GSs formation. While magnesium and zinc, with their antioxidant effects, are negatively correlated with GSs formation. Metal ions are not only a component of GSs but are also important biological signals. Metal ion metabolism affects the formation of GSs and understanding its mechanism of action is of clinical significance for the prevention, diagnosis and treatment of GSs.

A frozen suspension external calibration strategy for elemental quantitative imaging of fresh plant soft tissues by LA-ICP-MS with cryogenic ablation cell.

A simple and reliable external calibration strategy of LA-ICP-MS for fresh plant soft tissues was developed. The prepared plant suspension was frozen by the designed cryogenic ablation cell and used as external standard for quantitative elemental imaging analysis of fresh plant tissues. The controllable water content of the prepared external standards provides a similar matrix with fresh soft tissues, and a homogeneous elemental distribution could be ensured due to the fine grinding particle sizes. More interestingly, the presence of water increased the signal intensity produced by the suspension by a factor of 1.6 (Pb) to 66.6 (La) compared to that of the pressed cake. The excellent dispersing property and advantage of long-term use were achieved owing to the employment of 0.1% PAANa as suspending agent. A series of plant reference materials were analyzed, and the relative errors of most elements were less than 10 %, indicating that there is a reliable accuracy of the proposed method. The limits of detection (LODs) ranged from 0.1 ng·g-1 (La) to 1279 ng·g-1 (S). This method was used for elemental imaging analysis in rice leaves under arsenic stress, and the results were consistent with previous studies, which mean that the proposed method could provide technical support for researchers in the fields of agriculture and environment.

An agonist of the adenosine A2A receptor, CGS21680, promotes corneal epithelial wound healing via the YAP signalling pathway.

BACKGROUND AND PURPOSE: The adenosine A2A receptor (A2AR) is involved in various physiological and pathological processes in the eye; however, the role of the A2AR signalling in corneal epithelial wound healing is not known. Here, the expression, therapeutic effects and signalling mechanism of A2AR in corneal epithelial wound healing were investigated using the A2AR agonist CGS21680. EXPERIMENTAL APPROACH: A2AR localization and expression during wound healing in the murine cornea were determined by immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. The effect of CGS21680 on corneal epithelial wound healing in the lesioned corneal and cultured human corneal epithelial cells (hCECs) by modulating cellular proliferation and migration was critically evaluated. The role of Hippo-YAP signalling in mediating the CGS21680 effect on wound healing by pharmacological inhibition of YAP signalling was explored. KEY RESULTS: A2AR expression was up-regulated after corneal epithelial injury. Topical administration of CGS21680 dose-dependently promoted corneal epithelial wound healing in the injured corneal epithelium by promoting cellular proliferation. Furthermore, CGS21680 accelerated the cellular proliferation and migration of hCECs in vitro. A2AR activation promoted early up-regulation and later down-regulation of YAP signalling molecules, and pharmacological inhibition of YAP signalling reverted CGS21680-mediated wound healing effect in vivo and in vitro. CONCLUSION AND IMPLICATIONS: A2AR activation promotes wound healing by enhancing cellular proliferation and migration through the YAP signalling pathway. A2ARs play an important role in the maintenance of corneal epithelium integrity and may represent a novel therapeutic target for facilitating corneal epithelial wound healing.

Correlation of tuberculosis-related anemia severity with tuberculosis-induced inflammation in children: a six-year retrospective study.

BACKGROUND: Anemia is a common complication of tuberculosis (TB), and there is evidence that its prevalence is higher in patients with TB. Although TB is very important in epidemiology, careful investigation of TB-related anemia in children has not been carried out systematically. This study aimed to describe the details of anemia in children with TB and its association with clinical characteristics and the severity of inflammation. METHODS: In this retrospective study, we explored Hb levels in 103 children with pulmonary TB (PTB) and they were divided into anemic or non-anemic groups. Logistics regression analysis was used to study the associations between anemia and demographic characteristics. Spearman correlations analysis was performed to analyse the associations between the biochemical parameters and hemoglobin levels in blood. RESULTS: The prevalence of anemia in children with TB was 37.9% (48.7% showed microcytic hypochromic anemia, and 5.1% showed normal cell anemia). Compared with the anemia (n = 39) group, the non-anemic group (n = 64) had longer fever duration and increased respiratory rate (P < 0.05). In logistic regression analysis, anemia was associated with lower levels of Alb and higher levels of WBC, CRP, LDH, and ESR (P < 0.05). Spearman correlations analysis showed a significant negative correlation between hemoglobin (Hb) levels and inflammatory markers. After one month of antitubercular therapy (ATT), the Hb levels of 76.9% children returned to normal. CONCLUSIONS: Anemia is common among children with TB at diagnosis. The majority of children with TB-related anemia are mild to moderate microcytic hypochromic anemia. There is a strong correlation between the severity of anemia and the inflammation induced by TB. This suggests that anemia is a biomarker of the severity of TB in clinical practice among children.

Superconductivity in Freestanding Infinite-Layer Nickelate Membranes.

The observation of superconductivity in infinite-layer nickelates has attracted significant attention due to its potential as a new platform for exploring high-Tc superconductivity. However, thus far, superconductivity has only been observed in epitaxial thin films, which limits the manipulation capabilities and modulation methods compared to two-dimensional exfoliated materials. Given the exceptionally giant strain tunability and stacking capability of freestanding membranes, separating superconducting nickelates from the as-grown substrate is a novel way to engineer the superconductivity and uncover the underlying physics. Herein, this work reports the synthesis of the superconducting freestanding La0.8Sr0.2NiO2 membranes ( T c zero = 10.6 K ${T}_{\mathrm{c}}^{\mathrm{zero}}\ =\ 10.6\ \mathrm{K}$ ), emphasizing the crucial roles of the interface engineering in the precursor phase film growth and the quick transfer process in achieving superconductivity. This work offers a new versatile platform for investigating superconductivity in nickelates, such as the pairing symmetry via constructing Josephson tunneling junctions and higher Tc values via high-pressure experiments.

AKI-Pro score for predicting progression to severe acute kidney injury or death in patients with early acute kidney injury after cardiac surgery.

BACKGROUND: No reliable clinical tools exist to predict acute kidney injury (AKI) progression. We aim to explore a scoring system for predicting the composite outcome of progression to severe AKI or death within seven days among early AKI patients after cardiac surgery. METHODS: In this study, we used two independent cohorts, and patients who experienced mild/moderate AKI within 48 h after cardiac surgery were enrolled. Eventually, 3188 patients from the MIMIC-IV database were used as the derivation cohort, while 499 patients from the Zhongshan cohort were used as external validation. The primary outcome was defined by the composite outcome of progression to severe AKI or death within seven days after enrollment. The variables identified by LASSO regression analysis were entered into logistic regression models and were used to construct the risk score. RESULTS: The composite outcome accounted for 3.7% (n = 119) and 7.6% (n = 38) of the derivation and validation cohorts, respectively. Six predictors were assembled into a risk score (AKI-Pro score), including female, baseline eGFR, aortic surgery, modified furosemide responsiveness index (mFRI), SOFA, and AKI stage. And we stratified the risk score into four groups: low, moderate, high, and very high risk. The risk score displayed satisfied predictive discrimination and calibration in the derivation and validation cohort. The AKI-Pro score discriminated the composite outcome better than CRATE score, Cleveland score, AKICS score, Simplified renal index, and SRI risk score (all P < 0.05). CONCLUSIONS: The AKI-Pro score is a new clinical tool that could assist clinicians to identify early AKI patients at high risk for AKI progression or death.

Hybrid multimodal fusion for graph learning in disease prediction.

Graph neural networks (GNNs) have gained significant attention in disease prediction where the latent embeddings of patients are modeled as nodes and the similarities among patients are represented through edges. The graph structure, which determines how information is aggregated and propagated, plays a crucial role in graph learning. Recent approaches typically create graphs based on patients' latent embeddings, which may not accurately reflect their real-world closeness. Our analysis reveals that raw data, such as demographic attributes and laboratory results, offers a wealth of information for assessing patient similarities and can serve as a compensatory measure for graphs constructed exclusively from latent embeddings. In this study, we first construct adaptive graphs from both latent representations and raw data respectively, and then merge these graphs via weighted summation. Given that the graphs may contain extraneous and noisy connections, we apply degree-sensitive edge pruning and kNN sparsification techniques to selectively sparsify and prune these edges. We conducted intensive experiments on two diagnostic prediction datasets, and the results demonstrate that our proposed method surpasses current state-of-the-art techniques.

Aortic mineralization triggers the risk of acute type B aortic dissection.

BACKGROUND AND AIMS: The role of aortic mineralization in the pathogenesis of acute type B aortic dissection (TBAD) is unclear. Whether thoracic aortic calcification (TAC) and circulating alkaline phosphatase (ALP) activity are associated with acute TBAD risk remains elusive. METHODS: Observational and Mendelian randomization (MR) studies were conducted sequentially. Using propensity score matching (1:1) by age and sex, patients with acute TBAD (n = 125) were compared with control patients (n = 125). Qualitative (score) and quantitative (volume) analyses of the TAC burden on different thoracic aortic segments were conducted using non-enhanced computed tomography. Univariate and multivariate analyses were used to identify significant independent risk factors for TBAD and TAC burden, respectively. MR was finally used to determine the causal relationship between elevated ALP activity and TBAD risk. RESULTS: The qualitative and quantitative analyses revealed that TAC burden was significantly higher in the TBAD group, except for in the ascending aortic segment (both p < 0.05). Preoperative circulating ALP was significantly elevated in the TBAD group (p < 0.001). The elevated TAC burden score on the descending thoracic aortic segment (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.31-8.37) and increased ALP activity (OR 1.03, 95% CI 1.01-1.06) was independently associated with TBAD risk. Interestingly, ALP was significantly positively associated with TAC burden, and MR analyses confirmed that ALP genetically predicted TBAD risk. CONCLUSIONS: Elevated ALP may trigger TBAD risk via the increased volume of TAC. Aortic mineralization may not protect the aorta itself.

Nanopore sequencing demonstrates the roles of spermatozoal DNA N6-methyladenine in mediating transgenerational lipid metabolism disorder induced by excessive folate consumpton.

Increased consumption of folic acid is prevalent due to its beneficial effects, but growing evidence emphasizes the side effects pointing to excessive dietary folate intake. The effects of excessive paternal folic acid consumption on offspring and its transgenerational inheritance mechanism have not been elucidated. We hypothesize that excessive folic acid consumption will alter sperm DNA N6-methyladenine (6mA) and 5-methylcytosine (5mC) methylation and heritably influence offspring metabolic homeostasis. Here, we fed roosters either folic acid-control or folic acid-excess diet throughout life. Paternal chronic folic acid excessive supplementation increased hepatic lipogenesis and lipid accumulation but reduced lipolysis both in the roosters and their offspring, which was further confirmed to be induced by one-carbon metabolism inhibition and gene expression alteration associated with the Peroxisome proliferator-activated receptor pathway. Based on the spermatozoal genome-wide DNA methylome identified by Nanopore sequencing, multi-omics association analysis of spermatozoal and hepatic DNA methylome, transcriptome, and metabolome suggested that differential spermatozoal DNA 6mA and 5mC methylation could be involved in regulating lipid metabolism-related gene expression in offspring chickens. This model suggests that sperm DNA N6-methyladenine and 5-methylcytosine methylation were involved in epigenetic transmission and that paternal dietary excess folic acid leads to hepatic lipid accumulation in offspring.