Simultaneous Cu(II)-EDTA decomplexation and Cu(II) recovery using integrated contact-electro-catalysis and capacitive deionization from electroplating wastewater.

The complex of heavy metals and organic acids leads to high difficulty in heavy metals separation by traditional technologies. Meanwhile, alkaline precipitation commonly used in industry causes the great consumption of resources and extra pollution. Herein, the effective decomplexation of Cu(Ⅱ)-EDTA and synchronous recycling of Cu2+ were realized by contact-electro-catalysis (CEC) coupled with capacitive deionization (CDI) innovatively. In particular, fluorinated ethylene propylene (FEP) as dielectric powders could generate reactive oxygen species under ultrasonic stimulation, realizing continuous deaminization and decarboxylation of Cu(Ⅱ)-EDTA and accelerating the totally breakage of Cu-O and Cu-N bonds. Additionally, the degradation pathway and intermediates evolution of Cu(Ⅱ)-EDTA were investigated using various characterization methods. It was confirmed that decarboxylation predominantly governed the degradation process of Cu(Ⅱ)-EDTA in CEC. During the course of treatment, the degradation ratio of Cu(Ⅱ)-EDTA reached 86.4 % within 150 min. Impressively, this strategy had satisfactory applicability to other metal combinations and excellent cycle stability. Subsequently, the released Cu ions were captured by CuSe cathode electrode through CDI. This research elucidated the degradation mechanism of persistent organic pollutant during CEC, and provided a novel approach for efficiently treating industrial wastewater containing metal complexes and advancing the exploitation and utilization of new technologies for metal recovery.

Eco-climate drivers shape virome diversity in a globally invasive tick species.

Spillovers of viruses into human occur more frequently under warmer conditions, particularly arboviruses. The invasive tick species Haemaphysalis longicornis poses a significant public health threat due to its global expansion and its potential to carry a wide range of pathogens. We analyzed meta-transcriptomic data from 3595 adult H. longicornis ticks collected between 2016 and 2019 in 22 provinces across China, encompassing diverse ecological conditions. Generalized additive modelling revealed that climate factors exerted a stronger influence on the virome of H. longicornis compared to other ecological factors, such as ecotypes, distance to coastline, animal host, tick gender, and anti-viral immunity. We investigated the mechanistic understanding of how climate changes drive the tick virome using causality inference and emphasized its significance for public health. Our findings demonstrated that higher temperatures and lower relative humidity/precipitation contribute to variations in animal host diversity, leading to an increased diversity of tick virome, particularly the evenness of vertebrate associated viruses. This finding may explain the evolution of tick-borne viruses into generalists across multiple hosts, thereby increasing the probability of spillover events involving tick-borne pathogens. Deep learning projections indicate that the diversity of H. longicornis virome is expected to increase in 81.9% of regions under the SSP8.5 scenario from 2019-2030. Extension of surveillance should be implemented to avert the spread of tick-borne diseases.

Comparison of the analgesic effects of oxycodone vs. sufentanil on postoperative pain after laparoscopic gallbladder-preserving cholecystolithotomy: a prospective randomized controlled trial.

Background: We aimed to compare the anesthesia induction effects of oxycodone and sufentanil on postoperative pain in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy, as well as changes in serum levels of inflammatory factors (TNF-α, IL-6, and IL-10) in the perioperative period. Methods: Sixty patients who underwent laparoscopic gallbladder-preserving cholecystolithotomy were evenly divided into oxycodone (O) and sufentanil (S) groups. In groups O and S, oxycodone (0.3 mg/kg) and sufentanil (0.3 ug/kg) were administered, respectively, followed by propofol (2 mg/kg) and rocuronium (0.6 mg/kg). In both groups, the intraoperative electroencephalography double-frequency index was used to guide the use of sedative and analgesic drugs, assessing the follow-up analgesic effect (VAS), degree of sedation (Ramsey), and postoperative complications at seven different time points (0, 0.5, 2, 4, 6, 8, and 24 h postoperatively). Results: Compared with the S group, patients in the O group exhibited lower VAS scores within 24 h postoperatively (P < 0.001), but there was no statistical difference between wound and shoulder pain scores (P > 0.05). Regarding postoperative awakening and extubation duration, O group patients experienced shorter times and better remedial analgesia (P < 0.05). In terms of the degree of sedation, the Ramsay score decreased at 0 h postoperatively compared with the S group (P < 0.001). Conclusion: Compared with sufentanil, oxycodone anesthesia induced better postoperative analgesia and less inflammatory responses in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy. Clinical Trial Registration: This study has been approved by the Ethics Committee of Peking University Shougang Hospital, with ethical approval (No. IRBK-2020-009), and has completed registration in the Chinese Clinical Trials Register (http://www.chictr.org.cn/) (ChiCTR2000031230).

Porous Se@SiO2 nanocomposites play a potential inhibition role in hyperoxaluria associated kidney stone by exerting antioxidant effects.

Background: Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO2 groups (Se@SiO2 6.905±0.074 mg/kg; GAM + Se@SiO2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.

Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes.

PURPOSE: Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only potentially curative treatment for patients with myelodysplastic syndromes (MDS). Several issues must be considered when evaluating the benefits and risks of HSCT for patients with MDS, with the timing of transplantation being a crucial question. Here, we aimed to develop and validate a decision support system to define the optimal timing of HSCT for patients with MDS on the basis of clinical and genomic information as provided by the Molecular International Prognostic Scoring System (IPSS-M). PATIENTS AND METHODS: We studied a retrospective population of 7,118 patients, stratified into training and validation cohorts. A decision strategy was built to estimate the average survival over an 8-year time horizon (restricted mean survival time [RMST]) for each combination of clinical and genomic covariates and to determine the optimal transplantation policy by comparing different strategies. RESULTS: Under an IPSS-M based policy, patients with either low and moderate-low risk benefited from a delayed transplantation policy, whereas in those belonging to moderately high-, high- and very high-risk categories, immediate transplantation was associated with a prolonged life expectancy (RMST). Modeling decision analysis on IPSS-M versus conventional Revised IPSS (IPSS-R) changed the transplantation policy in a significant proportion of patients (15% of patient candidate to be immediately transplanted under an IPSS-R-based policy would benefit from a delayed strategy by IPSS-M, whereas 19% of candidates to delayed transplantation by IPSS-R would benefit from immediate HSCT by IPSS-M), resulting in a significant gain-in-life expectancy under an IPSS-M-based policy (P = .001). CONCLUSION: These results provide evidence for the clinical relevance of including genomic features into the transplantation decision making process, allowing personalizing the hazards and effectiveness of HSCT in patients with MDS.

Hepatic IRE1α-XBP1 signaling promotes GDF15-mediated anorexia and body weight loss in chemotherapy.

Platinum-based chemotherapy drugs can lead to the development of anorexia, a detrimental effect on the overall health of cancer patients. However, managing chemotherapy-induced anorexia and subsequent weight loss remains challenging due to limited effective therapeutic strategies. Growth differentiation factor 15 (GDF15) has recently gained significant attention in the context of chemotherapy-induced anorexia. Here, we report that hepatic GDF15 plays a crucial role in regulating body weight in response to chemo drugs cisplatin and doxorubicin. Cisplatin and doxorubicin treatments induce hepatic Gdf15 expression and elevate circulating GDF15 levels, leading to hunger suppression and subsequent weight loss. Mechanistically, selective activation by chemotherapy of hepatic IRE1α-XBP1 pathway of the unfolded protein response (UPR) upregulates Gdf15 expression. Genetic and pharmacological inactivation of IRE1α is sufficient to ameliorate chemotherapy-induced anorexia and body weight loss. These results identify hepatic IRE1α as a molecular driver of GDF15-mediated anorexia and suggest that blocking IRE1α RNase activity offers a therapeutic strategy to alleviate the adverse anorexia effects in chemotherapy.

Chlorin e6 and BLZ945 Based Self-Assembly for Photodynamic Immunotherapy through Immunogenic Tumor Induction and Tumor Associated Macrophage Depletion.

Immunotherapeutic effect is restricted by the non-immunogenic tumor phenotype and immunosuppression behaviors of tumor associated macrophages (TAMs). In this work, a drug self-assembly (designated as CeBLZ) is fabricated based on chlorin e6 (Ce6) and BLZ945 to activate photodynamic immunotherapy through tumor immunogenic induction and tumor associated macrophage depletion. It is found that Ce6 tends to assemble with BLZ945 without any drug excipients, which can enhance the cellular uptake, tumor penetration and blood circulation behaviors. The robust photodynamic therapy effect of CeBLZ efficiently suppresses the primary tumor growth and also triggers immunogenic cell death to reverse the non-immunogenic tumor phenotype. Moreover, CeBLZ can deplete TAMs in tumor tissues to reverse the immunosuppression microenvironment, activating abscopal effect for distant tumor inhibition. In vitro and in vivo results confirm the superior anti-tumor effect of CeBLZ with negligible side effect, which might promote the development of sophisticated drug combinations for systematic tumor management. This article is protected by copyright. All rights reserved.

Britanin - a beacon of hope against gastrointestinal tumors?

Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties. It also exhibits significant anti-tumor activity, suppressing tumor growth in vitro and in vivo. The current body of research on Britanin includes thirty papers predominantly related to neoplasms, the majority of which are gastrointestinal tumors that have not been summarized before. To drive academic debate, the present paper reviews the available research on Britanin in gastrointestinal tumors. It also outlines novel research directions using data not directly concerned with the digestive system, but which could be adopted in future gastrointestinal research. Britanin was found to counteract liver, colorectal, pancreatic, and gastric tumors, by regulating proliferation, apoptosis, autophagy, immune response, migration, and angiogenesis. As confirmed in pancreatic, gastric, and liver cancer, its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation, as well as Bcl-2-associated X protein upregulation. Moreover, it has been found to induce the Akt kinase and Forkhead box O1 axis, activate the AMP-activated protein kinase pathway, elevate interleukin-2 and peroxisome proliferator-activated receptor-γ levels, reduce interleukin-10, as well as downregulate matrix metalloproteinase-9, Twist family bHLH transcription factor 1, and cyclooxygenase-2. It also inhibits Myc-HIF1α interaction and programmed death ligand 1 transcription by interrupting the Ras/ RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling. Future research should aim to unravel the link between Britanin and acetylcholinesterase, mast cells, osteolysis, and ischemia, as compelling data have been provided by studies outside the gastrointestinal context. Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells, while still being effective against the latter, further in-depth studies with the use of animal models are merited. The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent, which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.

Metal-organic framework-derived trimetallic particles encapsulated by ultrathin nitrogen-doped carbon nanosheets on a network of nitrogen-doped carbon nanotubes as bifunctional catalysts for rechargeable zinc-air batteries.

Economical oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) bifunctional catalysts with high activity aimed at replacing precious metal catalysts for rechargeable zinc-air batteries (ZABs) must be developed. In this study, a multiple hierarchical-structural material is developed using a facile dielectric barrier discharge (DBD) plasma surface treatment, solvothermal reaction, and high-temperature carbonization strategy. This strategy allows for the construction of nanosheets using nitrogen-doped carbon (NC) material-encapsulated ternary CoNiFe alloy nanoparticles (NPs) on a network of NC nanotubes (NCNTs), denoted as CoNiFe-NC@p-NCNTs. Precisely, the presence of abundant CoNiFe alloy NPs and the formation of M-N-C active sites created by transition metals (cobalt, nickel, and iron) coupled with NC can provide superior OER/ORR bifunctional properties. Moreover, the prepared NC layers with a multilevel pore structure contribute to a larger specific surface area, exposing numerous active sites and enhancing the uniformity of electron and mass movement. The CoNiFe0.08-NC@p-NCNTs show remarkable dual functionality for electrochemical oxygen reactions (ORR half-wave potential of 0.811 V, limiting current density of 5.73 mA cm-2 measured with a rotating disk electrode at a rotation speed of 1600 rpm, and OER overpotential of 351 mV at 10 mA cm-2), which demonstrates similar ORR performance to 20 wt% Pt/C and better OER performance than the commercial RuO2. A liquid ZAB prepared using the proposed material has excellent bifunctionality with an open-circuit voltage of 1.450 V and long-term cycling stability of 230 h@10 mA cm-2.

Head-to-head comparison of three different US-based quantitative parameters for hepatic steatosis assessment: a prospective study.

PURPOSE: To evaluate the diagnostic performance of attenuation coefficient (AC), hepato-renal index (HRI) and controlled attenuation parameter (CAP) in quantitative assessment of hepatic steatosis by employing histopathology as reference standard. METHODS: Participants with suspected metabolic-associated fatty liver disease (MAFLD) who underwent US-based parameter examinations and liver biopsy were prospectively recruited. The distributions of US parameters across different grades of steatosis were calculated, and diagnostic performance was determined based on the areas under the receiver operating characteristic curve (AUC). RESULTS: A total of 73 participants were included, with hepatic steatosis grades S0, S1, S2, and S3 distributed as follows: 13, 20, 27, and 13 respectively. The correlation coefficients for CAP, AC, and HRI ranged from 0.67 to 0.74. AC and HRI showed a strong correlation with steatosis grade. The AUC for CAP and AC in diagnosing steatosis ≥ S1 were significantly higher at 0.99 and 0.98 compared to HRI's value. For diagnosing steatosis ≥ S2, the AUC of CAP (AUC: 0.85) was lower than that of AC (AUC: 0.94), and HRI (AUC: 0.94). Similarly for diagnosing steatosis S3, the AUC of CAP (AUC: 0.68) was lower than that of AC (AUC: 0.88), and HRI (AUC: 0.88). CONCLUSION: The AC and HRI values increased with the progression of hepatic steatosis grade, while CAP increased from S0 to S2 but not from S2 to S3. For mild steatosis diagnosis, CAP and AC showed superior diagnostic performance compared to HRI, while AC and HRI were more advantageous in differentiating moderate and severe steatosis.

Phosphorus Nitride Imide Nanotubes for Uranium Capture from Seawater.

Nuclear power plays a pivotal role in the global energy supply. The adsorption-based extraction of uranium from seawater is crucial for the rapid advancement of nuclear power. The phosphorus nitride imide (PN) nanotubes were synthesized in this study using a solvothermal method, resulting in chemically stable cross-linked tubular hollow structures that draw inspiration from the intricate snowflake fractal pattern. Detailed characterization showed that these nanotubes possess a uniformly distributed five-coordinated nanopocket, which exhibited great selectivity and efficiency in binding uranium. PN nanotubes captured 97.34% uranium from the low U-spiked natural seawater (∼355 µg L-1) and showed a high adsorption capacity (435.58 mg g-1), along with a distribution coefficient, KdU > 8.71 × 107 mL g-1. In addition, PN nanotubes showed a high adsorption capacity of 7.01 mg g-1 in natural seawater. The facile and scalable production of PN nanotubes presented in this study holds implications for advancing their large-scale implementation in the selective extraction of uranium from seawater.

Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization.

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. RESULTS: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. CONCLUSION: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.

Successful treatment of gastric cancer 10 years after heart transplantation: A case report.

BACKGROUND: While survival rates among cardiac allograft recipients have improved, there has been a rise in post-transplant malignancies, with gastric cancer being less commonly reported. This study presented a successful treatment of gastric cancer in an individual 10 years after undergoing a heart transplant. CASE PRESENTATION: A 66-year-old Chinese man presented to the gastrointestinal clinic with a complaint of diagnosis of gastric cancer for 4 months and treated with neoadjuvant therapy for 1 month. He has undergone orthotopic heart transplantation 10 years earlier due to a myocardial infarction. Physical examination and laboratory tests did not reveal any significant abnormalities. Abdominal contrast-enhanced computed tomography (CT) imaging indicated a gastric mass near the greater curvature, with gastroscopy suggesting a carcinoma at the esophagogastric junction, Siewert III. An echocardiogram indicated left atrial enlargement with mild mitral and tricuspid regurgitation. The diagnosis suggested that his gastric cancer at the esophagogastric junction was a consequence of long-term immunosuppressive therapy. A multidisciplinary team (MDT) consultation recommended a proximal radical gastrectomy. Postoperatively, the patient received 4 cycles of adjuvant chemotherapy with XELOX combined with Herceptin, initiated a month after surgery. During the 1-year follow-up, the patient showed commendable recovery, with no signs of tumor recurrence or metastasis. CONCLUSION: This case underscores the potential risk of malignancy from immunosuppressive agents in transplant recipients. The successful management of this complex scenario underscores the indispensable role of an MDT approach in treating such unique and challenging cases.

Entropy Engineering Constrain Phase Transitions Enable Ultralong-life Prussian Blue Analogs Cathodes.

Prussian blue analogs (PBAs) are considered as one of the most potential electrode materials in capacitive deionization (CDI) due to their unique 3D framework structure. However, their practical applications suffer from low desalination capacity and poor cyclic stability. Here, an entropy engineering strategy is proposed that incorporates high-entropy (HE) concept into PBAs to address the unfavorable multistage phase transitions during CDI desalination. By introducing five or more metals, which share N coordination site, high-entropy hexacyanoferrate (HE-HCF) is constructed, thereby increasing the configurational entropy of the system to above 1.5R and placing it into the high-entropy category. As a result, the developed HE-HCF demonstrates remarkable cycling performance, with a capacity retention rate of over 97% after undergoing 350 ultralong-life cycles of adsorption/desorption. Additionally, it exhibits a high desalination capacity of 77.24 mg g-1 at 1.2 V. Structural characterization and theoretical calculation reveal that high configurational entropy not only helps to restrain phase transition and strengthen structural stability, but also optimizes Na+ ions diffusion path and energy barrier, accelerates reaction kinetics and thus improves performance. This research introduces a new approach for designing electrodes with high performance, low cost, and long-lasting durability for capacitive deionization applications.

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

The role of macrophage polarization in vascular calcification.

Vascular calcification is an important factor in the high morbidity and mortality of Cardiovascular and cerebrovascular diseases. Vascular damage caused by calcification of the intima or media impairs the physiological function of the vascular wall. Inflammation is a central factor in the development of vascular calcification. Macrophages are the main inflammatory cells. Dynamic changes of macrophages with different phenotypes play an important role in the occurrence, progression and stability of calcification. This review focuses on macrophage polarization and the relationship between macrophages of different phenotypes and calcification environment, as well as the mechanism of interaction, it is considered that macrophages can promote vascular calcification by releasing inflammatory mediators and promoting the osteogenic transdifferentiation of smooth muscle cells and so on. In addition, several therapeutic strategies aimed at macrophage polarization for vascular calcification are described, which are of great significance for targeted treatment of vascular calcification.

BMSC-derived Exosomes Ameliorate Peritoneal Dialysis-associated Peritoneal Fibrosis via the Mir-27a-3p/TP53 Pathway.

OBJECTIVE: Peritoneal fibrosis (PF) is the main cause of declining efficiency and ultrafiltration failure of the peritoneum, which restricts the long-term application of peritoneal dialysis (PD). This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes (BMSC-Exos) on PF in response to PD. METHODS: Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing. C57BL/6J mice were infused with 4.25% glucose-based peritoneal dialysis fluid (PDF) for 6 consecutive weeks to establish a PF model. A total of 36 mice were randomly divided into 6 groups: control group, 1.5% PDF group, 2.5% PDF group, 4.25% PDF group, BMSC-Exos treatment group, and BMSC-Exos+TP53 treatment group. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF. HE and Masson staining were performed to evaluate the extent of PF. The therapeutic potential of BMSC-Exos for PF was examined through pathological examination, RT-qPCR, Western blotting, and peritoneal function analyses. Epithelial-mesenchymal transition (EMT) of HMrSV5 was induced with 4.25% PDF. Cells were divided into control group, 4.25% PDF group, BMSC-Exos treatment group, and BMSC-Exos+TP53 treatment group. Cell Counting Kit-8 assay was used to measure cell viability, and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells. RESULTS: Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs. The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos, but decreased in PD mice. We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice. Compared with the control mice, the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response, with markedly increased peritoneal thickness and higher expression of α-SMA, collagen-I, fibronectin, and ECM1. The mice with PD showed decreased miR-27a-3p. Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment, while PF and mesothelial damage were significantly ameliorated. Additionally, markers of fibrosis (α-SMA, collagen-I, fibronectin, ECM1) and profibrotic cytokines (TGF-ß1, PDGF) were downregulated at the mRNA and protein levels after BMSC-Exos treatment. In HMrSV5 cells, BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF. Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin (epithelial marker) and decreased expression of α-SMA, Snail, and vimentin (mesenchymal markers) compared to those of the 4.25% PDF-treated cells. Importantly, a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p. TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos. CONCLUSION: The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53.

Dynamic Contrast-Enhanced Ultrasonography Combined With LR-M Classification Criteria for Differentiating Malignant Liver Nodules at High Risk for Hepatocellular Carcinoma.

OBJECTIVE: We aimed to investigate the value of quantitative parameters derived from dynamic contrast-enhanced ultrasonography (DCE-US) and a combination of these quantitative parameters with the LR-M classification criteria in distinguishing hepatocellular carcinoma (HCC) nodules and non-HCC malignancies. METHODS: HCC and non-HCC malignant nodules were grouped using pathologic results, and each nodule was classified using CEUS LI-RADS 2017. Quantitative CEUS analysis of each nodule was performed using VueBox, and quantitative parameters were compared between the HCC and non-HCC groups. The diagnostic efficacy of the LR-5 category for HCC was analyzed using the LR-M classification criteria along with time-related quantitative parameters. RESULTS: Of the 190 malignant liver nodules, 137 and 53 were HCCs and non-HCC malignancies, respectively. The median values of quantitative parameters RT (rise time), TTP (time to peak), mTTl (mean transit time local), and FT (fall time) in the non-HCC malignant group were lower than those in the HCC group, with p < 0.05. There was a statistically significant difference in WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve), and WoR (wash-out rate) values between HCC and non-HCC malignant groups, with p < 0.05. Using LR-M washout time <60 s and FT ≤21.2 s as the new diagnostic standard, the LR-5 category showed a sensitivity of 83.9%, specificity of 96.2%, and positive predictive value of 98.3% for HCC diagnosis. CONCLUSION: DCE-US can facilitate the distinction of HCCs and non-HCC malignancies. Non-HCC malignancies present with earlier peak enhancement and more rapid and marked washout than HCC nodules. The combination of the LR-M classification criteria and FT ≤21.2 s can significantly improve the diagnostic sensitivity of the LR-5 category for HCC.

National survey on understanding nursing academics' perspectives on digital health education.

AIM: This study explored the knowledge and confidence levels of nursing academics in teaching both the theories and practical skills of digital health in undergraduate nursing programs. DESIGN: A cross-sectional study. METHODS: A structured online survey was distributed among nursing academics across Australian universities. The survey included two sections: (1) the participants' demographics and their nursing and digital health teaching experience; (2) likert scales asking the participants to rate their knowledge and confidence to teach the theories and practical skills of four main themes; digital health technologies, information exchange, quality and digital professionalism. RESULTS: One hundred and nineteen nursing academics completed part one, and 97 individuals completed part two of the survey. Only 6% (n = 5) of the participants reported having formal training in digital health. Digital health was mainly taught as a module (n = 57, 45.9%), and assessments of theory or practical application of digital health in the nursing curriculum were uncommon, with 79 (69.9%) responding that there was no digital health assessment in their entry to practice nursing programs. Among the four core digital health themes, the participants rated high on knowledge of digital professionalism (22.4% significant knowledge vs. 5.9% no knowledge) but low on information exchange (30% significant knowledge vs. 28.3% no knowledge). Statistically significant (p < .001) associations were found between different themes of digital health knowledge and the level of confidence in teaching its application. Nursing academics with more than 15 years of teaching experience had a significantly higher level of knowledge and confidence in teaching digital health content compared with those with fewer years of teaching experience. CONCLUSION: There is a significant gap in nursing academics' knowledge and confidence to teach digital health theory and its application in nursing. Nursing academics need to upskill in digital health to prepare the future workforce to be capable in digitally enabled health care settings. IMPLICATIONS FOR THE PROFESSION: Nursing academics have a limited level of digital knowledge and confidence in preparing future nurses to work in increasingly technology-driven health care environments. Addressing this competency gap and providing sufficient support for nursing academics in this regard is essential. IMPACT: What problem did the study address? Level of knowledge and confidence among nursing academics to teach digital health in nursing practice. What were the main findings? There is a significant gap in nursing academics' knowledge and confidence to teach digital health theory and its application in nursing. Where and on whom will the research have an impact? Professional nursing education globally. REPORTING METHOD: The STROBE guideline was used to guide the reporting of the study. PATIENT OR PUBLIC CONTRIBUTION: The call for participation from nursing academics across Australia provided an introductory statement about the project, its aim and scope, and the contact information of the principal researcher. A participant information sheet was shared with the call providing a detailed explanation of participation. Nursing academics across Australia participated in the survey through the link embedded in the participation invite.

Ferroptosis Is Crucial for Cisplatin Induced Sertoli Cell Injury via N6-Methyladenosine Dependent Manner.

PURPOSE: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. MATERIALS AND METHODS: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2',7'-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. RESULTS: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. CONCLUSIONS: Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.