Highlighting immune features of the tumor ecosystem and prognostic value of Tfh and Th17 cell infiltration in head and neck squamous cell carcinoma by single-cell RNA-seq.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) typically present with a complex anatomical distribution, often accompanied by insidious symptoms. This combination contributes to its high incidence and poor prognosis. It is now understood that the immune features of cellular components within the tumor ecosystem and their complex interactions are critical factors influencing both tumor progression and the effective immune response. METHODS: We obtained single-cell RNA sequencing data of 26,496 cells from three tumor tissues and five normal tissues and performed subsequent analyses. Immunohistochemical staining on tumor sections was used to validate the presence of malignant cells. Additionally, we included bulk RNA sequencing data from 502 HNSCC patients. Kaplan-Meier analysis and the log-rank test were employed to assess predictors of patient outcomes. RESULTS: We identified three epithelial subclusters exhibiting immune-related features. These subclusters promoted the infiltration of T cells, dendritic cells, and monocytes into the tumor microenvironment. Additionally, cancer-associated fibroblasts displayed tumor-promoting and angiogenesis characteristics, contrasting with the predominant antigen-presenting and inflammatory roles observed in fibroblasts from normal tissues. Furthermore, tumor endothelial subsets exhibited a double-sided effect, promoting tumor progression and enhancing the effectiveness of immune response. Finally, follicular helper T cells and T helper 17 cells were found to be significantly correlated with improved outcomes in HNSCC patients. These CD4+ T cell subpopulations could promote the anti-tumor immune response by recruiting and activating B and T cells. CONCLUSION: Our findings provide deeper insights into the immune features of the tumor ecosystem and reveal the prognostic significance of follicular helper T cells and T helper 17 cells. These findings may pave the way for the development of therapeutic approaches.

HTINet2: herb-target prediction via knowledge graph embedding and residual-like graph neural network.

Target identification is one of the crucial tasks in drug research and development, as it aids in uncovering the action mechanism of herbs/drugs and discovering new therapeutic targets. Although multiple algorithms of herb target prediction have been proposed, due to the incompleteness of clinical knowledge and the limitation of unsupervised models, accurate identification for herb targets still faces huge challenges of data and models. To address this, we proposed a deep learning-based target prediction framework termed HTINet2, which designed three key modules, namely, traditional Chinese medicine (TCM) and clinical knowledge graph embedding, residual graph representation learning, and supervised target prediction. In the first module, we constructed a large-scale knowledge graph that covers the TCM properties and clinical treatment knowledge of herbs, and designed a component of deep knowledge embedding to learn the deep knowledge embedding of herbs and targets. In the remaining two modules, we designed a residual-like graph convolution network to capture the deep interactions among herbs and targets, and a Bayesian personalized ranking loss to conduct supervised training and target prediction. Finally, we designed comprehensive experiments, of which comparison with baselines indicated the excellent performance of HTINet2 (HR@10 increased by 122.7% and NDCG@10 by 35.7%), ablation experiments illustrated the positive effect of our designed modules of HTINet2, and case study demonstrated the reliability of the predicted targets of Artemisia annua and Coptis chinensis based on the knowledge base, literature, and molecular docking.

Comparison of the Long-term Survival Outcome of Surgery versus Stereotactic Body Radiation Therapy as Initial Local Treatment for Pulmonary Oligometastases from Colorectal Cancer: A Propensity Score Analysis.

PURPOSE: Optimal local treatment for pulmonary oligometastases from colorectal cancer (CRC) remains unclear. We aimed to compare the long-term survival outcomes between surgery and stereotactic body radiation therapy (SBRT) as the initial local treatment for CRC pulmonary oligometastases. MATERIALS AND METHODS: We retrospectively reviewed 335 consecutive patients who initially underwent surgery or SBRT for CRC pulmonary metastases from 2011 to 2022, and 251 patients (173 surgery and 78 SBRT) were ultimately included. Freedom from intrathoracic progression (FFIP), progression-free survival (PFS), and overall survival (OS) were compared using stabilized inverse probability of treatment weighting (sIPTW) analysis. In addition, patterns of intrathoracic progression and subsequent treatment were analyzed. RESULTS: Median follow-up was 61.6 months for surgery and 54.4 months for SBRT. After sIPTW adjustment, significant differences emerged in both FFIP and PFS between surgery and SBRT (FFIP: hazard ratio [HR] = 0.50, 95% confidence interval [CI], 0.31-0.79; PFS: HR = 0.56, 95% CI, 0.36-0.87). The 3- and 5-year FFIP rates were 58.6% and 54.8%, respectively, after surgery, and 34.6% and 31.3%, respectively, after SBRT (P = .006). The 3- and 5-year PFS rates were 49.4% and 45.2%, respectively, after surgery, and 28.8% and 26.1%, respectively, after SBRT (P = .010). However, OS was not significantly affected by treatment approach (HR = 0.93, 95% CI, 0.49-1.76). The 3- and 5-year OS rates were 85.9% and 73.1%, respectively, after surgery, and 78.9% and 68.7%, respectively, after SBRT (P = .849). Recurrence at the treated site was more prevalent after SBRT than after surgery (33.3% vs 16.9%), whereas new intrathoracic tumors occurred more frequently after surgery than after SBRT (71.8% vs 43.1%). Both groups chose radiation therapy as the primary local salvage treatment. CONCLUSIONS: Notwithstanding the significant differences in FFIP and PFS between surgery and SBRT, the long-term survival of patients with CRC pulmonary oligometastases did not depend on the initial choice of the local treatment approach.

[Spatial and Temporal Scale Effects of Landscape Pattern on Riverine Nitrogen and Phosphorus Nutrients in the Qingshan Lake Watershed].

The influences of landscape pattern on water quality are dependent on spatial-temporal scales. However, the effects of landscape composition, landscape configuration, and landscape slope metrics on seasonal water quality at different spatial scales remain unclear. Based on the total nitrogen, total phosphorus, nitrate-N, and ammonium-N data from 26 sampling sites in the Qingshan Lake watershed, this study coupled landscape pattern analysis, redundancy analysis, and partial redundancy analysis to quantify the spatiotemporal scale effects of landscape pattern on riverine nitrogen （N） and phosphorus （P） concentrations. The results showed that： ① The explanatory ability of landscape pattern at the sub-watershed scale on riverine N and P concentrations was 6.8%-8.4% higher than that at the buffer scale, and this effect was more obvious in the dry season. ② At the sub-watershed scale, the percentage of forestland and the interspersion and juxtaposition degree of residential land had a greater influence on riverine N and P concentrations. At the buffer scale, the slope of farmland and residential land and the aggregation degree of forestland patches were the key factors affecting riverine N and P concentrations. ③ The contribution rate of landscape configuration to riverine N and P concentration variations （20.1%-36.5%） was the highest. The sensitivity of the effect of landscape configuration on riverine N and P concentrations to seasonal changes was the highest, and the effect of landscape slope on riverine N and P concentrations had the highest sensitivity to spatial scale changes. Therefore, landscape pattern-regulated non-point source pollution should be considered from a multi-scale perspective. These results can provide scientific basis for the formulation of landscape pattern optimization measures aiming at non-point source pollution control.

Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

Lingdan: enhancing encoding of traditional Chinese medicine knowledge for clinical reasoning tasks with large language models.

OBJECTIVE: The recent surge in large language models (LLMs) across various fields has yet to be fully realized in traditional Chinese medicine (TCM). This study aims to bridge this gap by developing a large language model tailored to TCM knowledge, enhancing its performance and accuracy in clinical reasoning tasks such as diagnosis, treatment, and prescription recommendations. MATERIALS AND METHODS: This study harnessed a wide array of TCM data resources, including TCM ancient books, textbooks, and clinical data, to create 3 key datasets: the TCM Pre-trained Dataset, the Traditional Chinese Patent Medicine (TCPM) Question Answering Dataset, and the Spleen and Stomach Herbal Prescription Recommendation Dataset. These datasets underpinned the development of the Lingdan Pre-trained LLM and 2 specialized models: the Lingdan-TCPM-Chat Model, which uses a Chain-of-Thought process for symptom analysis and TCPM recommendation, and a Lingdan Prescription Recommendation model (Lingdan-PR) that proposes herbal prescriptions based on electronic medical records. RESULTS: The Lingdan-TCPM-Chat and the Lingdan-PR Model, fine-tuned on the Lingdan Pre-trained LLM, demonstrated state-of-the art performances for the tasks of TCM clinical knowledge answering and herbal prescription recommendation. Notably, Lingdan-PR outperformed all state-of-the-art baseline models, achieving an improvement of 18.39% in the Top@20 F1-score compared with the best baseline. CONCLUSION: This study marks a pivotal step in merging advanced LLMs with TCM, showcasing the potential of artificial intelligence to help improve clinical decision-making of medical diagnostics and treatment strategies. The success of the Lingdan Pre-trained LLM and its derivative models, Lingdan-TCPM-Chat and Lingdan-PR, not only revolutionizes TCM practices but also opens new avenues for the application of artificial intelligence in other specialized medical fields. Our project is available at https://github.com/TCMAI-BJTU/LingdanLLM.

Climate change impacts on magnitude and frequency of urban floods under scenario and model uncertainties.

Many studies have confirmed that climate change leads to frequent urban flooding, which can lead to significant socioeconomic repercussions. However, most existing studies have not evaluated the impacts of climate change on urban flood from both event-scale and annual-scale dimensions. In addition, there are only few studies that simultaneously consider scenario and model uncertainties of climate change, and combine flood risk assessment and uncertainty analysis results to provide practical suggestions for urban drainage system management. This study uses the statistical downscaling method to calculate the design rainfall under ten rainfall return periods of four climate models and three climate change scenarios in 2040s, 2060s, and 2080s in various prefecture-level cities in China. The four climate models are HadGEM2- ES, MPI-ESM-MR, NorESM1-M and FGOALS-g2 models and the three climate change scenarios are constructed by different representative concentration pathways (RCP), namely RCP2.6, RCP4.5 and RCP8.5. On this basis, relying on the generated drainage systems using geographical information and other data, event-scale and annual-scale precipitation are combined to calculate the change ratio of annual flood volume expectation in prefecture-level cities in each future year compared with the current situation. Furthermore, the study evaluates scenario and model uncertainties of climate change, and then comprehensively integrates the flood risk and its uncertainties to provides suggestions for urban drainage system management.

Additional Yield of Random Biopsy in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited clinical data regarding the additional yields of random biopsies (RBs) during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for inflammatory bowel disease patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis and 16.20% in per-lesion analysis. The detection rates were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for primary sclerosing cholangitis (PSC) proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating RB in the standard colonoscopy surveillance for inflammatory bowel disease patients, especially in those with PSC.

Multimodal locomotion ultra-thin soft robots for exploration of narrow spaces.

From power plants on land to bridges over the sea, safety-critical built environments require periodic inspections for detecting issues to avoid functional discontinuities of these installations. However, navigation paths in these environments are usually challenging as they often contain difficult-to-access spaces (near-millimetre and submillimetre-high gaps) and multiple domains (solid, liquid and even aerial). In this paper, we address these challenges by developing a class of Thin Soft Robots (TS-Robot: thickness, 1.7 mm) that can access narrow spaces and perform cross-domain multimodal locomotion. We adopted a dual-actuation sandwich structure with a tuneable Poisson's ratio tensioning mechanism for developing the TS-Robots driven by dielectric elastomers, providing them with two types of gaits (linear and undulating), remarkable output force ( ~ 41 times their weight) and speed (1.16 times Body Length/s and 13.06 times Body Thickness/s). Here, we demonstrated that TS-Robots can crawl, climb, swim and collaborate for transitioning between domains in environments with narrow entries.

ShengqingJiangzhuo capsule ameliorates diabetic nephropathy by improving Keap1/Nrf2 signaling pathway.

BACKGROUND: Diabetic nephropathy (DN) is a major contributor to end-stage renal failure, and lacking effective treatment options. Shengqing Jiangzhuo capsule (SQJZJN), a traditional Chinese medicine prescription with known efficacy in chronic kidney disease, has not been thoroughly investigated for its potential in DN protection. METHODS: Eight-week-old male C57BLKS/J db/db, C57BLKS/J db/m mice, and human glomerular mesangial cell (HMC) cells cultured with high glucose were used as experimental models in this study. RESULTS: The in vivo investigation showed that SQJZJN can significantly ameliorate renal pathological damage, reduce serum creatinine, and lower urinary microalbumin levels in db/db mice. In vitro, SQJZJN treatment mitigated advanced glycation end products (AGEs) and reactive oxygen species (ROS), leading to a reduction in renal cell apoptosis. Mechanistically, SQJZJN activated the Keap1/Nrf2/ARE pathway by promoting nuclear factor erythroid-derived 2-related factor 2 (Nrf2), γ-glutamylcysteine synthetase heavy subunit (γ-GCS), and Heme oxygenase-1 (HO-1) expressions, while decreasing Kelch-like ECH-associated protein 1 (KEAP1) expressions. CONCLUSION: These findings suggest that SQJZJN exerts a protective effect on DN, potentially through the activation of the Keap1/Nrf2/ARE pathway.

Single-cell omics: experimental workflow, data analyses and applications.

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome, proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial scRNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field, offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

Gut microbiome and metabolism alterations in schizophrenia with metabolic syndrome severity.

BACKGROUND: Schizophrenia (SCZ) patients undergoing antipsychotic treatment demonstrated a high prevalence and harmful effects of metabolic syndrome (MetS), which acted as the major cause of cardiovascular disease. The major clinical challenge is the lack of biomarkers to identify MetS episodes and prevent further damage, while the mechanisms underlying these drug-induced MetS remain unknown. METHODS: This study divided 173 participants with SCZ into 3 groups (None, High risk, and MetS, consisting of 22, 88, and 63 participants, respectively). The potential biomarkers were searched based on 16S rRNA gene sequence together with metabolism analysis. Logistic regression was used to test the effects of the genus-metabolites panel on early MetS diagnoses. RESULTS: A genus-metabolites panel, consisting of Senegalimassilia, sphinganine, dihomo-gamma-linolenoylcholine, isodeoxycholic acid, and MG (0:0/22:5/0:0), which involved in sphigolipid metabolism, fatty acid metabolism, secondary bile acid biosynthesis and glycerolipid metabolism, has a great discrimination efficiency to MetS with an area under the curve (AUC) value of 0.911 compared to the None MetS group (P = 1.08E-8). Besides, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) distinguished between subgroups robustly and exhibited a potential correlation with the severity of MetS in patients with SCZ, and may act as the biomarkers for early MetS diagnosis. CONCLUSIONS: Our multi-omics study showed that one bacterial genus-five lipid metabolites panel is the potential risk factor for MetS in SCZ. Furthermore, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) could serve as novel diagnostic markers in the early stage. So, it is obvious that the combination of bacterial genus and metabolites yields excellent discriminatory power, and the lipid metabolism provide new understanding to the pathogenesis, prevention, and therapy for MetS in SCZ.

Integrated modeling of urban mobility, flood inundation, and sewer hydrodynamics processes to support resilience assessment of urban drainage systems.

With the increasing frequency of extreme weather events and a deepening understanding of disasters, resilience has received widespread attention in urban drainage systems. The studies on the resilience assessment of urban drainage systems are mostly indirect assessments that did not simulate human behavior affected by rainfall or semi-quantitative assessments that did not build simulation models, but few research characterizes the processes between people and infrastructure to assess resilience directly. Our study developed a dynamic model that integrates urban mobility, flood inundation, and sewer hydrodynamics processes. The model can simulate the impact of rainfall on people's mobility behavior and the full process including runoff generation, runoff entering pipes, node overflow, flood migration, urban mobility, and residential water usage. Then, we assessed the resilience of the urban drainage system under rainfall events from the perspectives of property loss and urban mobility. The study found that the average percentage increase in commuting time under different return periods of rainfall ranged from 6.4 to 203.9%. Calculating the annual expectation of property loss and traffic obstruction, the study found that the annual expectation loss in urban mobility is 9.1% of the annual expectation of property loss if the rainfall is near the morning commuting peak.

Facilitating giant panda crossings of national highway in Wolong area of Giant Panda National Park amid human activities.

As human activities continue to expand, wildlife persistence faces escalating threats from roads. In Wolong area of Giant Panda National Park, the local giant pandas (Ailuropoda melanoleuca) are divided into two population groups along the National Highway G350 (NHG). Therefore, selecting suitable areas to help those giant pandas communicate across the NHG is necessary. In this research, we evaluated the presence of human activities and simulated their absence to analyze how they affect the giant panda's habitat in Wolong. Subsequently, based on the kernel density estimation (KDE) for giant pandas and the main human distribution locations, we selected suitable areas for the population link between the two road sections on the NHG. We simulated the absence of human activities on the two road sections to compare changes in the habitat suitability index (HSI) and connectivity value (CV) relative to their presence. We aimed to carefully select the area for future giant panda corridor plans and simulate whether eliminating human activities will significantly improve the HSI and CV of the area. Our results show that: (1) Human activities presence has led to subtle changes in the landscape pattern of suitable habitats and a decrease in Wolong by 78.76 km2 compared to their absence. (2) Human activities presence significantly reduced HSI and CV in the 1000 m buffer along the NHG compared to their absence. (3) The HSI and CV of the 1000 m buffer in the simulated absence of human activities for the two road sections were significantly higher than their presence. This research identified the optimal road section for crossing the NHG to link giant panda population groups and habitats in Wolong. These insights are significant for formulating conservation decisions and corridor plans and for promoting wildlife conservation in reserves amid high levels of human activity.

Single-cell and spatial multiomic inference of gene regulatory networks using SCRIPro.

MOTIVATION: The burgeoning generation of single-cell or spatial multiomic data allows for the characterization of gene regulation networks (GRNs) at an unprecedented resolution. However, the accurate reconstruction of GRNs from sparse and noisy single-cell or spatial multiomic data remains challenging. RESULTS: Here, we present SCRIPro, a comprehensive computational framework that robustly infers GRNs for both single-cell and spatial multi-omics data. SCRIPro first improves sample coverage through a density clustering approach based on multiomic and spatial similarities. Additionally, SCRIPro scans transcriptional regulator (TR) importance by performing chromatin reconstruction and in silico deletion analyses using a comprehensive reference covering 1,292 human and 994 mouse TRs. Finally, SCRIPro combines TR-target importance scores derived from multiomic data with TR-target expression levels to ensure precise GRN reconstruction. We benchmarked SCRIPro on various datasets, including single-cell multiomic data from human B-cell lymphoma, mouse hair follicle development, Stereo-seq of mouse embryos, and Spatial-ATAC-RNA from mouse brain. SCRIPro outperforms existing motif-based methods and accurately reconstructs cell type-specific, stage-specific, and region-specific GRNs. Overall, SCRIPro emerges as a streamlined and fast method capable of reconstructing TR activities and GRNs for both single-cell and spatial multi-omic data. AVAILABILITY: SCRIPro is available at https://github.com/wanglabtongji/SCRIPro. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Modifications of the Structural, Nutritional, and Allergenic Properties of Atlantic Cod Induced by Novel Thermal Glycation Treatments.

This study aimed to assess the effect of novel thermal glycation, utilizing microwave processing (100-150 °C) combined with sugars (glucose and lactose), on the in vitro protein digestibility, peptides, secondary structures, microstructures, and allergenic properties of Atlantic cod. The research demonstrated that microwave heating at 150 °C with glucose significantly reduced cod allergenicity by up to 16.16%, while also enhancing in vitro protein digestibility to 69.05%. Glucose was found to be more effective than lactose in conjunction with microwave heating in reducing the allergenicity of Atlantic cod. Moreover, treatments conducted at 150 °C were more effective in increasing in vitro protein digestibility and peptide content compared to those at 100 °C. This study revealed that the novel processing technique of thermal glycation effectively reduced the allergenicity of Atlantic cod. It also offered fresh insights into the potential benefits of combining microwave heating with sugars.

[Effects of Different Proportions of Ammonium Sulfate Replacing Urea on Soil Nutrients and Rhizosphere Microbial Communities].

In order to investigate the effects of ammonium sulfate, an industrial by-product, on soil nutrients and microbial community when applied in different proportions instead of using urea as nitrogen fertilizer, a pot corn experiment was conducted. A completely randomized block experimental design was used, with a total of five treatments:CK (no fertilization), U10S0 (100 % urea), U8S2 (80 % urea + 20 % ammonium sulfate), U6S4(60 % urea + 40 % ammonium sulfate), and U0S10 (100 % ammonium sulfate). The basic physical and chemical properties of soil and the dry weight of maize plants were determined by conventional methods, and microbial sequencing was performed using the Illumina NovaSeq platform. The experiment results showed that:① In each growth stage of maize, the pH of soil treated with fertilization (7.85-8.15) was decreased compared with that of CK (8.1-8.21), and the pH showed a decreasing trend with the increase in ammonium sulfate content. ② The soil available nitrogen content increased gradually with the increase in the ammonium sulfate ratio at each growth stage of maize. Compared with that in the CK and U10S0 treatments, the ratio in the U0S10 treatment increased 30.56 % to 63.68 % and 13.22 % to 38.43 %, respectively. The variation trend of organic carbon content was opposite to that of available nitrogen (U8S2 > U6S4 > U0S10), and the addition of ammonium sulfate was still higher than that of U10S0 at other growth stages except for the seedling stage. ③ The protease activity of all fertilization treatments was higher than that of the control, and the protease activity was gradually enhanced with the continuous growth of corn and the increase in the ammonium sulfate ratio. The protease activity of the U0S10 treatment was higher than that of the U10S0 treatment at each growth stage of corn, which increased by 10.54 %-100 %. Soil sucrase activity ranged from 0.04 to 0.24 mg·(g·24 h)-1, and those in the U0S10 treatments were significantly higher than those in the U10S0 and CK treatments at all growth stages, increasing by 20.32 % to 99.16 % and 24.31 % to 79.33 %, respectively. ④ The species abundance of bacteria and fungi in maize rhizosphere under all fertilization treatments were lower than those under the CK treatment, followed by those under the U10S0 treatment. The species diversity trend of the bacterial community in the three treatments with ammonium sulfate replacing urea were U8S2 > U0S10 > U6S4, and that of fungi were U6S4 > U8S2 > U0S10. ⑤ The maize dry weight of the U10S0 treatment and U0S10 treatment was the highest, which was 39.47 % and 36.16 % higher than that of the CK treatment, respectively, but the difference was not significant. The Pearson model showed that the species abundance and diversity of soil rhizosphere fungi and bacteria were affected by relevant environmental variables, among which pH value and soil available nitrogen content were the most important factors affecting microbial diversity. In conclusion, when corn planting in calcareous brown soil, replacing urea with a certain proportion of ammonium sulfate can improve soil nutrients more than urea alone, which affects the growth and rhizosphere microbial community of corn to a certain extent and has a greater yield.

The Bioactive Compounds of Epimedium and Their Potential Mechanism of Action in Treating Osteoporosis: A Network Pharmacology and Experimental Validation Study.

Osteoporosis is a global health challenge characterized by bone loss and microstructure deterioration, which urgently requires the development of safer and more effective treatments due to the significant adverse effects and limitations of existing drugs for long-term treatment. Traditional Chinese medicine, like Epimedium, offers fewer side effects and has been used to treat osteoporosis, yet its active compounds and pharmacological mechanisms remain unclear. In this study, 65 potential active compounds, 258 potential target proteins, and 488 pathways of Epimedium were identified through network pharmacology analysis. Further network analysis and review of the literature identified six potential active compounds and HIF-1α for subsequent experimental validation. In vitro experiments confirmed that 2″-O-RhamnosylIcariside II is the most effective compound among the six potential active compounds. It can promote osteoblast differentiation, bind with HIF-1α, and inhibit both HIF-1α gene and protein expression, as well as enhance COL1A1 protein expression under hypoxic conditions. In vivo experiments demonstrated its ability to improve bone microstructures and reduce bone loss by decreasing bone marrow adipose tissue, enhancing bone formation, and suppressing HIF-1α protein expression. This study is the first to describe the therapeutic effects of 2-O-RhamnosylIcariside II on osteoporosis, which was done, specifically, through a mechanism that targets and inhibits HIF-1α. This study provides a scientific basis for the clinical application of Epimedium and offers a new candidate drug for the treatment of osteoporosis. Additionally, it provides new evidence supporting HIF-1α as a therapeutic target for osteoporosis.

Massive hemothorax induced by pulmonary arteriovenous malformation rupture: a case report and literature review.

BACKGROUND: Pulmonary arteriovenous malformation (PAVM), also known as pulmonary arteriovenous fistula, is a rare vascular developmental anomaly. Most cases of PAVM are associated with hereditary hemorrhagic telangiectasia (HHT). Hemothorax associated with PAVM is even rarer, and management concerning this complication still challenges. CASE PRESENTATION: A 55-year-old man with sudden onset of dyspnea and chest pain was admitted to our hospital. He had a medical history of epistaxis, intraperitoneal germ cell tumor and PAVM. Chest unenhanced CT revealed the left-sided pleural effusion together with partial passive atelectasis and gradual increase at the interval of six days. Diagnostic thoracocentesis further revealed hemorrhagic effusion. CT angiography (CTA) showed tortuously dilated lumen of the left lower pulmonary artery and PAVM with the formation of aneurysm. Due to his family's refusal of surgery, the patient underwent transcatheter embolization therapy. However, the left pleural effusion did not significantly reduce and there was a slow drop in hemoglobin value even after interventional treatment, indicating the possibility of ongoing active bleeding. Eventually, the patient received lobectomy of the left lower lobe with a satisfactory outcome. CONCLUSIONS: Massive hemothorax resulting from PAVM rupture into the pleural space can lead to fatal outcomes. CTA can accurately diagnose this pathologic condition. Transcatheter embolization is frequently used in the treatment of PAVM, but it may be challenging to achieve the desirable effect in patients with hemothorax. Combined with our case and literature review, direct radical surgery can lead to a successful outcome when PAVM complicated with hemothorax and a large diameter of the draining vein.