Icariin suppresses nephrotic syndrome by inhibiting pyroptosis and epithelial-to-mesenchymal transition.

CONTEXT: Nephrotic syndrome(NS) has emerged as a worldwide public health problem. Renal fibrosis is the most common pathological change from NS to end-stage renal failure, seriously affecting the prognosis of renal disease. Although tremendous efforts have been made to treat NS, specific drug therapies to delay the progression of NS toward end-stage renal failure are limited. Epimedium is generally used to treat kidney disease in traditional Chinese medicine. Icariin is a principal active component of Epimedium. METHODS: We used Sprague Dawley rats to establish NS models by injecting doxorubicin through the tail vein. Then icariin and prednisone were intragastric administration. Renal function was examined by an automatic biochemical analyzer. Pathology of the kidney was detected by Hematoxylin-Eosin and Masson staining respectively. Furthermore, RT-PCR, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Western Blot and Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling staining were employed to detect the proteins related to pyroptosis and EMT. HK-2 cells exposed to doxorubicin were treated with icariin, and cell viability was assessed using the MTT. EMT was assessed using Enzyme-Linked Immunosorbent Assay and Western Blot. RESULTS: The study showed that icariin significantly improved renal function and renal fibrosis in rats. In addition, icariin effectively decreased NOD-like receptor thermal protein domain associated protein 3,Caspase-1, Gasdermin D, Ly6C, and interleukin (IL)-1ß. Notably, treatment with icariin also inhibited the levels of TGF-ß, α-SMA and E-cadherin. DISCUSSION AND CONCLUSIONS: It is confirmed that icariin can improve renal function and alleviate renal fibrosis by inhibiting pyroptosis and the mechanism may be related to epithelial-to-mesenchymal transition. Icariin treatment might be recommended as a new approach for NS.

Dynamics of single-nuclei transcriptomic profiling of adipose tissue from diverse anatomical locations during mouse aging process.

Adipose tissue plays critical roles in an individual's aging process. In this research, we use single-nucleus RNA sequencing to create highly detailed transcriptional maps of subcutaneous adipose tissue and visceral adipose tissue in young and aged mice. We comprehensively identify the various cell types within the white adipose tissue of mice, our study has elucidated seven distinct cell types within this tissue. Further analyses focus on adipocytes, fibro-adipogenic progenitors, and immune cells, revealing age-related declines in the synthetic metabolic activity of adipocytes, diminished immune regulation, and reduced maturation or proliferation of fibroblasts in undifferentiated adipocytes. We confirm the presence of distinct subpopulations of adipocytes, highlighting decreases in adipogenesis subgroups due to aging. Additionally, we uncover a reduction in immune cell subpopulations, driven by age-associated immune system dysregulation. Furthermore, pseudo-time analyses indicate that Adipocyte1 represents the 'nascent' phase of adipocyte development, while Adipocyte2 represents the 'mature' phase. We use cell-cell interaction to explore the age-dependent complexities of the interactions between FAPs and adipocytes, and observed increased expression of the inflammation-related Retn-Tlr4 interaction in older mice, while the anti-inflammatory Angpt1-Tek interaction was only detected in young mice. These transcriptional profiles serve as a valuable resource for understanding the functional genomics underlying metabolic disorders associated with aging in human adipose tissue.

Understanding epitaxial growth of two-dimensional materials and their homostructures.

The exceptional physical properties of two-dimensional (2D) van der Waals (vdW) materials have been extensively researched, driving advances in material synthesis. Epitaxial growth, a prominent synthesis strategy, enables the production of large-area, high-quality 2D films compatible with advanced integrated circuits. Typical 2D single crystals, such as graphene, transition metal dichalcogenides and hexagonal boron nitride, have been epitaxially grown at a wafer scale. A systematic summary is required to offer strategic guidance for the epitaxy of emerging 2D materials. Here we focus on the epitaxy methodologies for 2D vdW materials in two directions: the growth of in-plane single-crystal monolayers and the fabrication of out-of-plane homostructures. We first discuss nucleation control of a single domain and orientation control over multiple domains to achieve large-scale single-crystal monolayers. We analyse the defect levels and measures of crystalline quality of typical 2D vdW materials with various epitaxial growth techniques. We then outline technical routes for the growth of homogeneous multilayers and twisted homostructures. We further summarize the current strategies to guide future efforts in optimizing on-demand fabrication of 2D vdW materials, as well as subsequent device manufacturing for their industrial applications.

Transcriptome sequencing of garlic reveals key genes related to the heat stress response.

With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, 'Xusuan No. 6' was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms.

Interfacial epitaxy of multilayer rhombohedral transition-metal dichalcogenide single crystals.

Rhombohedral-stacked transition-metal dichalcogenides (3R-TMDs), which are distinct from their hexagonal counterparts, exhibit higher carrier mobility, sliding ferroelectricity, and coherently enhanced nonlinear optical responses. However, surface epitaxial growth of large multilayer 3R-TMD single crystals is difficult. We report an interfacial epitaxy methodology for their growth of several compositions, including molybdenum disulfide (MoS2), molybdenum diselenide, tungsten disulfide, tungsten diselenide, niobium disulfide, niobium diselenide, and molybdenum sulfoselenide. Feeding of metals and chalcogens continuously to the interface between a single-crystal Ni substrate and grown layers ensured consistent 3R stacking sequence and controlled thickness from a few to 15,000 layers. Comprehensive characterizations confirmed the large-scale uniformity, high crystallinity, and phase purity of these films. The as-grown 3R-MoS2 exhibited room-temperature mobilities up to 155 and 190 square centimeters per volt second for bi- and trilayers, respectively. Optical difference frequency generation with thick 3R-MoS2 showed markedly enhanced nonlinear response under a quasi-phase matching condition (five orders of magnitude greater than monolayers).

Monocyte distribution width as a promising biomarker for differential diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Objective: We aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Methods: MDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes. Results: Our findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC. Conclusion: MDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.

Intersectional socioeconomic disparities in continuous smoking through pregnancy among pre-pregnant smokers in Sweden between 2006 and 2016.

BACKGROUND: While well-established associations exist between socioeconomic conditions and smoking during pregnancy (SDP), less is known about social disparities in the risk of continuous SDP. Intersectional analyses that consider multiple social factors simultaneously can offer valuable insight for planning smoking cessation interventions. METHODS: We include all 146,222 pregnancies in Sweden between 2006 and 2016 where the mother smoked at three months before pregnancy. The outcome was continuous SDP defined as self-reported smoking in the third trimester. Exposures were age, education, migration status and civil status. We examined all exposures in a mutually adjusted unidimensional analysis and in an intersectional model including 36 possible combinations. We present ORs with 95% Confidence Intervals, and the Area Under the Curve (AUC) as a measure of discriminatory accuracy (DA). RESULTS: In our study, education status was the factor most strongly associated to continuous SDP among women who smoked at three months before pregnancy. In the unidimensional analysis women with low and middle education had ORs for continuous SDP of 6.92 (95%CI 6.63-7.22) and 3.06 (95%CI 2.94-3.18) respectively compared to women with high education. In the intersectional analysis, odds of continuous SDP were 17.50 (95%CI 14.56-21.03) for married women born in Sweden aged ≥ 35 years with low education, compared to the reference group of married women born in Sweden aged 25-34 with high education. AUC-values were 0.658 and 0.660 for the unidimensional and intersectional models, respectively. CONCLUSION: The unidimensional and intersectional analyses showed that low education status increases odds of continuous SDP but that in isolation education status is insufficient to identify the women at highest odds of continuous SDP. Interventions targeted to social groups should be preceded by intersectional analyses but further research is needed before recommending intensified smoking cessation to specific social groups.

Roles of combined femoral and acetabular anteversion in pathological changes of hip dysplasia and hip reconstructive surgery.

Combined femoral and acetabular anteversion is the sum of femoral and acetabular anteversion, representing their morphological relationship in the axial plane. Along with the increasing understanding of hip dysplasia in recent years, numerous scholars have confirmed the role of combined femoral and acetabular anteversion in the pathological changes of hip dysplasia. At present, the reconstructive surgery for hip dysplasia includes total hip replacement and redirectional hip preservation surgery. As an important surgery index, combined femoral and acetabular anteversion have a crucial role in these surgeries. Herein, we discuss the role of combined femoral and acetabular anteversion in pathological changes of hip dysplasia, total hip replacement, and redirectional hip preservation surgery.

GastroBot: a Chinese gastrointestinal disease chatbot based on the retrieval-augmented generation.

Introduction: Large Language Models (LLMs) play a crucial role in clinical information processing, showcasing robust generalization across diverse language tasks. However, existing LLMs, despite their significance, lack optimization for clinical applications, presenting challenges in terms of illusions and interpretability. The Retrieval-Augmented Generation (RAG) model addresses these issues by providing sources for answer generation, thereby reducing errors. This study explores the application of RAG technology in clinical gastroenterology to enhance knowledge generation on gastrointestinal diseases. Methods: We fine-tuned the embedding model using a corpus consisting of 25 guidelines on gastrointestinal diseases. The fine-tuned model exhibited an 18% improvement in hit rate compared to its base model, gte-base-zh. Moreover, it outperformed OpenAI's Embedding model by 20%. Employing the RAG framework with the llama-index, we developed a Chinese gastroenterology chatbot named "GastroBot," which significantly improves answer accuracy and contextual relevance, minimizing errors and the risk of disseminating misleading information. Results: When evaluating GastroBot using the RAGAS framework, we observed a context recall rate of 95%. The faithfulness to the source, stands at 93.73%. The relevance of answers exhibits a strong correlation, reaching 92.28%. These findings highlight the effectiveness of GastroBot in providing accurate and contextually relevant information about gastrointestinal diseases. During manual assessment of GastroBot, in comparison with other models, our GastroBot model delivers a substantial amount of valuable knowledge while ensuring the completeness and consistency of the results. Discussion: Research findings suggest that incorporating the RAG method into clinical gastroenterology can enhance the accuracy and reliability of large language models. Serving as a practical implementation of this method, GastroBot has demonstrated significant enhancements in contextual comprehension and response quality. Continued exploration and refinement of the model are poised to drive forward clinical information processing and decision support in the gastroenterology field.

WS2 ribbon arrays with defined chirality and coherent polarity.

One-dimensional transition metal dichalcogenides exhibiting an enhanced bulk photovoltaic effect have the potential to exceed the Shockley-Queisser limit efficiency in solar energy harvest within p-n junction architectures. However, the collective output of these prototype devices remains a challenge. We report on the synthesis of single-crystalline WS2 ribbon arrays with defined chirality and coherent polarity through an atomic manufacturing strategy. The chirality of WS2 ribbon was defined by substrate couplings into tunable armchair, zigzag, and chiral species, and the polarity direction was determined by the ribbon-precursor interfacial energy along a coherent direction. A single armchair ribbon showed strong bulk photovoltaic effect and the further integration of ~1000 aligned ribbons with coherent polarity enabled upscaling of the photocurrent.

Advances in drug resistance of osteosarcoma caused by pregnane X receptor.

Osteosarcoma (OS) is a prevalent malignancy among adolescents, commonly manifesting during childhood and adolescence. It exhibits a high degree of malignancy, propensity for metastasis, rapid progression, and poses challenges in clinical management. Chemotherapy represents an efficacious therapeutic modality for OS treatment. However, chemotherapy resistance of OS is a major problem in clinical treatment. In order to treat OS effectively, it is particularly important to explore the mechanism of chemotherapy resistance in OS.The Pregnane X receptor (PXR) is a nuclear receptor primarily involved in the metabolism, transport, and elimination of xenobiotics, including chemotherapeutic agents. PXR involves three stages of drug metabolism: stage I: drug metabolism enzymes; stage II: drug binding enzyme; stage III: drug transporter.PXR has been confirmed to be involved in the process of chemotherapy resistance in malignant tumors. The expression of PXR is increased in OS, which may be related to drug resistance of OS. Therefore, wereviewed in detail the role of PXR in chemotherapy drug resistance in OS.

Activation of AMPK inhibits cervical cancer growth by hyperacetylation of H3K9 through PCAF.

BACKGROUND: Dysregulation in histone acetylation, a significant epigenetic alteration closely associated with major pathologies including cancer, promotes tumorigenesis, inactivating tumor-suppressor genes and activating oncogenic pathways. AMP-activated protein kinase (AMPK) is a cellular energy sensor that regulates a multitude of biological processes. Although a number of studies have identified the mechanisms by which AMPK regulates cancer growth, the underlying epigenetic mechanisms remain unknown. METHODS: The impact of metformin, an AMPK activator, on cervical cancer was evaluated through assessments of cell viability, tumor xenograft model, pan-acetylation analysis, and the role of the AMPK-PCAF-H3K9ac signaling pathway. Using label-free quantitative acetylproteomics and chromatin immunoprecipitation-sequencing (ChIP) technology, the activation of AMPK-induced H3K9 acetylation was further investigated. RESULTS: In this study, we found that metformin, acting as an AMPK agonist, activates AMPK, thereby inhibiting the proliferation of cervical cancer both in vitro and in vivo. Mechanistically, AMPK activation induces H3K9 acetylation at epigenetic level, leading to chromatin remodeling in cervical cancer. This also enhances the binding of H3K9ac to the promoter regions of multiple tumor suppressor genes, thereby promoting their transcriptional activation. Furthermore, the absence of PCAF renders AMPK activation incapable of inducing H3K9 acetylation. CONCLUSIONS: In conclusion, our findings demonstrate that AMPK mediates the inhibition of cervical cancer growth through PCAF-dependent H3K9 acetylation. This discovery not only facilitates the clinical application of metformin but also underscores the essential role of PCAF in AMPK activation-induced H3K9 hyperacetylation.

ChatGPT Combining Machine Learning for the Prediction of Nanozyme Catalytic Types and Activities.

The design of nanozymes with superior catalytic activities is a prerequisite for broadening their biomedical applications. Previous studies have exerted significant effort in theoretical calculation and experimental trials for enhancing the catalytic activity of nanozyme. Machine learning (ML) provides a forward-looking aid in predicting nanozyme catalytic activity. However, this requires a significant amount of human effort for data collection. In addition, the prediction accuracy urgently needs to be improved. Herein, we demonstrate that ChatGPT can collaborate with humans to efficiently collect data. We establish four qualitative models (random forest (RF), decision tree (DT), adaboost random forest (adaboost-RF), and adaboost decision tree (adaboost-DT)) for predicting nanozyme catalytic types, such as peroxidase, oxidase, catalase, superoxide dismutase, and glutathione peroxidase. Furthermore, we use five quantitative models (random forest (RF), decision tree (DT), Support Vector Regression (SVR), gradient boosting regression (GBR), and fully connected deep neuron network (DNN)) to predict nanozyme catalytic activities. We find that GBR model demonstrates superior prediction performance for nanozyme catalytic activities (R2 = 0.6476 for Km and R2 = 0.95 for Kcat). Moreover, an open-access web resource, AI-ZYMES, with a ChatGPT-based nanozyme copilot is developed for predicting nanozyme catalytic types and activities and guiding the synthesis of nanozyme. The accuracy of the nanozyme copilot's responses reaches more than 90% through the retrieval augmented generation. This study provides a new potential application for ChatGPT in the field of nanozymes.

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

PrompTHis: Visualizing the Process and Influence of Prompt Editing during Text-to-Image Creation.

Generative text-to-image models, which allow users to create appealing images through a text prompt, have seen a dramatic increase in popularity in recent years. However, most users have a limited understanding of how such models work and often rely on trial and error strategies to achieve satisfactory results. The prompt history contains a wealth of information that could provide users with insights into what has been explored and how the prompt changes impact the output image, yet little research attention has been paid to the visual analysis of such process to support users. We propose the Image Variant Graph, a novel visual representation designed to support comparing prompt-image pairs and exploring the editing history. The Image Variant Graph models prompt differences as edges between corresponding images and presents the distances between images through projection. Based on the graph, we developed the PrompTHis system through co-design with artists. Based on the review and analysis of the prompting history, users can better understand the impact of prompt changes and have a more effective control of image generation. A quantitative user study and qualitative interviews demonstrate that PrompTHis can help users review the prompt history, make sense of the model, and plan their creative process.

Construction of an Infectious DNA Clone of Grapevine Geminivirus A Isolate GN and Its Biological Activity in Plants Analyzed Using an Efficient and Simple Inoculation Method.

The pathogenicity of grapevine geminivirus A (GGVA), a recently identified DNA virus, to grapevine plants remains largely unclear. Here, we report a new GGVA isolate (named GGVAQN) obtained from grapevine 'Queen Nina' plants with severe disease symptoms. The infectious clone of GGVAQN (pXT-GGVAQN) was constructed to investigate its pathogenicity. Nicotiana benthamiana plants inoculated with GGVAQN by agroinfiltration displayed upward leaf curling and chlorotic mottling symptoms. A simple, quick, and efficient method for delivering DNA clones of GGVAQN into grapevine plants was developed, by which Agrobacterium tumefaciens cells carrying pXT-GGVAQN were introduced into the roots of in vitro-grown 'Red Globe' grape plantlets with a syringe. By this method, all 'Red Globe' grape plants were systemically infected with GGVAQN, and the plants exhibited chlorotic mottling symptoms on their upper leaves and downward curling, interveinal yellowing, and leaf-margin necrosis symptoms on their lower leaves. Our results provide insights into the pathogenicity of GGVA and a simple and efficient inoculation method to deliver infectious viral clones to woody perennial plants.

Studies on the Phosphorus-Solubilizing Ability of Isaria cateinannulata and Its Influence on the Growth of Fagopyrum tataricum Plants.

I. cateinannulata has been shown to promote the growth of F. tataricum. However, whether its growth-promoting capacity is related to its ability to solubilize phosphorus has not been reported. Therefore, in this study, we sought to assess the phosphorus-solubilizing ability of 18 strains of I. cateinannulata by analyzing their growth in an inorganic phosphorus culture medium. The effects of F. tataricum on growth and effective phosphorus content were analyzed through field experiments. The results showed that all 18 strains of I. cateinannulata had a phosphorus release capacity, with phosphorus solubilization ranging from 5.14 ± 0.37 mg/L to 6.21 ± 0.01 mg/L, and strain 9 exhibited the best phosphorus solubilization effect. Additionally, the field results demonstrated that I. cateinannulata positively influenced the growth, root length, and yield of F. tataricum by increasing the chlorophyll and soluble phosphorus content. This study will provide a material basis and theoretical support for investigating the interaction mechanism between I. cateinannulata and F. tataricum.

Preparation of Conductive Cellulose Coated with Conductive Polymer and Its Application in the Detection of pH and Characteristic Substances in Sweat.

Rich biological information in sweat provides great potential for health monitoring and management. However, due to the complexity of sweat, the development of environmentally friendly green electronic products is of great significance to the construction of ecological civilization. This study utilized a simple combination of polystyrene sulfonate sodium (PSS) and filter paper (FP) to prepare cellulose materials coated with conductive polymers, developing an electrochemical sensor based on the modified materials. The mechanical and electrochemical properties of the fabricated PSS/FP membrane were optimized by adjusting the feeding dosage of PSS. The realized PSS/FP composite containing 7% PSS displayed good conductivity (9.1 × 10-2 S/m), reducing electric resistance by 99.2% compared with the original FP membrane (6.7 × 10-4 S/m). The stable current of the membrane in simulated sweat under different pH environments is highly correlated with the pH values. Additionally, when the membrane is exposed to simulated sweat with varying ion concentrations, the current signal changes in real time with the concentration variations. The response time averages around 0.3 s.