A generalist vision-language foundation model for diverse biomedical tasks.

Traditional biomedical artificial intelligence (AI) models, designed for specific tasks or modalities, often exhibit limited flexibility in real-world deployment and struggle to utilize holistic information. Generalist AI holds the potential to address these limitations due to its versatility in interpreting different data types and generating tailored outputs for diverse needs. However, existing biomedical generalist AI solutions are typically heavyweight and closed source to researchers, practitioners and patients. Here, we describe BiomedGPT, the first open-source and lightweight vision-language foundation model, designed as a generalist capable of performing various biomedical tasks. BiomedGPT achieved state-of-the-art results in 16 out of 25 experiments while maintaining a computing-friendly model scale. We also conducted human evaluations to assess the capabilities of BiomedGPT in radiology visual question answering, report generation and summarization. BiomedGPT exhibits robust prediction ability with a low error rate of 3.8% in question answering, satisfactory performance with an error rate of 8.3% in writing complex radiology reports, and competitive summarization ability with a nearly equivalent preference score to human experts. Our method demonstrates that effective training with diverse data can lead to more practical biomedical AI for improving diagnosis and workflow efficiency.

Glucocorticoid therapy in pancreatic portal hypertension associated with autoimmune pancreatitis: A case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct. Some studies have reported that AIP can cause hemorrhage of gastric varices (GV) related to portal hypertension (PH). However, such cases are rare. In addition, the association of PH with AIP is unclear. At the same time, the efficacy and duration of glucocorticoid therapy is also controversial. CASE SUMMARY: In this case, we reported a case of GV in pancreatic PH associated with AIP. Enhanced abdominal computed tomography (CT) suggested splenic vein (SV) and superior mesenteric vein (SMV) thromboses. The patient received a long-term glucocorticoid therapy, that the initial dose of 40 mg is reduced weekly by 5 mg, and then reduced to 5 mg for long-term maintenance. CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized, pancreatic stiffness and swelling were ameliorated, and the GV almost completely disappeared. CONCLUSION: Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.

Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis.

Background: Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. A reliable estimate of the burden and clinical outcomes of pregnant women with HCV infection is crucial for HCV elimination. We aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV infection in pregnant women. Methods: We searched PubMed, EMBASE, Scopus, Web of Science from inception until March 1, 2024, for studies reporting on the prevalence, MTCT, complications of HCV infection, and treatment outcomes of DAA in pregnant women. Study quality was assessed using the Newcastle-Ottawa Scale. We performed subgroup analysis based on 9 variables to explore the source of heterogeneity in HCV prevalence. The PROSPERO registration number is CRD42024500023. Findings: From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95% CI: 2.0-3.2, I 2 = 100%) which increased in patients with intravenous drug use and HIV. Majority of the HCV cases in pregnant women (75%) are diagnosed through universal screening. The pooled MTCT rate was 9.0% (95% CI: 6.6-11.7, I 2 = 79%), which was higher with HIV co-infection (OR: 3.1, 95% CI: 2.1-4.6, I 2 = 10%), but was not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis, preterm delivery, and antepartum hemorrhage. Neonates of mothers with HCV had higher odds of being small for gestational age. The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 98.4%, with no serious adverse events reported. Interpretation: HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. The incidence of both maternal and neonatal complications is significantly higher in patients with HCV infection. Limited data suggest that DAA are safe in pregnant women with HCV infection. Funding: None.

A Retrospective Comparison of Diagnostic Tools of Bullous Pemphigoid for Elderly Patients.

BACKGROUND: Older patients who are predisposed to bullous pemphigoid (BP) may exhibit reluctance to undergo skin biopsy due to potential complications. OBJECTIVES: This study aimed to conduct a comparative evaluation among histology, direct immunofluorescence (DIF), and indirect immunofluorescence (IIF) to determine the optimal diagnostic tool in elderly patients. METHODS: A retrospective study was conducted on 841 patients suspected of having BP. All cases were initially classified as BP and non-BP in accordance with the diagnostic criteria. Student's t-test and chi-squared test examined differences between the 2 groups. We evaluated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio detected by the 3 tools. We stratified the analysis by age to compare the performance of the diagnostic tools and examined the risk factors associated with BP using logistic regression. RESULTS: Overall, histology exhibited the highest sensitivity (89.4%), while DIF demonstrated the highest specificity (67.1%). In the elderly, the IIF test exhibited the highest specificity (57.5%), the highest positive likelihood ratio (2.047), and the lowest negative likelihood ratio (0.226). Among patients taking Dipeptidyl Peptidase-4 (DPP-4) inhibitors, IIF demonstrated the highest positive likelihood ratio (3.194) and the second-lowest negative likelihood ratio (0.235). CONCLUSIONS: In cases that elderly patients suspected of having BP are reluctant to undergo skin biopsy, IIF demonstrates the optimal diagnostic method due to its highest positive likelihood ratio, the lowest negative likelihood ratio among the 3 diagnostic measures. Moreover, IIF is found to be a more effective tool for detecting BP in patients using DPP-4 inhibitors.

A preliminary study of T-2 toxin that cause liver injury in rats via the NF-kB and NLRP3-mediated pyroptosis pathway.

T-2 toxin is recognized as the most potent and prevalent secondary metabolite among monotrichous mycotoxins produced by Fusarium species. Multiple studies have substantiated the hepatotoxic effects of T-2 toxin. This study aimed to investigate whether NF-κB and NLRP3-mediated pyroptosis is involved in the underlying mechanism of T-2 toxin hepatotoxicity. We designed three groups of rat models, blank control; solvent control and T-2 toxin (0.2 mg/kg body weight/day), which were euthanized at week 8 after gavage staining of the toxin. Through HE staining and biochemical indicators associated with liver injury, we observed that T-2 toxin induced liver damage in rats. By Western blot analysis and qRT-PCR, we found that the expression levels of pyroptosis-related genes and proteins were significantly higher in the T-2 toxin group. In addition, we also found a significant increase in the expression of p-NF-κB protein, an upstream regulator of NLRP3. In conclusion, NF-κB and NLRP3-mediated pyroptosis may be involved in the mechanism of hepatotoxic action of T-2 toxin, which provides a new perspective.

Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers.

Changes in plasma and fecal metabolomes in colorectal cancer (CRC) progression (normal-adenoma-CRC) remain unclear. Here, plasma and fecal samples were collected from four independent cohorts of 1,251 individuals (422 CRC, 399 colorectal adenoma [CRA], and 430 normal controls [NC]). By metabolomic profiling, signature plasma and fecal metabolites with consistent shift across NC, CRA, and CRC are identified, including CRC-enriched oleic acid and CRC-depleted allocholic acid. Oleic acid exhibits pro-tumorigenic effects in CRC cells, patient-derived organoids, and two murine CRC models, whereas allocholic acid has opposing effects. By integrative analysis, we found that oleic acid or allocholic acid directly binds to α-enolase or farnesoid X receptor-1 in CRC cells, respectively, to modulate cancer-associated pathways. Clinically, we establish a panel of 17 plasma metabolites that accurately diagnoses CRC in a discovery and three validation cohorts (AUC = 0.848-0.987). Overall, we characterize metabolite signatures, mechanistic significance, and diagnostic potential of plasma and fecal metabolomes in CRC.

Highly efficient recovery of phosphate and fluoride from phosphogypsum leachate: Selective precipitation and adsorption.

Phosphogypsum, a typical by-product in the phosphorus chemical industry, could generate a large amount of leachate containing phosphate and fluoride in the process of rainfall and long-term stacking, which not only causes serious environmental pollution, but also leads to a waste of resources. In this study, a united treatment of calcium hydroxide precipitation and lanthanum zeolite (La-ZFA) adsorption was proposed to achieve the recovery of phosphate and fluoride from phosphogypsum leachate. In phosphogypsum, most phosphorus could be leached except P in the residual occurrence form, while for fluoride, only water-soluble F could be effectively leached. The optimum leaching amounts of phosphate and fluoride were 22.59 and 4.64 mg/g, respectively, at liquid-solid ratio of 400:1, leaching time of 120 min, pH of 6.0, particle size of >200 mesh (<0.075 mm), and leaching temperature of 25°C. Using Ca(OH)2 as the precipitant, the phosphate could be precipitated selectively from phosphogypsum leachate by controlling pH and time, and the concentrations of it decreased significantly to 0.29 mg/L at pH 10.0, with a removal efficiency of 99.48%. XRD, SEM and Visual MINTEQ software analysis proved that the main component of the precipitate was hydroxyapatite (Ca5(PO4)3(OH)). After P precipitation, a series of sorbents for fluoride were investigated, and La-ZFA sorbent was chosen and utilized to recover the fluoride from the leachate through a cyclic fixed-bed column. The efficiency of La-ZFA was basically not affected by the high concentration sulfate, and it can selectively adsorb fluoride from phosphogypsum leachate, leading to a final fluoride concentration of 0.29 mg/L in the effluent. The characterization demonstrated that fluoride might be adsorbed onto the La-ZFA via ligand exchange with hydroxy groups. The proposed method in this study is expected to sequentially recover phosphate and fluorine from the leachate of phosphogypsum, and it has great guiding significance for resource utilization and management of phosphogypsum.

Discovering New Metallo-Deubiquitinase CSN5 Inhibitors by a Non-Catalytic Activity Assay Platform.

COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, CFP-1, that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5. By using this platform, we identified 2-aminothiazole-4-carboxylic acids as new CSN5 inhibitors, which inhibited CSN5 but slightly downregulated PD-L1 in cancer cells. Furthermore, through the integration of deep learning-enabled virtual screening, we discovered that shikonins are nanomolar CSN5 inhibitors, which can upregulate PD-L1 in HCT116 cells. The binding modes of these structurally distinct inhibitors with CSN5 were explored by using microsecond-scale molecular dynamics simulations and tryptophan quenching assays.

Adenosine-to-Inosine RNA editing in cancer: molecular mechanisms and downstream targets.

Adenosine-to-Inosine (A-to-I), one of the most prevalent RNA modifications, has recently garnered significant attention. The A-to-I modification actively contributes to biological and pathological processes by affecting the structure and function of various RNA molecules, including double stranded RNA, transfer RNA, microRNA, and viral RNA. Increasing evidence suggests that A-to-I plays a crucial role in the development of human disease, particularly in cancer, and aberrant A-to-I levels are closely associated with tumorigenesis and progression through regulation of the expression of multiple oncogenes and tumor suppressor genes. Currently, the underlying molecular mechanisms of A-to-I modification in cancer are not comprehensively understood. Here, we review the latest advances regarding the A-to-I editing pathways implicated in cancer, describing their biological functions and their connections to the disease.

The impact of fangxian huangjiu on the fermentation quality and microbial community dynamics of cigar wrapper leaves.

Introduction: Cigar wrapper leaves (CWLs) plays a crucial role in reflecting cigar overall quality. Originating from the Qinba region of China, Fangxian Huangjiu (FHJ) is distinctive from other varieties of Huangjiu. Methods: To investigate the effects of FHJ on enhancing the aroma and quality of CWLs, as well as the consequent alterations in microbial communities, Gas Chromatography-Mass Spectrometry (GC-MS) coupled with Odor Active Value (OAV) analysis was utilized to evaluate the volatile aroma components of CWLs. Results and Discussion: The results indicated that the total amount of aroma compounds in CWLs reached 3,086.88 ug/g, increasing of 270.50% and 166.31% compared to the unfermented and naturally fermented groups, respectively. Among them, ß-ionone and 4,7,9-megastigmatrien-3-one from the FHJ fermentation group significantly influenced the sensory characteristics of CWLs. Metagenomic results demonstrated that FHJ fermentation enriched the abundance of both shared and unique microbial species in CWLs, while also increased the diversity of differential microbial species. Addition of FHJ effectively altered the microbial community structure of CWLs from a dominance of Staphylococcus to a prevalence of Staphylococcus, Aspergillus, Pseudomonas, and Acinetobacter. The interactions among these diverse microorganisms collectively contribute to the enhancement of the intrinsic quality of CWLs. This paper provides a theoretical basis for improving the quality of CWLs by FHJ and exploring the changes of microbial community structure and interaction between CWLs and FHJ.

Insights from Ab Initio Molecular Dynamics on the Interface Reaction between Electrolyte and Li2MnO3 Cathode during the Charging Process.

The complex interface reactions are crucial to the performance of the Li2MnO3 cathode material. Here, the interface reactions between the liquid electrolyte and the typical surfaces of Li2MnO3 during the charging process are systematically investigated by ab initio molecular dynamics (AIMD) simulation and first-principles calculation. The results indicate that these interface reactions lead to the formation of hydroxide radicals, oxygen, carbon dioxide, carbonate radicals, and other products, which are consistent with the experimental findings. These processes primarily result from the conversion of the stable closed-shell O2- into reactive oxygen ions by electron loss. All surfaces exhibit some degree of layered- and spinel-like phase transitions during the AIMD simulations, consistent with the experiment. This is mainly attributed to the decrease in the Mn-O bond strength and the increase in the Li/O ion vacancy concentration. This study offers valuable theoretical insights into the interface reaction between lithium-rich cathode materials and liquid electrolytes.

Thin-Film Transistor Digital Microfluidics Circuit Design with Capacitance-Based Droplet Sensing.

With the continuous expansion of pixel arrays in digital microfluidics (DMF) chips, precise droplet control has emerged as a critical issue requiring detailed consideration. This paper proposes a novel capacitance-based droplet sensing system for thin-film transistor DMF. The proposed circuit features a distinctive inner and outer dual-pixel electrode structure, integrating droplet driving and sensing functionalities. Discharge occurs exclusively at the inner electrode during droplet sensing, effectively addressing droplet perturbation in existing sensing circuits. The circuit employs a novel fan-shaped structure of thin-film transistors. Simulation results show that it can provide a 48 V pixel voltage and demonstrate a sensing voltage difference of over 10 V between deionized water and silicone oil, illustrating its proficiency in droplet driving and accurate sensing. The stability of threshold voltage drift and temperature was also verified for the circuit. The design is tailored for integration into active matrix electrowetting-on-dielectric (AM-EWOD) chips, offering a novel approach to achieve precise closed-loop control of droplets.

Experimental and Density Functional Theory Simulation Research on PdO-SnO2 Nanosheet Ethanol Gas Sensors.

Pure SnO2 and 1 at.% PdO-SnO2 materials were prepared using a simple hydrothermal method. The micromorphology and element valence state of the material were characterized using XRD, SEM, TEM, and XPS methods. The SEM results showed that the prepared material had a two-dimensional nanosheet morphology, and the formation of PdO and SnO2 heterostructures was validated through TEM. Due to the influence of the heterojunction, in the XPS test, the energy spectrum peaks of Sn and O in PdO-SnO2 were shifted by 0.2 eV compared with SnO2. The PdO-SnO2 sensor showed improved ethanol sensing performance compared to the pure SnO2 sensor, since it benefited from the large specific surface area of the nanosheet structure, the modulation effect of the PdO-SnO2 heterojunction on resistance, and the catalyst effect of PdO on the adsorption of oxygen. A DFT calculation study of the ethanol adsorption characteristics of the PdO-SnO2 surface was conducted to provide a detailed explanation of the gas-sensing mechanism. PdO was found to improve the reducibility of ethanol, enhance the adsorption of ethanol's methyl group, and increase the number of adsorption sites. A synergistic effect based on the continuous adsorption sites was also deduced.

Association of triglyceride-glucose index with helicobacter pylori infection and mortality among the US population.

BACKGROUND: Limited research has explored the potential association between the Triglyceride-Glucose (TyG) and mortality, especially in individuals with Helicobacter pylori (H. pylori) infection. This study seeks to investigate the correlation between the TyG index and H. pylori infection and investigate whether the associations between the TyG index exposure and all-cause mortality are mediated by H. pylori infection. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 2,187 participants. Both univariable and multivariable-adjusted logistic regression analyses were employed to examine the relationship between H. pylori infection and relevant covariates. To assess the association between TyG index, and all-cause mortality in individuals with or without H. pylori infection, Cox regression analysis, and restricted regression cubic spline analysis were implemented. RESULTS: A significant positive correlation was observed between the TyG index and an elevated risk of H. pylori infection [OR 1.157, 95% CI (1.383 ~ 1.664)]. This correlation persisted even after adjusting for confounding factors [OR 1.189, 95% CI (1.003, 1.411), P < 0.05]. Furthermore, in patients with positive H. pylori infection, a noteworthy nonlinear correlation between the TyG index and all-cause mortality was identified (P = 0.0361). With an increase in the TyG index, all-cause mortality exhibited a corresponding rise, particularly following adjustment for all potential confounding factors. Conversely, in patients with negative H. pylori infection, no significant association was observed between the TyG index and all-cause mortality after adjusting for potential confounding factors. CONCLUSION: A higher TyG index was linked to increased H. pylori infection risks. Participants in the higher quantile group of the TyG index are positively associated with higher all-cause mortality compared to the higher quantile group of the TyG index in H. pylori-positive participants instead of H. pylori-negative participants.

Association of frailty index with all-cause and cardiovascular mortality with different diabetic status: NHANES 1999-2018.

AIMS: The relationship between frailty and mortality among individuals with varying diabetic statuses represents a burgeoning area of concern and scholarly interest within the medical community. However, there are limited studies that explore the relationship between frailty and mortality, as well as cause-specific mortality among individuals with non-diabetes, prediabetes, and diabetes patients. Hence, this study aims to investigate the relationship between the frailty statues and all-cause mortality, as well as cause-specific mortality in individuals with varying diabetic statuses using the data in the NHANES database. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 57, 098 participants. Both univariable and multivariable-adjusted logistic regression analyses, as well as Cox regression analysis were employed to examine the relationship between frailty index (FI) and mortality. RESULTS: This study, found a significant positive correlation between the frailty and the increased risk of all-cause mortality non-diabetic [OR 4.277, 95%CI (3.982, 4.594), P < 0.001], prediabetic [OR 2.312, 95%CI (2.133, 2.506), P < 0.001], and diabetic patients [OR 3.947, 95%CI (3.378, 4.611), P < 0.001]. This correlation still existed even after adjusting for confounding factors including age, sex, BMI, poverty, fasting insulin, education, smoke, alcohol drink, waist, hypertension, hyperlipidemia, fasting glucose, HbA1c, eGFR, creatinine and total bilirubin. Our result also suggested a significant positive correlation between the frailty index and the increased risk of CVD mortality among non-diabetic [OR 3.095, 95%CI (2.858, 3.352), P < 0.001] and prediabetic [OR 5.985, 95%CI (5.188, 6.904), P < 0.001] individuals. However, in patients with diabetes, the correlation between frailty and CVD mortality lost significance after adjusting for possible confounding factors [OR 1.139, 95%CI (0.794, 1.634), P > 0.05]. CONCLUSION: A nonlinear relationship has been identified between the FI and all-cause mortality, as well as CVD mortality in non-diabetic and pre-diabetic population. In diabetic patients, there was a significant positive correlation between the frailty and the increased risk of all-cause mortality, but not with CVD mortality. Renal function and liver function might potentially acted as an intermediary factor that elevated the risk of CVD mortality in frail patients with diabetes.

MDSCs promote pathological angiogenesis in ocular neovascular disease.

BACKGROUND: Ocular neovascular diseases, which contribute significantly to vision loss, lack effective preventive treatments. Recent studies have highlighted the significant involvement of immune cells in neovascular retinopathy. Myeloid-derived suppressor cells (MDSCs) promote the development of neovascularization, but it is unknown whether they participate in pathological neovascularization and whether they are expected to be a therapeutic target. METHOD: We investigated the role of MDSCs in promoting pathological angiogenesis using an oxygen-induced retinopathy (OIR) model, employing flow cytometry, immunofluorescence, and smart-seq analysis. Then, we evaluated the proportion of MDSCs in patient blood samples using flow cytometry. Additionally, we assessed the effect of MDSC depletion using an anti-Gr-1 monoclonal antibody on retinal vasculopathy and alterations in retinal microglia. RESULTS: In the OIR model, an elevated ratio of MDSCs was observed in both blood and retinal tissue during phase II (Neovascularization). The depletion of MDSCs resulted in reduced retinal neovascularization and vaso-obliteration, along with a decrease in microglia within the neovascularization area. Furthermore, analysis of gene transcripts associated with MDSCs indicated activation of vascular endothelial growth factor (VEGF) regulation and inflammation. Importantly, infants with ROP exhibited a higher proportion of MDSCs in their blood samples. CONCLUSION: Our results suggested that excessive MDSCs represent an unrecognized feature of ocular neovascular diseases and be responsible for the retinal vascular inflammation and angiogenesis, providing opportunities for new therapeutic approaches to ocular neovascular disease.

[Medicinal plant biodiversity in Jilin province based on big data of the fourth national survey of traditional Chinese medicine resources].

Using Origin2022Pro, PAST4.09, GraphPad, and ArcGIS, this study analyzed the big data of the fourth national survey of traditional Chinese medicine resources in Jilin province from five dimensions: differences in resource quantity, taxonomic group, family, and genus, regional distribution, and spatiotemporal distribution, aiming to fully elucidate the biodiversity of medicinal plants in Jilin province. The results indicated that 2 241 species of medicinal plants existed in Jilin province, belonging to 881 genera of 243 families, with 20 dominant families and 3 dominant genera. There were 1 901 species of medicinal plants(belonging to 778 genera of 227 families) in the eastern mountainous region, 1 503 species(belonging to 690 genera of 225 families) in the mid-mountainous areas of the central mountainous region, and 811 species(belonging to 436 genera of 136 families) in the western plain region. The biodiversity of medicinal plants in Jilin province was high and presented a trend of high in the east and low in the west. The medicinal plant resources were mainly concentrated in the eastern mountainous region, and the number of medicinal plant groups had significant diffe-rences between regions, following the trend of western region > central region > eastern region. The species richness was in the order of eastern region > western region > central region. The species diversity structure in the central region was similar to that in the eastern and western regions, while it was significantly different between the western and eastern regions. Compared with the third national survey of traditional Chinese medicine resources, the fourth survey showed an increase of 1 417 species, a decrease of 580 species, and 824 common species, indicating significant changes in the biodiversity of medicinal plants in Jilin province. The reasons for these changes need to be further explored. This article elucidates the background and biodiversity changes of medicinal plant resources in Jilin province, laying a foundation for the protection, utilization, and industrial development of traditional Chinese medicine resources in Jilin province.

Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation, causing structural damage and lung failure. Stem cell therapy and mesenchymal stem cells-extracellular vesicles (MSC-EVs) offer new hope for PF treatment. AIM: To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis, oxidative stress, and immune inflammation in A549 cells and bleomycin (BLM)-induced mouse model. METHODS: The effect of MSC-EVs on A549 cells was assessed by fibrosis markers [collagen I and α-smooth muscle actin (α-SMA), oxidative stress regulators [nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and inflammatory regulators [nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-1ß, and IL-2]. Similarly, they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection. MSC-EVs ion PF mice were detected by pathological staining and western blot. Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice. RESULTS: Transforming growth factor (TGF)-ß1 enhanced fibrosis in A549 cells, significantly increasing collagen I and α-SMA levels. Notably, treatment with MSC-EVs demonstrated a remarkable alleviation of these effects. Similarly, the expression of oxidative stress regulators, such as Nrf2 and HO-1, along with inflammatory regulators, including NF-κB p65 and IL-1ß, were mitigated by MSC-EV treatment. Furthermore, in a parallel manner, MSC-EVs exhibited a downregulatory impact on collagen deposition, oxidative stress injuries, and inflammatory-related cytokines in the lungs of mice with PF. Additionally, the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response. The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes, oxidative stress, and inflammatory responses associated with PF. CONCLUSION: MSC-EVs could ameliorate fibrosis in vitro and in vivo by downregulating collagen deposition, oxidative stress, and immune-inflammatory responses.

Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of liver injuries, ranging from hepatic steatosis, metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and the gut microbial community. Host genetics influence the composition of gut microbiome, while the gut microbiota and their derived metabolites can induce host epigenetic modifications to affect the development of MASLD. The exploration of the intricate relationship between the gut microbiome and the genetic/epigenetic makeup of the host is anticipated to yield promising avenues for therapeutic interventions targeting MASLD and its associated conditions. In this review, we summarise the effects of gut microbiome, host genetics and epigenetic alterations in MASLD and MASLD-HCC. We further discuss research findings demonstrating the bidirectional impacts between gut microbiome and host genetics/epigenetics, emphasising the significance of this interconnection in MASLD prevention and treatment.

Attribute Prototype-guided Iterative Scene Graph for Explainable Radiology Report Generation.

The potential of automated radiology report generation in alleviating the time-consuming tasks of radiologists is increasingly being recognized in medical practice. Existing report generation methods have evolved from using image-level features to the latest approach of utilizing anatomical regions, significantly enhancing interpretability. However, directly and simplistically using region features for report generation compromises the capability of relation reasoning and overlooks the common attributes potentially shared across regions. To address these limitations, we propose a novel region-based Attribute Prototype-guided Iterative Scene Graph generation framework (AP-ISG) for report generation, utilizing scene graph generation as an auxiliary task to further enhance interpretability and relational reasoning capability. The core components of AP-ISG are the Iterative Scene Graph Generation (ISGG) module and the Attribute Prototype-guided Learning (APL) module. Specifically, ISSG employs an autoregressive scheme for structural edge reasoning and a contextualization mechanism for relational reasoning. APL enhances intra-prototype matching and reduces inter-prototype semantic overlap in the visual space to fully model the potential attribute commonalities among regions. Extensive experiments on the MIMIC-CXR with Chest ImaGenome datasets demonstrate the superiority of AP-ISG across multiple metrics.