Development and validation of a model for early survival prediction following liver transplantation based on donor and recipient characteristics.

BACKGROUND: Circulating cytokine levels not only correlate with the progression of liver disease but also serve as indicators for the infection status of the body. Growing evidence points to the connection between donor cytokines and graft function following transplantation. This study set out to explore the clinical significance of donor cytokines in predicting liver transplantation prognosis. METHODS: Data from 172 deceased donor liver transplantations conducted between 2017 and 2022, with available donor serum cytokine information, were collected. The subjects were randomly divided into estimation (n = 120) and validation (n = 52) groups to establish and validate the model. The newly developed SA10 score was compared against established models EAD, MEAF, L-GrAFT7, and L-GrAFT10. RESULTS: Donor IL-10, along with donor age and recipient AST peak value within the first 7 days post-operation, was identified as an independent factor associated with recipient survival and was incorporated into the SA10 score. SA10 exhibited robust predictive capability, particularly for 1-month survival (AUC = 0.90, 95% CI = 0.84-0.96), outperforming EAD (AUC = 0.75, 95% CI = 0.60-0.90, p = 0.04) and L-GrAFT7 (AUC = 0.65, 95% CI = 0.49-0.81, p < 0.01). Comparable performance was observed between SA10, MEAF, and L-GrAFT10. CONCLUSION: Donor IL-10 independently influences recipient survival, with the SA10 score demonstrating comparable and even superior predictive ability compared to existing models.

Serum dsDNA is environmentally contingent.

Psoriasis is a recurrent autoimmune disease characterized by seasonal and latitudinal variations. Double-stranded DNA (dsDNA) is a crucial component of nucleic acids and nucleosomes that provoke innate immune responses. Given the potential influence of climate on immunity and the development of autoimmune diseases, a comprehensive quantitative analysis of dsDNA levels in the population is warranted. In this case-control study conducted from 2016 to 2020, 10,110 psoriasis patients and matched controls from 12 regions in China were included. This study examined variations in serum dsDNA levels based on season and latitude. The results revealed significant associations between geographical location, climatic conditions, and season with serum dsDNA concentration. Individuals residing in Northern China exhibited significantly higher serum dsDNA levels compared to those in the South (1.00 vs. 0.96 ng/ml), and those in medium latitude regions had higher levels than their counterparts in areas with extreme latitudes (0.98 vs. 0.96 ng/ml). Furthermore, individuals in regions with low to medium ultraviolet exposure demonstrated higher serum dsDNA concentrations than those in areas with high ultraviolet levels (1.03 vs. 0.93 ng/ml), and individuals in winter showed higher levels than those in summer (1.03 vs. 0.92 ng/ml). Factors such as sex, UV index, humidity, and sunshine duration were inversely related to serum dsDNA levels, while age and daylight hours showed a positive association. These findings suggest that meteorological and climatic factors play a role in influencing serum dsDNA levels.

Spinal Cord Infarction During Extracorporeal Membrane Oxygenation：A Case Series and Review of the Literature.

Background: Little is known about extracorporeal membrane oxygenation (ECMO)-related spinal cord infarction (SCI), and reports regarding this rare and catastrophic complication are rare. Here, we report two cases of ECMO-related SCI that occurred between April and December 2023. Data were collected from patients' medical records, with SCI as the endpoint. We reviewed previously published reports by searching PubMed and summarizing the findings. Case summary: One female patient presenting with multiple traumas required oxygenation support through veno-venous ECMO (VV ECMO) due to pulmonary hemorrhage, while one male patient required circulatory support via veno-arterial ECMO (VA ECMO) concurrently with an intra-aortic balloon pump due to cardiac arrest. Neither patient had preexisting neurological deficits; however, upon weaning from ECMO, they presented with severe neurological deficits of uncertain etiology, subsequently confirmed as SCI using magnetic resonance imaging. Conclusion: ECMO-related SCI remains elusive and intricate, and this is the first report of adult VV ECMO-related SCI.

Combining recognition, conflict-monitoring and feedback-related ERPs to detect concealed autobiographical information.

This study examined the neural signatures associated with conflict-monitoring, recognition and feedback processing in a feedback Concealed Information Test (fCIT), and also examined whether all the ERPs can be used to detect concealed autobiographical information. Participants were randomly assigned to one of two groups (guilty or innocent) and then tested in the fCIT while undergoing electroencephalograms (EEGs). The results showed that the probe (participants' name) elicited a more negative N200, and a more positive recognition P300 than irrelevants among guilty participants. Additionally, feedback following the probe elicited a larger feedback P300 than feedback following irrelevants. Further, we found that three indicators, including the conflict-monitoring N200, recognition P300, and feedback P300, could significantly discriminate between guilty and innocent participants, whereas the FRN could not. Combining them is highly effective in discriminating between guilty and innocent participants (AUC = 0.91). These findings not only shed light on the neural processing of the fCIT but also suggest the potential of using the fCIT to detect concealed autobiographical information.

B-cell depletion limits HTLV-1-infected T-cell expansion and ameliorate HTLV-1-associated myelopathy.

OBJECTIVE: Human T-cell leukemia virus type 1-associated myelopathy (HAM) is a chronic, progressive, inflammatory disease with unclear pathogenesis and no effective treatments. We aimed to investigate a novel mechanistic theory and treat HAM patients with rituximab, which can deplete CD20+ B lymphocytes in circulation. METHODS: Single-cell RNA sequencing (scRNA-seq) data was analyzed to identify HTLV-1-associated B cells and their effect on T cells. An observational analysis of our HAM cohort was conducted to elucidate changes in the immunological microenvironment of these patients. Peripheral blood mononuclear cells (PBMC) from HAM patients were isolated to explore the efficacy of B cell depletion in vitro. To assess the effect of B-cell depletion on HAM patients, eligible participants in our cohort received rituximab therapy (NCT04004819). RESULTS: ScRNA-seq results suggest a significant effect of HTLV-1-associated B cells on T cells. Additionally, HTLV-1 was found to infect B cells and depletion of B cells inhibited the proliferation of T cells. Number of B cells in HAM patients had positive correlation with the proviral load and infected cell counts. Depletion of B cells led to a reduction in HTLV-1 proviral load in vitro. Furthermore, in clinical trial, 14 HAM patients were enrolled. Three patients (21.4%) who received rituximab failed to achieve remission, compared to 24 (85.7%) patients received any other therapy that failed to achieve remission. With a low level of circulating B cells, the proportion of Ki67-positive cells in CD4+ T cells fell. INTERPRETATION: This study provided evidence that depleting B-lymphocytes is an innovative strategy for treating patients with HAM and broadens the understanding of the role of B cells in infectious immunity.

Simulation of red mud/phosphogypsum-based artificial soil engineering applications in vegetation restoration and ecological reconstruction.

Red mud and phosphogypsum are two of the most typical bulk industrial solid wastes. How they can be efficiently recycled as resources on a large scale and at low costs has always been a global issue that urgently needs to be solved. By constructing a small-scale test site and preparing two types of artificial soils using red mud and phosphogypsum, this study simulated their engineering applications in vegetation restoration and ecological reconstruction. According to the results of this study, the artificial soils contained a series of major elements (e.g. O, Si, Al, Fe, Ca, Na, K, and Mg) similar to those in common natural soil, and preliminarily possessed basic physicochemical properties (pH, moisture, organic matter, and cation exchange capacity), main nutrient conditions (nitrogen, phosphorus and potassium), and biochemical characteristics that could meet the demands of plant growth. A total of 18 different types of adaptable plants (e.g. wood, herbs, flowers, succulents, etc) grew in the test sites, indicating that the artificial soils could be used for vegetation greening and landscaping. The preliminary formation of microbial (fungal and bacterial) community diversity and the gradually enriched arthropod community diversity reflected the constantly improving quality of the artificial soils, suggesting that they could be used for the gradual construction of artificial soil micro-ecosystems. Overall, the artificial soils provided a feasible solution for the large-scale, low-cost, and highly efficient synergistic disposal of red mud and phosphogypsum, with enormous potential for future engineering applications. They are expected to be used for vegetation greening, landscaping, and ecological environment improvement in tailings, collapse, and soil-deficient areas, as well as along municipal roads.

Polarization and wavelength routers based on diffractive neural network.

In the field of information processing, all-optical routers are significant for achieving high-speed, high-capacity signal processing and transmission. In this study, we developed three types of structurally simple and flexible routers using the deep diffractive neural network (D2NN), capable of routing incident light based on wavelength and polarization. First, we implemented a polarization router for routing two orthogonally polarized light beams. The second type is the wavelength router that can route light with wavelengths of 1550, 1300, and 1100 nm, demonstrating outstanding performance with insertion loss as low as 0.013 dB and an extinction ratio of up to 18.96 dB, while also maintaining excellent polarization preservation. The final router is the polarization-wavelength composite router, capable of routing six types of input light formed by pairwise combinations of three wavelengths (1550, 1300, and 1100 nm) and two orthogonal linearly polarized lights, thereby enhancing the information processing capability of the device. These devices feature compact structures, maintaining high contrast while exhibiting low loss and passive characteristics, making them suitable for integration into future optical components. This study introduces new avenues and methodologies to enhance performance and broaden the applications of future optical information processing systems.

[Prediction of quality markers of Angong Niuhuang Pills based on LC-MS and pull-down with SPR chips].

Elucidating the quality markers(Q-markers) of traditional Chinese medicines is essential for understanding the mechanisms of action and promoting the rational use of traditional Chinese medicines as well as for developing traditional Chinese medicine-derived drugs. Studies have shown that surface plasmon resonance(SPR) is promising in this field. This study proposed a method based on pull-down with SPR chips to predict the Q-markers of Angong Niuhuang pills(AGNHP). Firstly, 71 main chemical components of AGNHP were analyzed by UPLC-Q-TOF-MS, and then network pharmacology was employed to predict the potential targets of AGNHP against stroke. Secondly, the STAT3 protein chip was constructed, and the extract of AGNHP was recovered by pull-down of the SPR system for STAT3 ligand. The potential active ingredients were collected, enriched, and identified as coptisine, palmatine, epiberberine, berberine, worenine, demethyleneberberine, jatrorrhizine, tetrahydrocoptisine, baicalein, and baicalin methyl ester. Next, the affinity constants of the 10 active ingredients were determined as 44.7, 44, 58.1, 51.3, 39.7, 32.1, 49.2, 69.1, 19.7, and 24.9 µmol·L~(-1), respectively. The molecular docking results showed that the 10 compounds could compete for binding with STAT3. This is the first report that SPR combined with UPLC-Q-TOF-MS is reliable and feasible for determining the active ingredients of AGNHP at the molecular level from complex systems. STAT3 could be used as a potential target for the biological quality evaluation of AGNHP.

Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts.

BACKGROUND/AIMS: The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. METHODS: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. RESULTS: FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). CONCLUSION: FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.

Decoding the genetic landscape of allergic rhinitis: a comprehensive network analysis revealing key genes and potential therapeutic targets.

BACKGROUND: Allergic Rhinitis (AR), an inflammatory affliction impacting the upper respiratory tract, has been registering a substantial surge in incidence across the globe. METHODS: We embarked on examination of differentially expressed genes (DEGs) and the Weighted Gene Co-Expression Network Analysis (WGCNA). With this armory of genes identified, we engaged the tools of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Our study continued with the establishment of a protein-protein interaction (PPI) network and the application of LASSO regression. Finally, we leveraged a docking model to elucidate potential drug-gene interactions involving these key genes. RESULTS: Through WGCNA and different express genes screening, PPI network was performed, identifying top 20 key genes, including CD44, CD69, CD274. LASSO regression identified three independent factors, STARD5, CST1, and CHAC1, that were significantly associated with AR. A predictive model was developed with an AUC value over 0.75. Also, 105 potential therapeutic agents were discovered, including Fluorouracil, Cyclophosphamide, Doxorubicin, and Hydrocortisone, offering promising therapeutic strategies for AR. CONCLUSION: By fuzing DEGs with key genes derived from WGCNA, this study has illuminated a comprehensive network of gene interactions involved in the pathogenesis of AR, paving the way for future biomarker and therapeutic target discovery in AR.

Association Between the Serum Copper Levels and Environmental Tobacco Exposure on the Risk of Overweight and Obesity in Children: a Study Based on the National Health and Nutrition Examination Survey.

This study was to assess the individual effects of serum copper levels and environmental tobacco exposure and their joint effects on the risk of overweight and obesity among children and adolescents of 6 to 19 year olds. We analyzed cross-sectional data from 1849 children and adolescents participating in the National Health and Nutrition Examination Survey (NHANES) collected between 2011 and 2016. Environmental tobacco exposure was determined by cotinine levels. The serum copper level was divided into < median group and ≥ median groups according to the median of 109.81 µg/dL. The outcome was overweight/obese in children and adolescents. Weighted multinomial multivariate logistic regression models were used to assess the association of serum copper and cotinine levels, with the risk of overweight/obesity, and the joint effects on the risk of overweight and obesity among children and adolescents. The subgroup analyses based on age, gender, and household smoking status were conducted. Among 1849 children and adolescents, 332 children and adolescents had overweight BMI, and 450 children and adolescents had obese BMI. Higher serum copper levels were associated with the risk of obesity in children and adolescents (odds ratio (OR) 2.96, 95% confidence interval (CI) 1.39-6.31, P = 0.006). A positive association between increasing levels of cotinine levels and the risk of overweight (OR 1.83, 95% CI 1.16-2.87, P = 0.010) and obesity (OR 2.56, 95% CI 1.03-6.40, P = 0.044) in children and adolescents was observed. A remarkable association was found between higher serum copper in combination with higher cotinine levels and the risk of overweight (OR 3.23, 95% CI 1.19-8.83, P = 0.023) and obesity (OR 8.76, 95% CI 2.14-35.87, P = 0.003) in children and adolescents. The subgroup analyses revealed positive associations between high serum copper levels in combination with high cotinine levels and overweight and obesity in children and adolescents aged ≥ 12 years, of female sex, and without smoking family members. There may exist a joint effect of serum copper levels and environmental tobacco exposure on overweight/obesity among children and adolescents. These findings offer an insight that early weight control and reduction of tobacco exposure and the detection of serum copper levels may be important in reducing the risk of obesity in children.

Asymmetric Synthesis of the epi-Vinigrol Tricyclic Core Enabled by a Wolff Rearrangement Strategy and Formal Total Synthesis of (-)-Vinigrol.

A new approach to construct the tricyclic framework of the diterpenoid vinigrol is described. The challenging 1,5-butanodecahydronaphthalene core was established efficiently and diastereoselectively through a combination of type II [5 + 2] cycloaddition and Wolff rearrangement. In addition, a formal total synthesis of (-)-vinigrol was achieved in 12 steps, in which Baran's intermediate was efficiently produced from a known compound by a two-step sequence involving a stereoselective α-hydroxylation and a diastereoselective α-ketol rearrangement.

USP14 inhibition promotes recovery by protecting BBB integrity and attenuating neuroinflammation in MCAO mice.

AIM: Blood-brain barrier (BBB) dysfunction is one of the hallmarks of ischemic stroke. USP14 has been reported to play a detrimental role in ischemic brain injury. However, the role of USP14 in BBB dysfunction after ischemic stroke is unclear. METHODS: In this study, we tested the role of USP14 in disrupting BBB integrity after ischemic stroke. The USP14-specific inhibitor IU1 was injected into middle cerebral artery occlusion (MCAO) mice once a day. The Evans blue (EB) assay and IgG staining were used to assess BBB leakage 3 days after MCAO. FITC-detran test was slected to examine the BBB leakage in vitro. Behavior tests were conducted to evaluate recovery from ischemic stroke. RESULTS: Middle cerebral artery occlusion increased endothelial cell USP14 expression in the brain. Furthermore, the EB assay and IgG staining showed that USP14 inhibition through IU1 injection protected against BBB leakage after MCAO. Analysis of protein expression revealed a reduction in the inflammatory response and chemokine release after IU1 treatment. In addition, IU1 treatment was found to rescue neuronal loss resulting from ischemic stroke. Behavior tests showed a positive effect of IU1 in attenuating brain injury and improving motor function recovery. In vitro study showed that IU1 treatment could alleviate endothelial cell leakage induced by OGD in cultured bend.3 cells through modulating ZO-1 expression. CONCLUSIONS: Our results demonstrate a role for USP14 in disrupting the integrity of the BBB and promoting neuroinflammation after MCAO.

An outbreak of Amanita exitialis poisoning.

BACKGROUND: The mushroom Amanita exitialis is reported to cause acute liver injury. It is found in Southern China, and has been previously associated with a high incidence of mortality. METHODS: We described a series of 10 patients with Amanita exitialis poisoning admitted to The Second Affiliated Hospital of the Chinese University of Hong Kong (Shenzhen) in April 2022. Patient demographics, clinical features, laboratory results, therapeutic interventions, and outcome data were collected. RESULTS: Among the 10 patients, 9 survived, while 1 died. Gastrointestinal symptoms were the first to appear (average latency period, 11 ± 4.2 h). Diarrhea was the most common clinical symptom (average duration, 4.4 days). Abdominal distention was an important sign, especially in severely-ill patients. Thrombocytopenia occurred on day 2 after mushroom ingestion and persisted for 3-4 days. Alanine aminotransferase and total bilirubin peaked on days 2-3. CONCLUSION: Amanita exitialis poisoning is characterized by gastrointestinal symptoms and liver injury. In the patient who died, acute hepatic failure led to hepatic encephalopathy and cerebral edema. Abdominal distension accompanied by thrombocytopenia was common in critically ill patients in this outbreak.

Synthesis of Spirotricyclic Core of Bonnadiene.

We herein describe a new approach for the efficient synthesis of the tricyclic core of diterpene bonnadiene. The synthetically challenging and unusual [6-7-5] spirotricyclic skeleton including the all-carbon quaternary stereocenter, was installed diastereoselectively via a type II [5 + 2] cycloaddition, followed by a unique vinylogous semipinacol rearrangement. The described chemistry demonstrates the feasibility of making the [6-7-5] spirotricyclic skeleton of the final product from the strained bridged [7-8-5] ring system.

Exploring the mechanism of Xiaoqinglong decoction in the treatment of infantile asthma based on network pharmacology and molecular docking.

To explore the mechanism of Xiaoqinglong decoction (XQLD) in the treatment of infantile asthma (IA) based on network pharmacology and molecular docking. The active ingredients of fdrugs in XQLD were retrieved from Traditional Chinese Medicine Systems Pharmacology database and then the targets of drug ingredients were screened. The disease targets of IA were obtained from OMIM and Gencards databases, and the intersection targets of XQLD in the treatment of IA were obtained by Venny 2.1 mapping of ingredient targets and disease targets. Cytoscape software was used to construct active ingredient-intersection target network. The potential targets of XQLD in the treatment of IA were analyzed by protein-protein interaction network using STRING platform, and the Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were obtained by R Studio software. AutoDock was used to perform molecular docking for verification. In this study, 150 active ingredients of XQLD were obtained, including quercetin, kaempferol, ß-sitosterol, luteolin, stigmasterol, and so on. And 92 intersection targets of drugs and diseases were obtained, including interleukin 6 (IL6), cystatin 3, estrogen receptor 1, hypoxia inducible factor 1A, HSP90AA1, epidermal growth factor receptor and so on. There were 127 items of Gene Ontology enrichment analysis and 125 Kyoto Encyclopedia of Genes and Genomes enrichment results, showing that apoptosis, IL-17 signaling pathway, tumor necrosis factor signaling pathway, P13K-Akt signaling pathway and other pathways may play a key role in the treatment of IA by XQLD. The results of molecular docking showed that the key active ingredients including quercetin, kaempferol, ß-sitosterol, luteolin, stigmasterol, and the core targets including IL6, cystatin 3, estrogen receptor 1, hypoxia inducible factor 1A, HSP90AA1, and epidermal growth factor receptor had good binding activity. Through network pharmacology and molecular docking, the potential targets and modern biological mechanisms of XQLD in the treatment of IA were preliminarily revealed in the study, which will provide reference for subsequent animal experiments and clinical trials.

Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy.

BACKGROUND: High-intensity focused ultrasound (HIFU) has shown considerable promise in treating solid tumors, but its ultrasonic energy is easily attenuated, resulting in insufficient energy accumulation in the target area. Moreover, HIFU ablation alone may inevitably lead to the presence of residual tumors, which may cause tumor recurrence and metastasis. Here, we describe a synergistic regimen combining HIFU facilitation with immunomodulation based on a novel oxygen-carrying biomimetic perfluorocarbon nanoparticle (M@P-SOP) to stimulate immunogenic cell death in tumor cells while alleviating immune suppression tumor microenvironment. METHODS: M@P-SOP was prepared by double emulsion and film extrusion method. The anticancer and antimetastatic effects of M@P-SOP were evaluated on a preclinical transplanted 4T1 tumor model by combining HIFU and immunotherapy. Flow cytometry and immunofluorescence were used to clarify the potential mechanism of HIFU+M@P-SOP and their role in anti-programmed death ligand-1 (PD-L1) therapy. RESULTS: Guided by photoacoustic/MR/ultrasound (US) multimodal imaging, M@P-SOP was abundantly enriched in tumor, which greatly enhanced HIFU's killing of tumor tissue in situ, induced stronger tumor immunogenic cell death, stimulated dendritic cell maturation and activated CD8+ T cells. At the same time, M@P-SOP released oxygen to alleviate the tumor hypoxic environment, repolarizing the protumor M2-type macrophages into antitumor M1-type. With concurrent anti-PD-L1 treatment, the antitumor immune response was further amplified to the whole body, and the growth of mimic distant tumor was effectively suppressed. CONCLUSIONS: Our findings offer a highly promising HIFU synergist for effectively ameliorating acoustic and hypoxia environment, eventually inhibiting tumor growth and metastasis by stimulating host's antitumor immunity under HIFU ablation, especially in synergizing with PD-L1 antibody immunotherapy.

Biomimetic, pH-Responsive Nanoplatforms for Cancer Multimodal Imaging and Photothermal Immunotherapy.

Photothermal therapy (PTT), by converting light to thermal energy, has become a novel and noninvasive technique for tumor thermal ablation in clinical practice. However, as a result of phagocytosis of reticuloendothelial cells, current photothermal agents (PTAs) derived from exogenous materials suffer from incompetent tumor targeting and brief internal circulation time. The resulting poor accumulation of PTAs in the target area severely reduces the efficacy of PTT. In addition, the potential toxicity of PTAs, excessive laser exposure, and possibilities of tumor recurrence and metastasis following PTT are still intractable problems that severely influence patients' quality of life. Herein, a biomimetic pH-responsive nanoprobe was prepared via cancer cell membrane coating polydopamine (PDA)-CaCO3 nanoparticles (CPCaNPs) for photoacoustic (PA)/ultrasonic (US)/thermal imaging-guided PTT. When CPCaNPs targeted and infiltrated into the tumor's acidic microenvironment, the decomposed CO2 bubbles from homologous targeting CPCaNPs enhanced ultrasonic (US) signals obviously. At the same time, the PDA of CPCaNPs not only performed efficient PTT of primary tumors but also generated photoacoustic (PA) signals. In addition, an immune checkpoint pathway blockade was combined, which inhibited tumor recurrence and metastasis significantly and improved the immunosuppressive microenvironment after PTT to a large extent. Thus, these proposed biomimetic pH-responsive CPCaNPs provide a promising strategy for precise PTT immunotherapy under the intelligent guidance of PA/US/thermal imaging and show great potential for clinical translation.

Association between nonalcoholic fatty liver disease and increased glucose-to-albumin ratio in adults without diabetes.

Background: Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of individuals globally. Both serum glucose and albumin were demonstrated to be potential markers for the development of NAFLD. We hypothesized that the risk of NAFLD may be proportional to the glucose-to-albumin ratio (GAR). Methods: Based on information from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, it was determined that GAR was associated with an increased risk of NAFLD and liver fibrosis utilizing weighted multivariable logistic regression. Participants with a fatty liver index (FLI) over 60 were identified with NAFLD, and those with an NAFLD fibrosis score (NFS) >0.676 with evidence of NAFLD were labeled with advanced hepatic fibrosis (AHF). The liver biopsy was utilized to verify the relationship between GAR and FLD in our center cohort. Mendelian randomization analysis investigated the genetic relationship between GAR and NAFLD. Results: Of 15,534 eligible participants, 36.4% of participants were identified as NAFLD without AHF. GAR was positively correlated with the probability of NAFLD following full adjustment for possible variables (OR = 1.53, 95% CI: 1.39-1.67). It was confirmed that patients with NAFLD and AHF had an inferior prognosis. The relationship between GAR and NFS was favorable (R = 0.46, P< 0.0001), and NAFLD patients with a higher GAR tended to develop poor survival. In our center cohort, the association between GAR and NAFLD was verified. Conclusion: Among participants without diabetes, greater GAR was linked to higher risks of NAFLD. In addition, NAFLD patients with higher GAR tended to develop liver fibrosis and adverse outcomes.

Theaflavin-3,3'-Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts.

Globally, osteosarcoma (OS) is the most prevalent form of primary bone cancer in children and adolescents. Traditional neoadjuvant chemotherapy regimens have reached a bottleneck; thus, OS survivors have unsatisfactory outcomes. Theaflavin-3,3'-digallate (TF3) exhibits potent anticancer properties against many human cancers. Nevertheless, the biological effects and the underlying molecular mechanism of TF3 in human OS remain unclear. The objective of this study was to investigate the effects of TF3 on human OS cell lines and mouse xenograft models. The results showed that TF3 reduced cell viability, suppressed cell proliferation, and caused G0/G1 cell cycle arrest in both MG63 and HOS cell lines in a concentration-dependent manner. TF3 also altered the homeostatic mechanisms for iron storage in the examined cell lines, resulting in an excess of labile iron. Unsurprisingly, TF3 caused oxidative stress through reduced glutathione (GSH) exhaustion, reactive oxygen species (ROS) accumulation, and the Fenton reaction, which triggered ferroptosis and apoptosis in the cells. TF3 also induced MAPK signalling pathways, including the ERK, JNK, and p38 MAPK pathways. Furthermore, oxidative stress was shown to be the primary reason for TF3-induced proliferation inhibition, programmed cell death, and MAPK pathway activation in vitro. Moreover, TF3 exhibited markedly strong antitumour efficacy in vivo in mouse models. In summary, this study demonstrates that TF3 concomitantly plays dual roles in apoptotic and ferroptotic cell death by triggering the ROS and MAPK signalling pathways in both in vitro and in vivo models.