Phytochromes enhance SOS2-mediated PIF1 and PIF3 phosphorylation and degradation to promote Arabidopsis salt tolerance.

Soil salinity is one of the most detrimental abiotic stresses affecting plant survival, and light is a core environmental signal regulating plant growth and responses to abiotic stress. However, how light modulates the plant's response to salt stress remains largely obscure. Here, we show that Arabidopsis (Arabidopsis thaliana) seedlings are more tolerant to salt stress in the light than in the dark, and that the photoreceptors phytochrome A (phyA) and phyB are involved in this tolerance mechanism. We further show that phyA and phyB physically interact with the salt tolerance regulator SALT OVERLY SENSITIVE2 (SOS2) in the cytosol and nucleus, and enhance salt-activated SOS2 kinase activity in the light. Moreover, SOS2 directly interacts with and phosphorylates PHYTOCHROME-INTERACTING FACTORS PIF1 and PIF3 in the nucleus. Accordingly, PIFs act as negative regulators of plant salt tolerance, and SOS2 phosphorylation of PIF1 and PIF3 decreases their stability and relieves their repressive effect on plant salt tolerance in both light and dark conditions. Together, our study demonstrates that photoactivated phyA and phyB promote plant salt tolerance by increasing SOS2-mediated phosphorylation and degradation of PIF1 and PIF3, thus broadening our understanding of how plants adapt to salt stress according to their dynamic light environment.

Alternative Splicing Factor Heterogeneous Nuclear Ribonucleoprotein U as a Promising Biomarker for Gastric Cancer Risk and Prognosis with Tumor-Promoting Properties.

Gastric cancer (GC) is a major global health concern with poor outcomes. Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a multifunctional protein that participates in pre-mRNA packaging, alternative splicing regulation, and chromatin remodeling. Its potential role in GC remains unclear. In this study, the expression characteristics of HNRNPU were analyzed by The Cancer Genome Atlas data, Gene Expression Omnibus data, and then further identified by real-time quantitative PCR and immunohistochemistry using tissue specimens. From superficial gastritis, atrophic gastritis, and hyperplasia to GC, the in situ expression of HNRNPU protein gradually increased, and the areas under the curve for diagnosis of GC and its precancerous lesions were 0.911 and 0.847, respectively. A nomogram integrating HNRNPU expression, lymph node metastasis, and other prognostic indicators exhibited an area under the curve of 0.785 for predicting survival risk. Knockdown of HNRNPU significantly inhibited GC cell proliferation, migration, and invasion and promoted apoptosis in vitro. In addition, RNA-sequencing analysis showed that HNRNPU could affect alternative splicing events in GC cells, with functional enrichment analysis revealing that HNRNPU may exert malignant biological function in GC progression through alternative splicing regulation. In summary, the increased expression of HNRNPU was significantly associated with the development of GC, with a good performance in diagnosing and predicting the prognostic risk of GC. Functionally, HNRNPU may play an oncogenic role in GC by regulating alternative splicing.

US-guided Percutaneous Radiofrequency Ablation for Secondary Hyperparathyroidism: Long-term Outcomes and Prognostic Factors.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for secondary hyperparathyroidism (SHPT), the long-term efficacy remains insufficiently investigated. Purpose To evaluate the long-term efficacy and safety of US-guided percutaneous RFA in patients with SHPT undergoing dialysis and to identify possible predictors associated with treatment failure. Materials and Methods This retrospective study included consecutive patients with SHPT with at least one enlarged parathyroid gland accessible for RFA who were undergoing dialysis at seven tertiary centers from May 2013 to July 2022. The primary end point was the proportion of patients with parathyroid hormone (PTH) levels less than or equal to 585 pg/mL at the end of follow-up. Secondary end points were the proportion of patients with normal calcium and phosphorus levels, the technical success rate, procedure-related complications, and improvement in self-rated hyperparathyroidism-related symptoms (0-3 ranking scale). The Wilcoxon signed rank test and generalized estimating equation model were used to evaluate treatment outcomes. Univariable and multivariable regression analyses identified variables associated with treatment failure (recurrent or persistent hyperparathyroidism). Results This study included 165 patients (median age, 51 years [IQR, 44-60 years]; 92 female) and 582 glands. RFA effectively reduced PTH, calcium, and phosphorus levels, with targeted ranges achieved in 78.2% (129 of 165), 72.7% (120 of 165), and 60.0% (99 of 165) of patients, respectively, at the end of follow-up (mean, 51 months). For the RFA sessions, the technical success rate was 100% (214 of 214). Median symptom scores (ostealgia, arthralgia, pruritus) decreased (all P < .001). Regarding complications, only hypocalcemia (45.8%, 98 of 214) was common. Treatment failure occurred in 36 patients (recurrent [n = 5] or persistent [n = 31] hyperparathyroidism). The only potential independent predictor of treatment failure was having less than four treated glands (odds ratio, 17.18; 95% CI: 4.34, 67.95; P < .001). Conclusion US-guided percutaneous RFA was effective and safe in the long term as a nonsurgical alternative for patients with SHPT undergoing dialysis; the only potential independent predictor of treatment failure was a lower number (<4) of treated glands. © RSNA, 2024 Supplemental material is available for this article.

Tuning A-Site Cation Deficiency in Pr0.5La0.5BaCo2O5+ δ Perovskite to Realize Large-Scale Hydrogen Evolution at 2000 mA cm-2.

Industrial-level hydrogen production from the water electrolysis requires reducing the overpotential (η) as much as possible at high current density, which is closely related to intrinsic activity of the electrocatalysts. Herein, A-site cation deficiency engineering is proposed to screen high-performance catalysts, demonstrating effective Pr0.5- xLa0.5BaCo2O5+ δ (P0.5- xLBC) perovskites toward alkaline hydrogen evolution reaction (HER). Among all perovskite compositions, Pr0.4La0.5BaCo2O5+ δ (P0.4LBC) exhibits superior HER performance along with unique operating stability at large current densities (J = 500-2000 mA cm-2 geo). The overpotential of ≈636 mV is achieved in P0.4LBC at 2000 mA cm-2 geo, which outperforms commercial Pt/C benchmark (≈974 mV). Furthermore, the Tafel slope of P0.4LBC (34.1 mV dec-1) is close to that of Pt/C (35.6 mV dec-1), reflecting fast HER kinetics on the P0.4LBC catalyst. Combined with experimental and theoretical results, such catalytic activity may benefit from enhanced electrical conductivity, enlarged Co-O covalency, and decreased desorption energy of H* species. This results highlight effective A-site cation-deficient strategy for promoting electrochemical properties of perovskites, highlighting potential water electrolysis at ampere-level current density.

Deep Learning-Based Stratification of Gastric Cancer Patients from Hematoxylin and Eosin-Stained Whole Slide Images by Predicting Molecular Features for Immunotherapy Response.

Determining the molecular characteristics of cancer patients is crucial for optimal immunotherapy decisions. The aim of this study was to screen immunotherapy beneficiaries by predicting key molecular features from hematoxylin and eosin-stained images based on deep learning models. An independent data set from Asian gastric cancer patients was included for external validation. In addition, a segmentation model (Horizontal-Vertical Network) was used to quantify the cellular composition of tumor stroma. The model performance was evaluated by measuring the area under the curve (AUC). The tumor extraction model achieved an AUC of 0.9386 and 0.9062 in the internal and external test sets, respectively. The stratification model could predict the immunotherapy-sensitive subtypes (AUC range, 0.8685 to 0.9461), the genetic mutations (AUC range, 0.8283 to 0.9225), and the pathway activity (AUC range, 0.7568 to 0.8612) fairly accurately. In external validation, the prediction performance of Epstein-Barr virus and programmed cell death ligand 1 expression status achieved AUCs of 0.7906 and 0.6384, respectively. The segmentation model identified a relatively high proportion of inflammatory cells and connective cells in some immunotherapy-sensitive subtypes. The deep learning-based models potentially may serve as a valuable tool to screen for the beneficiaries of immunotherapy in gastric cancer patients.

Novel miniature transendoscopic telerobotic system for endoscopic submucosal dissection (with videos).

BACKGROUND AND AIMS: The lack of tissue traction and instrument dexterity to allow for adequate visualization and effective dissection were the main issues in performing endoscopic submucosal dissection (ESD). Robot-assisted systems may provide advantages. In this study we developed a novel transendoscopic telerobotic system and evaluated its performance in ESD. METHODS: A miniature dual-arm robotic endoscopic assistant for minimally invasive surgery (DREAMS) was developed. The DREAMS system contained the current smallest robotic ESD instruments and was compatible with the commercially available dual-channel endoscope. After the system was established, a prospective randomized controlled study was conducted to validate the performance of the DREAMS-assisted ESD in terms of efficacy, safety, and workload by comparing it with the conventional technique. RESULTS: Two robotic instruments can achieve safe collaboration and provide sufficient visualization and efficient dissection during ESD. Forty ESDs in the stomach and esophagus of 8 pigs were completed by DREAMS-assisted ESD or conventional ESD. Submucosal dissection time was comparable between the 2 techniques, but DREAMS-assisted ESD demonstrated a significantly lower muscular injury rate (15% vs 50%, P = .018) and workload scores (22.30 vs 32.45, P < .001). In the subgroup analysis of esophageal ESD, DREAMS-assisted ESD showed significantly improved submucosal dissection time (6.45 vs 16.37 minutes, P = .002), muscular injury rate (25% vs 87.5%, P = .041), and workload (21.13 vs 40.63, P = .001). CONCLUSIONS: We developed a novel transendoscopic telerobotic system, named DREAMS. The safety profile and technical feasibility of ESD were significantly improved with the assistance of the DREAMS system, especially in the narrower esophageal lumen.

A quadratic isothermal amplification fluorescent biosensor without intermediate purification for ultrasensitive detection of circulating tumor DNA.

Circulating tumor DNA (ctDNA) is an auspicious tumor biomarker released into the bloodstream by tumor cells, offering abundant information concerning cancer genes. It plays a crucial role in the early diagnosis of cancer. However, due to extremely low levels in body fluids, achieving a simple, sensitive, and highly specific detection of ctDNA remains challenging. Here, we constructed a purification-free fluorescence biosensor based on quadratic amplification of ctDNA by combining nicking enzyme mediated amplification (NEMA) and catalytic hairpin assembly (CHA) reactions. After double isothermal amplification, this biosensor achieved an impressive signal amplification of nearly 107-fold, enabling it to detect ctDNA with ultra-sensitivity. And the detection limit of this biosensor is as low as 2 aM. In addition, we explored the influence of human serum on the performance of the biosensor and found that it showed favorable sensitivity in the presence of serum. This biosensor eliminates the need for an intermediate purification step, resulting in enhanced sensitivity and convenience. Thus, our purification-free fluorescent biosensor exhibits ultra-high sensitivity when compared to other biosensors and has the potential to serve as an effective diagnostic tool for early detection of cancer.

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.

YiQi GuBen capsule alleviates OVA-induced asthma through improving mitochondrial dysfunction.

Objective: This study aims to explore the effect of YiQi GuBen capsule on improving mitochondrial dysfunction in an animal model of asthma.Methods: The mice (n = 8) were divided into four groups including control (NC), ovalbumin (OVA), dexamethasone (OVA + DEX), and YiQi GuBen (OVA + YQGB) groups. Firstly, we established an OVA-induced mouse asthma model except for the NC group, which then were treated with dexamethasone and YiQi GuBen capsule. Subsequently, HE staining and Masson staining were used for pathological analysis of mice lung tissues. Next, we used transmission electron microscopy (TEM) to observe the effect of the Yiqi Guben capsule on the ultrastructure of mitochondria. Flow cytometry was used to analyze the ROS level, membrane potential, and the number of mitochondria in lung tissue. Moreover, we analyzed the copy number of mitochondrial DNA (mtDNA) and the expression levels of activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM).Results: The results of the pathological analysis showed that after treatment with the YiQi GuBen capsule, the lung tissue damage was significantly reduced. In addition, we observed that the ultrastructural damage of mitochondria was improved. Flow cytometry proved that after treatment with the YiQi GuBen capsule, the level of ROS in the mitochondria was effectively reduced, while the mitochondrial membrane potential decreased and the number increased significantly. Moreover, we found that the copy number of mtDNA was significantly increased and the expression levels of PGC-1α and TFAM were significantly upgraded.Conclusion: This study suggests YiQi GuBen capsule can effectively improve mitochondrial dysfunction in the OVA-induced mouse model.

A meta-analysis of the effects of vitamin C supplementation for pregnant smokers on the pulmonary function of their offspring.

BACKGROUND: At present, the need for vitamin C supplementation for pregnant smokers has not been fully studied. This study is aimed at investigating whether vitamin C supplementation for pregnant smoking women can improve the pulmonary function of their offspring. METHODS: Four databases were searched from inception to April 1, 2023 for studies on the effect of vitamin C supplementation to pregnant smokers on the pulmonary function of their offspring. Meanwhile, the reference lists of relevant studies were manually searched. The risk of bias in the included studies was assessed using the Cochrane Collaboration tool, and the data was analyzed using STATA/SE 17.0. RESULTS: Four randomized controlled trials (RCTs), all of high quality, were enrolled in this meta-analysis, including 787 pregnant women. The offspring of pregnant smokers who received vitamin C supplementation exhibited improved Forced Expiratory Flow between 25 and 75% (FEF25-75), FEF50, FEF75, and Forced Vital Capacity (FVC) compared to those who did not receive vitamin C supplementation. However, there was no statistically significant difference in Forced Expiratory Volume at 0.5 s (FEV0.5) and the ratio of FEV0.5 to FVC between the offspring of pregnant smokers who received vitamin C and the control group. CONCLUSION: Vitamin C supplementation for smoking pregnant women may enhance the pulmonary function of their offspring, particularly in FEF25-75, FEF50, FEF75, and FVC. Nevertheless, there are no significant differences in FEV0.5 and the FEV0.5/FVC ratio. These findings suggest that vitamin C supplementation has potential benefits for specific pulmonary function. Further studies are needed to comprehensively assess the effects of vitamin C on pulmonary function in the context of maternal smoking during pregnancy.

Effect of Ciprofol on Left Ventricular Myocardial Strain and Myocardial Work in Children Undergoing Cardiac Surgery: A Single-center Double-blind Randomized Noninferiority Study.

OBJECTIVE: The current work was designed to compare the effects of ciprofol and propofol on left ventricular systolic function and myocardial work by noninvasive speckle-tracking echocardiography in children undergoing surgical repair of atrial septal or ventricular septal defects. DESIGN: A single-center double-blind randomized noninferiority study was conducted. SETTING: The research occurred at a tertiary care center affiliated with Shanghai Jiao Tong University, China. PARTICIPANTS: One hundred and twelve children aged 1 month to 16 years undergoing atrial septal or ventricular septal defect surgery with cardiopulmonary bypass were included. INTERVENTIONS: One hundred and twelve children were allocated randomly to receive ciprofol (n = 67) or propofol (n = 45) in a 1.5:1 ratio. Ciprofol or propofol were intravenously infused at loading doses of 0.4 mg/kg or 2.0 mg/kg, respectively, over 30 seconds, depending on the physical condition of each patient. When the bispectral index was maintained between 45 and 55 after induction, transthoracic echocardiography, including apical two-chamber, three-chamber, and four-chamber views, were collected bedside. MEASUREMENTS AND MAIN RESULTS: Of the 112 patients enrolled, 104 completed the study. Global longitudinal strain in the ciprofol and propofol groups after anesthesia was -17.3% (95% confidence interval [CI] -18.0% to -16.6%) and -17.8% (95% CI -18.7 to -17.0%) in the full analysis set and -17.5% (95% CI -18.2% to -16.9%) and -17.8% (95% CI -18.7% to -17.0%) in the per-protocol set, respectively. The noninferiority margin was set at 2% and confirmed with a lower limit of two-sided 95% CI for the intergroup difference of 1.58% in the full analysis set and 1.34% in the per-protocol set. There were no significant differences between the groups in left ventricular systolic and diastolic function and myocardial work indices. Postoperative vasoactive-inotropic score, NT-proBNP, duration of mechanical ventilation, and the length of stay in the cardiac intensive care unit and hospital were also comparable between the two groups (all p > 0.05). CONCLUSIONS: Ciprofol did not show different effects on myocardial function and postoperative outcomes from propofol. Further, on the sensitive cardiac systole marker global longitudinal strain, ciprofol demonstrated noninferiority to propofol. Ciprofol might be an alternative solution for cardiac anesthesia in children with congestive heart disease with mild lesion.

Bayesian metamodeling of complex biological systems across varying representations.

Comprehensive modeling of a whole cell requires an integration of vast amounts of information on various aspects of the cell and its parts. To divide and conquer this task, we introduce Bayesian metamodeling, a general approach to modeling complex systems by integrating a collection of heterogeneous input models. Each input model can in principle be based on any type of data and can describe a different aspect of the modeled system using any mathematical representation, scale, and level of granularity. These input models are 1) converted to a standardized statistical representation relying on probabilistic graphical models, 2) coupled by modeling their mutual relations with the physical world, and 3) finally harmonized with respect to each other. To illustrate Bayesian metamodeling, we provide a proof-of-principle metamodel of glucose-stimulated insulin secretion by human pancreatic ß-cells. The input models include a coarse-grained spatiotemporal simulation of insulin vesicle trafficking, docking, and exocytosis; a molecular network model of glucose-stimulated insulin secretion signaling; a network model of insulin metabolism; a structural model of glucagon-like peptide-1 receptor activation; a linear model of a pancreatic cell population; and ordinary differential equations for systemic postprandial insulin response. Metamodeling benefits from decentralized computing, while often producing a more accurate, precise, and complete model that contextualizes input models as well as resolves conflicting information. We anticipate Bayesian metamodeling will facilitate collaborative science by providing a framework for sharing expertise, resources, data, and models, as exemplified by the Pancreatic ß-Cell Consortium.

Assessing women's and health professionals' views on developing a midwifery-led mobile health app intervention in pregnancy: A descriptive qualitative study.

AIMS: To explore women's and health professionals' views on the development of a midwifery-led mHealth app intervention in antenatal care and their demands for app functionality. DESIGN: Descriptive qualitative research was utilized. METHODS: In total, 15 pregnant or postpartum women were interviewed via in-depth interviews and 10 health professionals including obstetricians, midwives and obstetric nurses were invited to participate in a focus group discussion (FGD). All interviews and the FGD were analysed using qualitative content analysis. RESULTS: Four key themes emerged from the data, including (1) limitations of current maternity care services; (2) potential benefits for mHealth app-based midwifery care; (3) possible challenges for providing midwifery care through mHealth apps and (4) suggestions and needs for developing a midwifery-led mHealth app. Participants agreed on the potential need of developing a midwifery-led mHealth app in antenatal care to increase access to midwifery care services and to meet women's diverse needs. Participants preferred to develop professional, reliable, full-featured and interactive mobile applications. The main functions of midwifery-led mHealth apps included personalized assessment and health education, self-monitoring and feedback, data sharing and interactive functions. Women mentioned that online communication and consultation with midwives could help them receive continuous support outside facilities. Health professionals expressed it would be of great convenience and timeliness to send personalized messages to women and to inform them of healthy lifestyles during pregnancy. The challenges included a shortage of human resources, medico-legal risks associated with mHealth and data security risks. CONCLUSIONS: This study explores the individual views and functional needs of target users and healthcare providers for developing a midwifery-led mHealth app in antenatal care, which will serve as a reference for future application development. IMPACT: Our study has important and practical implications for guiding the development of future midwifery-led mHealth app interventions. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Wogonin attenuates the pathogenicity of Streptococcus pneumoniae by double-target inhibition of Pneumolysin and Sortase A.

Streptococcus pneumoniae (S. pneumoniae) is a major causative agent of respiratory disease in patients and can cause respiratory distress and other symptoms in severe cases. Pneumolysin (PLY) is a pore-forming toxin that induces host tissue injury and inflammatory responses. Sortase A (SrtA), a catalytic enzyme that anchors surface-associated virulence factors, is critical for S. pneumoniae virulence. Here, we found that the active ingredient of the Chinese herb Scutellaria baicalensis, wogonin, simultaneously inhibited the haemolytic activity of PLY and SrtA activity. Consequently, wogonin decreased PLY-mediated cell damage and reduced SrtA-mediated biofilm formation by S. pneumoniae. Furthermore, our data indicated that wogonin did not affect PLY expression but directly altered its oligomerization, leading to reduced activity. Furthermore, the analysis of a mouse pneumonia model further revealed that wogonin reduced mortality in mice infected with S. pneumoniae laboratory strain D39 and S. pneumoniae clinical isolate E1, reduced the number of colony-forming units in infected mice and decreased the W/D ratio and levels of the inflammatory factors TNF-α, IL-6 and IL-1ß in the lungs of infected mice. Thus, wogonin reduces S. pneumoniae pathogenicity by inhibiting the dual targets PLY and SrtA, providing a treatment option for S. pneumoniae infection.

Prediction of gene co-expression from chromatin contacts with graph attention network.

MOTIVATION: The technology of high-throughput chromatin conformation capture (Hi-C) allows genome-wide measurement of chromatin interactions. Several studies have shown statistically significant relationships between gene-gene spatial contacts and their co-expression. It is desirable to uncover epigenetic mechanisms of transcriptional regulation behind such relationships using computational modeling. Existing methods for predicting gene co-expression from Hi-C data use manual feature engineering or unsupervised learning, which either limits the prediction accuracy or lacks interpretability. RESULTS: To address these issues, we propose HiCoEx (Hi-C predicts gene co-expression), a novel end-to-end framework for explainable prediction of gene co-expression from Hi-C data based on graph neural network. We apply graph attention mechanism to a gene contact network inferred from Hi-C data to distinguish the importance among different neighboring genes of each gene, and learn the gene representation to predict co-expression in a supervised and task-specific manner. Then, from the trained model, we extract the learned gene embeddings as a model interpretation to distill biological insights. Experimental results show that HiCoEx can learn gene representation from 3D genomics signals automatically to improve prediction accuracy, and make the black box model explainable by capturing some biologically meaningful patterns, e.g., in a gene contact network, the common neighbors of two central genes might contribute to the co-expression of the two central genes through sharing enhancers. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at https://github.com/JieZheng-ShanghaiTech/HiCoEx. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association of mitochondrial homeostasis and dynamic balance with malignant biological behaviors of gastrointestinal cancer.

Mitochondria determine the physiological status of most eukaryotes. Mitochondrial dynamics plays an important role in maintaining mitochondrial homeostasis, and the disorder in mitochondrial dynamics could affect cellular energy metabolism leading to tumorigenesis. In recent years, disrupted mitochondrial dynamics has been found to influence the biological behaviors of gastrointestinal cancer with the potential to be a novel target for its individualized therapy. This review systematically introduced the role of mitochondrial dynamics in maintaining mitochondrial homeostasis, and further elaborated the effects of disrupted mitochondrial dynamics on the cellular biological behaviors of gastrointestinal cancer as well as its association with cancer progression. We aim to provide clues for elucidating the etiology and pathogenesis of gastrointestinal cancer from the perspective of mitochondrial homeostasis and disorder.

Characterizations of the multi-kingdom gut microbiota in Chinese patients with gouty arthritis.

OBJECTIVE: The gut microbial composition has been linked to metabolic and autoimmune diseases, including arthritis. However, there is a dearth of knowledge on the gut bacteriome, mycobiome, and virome in patients with gouty arthritis (GA). METHODS: We conducted a comprehensive analysis of the multi-kingdom gut microbiome of 26 GA patients and 28 healthy controls, using whole-metagenome shotgun sequencing of their stool samples. RESULTS: Profound alterations were observed in the gut bacteriome, mycobiome, and virome of GA patients. We identified 1,117 differentially abundant bacterial species, 23 fungal species, and 4,115 viral operational taxonomic units (vOTUs). GA-enriched bacteria included Escherichia coli_D GENOME144544, Bifidobacterium infantis GENOME095938, Blautia_A wexlerae GENOME096067, and Klebsiella pneumoniae GENOME147598, while control-enriched bacteria comprised Faecalibacterium prausnitzii_G GENOME147678, Agathobacter rectalis GENOME143712, and Bacteroides_A plebeius_A GENOME239725. GA-enriched fungi included opportunistic pathogens like Cryptococcus neoformans GCA_011057565, Candida parapsilosis GCA_000182765, and Malassezia spp., while control-enriched fungi featured several Hortaea werneckii subclades and Aspergillus fumigatus GCA_000002655. GA-enriched vOTUs mainly attributed to Siphoviridae, Myoviridae, Podoviridae, and Microviridae, whereas control-enriched vOTUs spanned 13 families, including Siphoviridae, Myoviridae, Podoviridae, Quimbyviridae, Phycodnaviridae, and crAss-like. A co-abundance network revealed intricate interactions among these multi-kingdom signatures, signifying their collective influence on the disease. Furthermore, these microbial signatures demonstrated the potential to effectively discriminate between patients and controls, highlighting their diagnostic utility. CONCLUSIONS: This study yields crucial insights into the characteristics of the GA microbiota that may inform future mechanistic and therapeutic investigations.

Expression characteristics and their functional role of IGFBP gene family in pan-cancer.

BACKGROUND: Insulin-like growth factor binding proteins (IGFBPs) are critical regulators of the biological activities of insulin-like growth factors. The IGFBP family plays diverse roles in different types of cancer, which we still lack comprehensive and pleiotropic understandings so far. METHODS: Multi-source and multi-dimensional data, extracted from The Cancer Genome Atlas (TCGA), Oncomine, Cancer Cell Line Encyclopedia (CCLE), and the Human Protein Atlas (HPA) was used for bioinformatics analysis by R language. Immunohistochemistry and qRT-PCR were performed to validate the results of the database analysis results. Bibliometrics and literature review were used for summarizing the research progress of IGFBPs in the field of tumor. RESULTS: The members of IGFBP gene family are differentially expressed in various cancer types. IGFBPs expression can affect prognosis of different cancers. The expression of IGFBPs expression is associated with multiple signal transduction pathways. The expression of IGFBPs is significantly correlated with tumor mutational burden, microsatellite instability, tumor stemness and tumor immune microenvironment. The qRT-PCR experiments verified the lower expression of IGFBP2 and IGFBP6 in gastric cancer and the lower expression of IGFBP6 in colorectal cancer. Immunohistochemistry validated a marked downregulation of IGFBP2 protein in gastric cancer tissues. The keywords co-occurrence analysis of IGFBP related publications in cancer showed relative research have been more concentrating on the potential of IGFBPs as tumor diagnostic and prognostic markers and developing cancer therapies. CONCLUSIONS: These findings provide frontier trend of IGFBPs related research and new clues for identifying novel therapeutic targets for various cancers.

Alteromonas salexigens sp. nov., isolated from coastal seawater.

A Gram-negative, aerobic, short rod-shaped bacterium, designated ASW11-19T, was isolated from a coastal seawater sample of the Yellow Sea, PR China. Strain ASW11-19T grew optimally at 37 °C, 3.0-5.0% (w/v) NaCl and pH 7.5. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain ASW11-19T belonged to the genus Alteromonas and most closely related to Alteromonas profundi 345S023T and Alteromonas fortis 1T (98.4%, both). The draft genome was 3.55 Mb with 3150 protein-coding genes, 18 contigs, and a DNA G+C content was 44.4%. The digital DNA-DNA hybridization and average nucleotide identity values were below the species-delineating thresholds. The major fatty acids were summed feature 3 (C16:1ω7c/C16:1ω6c), summed feature 8 (C18:1ω7c/C18:1ω6c), and C16:0. The sole respiratory quinone was ubiquinone 8. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phospholipid, and two unidentified lipids. Based on these genomic data, phenotypic and chemotaxonomic properties, strain ASW11-19T is considered to represent a novel species of the genus Alteromonas. The name Alteromonas salexigens sp.nov. is proposed for ASW11-19T (=MCCC 1K07239T=KCTC 92247T).

Chemical composition, health benefits, food processing effects and applications of Boletus: a review.

Boletus are wild edible mushrooms that are consumed worldwide for their appealing taste and abundant production. The aim of this review was to summarize and discuss the characteristics, effects of food processing and application of Boletus worldwide. A better understanding of Boletus nutritional profiles with high carbohydrate and protein, low fat and energy. Volatile (odor compounds) and nonvolatile (free amino acids, 5'-nucleotide and nucleoside, free sugars, organic acids and umami peptides) compounds together contribute to the flavor of Boletus. Varies bioactive substances such as phenols, flavonoids, polysaccharides, tocopherols, lectins and pigment, have also been identified in Boletus, showing wide spectrum biological activities, including antioxidant, antimicrobial, antitumor, immunomodulatory, hepatoprotective, antihyperglycemic and hypotensive activities. In addition, drying, storage and cooking influenced the physical, chemical, sensory properties and biological activities of Boletus. The application of Boletus was focused on food dietary supplement, enhancement of food nutrition and function, indicating Boletus can be further developed as a functional food for human health. Further research suggestions focus on the mechanism of bioactive substances, the novel umami peptides, and the digestion and absorption of Boletus.