Melatonin pretreatment improves endometrial regenerative cell-mediated therapeutic effects in experimental colitis.

BACKGROUND: Endometrial regenerative cells (ERCs) have been proven to be an effective strategy for attenuating experimental colitis, but the complex in vivo microenvironment such as oxidative stress may largely limit and weaken ERC efficacy. Melatonin (MT) works as an anti-oxidative agent in a variety of preclinical diseases, and has been identified to promote mesenchymal stem cell-mediated therapeutic effects in different diseases. However, the ability of MT to enhance ERC-mediated effects in colitis is currently poorly understood. METHODS: Menstrual blood was collected from healthy female volunteers to obtain ERCs and identified. In vitro, H2O2-induced oxidative stress was introduced to test if MT could prevent ERCs from damage through detection of intracellular reactive oxidative species (ROS) and apoptosis assay. In vivo, dextran sodium sulfate (DSS)-induced acute colitis was treated by ERCs and MT-primed ERCs, therapeutic effects were assayed by the disease activity index (DAI), histological features, and macrophage and CD4+ T cell in the spleen and colon, and cytokine profiles in the sera and colon were also measured. RESULTS: In vitro, ERCs that underwent MT-precondition were found to possess more anti-oxidative potency in comparison to naïve ERCs, which were characterized by decreased apoptosis rate and intracellular ROS under H2O2 stimulation. In vivo, MT pretreatment can significantly enhance the therapeutic effects of ERCs in the attenuation of experimental colitis, including decreased DAI index and damage score. In addition, MT pretreatment was found to promote ERC-mediated inhibition of Th1, Th17, and M1 macrophage and pro-inflammatory cytokines, increase of Treg, and immunomodulation of cytokines in the spleen and colon. CONCLUSIONS: MT pretreatment facilitates the promotion of cell viability under oxidative stress in vitro, while also enhancing ERC-mediated therapeutic effects in experimental colitis.

FV-429 induces apoptosis by regulating nuclear translocation of PKM2 in pancreatic cancer cells.

Of all malignancies, pancreatic ductal adenocarcinoma (PDAC), constituting 90% of pancreatic cancers, has the worst prognosis. Glycolysis is overactive in PDAC patients and is associated with poor prognosis. Drugs that inhibit glycolysis as well as induce cell death need to be identified. However, glycolysis inhibitors often fail to induce cell death. We here found that FV-429, a derivative of the natural flavonoid wogonin, can induce mitochondrial apoptosis and inhibit glycolysis in PDAC in vivo and in vitro. In vitro, FV-429 inhibited intracellular ATP content, glucose uptake, and lactate generation, consequently leading to mitochondrial dysfunction and apoptosis in PDAC cells. Furthermore, it decreased the expression of PKM2 (a specific form of pyruvate kinase) through the ERK signaling pathway and enhanced PKM2 nuclear translocation. TEPP-46, the activator of PKM2, reversed FV-429-induced glycolysis inhibition and mitochondrial apoptosis in the PDAC cells. In addition, FV-429 exhibited significant tumor suppressor activity and high safety in BxPC-3 cell xenotransplantation models. These results thus demonstrated that FV-429 decreases PKM2 expression through the ERK signaling pathway and enhances PKM2 nuclear translocation, thereby resulting in glycolysis inhibition and mitochondrial apoptosis in PDAC in vitro and in vivo, which makes FV-429 a promising candidate for pancreatic cancer treatment.

A prognostic signature established based on genes related to tumor microenvironment for patients with hepatocellular carcinoma.

BACKGROUND: Complex cellular signaling network in the tumor microenvironment (TME) could serve as an indicator for the prognostic classification of hepatocellular carcinoma (HCC) patients. METHODS: Univariate Cox regression analysis was performed to screen prognosis-related TME-related genes (TRGs), based on which HCC samples were clustered by running non-negative matrix factorization (NMF) algorithm. Furthermore, the correlation between different molecular HCC subtypes and immune cell infiltration level was analyzed. Finally, a risk score (RS) model was established by LASSO and Cox regression analyses (CRA) using these TRGs. Functional enrichment analysis was performed using gene set enrichment analysis (GSEA). RESULTS: HCC patients were divided into three molecular subtypes (C1, C2, and C3) based on 704 prognosis-related TRGs. HCC subtype C1 had significantly better OS than C2 and C3. We selected 13 TRGs to construct the RS model. Univariate and multivariate CRA showed that the RS could independently predict patients' prognosis. A nomogram integrating the RS and clinicopathologic features of the patients was further created. We also validated the reliability of the model according to the area under the receiver operating characteristic (ROC) curve value, concordance index (C-index), and decision curve analysis. The current findings demonstrated that the RS was significantly correlated with CD8+ T cells, monocytic lineage, and myeloid dendritic cells. CONCLUSION: This study provided TRGs to help classify patients with HCC and predict their prognoses, contributing to personalized treatments for patients with HCC.

Single-cell data revealed exhaustion of characteristic NK cell subpopulations and T cell subpopulations in hepatocellular carcinoma.

BACKGROUND: The treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) have been a major medical challenge. Unraveling the landscape of tumor immune infiltrating cells (TIICs) in the immune microenvironment of HCC is of great significance to probe the molecular mechanisms. METHODS: Based on single-cell data of HCC, the cell landscape was revealed from the perspective of TIICs. Special cell subpopulations were determined by the expression levels of marker genes. Differential expression analysis was conducted. The activity of each subpopulation was determined based on the highly expressed genes. CTLA4+ T-cell subpopulations affecting the prognosis of HCC were determined based on survival analysis. A single-cell regulatory network inference and clustering analysis was also performed to determine the transcription factor regulatory networks in the CTLA4+ T cell subpopulations. RESULTS: 10 cell types were identified and NK cells and T cells showed high abundance in tumor tissues. Two NK cells subpopulations were present, FGFBP2+ NK cells, B3GNT7+ NK cells. Four T cells subpopulations were present, LAG3+ T cells, CTLA4+ T cells, RCAN3+ T cells, and HPGDS+ Th2 cells. FGFBP2+ NK cells, and CTLA4+ T cells were the exhaustive subpopulation. High CTLA4+ T cells contributed to poor prognostic outcomes and promoted tumor progression. Finally, a network of transcription factors regulated by NR3C1, STAT1, and STAT3, which were activated, was present in CTLA4+ T cells. CONCLUSION: CTLA4+ T cell subsets in HCC exhibited functional exhaustion characteristics that probably inhibited T cell function through a transcription factor network dominated by NR3C1, STAT1, and STAT3.

Hepatocyte-specific CCAAT/enhancer binding protein α restricts liver fibrosis progression.

Metabolic dysfunction-associated steatohepatitis (MASH) - previously described as nonalcoholic steatohepatitis (NASH) - is a major driver of liver fibrosis in humans, while liver fibrosis is a key determinant of all-cause mortality in liver disease independent of MASH occurrence. CCAAT/enhancer binding protein α (CEBPA), as a versatile ligand-independent transcriptional factor, has an important function in myeloid cells, and is under clinical evaluation for cancer therapy. CEBPA is also expressed in hepatocytes and regulates glucolipid homeostasis; however, the role of hepatocyte-specific CEBPA in modulating liver fibrosis progression is largely unknown. Here, hepatic CEBPA expression was found to be decreased during MASH progression both in humans and mice, and hepatic CEBPA mRNA was negatively correlated with MASH fibrosis in the human liver. CebpaΔHep mice had markedly enhanced liver fibrosis induced by a high-fat, high-cholesterol, high-fructose diet or carbon tetrachloride. Temporal and spatial hepatocyte-specific CEBPA loss at the progressive stage of MASH in CebpaΔHep,ERT2 mice functionally promoted liver fibrosis. Mechanistically, hepatocyte CEBPA directly repressed Spp1 transactivation to reduce the secretion of osteopontin, a fibrogenesis inducer of hepatic stellate cells. Forced hepatocyte-specific CEBPA expression reduced MASH-associated liver fibrosis. These results demonstrate an important role for hepatocyte-specific CEBPA in liver fibrosis progression, and may help guide the therapeutic discoveries targeting hepatocyte CEBPA for the treatment of liver fibrosis.

A nomogram prognostic model for early hepatocellular carcinoma with diabetes mellitus after primary liver resection based on the admission characteristics.

Background: Patients diagnosed with early-stage hepatocellular carcinoma (HCC) and diabetes mellitus (DM) are at a higher risk of experiencing complications and facing increased mortality rates. Hence, it is crucial to develop personalized clinical strategies for this particular subgroup upon their admission. The objective of this study is to determine the key prognostic factors in early HCC patients who received liver resection combined with DM and develop a practical personalized model for precise prediction of overall survival in these individuals. Method: A total of 1496 patients diagnosed hepatitis B virus (HBV) - related liver cancer from Beijing You'an Hospital were retrospectively enrolled, spanning from 1 January 2014, to 31 December 2019, and ultimately, 622 eligible patients of hepatocellular carcinoma (HCC) patients with diabetes were included in this present investigation. A multivariate COX regression analysis was conducted to identify prognostic factors that are independent of each other and develop a nomogram. The performance of the nomogram was evaluated using various statistical measures such as the C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) in both the training and validation groups. Survival rates were estimated using the Kaplan-Meier method. Results: The study included a total of 622 early HCC patients who underwent liver resection combined with DM. Random Forrest model and Multivariate Cox regression analysis revealed that drinking, tumor number, monocyte-to-lymphocyte ratio, white blood cell count and international normalized ratio at admission were identified as independent prognostic factors for early HCC patients who underwent liver resection combined with DM. The nomogram demonstrated good predictive performance in the training and validation cohorts based on the C-index values of 0 .756 and 0 .739 respectively, as well as the area under the curve values for 3-, 5-, and 8-year overall survival (0.797, 0.807, 0.840, and 0.725, 0.791, 0.855). Calibration curves and decision curve analysis indicated high accuracy and net clinical benefit rates. Furthermore, the nomogram successfully stratified enrolled patients into low-risk and high-risk groups based on their risk of overall survival. The difference in overall survival between these two groups was statistically significant in both the training and validation cohorts (p < 0.0001 and p = 0.0064). Conclusion: Our results indicate that the admission characteristics demonstrate a highly effective ability to predict the overall survival of early HCC patients who have undergone liver resection in combination with DM. The developed model has the potential to support healthcare professionals in making more informed initial clinical judgments for this particular subgroup of patients.

The Absence of Intra-Tumoral Tertiary Lymphoid Structures is Associated with a Worse Prognosis and mTOR Signaling Activation in Hepatocellular Carcinoma with Liver Transplantation: A Multicenter Retrospective Study.

Tertiary lymphoid structure (TLS) can predict the prognosis and sensitivity of tumors to immune checkpoint inhibitors (ICIs) therapy, whether it can be noninvasively predicted by radiomics in hepatocellular carcinoma with liver transplantation (HCC-LT) has not been explored. In this study, it is found that intra-tumoral TLS abundance is significantly correlated with recurrence-free survival (RFS) and overall survival (OS). Tumor tissues with TLS are characterized by inflammatory signatures and high infiltration of antitumor immune cells, while those without TLS exhibit uncontrolled cell cycle progression and activated mTOR signaling by bulk and single-cell RNA-seq analyses. The regulators involved in mTOR signaling (RHEB and LAMTOR4) and S-phase (RFC2, PSMC2, and ORC5) are highly expressed in HCC with low TLS. In addition, the largest cohort of HCC patients is studied with available radiomics data, and a classifier is built to detect the presence of TLS in a non-invasive manner. The classifier demonstrates remarkable performance in predicting intra-tumoral TLS abundance in both training and test sets, achieving areas under receiver operating characteristic curve (AUCs) of 92.9% and 90.2% respectively. In summary, the absence of intra-tumoral TLS abundance is associated with mTOR signaling activation and uncontrolled cell cycle progression in tumor cells, indicating unfavorable prognosis in HCC-LT.

Quantitative evaluation of gut microbiota composition in pancreatic cancer: A pooled study.

BACKGROUND: Prior research has demonstrated a positive association between the composition of gut microbiota and the incidence of pancreatic cancer. Nevertheless, a thorough quantitative and systematic evaluation of the distinct properties of gut microbiota in individuals diagnosed with pancreatic cancer has yet to be conducted. The objective of this study is to examine alterations in the diversity of intestinal microbiota in individuals diagnosed with pancreatic cancer. METHODS: Search for relevant literature published before July 2023 in 4 databases: PubMed, Embase, Web of Science, and Cochrane Library, without any language restrictions. RESULTS: A total of 12 studies were included, including 535 patients with pancreatic cancer and 677 healthy controls. Analysis was conducted on 6 phyla, 16 genera, and 6 species. The study found significant and distinctive changes in the α-diversity of gut microbiota, as well as in the relative abundance of multiple gut bacterial groups at the phylum, genus, and species levels in pancreatic cancer patients. CONCLUSION: Overall, there are certain characteristic changes in the gut microbiota of pancreatic cancer patients. However, further research is warranted to elucidate the specific mechanism of action and the potential for treatment.

Single-Atom Catalysts Mediated Bioorthogonal Modulation of N6-Methyladenosine Methylation for Boosting Cancer Immunotherapy.

Bioorthogonal reactions provide a powerful tool to manipulate biological processes in their native environment. However, the transition-metal catalysts (TMCs) for bioorthogonal catalysis are limited to low atomic utilization and moderate catalytic efficiency, resulting in unsatisfactory performance in a complex physiological environment. Herein, sulfur-doped Fe single-atom catalysts with atomically dispersed and uniform active sites are fabricated to serve as potent bioorthogonal catalysts (denoted as Fe-SA), which provide a powerful tool for in situ manipulation of cellular biological processes. As a proof of concept, the N6-methyladensoine (m6A) methylation in macrophages is selectively regulated by the mannose-modified Fe-SA nanocatalysts (denoted as Fe-SA@Man NCs) for potent cancer immunotherapy. Particularly, the agonist prodrug of m6A writer METTL3/14 complex protein (pro-MPCH) can be activated in situ by tumor-associated macrophage (TAM)-targeting Fe-SA@Man, which can upregulate METTL3/14 complex protein expression and then reprogram TAMs for tumor killing by hypermethylation of m6A modification. Additionally, we find the NCs exhibit an oxidase (OXD)-like activity that further boosts the upregulation of m6A methylation and the polarization of macrophages via producing reactive oxygen species (ROS). Ultimately, the reprogrammed M1 macrophages can elicit immune responses and inhibit tumor proliferation. Our study not only sheds light on the design of single-atom catalysts for potent bioorthogonal catalysis but also provides new insights into the spatiotemporal modulation of m6A RNA methylation for the treatment of various diseases.

Analysis and Validation of Tyrosine Metabolism-related Prognostic Features for Liver Hepatocellular Carcinoma Therapy.

AIMS: To explore tyrosine metabolism-related characteristics in liver hepatocellular carcinoma (LIHC) and to establish a risk signature for the prognostic prediction of LIHC. Novel prognostic signatures contribute to the mining of novel biomarkers, which are essential for the construction of a precision medicine system for LIHC and the improvement of survival. BACKGROUND: Tyrosine metabolism plays a critical role in the initiation and development of LIHC. Based on the tyrosine metabolism-related characteristics in LIHC, this study developed a risk signature to improve the prognostic prediction of patients with LIHC. OBJECTIVE: To investigate the correlation between tyrosine metabolism and progression of LIHC and to develop a tyrosine metabolism-related prognostic model. METHODS: Gene expression and clinicopathological information of LIHC were obtained from The Cancer Genome Atlas (TCGA) database. Distinct subtypes of LIHC were classified by performing consensus cluster analysis on the tyrosine metabolism-related genes. Univariate and Lasso Cox regression were used to develop a RiskScore prognosis model. Kaplan-Meier (KM) survival analysis with log-rank test and area under the curve (AUC) of receiver operating characteristic (ROC) were employed in the prognostic evaluation and prediction validation. Immune infiltration, tyrosine metabolism score, and pathway enrichment were evaluated using single-sample gene set enrichment analysis (ssGSEA). Finally, a nomogram model was developed with the RiskScore and other clinicopathological features. RESULTS: Based on the tyrosine metabolism genes in the TCGA cohort, we identified 3 tyrosine metabolism-related subtypes showing significant prognostic differences. Four candidate genes selected from the common differentially expressed genes (DEGs) between the 3 subtypes were used to develop a RiskScore model, which could effectively divide LIHC patients into high- and lowrisk groups. In both the training and validation sets, high-risk patients tended to have worse overall survival, less active immunotherapy response, higher immune infiltration and clinical grade, and higher oxidative, fatty, and xenobiotic metabolism pathways. Multivariate analysis confirmed that the RiskScore was an independent indicator for the prognosis of LIHC. The results from pan-- cancer analysis also supported that the RiskScore had a strong prognostic performance in other cancers. The nomogram demonstrated that the RiskScore contributed the most to the prediction of LIHC prognosis. CONCLUSION: Our study developed a tyrosine metabolism-related risk model that performed well in survival prediction, showing the potential to serve as an independent prognostic predictor for LIHC treatment.

Selective recovery of lithium from spent lithium iron phosphate batteries.

The recovery of lithium from spent lithium iron phosphate (LiFePO4) batteries is of great significance to prevent resource depletion and environmental pollution. In this study, through active ingredient separation, selective leaching and stepwise chemical precipitation develop a new method for the selective recovery of lithium from spent LiFePO4 batteries by using sodium persulphate (Na2S2O8) to oxidize LiFePO4 to FePO4. The impact of various variables on the efficiency of lithium leaching was investigated. Moreover, a combination of thermodynamic analysis and characterization techniques such as X-ray diffraction and X-ray photoelectron spectroscopy was employed to elucidate the leaching mechanism. It was found that 98.65% of lithium could be selectively leached in just 35 minutes at 60°C with only 0.2 times excess of Na2S2O8. This high leaching efficiency can be attributed to the stability and lack of structural damage during the oxidation leaching process. The proposed process is economically viable and environmentally friendly, thus showing great potential for the large-scale recycling of spent LiFePO4 batteries.

Development and Validation of a Deep Learning and Radiomics Combined Model for Differentiating Complicated From Uncomplicated Acute Appendicitis.

RATIONALE AND OBJECTIVES: This study aimed to develop and validate a deep learning and radiomics combined model for differentiating complicated from uncomplicated acute appendicitis (AA). MATERIALS AND METHODS: This retrospective multicenter study included 1165 adult AA patients (training cohort, 700 patients; validation cohort, 465 patients) with available abdominal pelvic computed tomography (CT) images. The reference standard for complicated/uncomplicated AA was the surgery and pathology records. We developed our combined model with CatBoost based on the selected clinical characteristics, CT visual features, deep learning features, and radiomics features. We externally validated our combined model and compared its performance with that of the conventional combined model, the deep learning radiomics (DLR) model, and the radiologist's visual diagnosis using receiver operating characteristic (ROC) curve analysis. RESULTS: In the training cohort, the area under the ROC curve (AUC) of our combined model in distinguishing complicated from uncomplicated AA was 0.816 (95% confidence interval [CI]: 0.785-0.844). In the validation cohort, our combined model showed robust performance across the data from three centers, with AUCs of 0.836 (95% CI: 0.785-0.879), 0.793 (95% CI: 0.695-0.872), and 0.723 (95% CI: 0.632-0.802). In the total validation cohort, our combined model (AUC = 0.799) performed better than the conventional combined model, DLR model, and radiologist's visual diagnosis (AUC = 0.723, 0.755, and 0.679, respectively; all P < 0.05). Decision curve analysis showed that our combined model provided greater net benefit in predicting complicated AA than the other three models. CONCLUSION: Our combined model allows the accurate differentiation of complicated and uncomplicated AA.

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Relationship between STAP1 methylation in peripheral blood T cells and the clinicopathological characteristics and prognosis of patients within 5-cm diameter HCC.

BACKGROUND: The aim of this study is to explore the methylation of signal transduction adaptor protein 1 (STAP1) in peripheral blood T cells as a prognostic marker for hepatocellular carcinoma (HCC) ≤5 cm. METHODS: A total of 66 HCC patients who visited our hospital from November 2012 to June 2016 were retrospectively analyzed, and 55 patients who met the inclusion and exclusion criteria were studied. Clinical and pathological data were collected from all patients to detect STAP1 methylation. STAP1 methylation expression was analyzed in HCC patients ≤5 cm with different clinicopathological features; univariate and independent prognostic factors were analyzed in HCC patients; and the relationship between STAP1 methylation expression and prognosis was analyzed in HCC patients. RESULTS: There was no significant difference in STAP1 methylation expression between patients with different gender, age, history of alcoholism, history of liver cirrhosis, recurrence, 3-year OS, 5-year OS, treatment, number of tumors, tumor diameter, HBV-DNA, HBSAg, Hbe-Ag expression, and AFP level (P>0.05); however, there was significant difference in STAP1 methylation expression between patients with different survival, 3-year DFS, and 5-year DFS (P<0.05). Multivariate Cox regression analysis showed that recurrence and STAP1 methylation were independent factors for OS and DFS (P<0.05). Kaplan-Meier survival curve results showed that the median survival time, OS, and DFS of STAP1 hypermethylation expression were shorter than those of hypomethylation (P<0.05). CONCLUSIONS: STAP1 methylation in peripheral blood T cells serves as a potential prognostic marker for HCC ≤5 cm.

Simultaneous Cr(VI) reduction and Cr(III) sequestration in a wide pH range by using magnetic chitosan-based biopolymer.

The simultaneous reduction of Cr(VI) and sequestration of the resulting Cr(III) in one process is highly desirable as a cost-effective and environmental-friendly approach for the decontamination of Cr(VI)-polluted wastewater. However, most of the existing adsorptive materials are only effective in low pH environments (pH = 1-3), severely restricting the adsorption efficiency and cost effectiveness. Herein, we proposed a chitosan-based magnetic porous microsphere (PPy@PMCS) for simultaneous Cr(VI) reduction and Cr(III) sequestration in a wide pH range. Benefiting from its abundant interaction sites, Cr(VI) was effectively adsorbed on the surface and then immediately reduced to Cr(III) with much lower toxicity. Most importantly, the resulting Cr(III) was in-situ sequestrated by the complexation of chitosan matrix. As a result, PPy@PMCS exhibited a maximum Cr(VI) adsorption capacity of 330.42 mg/g at pH 2.0 and an adsorption capacity of 167.82 mg/g even at near neutral pH (6.0), which is superior to most reported adsorbents. Furthermore, the exhausted PPy@PMCS can be rapidly separated from solutions under an external magnetic field and facilely regenerated. The proposed novel biopolymer-based material shows great application potentials in wastewater treatment.

Efficient HCl leaching of platinum group metals from waste three-way catalysts: A study on kinetics and mechanisms.

Waste three-way catalysts (TWCs) have attracted much attention due to the presence of platinum group metals (PGMs) and hazardous substances such as heavy metals and organic matter. The extraction of PGMs from waste TWCs using hydrochloric acid (HCl) has been extensively researched. However, the addition of oxidizing agents like H2O2 and aqua regia is necessary to facilitate PGMs dissolution, which poses significant environmental and operational hazards. Hence, developing a green PGMs recovery process without oxidants is imperative. Previously, we investigated the process of Li2CO3 calcination pretreatment to enhance the leaching of PGMs from waste TWCs by HCl, focusing on the process and mechanism of Li2CO3 calcination pretreatment. In this study, we focused on the leaching process of HCl after pretreatment. Our investigation includes a detailed examination of leaching kinetics and mechanisms. The optimal leaching conditions were: leaching temperature of 150 °C, leaching time of 2 h, HCl concentration of 12 M, and liquid-solid ratio of 10 mL/g. The experiments resulted in maximum leaching rates of about 96%, 97%, and 97% for Pt, Pd, and Rh, respectively. However, given the presence of heavy metals, attention needs to be paid to the harmless treatment of waste acids and leaching residues. The Pt and Pd leaching process is controlled by a mixture of interfacial chemical reactions and internal diffusion, and dominated by internal diffusion, while the leaching process of Rh is controlled by interfacial chemical reactions. Li+ in Li2PtO3, Li2PdO2, and Li2RhO3 preferentially leached and underwent ion-exchange reactions with H+, promoting the dissolution of Pt, Pd, and Rh in HCl.

Development of a nomogram for the prediction of acute kidney injury after liver transplantation: a model based on clinical parameters and postoperative cystatin C level.

BACKGROUND: Acute kidney injury (AKI) is common after liver transplantation (LT). We developed a nomogram model to predict post-LT AKI. METHODS: A total of 120 patients were eligible for inclusion in the study. Clinical information was extracted from the institutional electronic medical record system. Blood samples were collected prior to surgery and immediately after surgery. Univariable and multivariate logistic regression were used to identify independent risk factors. Finally, a nomogram was developed based on the final multivariable logistic regression model. RESULTS: In total, 58 (48.3%) patients developed AKI. Multivariable logistic regression revealed four independent risk factors for post-LT AKI: operation duration [odds ratio (OR) = 1.728, 95% confidence interval (CI) = 1.121-2.663, p = 0.013], intraoperative hypotension (OR = 3.235, 95% CI = 1.316-7.952, p = 0.011), postoperative cystatin C level (OR = 1.002, 95% CI = 1.001-1.004, p = 0.005) and shock (OR = 4.002, 95% CI = 0.893-17.945, p = 0.070). Receiver operating characteristic curve analysis was used to evaluate model discrimination. The area under the curve value was 0.815 (95% CI = 0.737-0.894). CONCLUSION: The model based on combinations of clinical parameters and postoperative cystatin C levels had a higher predictive performance for post-LT AKI than the model based on clinical parameters or postoperative cystatin C level alone. Additionally, we developed an easy-to-use nomogram based on the final model, which could aid in the early detection of AKI and improve the prognosis of patients after LT.

Acute kidney injury (AKI) is one of the most common and important complications after liver transplantation (LT).We developed a nomogram model to predict post-LT AKI based on clinical parameters and postoperative cystatin C level.The model based on combinations of clinical parameters and postoperative cystatin C levels had a higher predictive performance, which could aid in the early detection of AKI and improve the prognosis of patients after LT.

Application of enhanced recovery after surgery following liver transplantation.

OBJECTIVE: To investigate the effect of an enhanced recovery after surgery (ERAS) programme following liver transplantation and to further clarify the safety and clinical application value of an ERAS programme. METHODS: A retrospective analysis of 250 patients who underwent liver transplant at Beijing You'an Hospital affiliated to Capital Medical University between March 2019 and December 2021 was conducted. According to different perioperative management methods, patients were divided into a control group (120 cases) and an ERAS group (130 cases). Postoperative safety indicators, efficacy indicators and economic indicators were compared between the two groups. RESULTS: There was no significant difference in the safety indicators between the two groups. The ERAS group showed significantly lower results compared with the control group in terms of ventilator-associated pneumonia, urinary tract infection, pressure injury of oral and nasal mucosa, postoperative pain score 5 days after surgery and the incidence of delirium, whereas the Barthel score 10 days after surgery was significantly higher. There was no significant difference between the two groups in skin pressure injury or the Subjective Global Assessment grade 10 days after surgery. The length of intensive care unit stay, the total length of stay after surgery and the 10-day medical expenses after surgery were significantly lower in the ERAS group than in the control group. CONCLUSION: The application of an ERAS programme after liver transplantation can effectively promote the postoperative recovery of patients and reduce medical costs. Studies have shown that the ERAS programme has important application value in improving the postoperative quality of life and reducing the economic burden of patients after liver transplantation. This programme provides a new concept for related clinical improvement and application.

Macrophage-Derived Cathepsin S Remodels the Extracellular Matrix to Promote Liver Fibrogenesis.

BACKGROUND & AIMS: Liver fibrosis is an intrinsic wound-healing response to chronic injury and the major cause of liver-related morbidity and mortality worldwide. However, no effective diagnostic or therapeutic strategies are available, owing to its poorly characterized molecular etiology. We aimed to elucidate the mechanisms underlying liver fibrogenesis. METHODS: We performed a quantitative proteomic analysis of clinical fibrotic liver samples to identify dysregulated proteins. Further analyses were performed on the sera of 164 patients with liver fibrosis. Two fibrosis mouse models and several biochemical experiments were used to elucidate liver fibrogenesis. RESULTS: We identified cathepsin S (CTSS) up-regulation as a central node for extracellular matrix remodeling in the human fibrotic liver by proteomic screening. Increased serum CTSS levels efficiently predicted liver fibrosis, even at an early stage. Secreted CTSS cleaved collagen 18A1 at its C-terminus, releasing endostatin peptide, which directly bound to and activated hepatic stellate cells via integrin α5ß1 signaling, whereas genetic ablation of Ctss remarkably suppressed liver fibrogenesis via endostatin reduction in vivo. Further studies identified macrophages as the main source of hepatic CTSS, and splenectomy effectively attenuated macrophage infiltration and CTSS expression in the fibrotic liver. Pharmacologic inhibition of CTSS ameliorated liver fibrosis progression in the mouse models. CONCLUSIONS: CTSS functions as a novel profibrotic factor by remodeling extracellular matrix proteins and may represent a promising target for the diagnosis and treatment of liver fibrosis.