Development and Validation of a Machine Learning-Based Model Used for Predicting Hepatocellular Carcinoma Risk in Patients with Hepatitis B-Related Cirrhosis: A Retrospective Study.

Object: Our objective was to estimate the 5-year cumulative risk of HCC in patients with HBC by utilizing an artificial neural network (ANN). Methods: We conducted this study with 1589 patients hospitalized at Beijing Ditan Hospital of Capital Medical University and People's Liberation Army Fifth Medical Center. The training cohort consisted of 913 subjects from Beijing Ditan Hospital of Capital Medical University, while the validation cohort comprised 676 subjects from People's Liberation Army Fifth Medical Center. Through univariate analysis, we identified factors that independently influenced the occurrence of HCC, which were then used to develop the ANN model. To evaluate the ANN model, we assessed its predictive accuracy, discriminative ability, and clinical net benefit using metrics such as the area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration curves. Results: In total, we included nine independent risk factors in the development of the ANN model. Remarkably, the AUC of the ANN model was 0.880, significantly outperforming the AUC values of other existing models including mPAGE-B (0.719) (95% CI 0.670-0.768), PAGE-B (0. 710) (95% CI 0.660-0.759), FIB-4 (0.693) (95% CI 0.640-0.745), and Toronto hepatoma risk index (THRI) (0.705) (95% CI 0.654-0.756) (p<0.001 for all). The ANN model effectively stratified patients into low, medium, and high-risk groups based on their 5-year In the training cohort, the positive predictive value (PPV) for low-risk patients was 26.2% (95% CI 25.0-27.4), and the negative predictive value (NPV) was 98.7% (95% CI 95.2-99.7). For high-risk patients, the PPV was 54.7% (95% CI 48.6-60.7), and the NPV was 91.6% (95% CI 89.4-93.4). These findings were validated in the independent validation cohort. Conclusion: The ANNs model has good individualized prediction performance and may be helpful to evaluate the probability of the 5-year risk of HCC in patients with HBC.

Competitive adsorption behavior of typical heavy metal ions from acid mine drainage by multigroup-functionalization cellulose: qualitative and quantitative mechanism.

In response to Cd, Pb, and Cu pollution in acid mine drainage (AMD), a multigroup cellulose material (TCIS) containing thiol (-SH), carboxyl (-COOH), and imine (-C = N) groups was prepared through oxidation and grafting reactions. At pH 5, the maximum Cd(II), Pb(II), and Cu(II) adsorption performances of TCIS were 53.60, 120.6, and 36.01 mg/g, respectively. In the binary system, the interaction between metal ions was mainly inhibited by competitive adsorption. Cu(II) exhibited the most fierce inhibitory effect and had a relatively stable adsorption performance. In the ternary system, the adsorption order was Cu(II) > Cd(II) > Pb(II). In density functional theory (DFT) calculations, we combined the molecular electrostatic potentials, binding energies, differential charges, and total potentials to illustrate the competitive behavior of metal ions at different binding sites. Moreover, X-ray photoelectron spectroscopy (XPS) and DFT analysis revealed that the adsorption process of TCIS was dominated by the above functional groups, which caused competitive adsorption among Cd(II), Pb(II), and Cu(II).

Association between inflammatory cytokines and symptoms of major depressive disorder in adults.

Objective: This study investigated the association between inflammatory cytokines and major depressive disorder. Methods: Plasma biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Statistical analysis of baseline biomarkers in the major depression disorder (MDD) group and healthy controls (HC) group, and differences in biomarkers before and after treatment. Spearman analysis was performed to correlate baseline and after treatment MDD biomarkers with the 17-item Hamilton Depression Rating Scale (HAMD-17) total scores. Receiver operator characteristic (ROC) curves were analyzed for the effect of biomarkers on MDD and HC classification and diagnosis. Results: Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were significantly higher in the MDD group than in the HC group, while high mobility group protein 1 (HMGB1) levels were significantly lower in the MDD group. The AUCs for HMGB1, TNF-α, and IL-6 were 0.375, 0.733, and 0.783, respectively, according to the ROC curves. MDD patients with brain-derived neurotrophic factor precursor (proBDNF) levels were positively correlated with total HAMD-17 scores. The levels of proBDNF levels were positively correlated with the total HAMD-17 score in male MDD patients, and brain-derived neurotrophic factor (BDNF) and interleukin 18 (IL-18) levels were negatively correlated with the total HAMD-17 score in female MDD patients. Conclusion: Inflammatory cytokines are associated with the severity of MDD, and TNF-α and IL-6 have the potential as objective biomarkers to aid in the diagnosis of MDD.

Effect of miRNA-200b on the proliferation of liver cancer cells via targeting SMYD2/p53 signaling pathway. / MiR-200b通过靶向调控SMYD2/p53信号通路抑制肝癌细胞增殖（英文）.

OBJECTIVES: Our previous study has verified that high level of SET and MYND domain-containing protein 2 (SMYD2) plays an important role in acquiring aggressive ability for liver cancer cells in hepatocellular carcinoma. MiR-200b as a tumor suppressor gene involves in a variety of cancers. This study aims to investigate the correlation between miR-200b and SMYD2 in hepatocellular carcinoma and the underlying mechanism. METHODS: Firstly, the levels of SMYD2 and miR-200b in hepatocellular carcinoma tissues and matched adjacent non-tumor liver tissues were tested with real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Secondly, we evaluated the interaction between miR-200b and SMYD2 using dual-luciferase reporter assay. Thirdly, we elucidated the effect of miR-200b on SMYD2 and its downstream targets p53/CyclinE1. Finally, we silenced SMYD2 in hepatocellular carcinoma cell lines to investigate its effect on tumor proliferation and cell cycle progression, and further confirmed the correlation among SMYD2 and p53/CyclinE1. RESULTS: Compared with the matched adjacent non-tumor liver tissues, miR-200b was obviously decreased, and SMYD2 was significantly increased in hepatocellular carcinoma (both P<0.05). Spearman's rank correlation revealed that miR-200b expression was negatively correlated with SMYD2 (P<0.01). Computer algorithm and dual-luciferase reporter assay revealed that miR-200b directly targeted and suppressed SMYD2 in HEK 293T cells. The down-regulated miR-200b expression promoted hepatoma cell proliferation (P<0.05) and increased SMYD2 expression(P<0.01), while the up-regulated expression of miR-200b had an opposite effect. The knockdown of SMYD2 suppressed the proliferation of MHCC-97L cells (P<0.01), down-regulated CyclinE1, and up-regulated p53 expression (both P<0.05). CONCLUSIONS: MiR-200b is involved in hepatocellular carcinoma progression via targeting SMYD2 and regulating SMYD2/p53/CyclinE1 signaling pathway and may be used as a potential target for hepatocellular carcinoma treatment.

Maternal exposure to atmospheric PM2.5 and fetal brain development: Associations with BAI1 methylation and thyroid hormones.

Maternal exposure to atmospheric fine particulate matter (PM2.5) during pregnancy is associated with adverse fetal development, including abnormal brain development. However, the underlying mechanisms and influencing factors remain uncertain. This study investigated the roles of DNA methylation in genes involving neurodevelopment and thyroid hormones (THs) in fetal brain development after maternal exposure to PM2.5 from e-waste. Among 939 healthy pregnant women recruited from June 2011 to September 2012, 101 e-waste-exposed and 103 reference mother-infant pairs (204 pairs totally) were included. Annual ground-level PM2.5 concentrations over e-waste-exposed area (116.38°E, 23.29°N) and reference area (116.67°E, 23.34°N) in 2011, 2012 were obtained by estimates and maternal exposure was evaluated by calculating individual chronic daily intakes (CDIs) of PM2.5. Methylation and THs including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) level were measured in umbilical cord blood collected shortly after delivery. We found higher ground-level PM2.5 concentrations led to greater individual CDI of PM2.5 in e-waste-exposed pregnant women. After adjustment for gender and birth BMI, significant mediation effects on the adverse associations of maternal PM2.5 exposure with birth head circumference were observed for methylations at positions +13 and + 32 (respectively mediated proportion of 9.8% and 5.3%, P < 0.05 and P < 0.01) in the brain-specific angiogenesis inhibitor 1 (BAI1) gene, but not for methylations in the catenin cadherin-associated protein, alpha 2 (CTNNA2) gene. BAI1 (position +13) methylation was also significantly correlated with FT3 levels (rs = -0.156, P = 0.032), although maternal CDI of PM2.5 was positively associated with higher odds of abnormal TSH levels (OR = 5.03, 95% CI: 1.00, 25.20, P = 0.05) rather than FT3 levels. Our findings suggest that methylation (likely linked to THs) in neonates may play mediation roles associated with abnormal brain development risk due to maternal exposure to atmospheric PM2.5 from e-waste.

Various detailed characteristics of a new enhanced neurotrophic factor secreting rat derived bone marrow mesenchymal stem cells and its preliminary application in rat models of ischemic stroke.

Because MSC-NTF has a higher ability to secrete neurotrophic factors, it may have a greater potential than ordinary MSC in clinical applications. At present, research on MSC-NTF mainly focuses on clinical aspects, but its basic research is relatively few. In particular, the research on the comprehensive and detailed characteristics of MSC-NTF is missing. And its in vivo research in animals is also rare. Since the transplantation of human-derived MSC-NTF into rats is cross-species, its survival in the rat and the therapeutic effect may be seriously affected due to severe immune rejection. This will inevitably affect the research on the basic characteristics and the therapeutic mechanisms of MSC-NTF in vivo. Therefore, we chose the rat-derived MSCs to be induced as the MSC-NTF which had a stronger neurotrophic factor secretion function. This will also be helpful to perform the research of the basic therapeutic mechanisms of MSC-NTF in vivo. In addition, we have established some important characteristics that can be used to distinguish between MSC-NTF and MSCs: different multi-factor secretion ability and secretion characteristics, immunogenicity, three-line differentiation ability, stemness, etc. In addition to paying attention to their safety differences, this study also explored the differences in their in vivo survivability. Finally, we applied this newly induced rat-derived MSC-NTF in a rat model of ischemic stroke, and obtained beneficial therapeutic effects.

Correlation of structural extracellular polymeric substances in the mesh biofilms with solids retention time and biofilm hydraulic resistance in dynamic membrane bioreactors.

Dynamic membrane bioreactor (DMBR), which mainly relied on the in-situ formed biofilms on support materials with large aperture (e.g., nylon mesh) to separate fine particles in wastewater, has attracted a lot of attentions due to low cost. The filtration performance of DMBR is mainly determined by the structure and hydraulic resistance of biofilms formed on the mesh. Therefore, understanding the correlation of operation conditions with mesh biofilm compositions and permeability are critically important for optimizing DMBR operation. In present study, how structural extracellular polymeric substances, including alginate-like extracellular polysaccharide (ALE) and amyloid-like protein (AP), in mesh biofilms correlate to solids retention time (SRT) and biofilm structures was explored in DMBRs. At 5d-SRT, compact and gel-like mesh biofilms were formed with a high specific filtration resistance (SFR) of 459 × 109 m/g, while at 40d-SRT porous mesh biofilms were developed with a low SFR of 24 × 109 m/g. Consequently, the 5d-SRT MBR experienced more rapid rise in transmembrane pressure. Further studies found that the 5d-SRT mesh biofilms had a higher AP content, which was positively correlated to biofilm hydraulic resistance. On the contrary, the 40d-SRT mesh biofilms contained a higher content of ALE, suggesting that ALE was negatively correlated to biofilm hydraulic resistance. Therefore, AP instead of ALE likely played a more important role in the formation of compact and gel-like mesh biofilms.

Highly TEMPO-oxidized cellulose for removal of ionic and complexed cadmium from a complicated water system.

TEMPO-NaDCC-oxidized cellulose (TNOCS) with a large surface area and an abundance of carboxyl groups was used to remove heavy metal ions (Cd, Cu, and Pb) and their organic acid complexes [HM-OAs] (OAs, i.e., citric acid (CA) and propionic acid (PA)), and then reveal their adsorption behaviors. Taking Cd and CA as examples, the results showed that some of Cd ions were first adsorbed onto TNOCS, and then, the existence of [Cd-CA-] complexes formed a coordinated structure with preloaded Cd ions to serve as a bridge for combining TNOCS and [Cd-CA]. The maximum adsorption capacities of TNOCS for Cd and Cd-CA were 16.50 and 22.15 mg/g, respectively. Moreover, adsorption energies and molecular orbital distributions indicated that the adsorption capacity of TNOCS for [Cd-CA] was better than that for Cd alone. TNOCS can maintain greater than 90% adsorption capacity in five times regeneration experiments using EDTA, indicating that it is very efficient and stable. In addition, the electron density, deformation charge, and Mulliken charge distribution were confirmed that the electron transfer direction was from carboxyl groups to cadmium, whether it was cadmium ions or complexed cadmium.

Predicting the prognosis of glioma by pyroptosis-related signature.

Glioma is the most common malignant primary brain tumour. It is of great significance for the prognosis and personalized treatment of glioma patients to accurate identification of glioma based on biomarkers. Pyroptosis, a kind of programmed cell death, is closely related to tumour progression and tumour immune microenvironment. However, the role of pyroptosis in glioma remained unclear. Herein, we used glioma clinical and expression data from TCGA and CGGA to explore the relationship between pyroptosis and glioma. We first summarized the incidence of copy number variations and somatic mutations of 33 pyroptosis-related genes and explored prognostic correlation of these genes. Based on pyroptosis-related genes, three molecular subgroups of glioma related to prognosis were identified. We also found that each subgroup has unique immune and biological behaviours characteristics. Finally, based on 7 pyroptosis-related genes (CASP3, CASP4, CASP6, CASP8, CASP9, PRKACA and ELANE), we constructed a prognosis model by Lasso and Cox regression, which had a strong predictive power for the overall survival in CGGA test cohort (p < 0.05). In summary, we explored the role of pyroptosis-related genes in gliomas and the association of these genes with tumour immunity. We found the biomarkers valuable to diagnosis and prognosis, hence, provide reference to the development and treatment of tumorigenesis in glioma.

Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. PURPOSE: To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. METHODS: We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. RESULTS: After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p < 0.0001), shorter time to negative conversion of viral nucleic acid (p < 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p < 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1ß, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation. CONCLUSION: YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway.

Shexiang Baoxin Pill for Acute Myocardial Infarction: Clinical Evidence and Molecular Mechanism of Antioxidative Stress.

Acute myocardial infarction (AMI) has been a preclinical and clinical concern due to high hospitalization rate and mortality. This study was aimed at evaluating the effectiveness and safety of Shexiang Baoxin Pill (SBP) for AMI and exploring the possible mechanism of oxidative stress. Six databases were searched on March 26, 2021. Twenty-four studies were included and accessed by the RoB 2.0 or SYRCLE tool. Compared with routine treatment (RT), SBP showed the effectiveness in the clinical efficacy (RR = 1.15, 95% CI [1.06, 1.25]), left ventricular ejection fraction (LVEF) (SMD = 0.73, 95% CI [0.62, 0.95]), glutathione (GSH) (SMD = 2.07, 95% CI [1.51, 2.64]), superoxide dismutase (SOD) (SMD = 0.92, 95% CI [0.58, 1.26]), malondialdehyde (MDA) (SMD = -4.23, 95% CI [-5.80, -2.66]), creatine kinase-myocardial band (CK-MB) (SMD = -4.98, 95% CI [-5.64, -4.33]), cardiac troponin I (cTnI) (SMD = -2.17, 95% CI [-2.57, -1.76]), high-sensitivity C-reactive protein (Hs-CRP) (SMD = -1.34, 95% CI [-1.56, -1.12]), interleukin-6 (IL-6) (SMD = -0.99, 95% CI [-1.26, -0.71]), triglycerides (TG) (SMD = -0.52, 95% CI [-0.83, -0.22]), flow-mediated dilation (FMD) (SMD = 1.39, 95% CI [1.06, 1.72]), von Willebrand Factor (vWF) (SMD = -1.77, 95% CI [-2.39, -1.15]), nitric oxide (NO) (SMD = 0.89, 95% CI [0.65, 1.13]), and recurrent rate (RR = 0.30, 95% CI [0.15, 0.59]). But SBP adjunctive to RT plus PCI had no improvements in almost pooled outcomes except for the Hs-CRP (SMD = -1.19, 95% CI [-1.44, -0.94]) and TG (SMD = -0.25, 95% CI [-0.48, -0.02]). Laboratory findings showed that SBP enhanced the endothelial nitric oxide synthase (eNOS) activity and regulated laboratory indexes especially for homocysteine. In conclusion, SBP has adjunctive effects on AMI via the mechanism of antioxidative stress. The current evidence supports the use of SBP for mild and moderate AMI patients.

Molecular Mechanism of Astragaloside IV in Improving Endothelial Dysfunction of Cardiovascular Diseases Mediated by Oxidative Stress.

Endothelial dysfunction, induced by oxidative stress, is an essential factor affecting cardiovascular disease. Uncoupling of endothelial nitric oxide synthase (eNOS) leads to a decrease in nitric oxide (NO) production, an increase in reactive oxygen species (ROS) production, NO consumption, and NO synthesis. As a main active ingredient of astragalus, astragaloside IV can reduce the apoptosis of endothelial cells during oxidative stress. This review is aimed at exploring the mechanism of astragaloside IV in improving oxidative stress-mediated endothelial dysfunction relevant to cardiovascular diseases. The findings showed that the astragaloside IV can prevent or reverse the uncoupling of eNOS, increase eNOS and NO, and enhance several activating enzymes to activate the antioxidant system. In-depth validation and quantitative experiments still need to be implemented.

Exploring the Biological Mechanism of Huang Yam in Treating Tumors and Preventing Antitumor Drug-Induced Cardiotoxicity Using Network Pharmacology and Molecular Docking Technology.

Drugs for the treatment of tumors could result in cardiotoxicity and cardiovascular diseases. We aimed to explore the anticancer properties of Huang yam as well as its cardioprotective properties using network pharmacology and molecular docking technology. The cardiovascular targets of the major chemical components of Huang yam were obtained from the following databases: TCMSP, ETCM, and BATMAN-TCM. The active ingredients of Huang yam were obtained from SwissADME. The cardiovascular targets of antitumor drugs were obtained using GeneCards, OMIM, DrugBank, DisGeNET, and SwissTargetPrediction databases. The drug-disease intersection genes were used to construct a drug-compound-target network using Cytoscape 3.7.1. A protein-protein interaction network was constructed using Cytoscape's BisoGenet, and the core targets of Huang yam were screened to determine their antitumor properties and identify the cardiovascular targets based on topological parameters. Potential targets were imported into the Metascape platform for GO and KEGG analysis. The results were saved and visualized using R software. The components with higher median values in the network were molecularly docked with the core targets. The network contained 10 compounds, including daucosterol, delusive, dioxin, panthogenin-B, and 124 targets, such as TP53, RPS27A, and UBC. The GO function enrichment analysis showed that there were 478 items in total. KEGG enrichment analysis showed a total of 140 main pathways associated with abnormal transcription of cancer, PI3K-Akt signaling pathway, cell cycle, cancer pathway, ubiquitination-mediated proteolysis, and other pathways. Molecular docking results showed that daucosterol, delusive, dioxin, and panthogenin-B had the highest affinity for TP53, RPS27A, and UBC. The treatment of diseases using traditional Chinese medicine encompasses multiple active ingredients, targets, and pathways. Huang yam has the potential to treat cardiotoxicity caused by antitumor drugs.

Discovery of hydrazide-containing oseltamivir analogues as potent inhibitors of influenza A neuraminidase.

Neuraminidase (NA) inhibitors play a prime role in treating influenza. However, a variety of viruses containing mutant NAs have developed severe drug resistance towards NA inhibitors, so it is of crucial significance to solve this problem. Encouraged by urea-containing compound 12 disclosed by our lab, we designed a series of oseltamivir derivatives bearing hydrazide fragment for targeting the 150 cavity. Among the synthesized compounds, compound 17a showed 8.77-fold, 4.12-fold, 203-fold and 6.23-fold more potent activity than oseltamivir carboxylate against NAs from H5N1, H1N1, H5N1-H274Y, H1N1-H274Y, respectively. Meanwhile, the best compound 17a exhibited satisfactory metabolic stability in vitro. This study offers an important reference for the structural optimization of oseltamivir aiming at potent inhibition against H274Y mutant of NAs.

Multiple adsorption systems and electron-scale insights into the high efficiency coadsorption of a novel assembled cellulose via experiments and DFT calculations.

In view of the characteristics of heavy metal and antibiotic compound pollution in the Pearl River Basin in Guangzhou. More scientifically modified cellulose, named HVUC, is characterized by multiple hydrophilic groups, long chains and large space and displays highly efficient adsorption of both Cd and sulfamethoxazole (SMZ) and good adaptability in a wide pH range and at high ion strength. Furthermore, the coadsorption mechanism was elaborated from multiple angles. Multiple adsorption experiments explained the competition and synergy effect in the adsorption process. The electrostatic potential maps indicated that HVUC had advantageous adsorption sites for both Cd and SMZ and that electrostatic interactions had the greatest impact on the adsorption of Cd and SMZ. The electron density and differential charge density images proved that Cd more easily overlapped electron clouds and transferred electrons with HVUC and that SMZ- and could act as a bridge for SMZ-. The equilibrium configuration indicated that the formation of Cd-SMZ- complexes led to the bending and folding of SMZ-, which was not conducive to overall adsorption when SMZ- was close to HVUC and could lead to the release of SMZ- when Cd was close to HVUC, which confirmed the proposed mechanism of complexation-decomplexation-complexation.

AKR1B10 negatively regulates autophagy through reducing GAPDH upon glucose starvation in colon cancer.

Autophagy is considered to be an important switch for facilitating normal to malignant cell transformation during colorectal cancer development. Consistent with other reports, we found that the membrane receptor Neuropilin1 (NRP1) is greatly upregulated in colon cancer cells that underwent autophagy upon glucose deprivation. However, the mechanism underlying NRP1 regulation of autophagy is unknown. We found that knockdown of NRP1 inhibits autophagy and largely upregulates the expression of aldo-keto reductase family 1 B10 (AKR1B10). Moreover, we demonstrated that AKR1B10 interacts with and inhibits the nuclear importation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and then subsequently represses autophagy. Interestingly, we also found that an NADPH-dependent reduction reaction could be induced when AKR1B10 interacts with GAPDH, and the reductase activity of AKR1B10 is important for its repression of autophagy. Together, our findings unravel a novel mechanism of NRP1 in regulating autophagy through AKR1B10.

Adsorption behavior of Cd (II) on TEMPO-oxidized cellulose in inorganic/ organic complex systems.

2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) was oxidized to produce TEMPO-oxidized cellulose (TOCS) with a nanofunctionalized surface and abundant carboxyl groups. In a batch experiment, three pH values (2, 5 and 7), three modes (single, binary and multiple systems), and systems with inorganic and organic materials were applied to explore the adsorption of coexisting metals and antibiotics on TOCS. The adsorption capacity of TOCS was substantially influenced by these factors, and the adsorption behaviors were also different in these systems. In general, the coordination behaviors and electrostatic attraction between Cd(II) and carboxyl groups were identified as the mechanism employed by the single system, while hydrophobic interactions, π interactions, hydrogen bonding and pore filling contributed to the adsorption of sulfonamides (SAs) on TOCS in the binary system. The bridging effect was determined to be the key mechanism; i.e., most Cd(II) and SAs in the form of [SA-Cd] complexes interacted with carboxyl groups, especially in the presence of high concentrations of Cd(II) and SAs. These adsorption behaviors were determined quantitatively by performing density functional theory (DFT) calculations. In addition, TOCS showed excellent adsorption capacity in a more complex interference system, and the maximum adsorption capacity was 5.83 mg/g.

Solution pH affects single, sequential and binary systems of sulfamethoxazole and cadmium adsorption by self-assembled cellulose: Promotion or inhibition?

A new self-assembled cellulose (SACS) containing multi-functional amine, carboxyl and hydroxyl groups was successfully obtained through etherification, cross-linking and grafting processes. Then, the adsorption of sulfamethoxazole (SMZ) and Cd(II) onto SACS at pH values of 3, 5.7 and 7.5 was systematically investigated by batch experiments of single, sequential and binary systems, characterization and density functional theory (DFT) calculations. The presence of Cd(II) decreased the adsorption of SMZ because of hydrophilic site competition, while SMZ inversely increased the adsorption of Cd(II), which was attributed to bridging and especially to electrostatic shielding effects; moreover, both the inhibitory and synergistic effects were more obvious in the binary system and at a pH of 7.5. There was a dynamic balance between the inhibitory and synergistic effects that depended on the system, pH value and concentration ratio. DFT results further indicated that SMZ- more easily coordinated with Cd(II) at sulfonyl oxygen and nitrogen sites, and the cationic bridge of Cd(II) with SMZ- mainly occurred in the sequential system. Moreover, a complexation-decomplexation-complexation balance of SMZ- and Cd(II) probably occurred in the binary system.

Serum Clusterin: A Potential Marker for Assessing the Clinical Severity and Short-Term Prognosis of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by acute deterioration of liver function and high short-term mortality. Clusterin, with biological functions similar to small heat shock proteins, can protect cells from apoptosis induced by various stressors. The aim of this study was to detect the level of serum clusterin in hepatitis B virus- (HBV-) related ACLF and to assess the predictive value of clusterin for the short-term prognosis of HBV-ACLF. METHODS: We detected serum clusterin by ELISA in 108 HBV-ACLF patients, 63 HBV-non-ACLF patients, and 44 normal controls. RESULTS: Serum clusterin was markedly lower in HBV-ACLF patients (median, 51.09 µg/mL) than in HBV-non-ACLF patients (median, 188.56 µg/mL) and normal controls (median, 213.45 µg/mL; all P < 0.05). Nonsurviving HBV-ACLF patients who died within 90 days had much lower clusterin levels than did surviving patients, especially those who died within 28 days (nonsurvival group vs. survival group: 39.82 ± 19.34 vs. 72.26 ± 43.52, P < 0.001; survival time ≤ 28 vs. survival time > 28: median 28.39 vs. 43.22, P = 0.013). The results showed that for identifying HBV-ACLF, the sensitivity of clusterin (93.7%) was similar to the sensitivities of the international normalized ratio (INR; 94.4%) and total bilirubin (TBIL; 94.8%), but its specificity (90.7%) was higher than that of prothrombin activity (PTA; 65.8%) and TBIL (69.8%) and was similar to INR (88.9%). As the concentration of clusterin increased, the mortality of HBV-ACLF patients decreased significantly from 59.3% to 7.0%. Clusterin had better ability for predicting the prognosis of HBV-ACLF patients than did the model for end-stage liver disease (MELD) score and the chronic liver failure consortium (CLIF-C) ACLF score (MELD vs. clusterin: P = 0.012; CLIF-C ACLF vs. clusterin: P = 0.031). CONCLUSION: Serum clusterin is a potential biomarker for HBV-ACLF which can be used to assess clinical severity and the short-term prognosis of patients with this disease and may help clinicians identify HBV-ACLF with greater specificity and improved prognostic accuracy than existing prognostic markers.

A randomized controlled trial for gualou danshen granules in the treatment of unstable angina pectoris patients with phlegm-blood stasis syndrome.

INTRODUCTION: Unstable angina pectoris is an acute exacerbation secondary to coronary artery occlusion. In routine clinical treatment, patients with unstable angina pectoris are prone to recurrence or aggravation of symptoms. Based on the traditional Chinese medicine (TCM) theory, phlegm, and blood stasis are one of the main pathological factors of unstable angina pectoris. The treatment of unstable angina pectoris with phlegm-blood stasis syndrome by Gualou Danshen granules (GLDS) has been the focus of many clinical trials. However, there is no evidence to prove the safety or clinical efficacy of GLDS. METHODS AND ANALYSIS: In this study, we will conduct a 4-week randomized, controlled feasibility study, with participants recruited from Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine. Sixty subjects are to be diagnosed as having phlegm-blood stasis syndrome and randomly divided into a treatment group (GLDS) and placebo group in a 1:1 ratio. Result measurements will include therapeutic indicators (Clinical Symptom Rating Scale, Phlegm-Blood Stasis Syndrome Scale, and Seattle Angina Questionnaire) and safety indicators (blood routine, urine routine, electrocardiogram, liver function, and kidney function). The clinical data management system (http://www.tcmcec.net/) will be used to collect and manage data. Quality control will be implemented according to good clinical practice. DISCUSSION: Previous TCM clinical trials have investigated if adding GLDS to standard routine treatment can improve the therapeutic effect in patients with unstable angina pectoris. This study focuses on the safety and efficacy of GLDS on unstable angina pectoris of phlegm-blood stasis type, in order to obtain relevant clinical evidence. TRIAL REGISTRATION: This study is approved by the Ethics Committee of Guang'anmen Hospital of the China Academy of Chinese Medical Sciences (no. 2019-187-KY-02) and is registered with chictr.org (registration number ChiCTR2000031780).