Comprehensive metabolome characterization and comparison between two sources of Dragon's blood by integrating liquid chromatography/mass spectrometry and chemometrics.

Dragon's Blood (DB) serves as a precious Chinese medicine facilitating blood circulation and stasis dispersion. Daemonorops draco (D. draco; Qi-Lin-Jie) and Dracaena cochinchinensis (D. cochinchinenesis; Long-Xue-Jie) are two reputable plant sources for preparing DB. This work was designed to comprehensively characterize and compare the metabolome differences between D. draco and D. cochinchinenesis, by integrating liquid chromatography/mass spectrometry and untargeted metabolomics analysis. Offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), by utilizing a powerful hybrid scan approach, was elaborated for multicomponent characterization. Configuration of an XBridge Amide column and an HSS T3 column in offline mode exhibited high orthogonality (A0 0.80) in separating the complex components in DB. Particularly, the hybrid high-definition MSE-high definition data-dependent acquisition (HDMSE-HDDDA) in both positive and negative ion modes was applied for data acquisition. Streamlined intelligent data processing facilitated by the UNIFI™ (Waters) bioinformatics platform and searching against an in-house chemical library (recording 223 known compounds) enabled efficient structural elucidation. We could characterize 285 components, including 143 from D. draco and 174 from D. cochinchinensis. Holistic comparison of the metabolomes among 21 batches of DB samples by the untargeted metabolomics workflows unveiled 43 significantly differential components. Separately, four and three components were considered as the marker compounds for identifying D. draco and D. cochinchinenesis, respectively. Conclusively, the chemical composition and metabolomic differences of two DB resources were investigated by a dimension-enhanced analytical approach, with the results being beneficial to quality control and the differentiated clinical application of DB.

Inhaled nanoparticles for treating idiopathic pulmonary fibrosis by inhibiting honeycomb cyst and alveoli interstitium remodeling.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality. The Food and Drug Administration-approved drugs, nintedanib and pirfenidone, could delay progressive fibrosis by inhibiting the overactivation of fibroblast, however, there was no significant improvement in patient survival due to low levels of drug accumulation and remodeling of honeycomb cyst and interstitium surrounding the alveoli. Herein, we constructed a dual drug (verteporfin and pirfenidone)-loaded nanoparticle (Lip@VP) with the function of inhibiting airway epithelium fluidization and fibroblast overactivation to prevent honeycomb cyst and interstitium remodeling. Specifically, Lip@VP extensively accumulated in lung tissues via atomized inhalation. Released verteporfin inhibited the fluidization of airway epithelium and the formation of honeycomb cyst, and pirfenidone inhibited fibroblast overactivation and reduced cytokine secretion that promoted the fluidization of airway epithelium. Our results indicated that Lip@VP successfully rescued lung function through inhibiting honeycomb cyst and interstitium remodeling. This study provided a promising strategy to improve the therapeutic efficacy for IPF.

Loss of ZNRF3/RNF43 Unleashes EGFR in Cancer.

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the most negatively correlated protein with ZNRF3/RNF43 mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression of ZNRF3 reduces EGFR levels and suppresses cancer cell growth in vitro and in vivo, whereas knockout of ZNRF3/RNF43 stimulates cell growth and tumorigenesis through upregulated EGFR signaling. Together, these data highlight ZNRF3 and RNF43 as novel E3 ubiquitin ligases of EGFR and establish the inactivation of ZNRF3/RNF43 as a driver of increased EGFR signaling, ultimately promoting cancer progression. This discovery establishes a connection between two fundamental signaling pathways, EGFR and WNT, at the level of cytoplasmic membrane receptor, uncovering a novel mechanism underlying the frequent co-activation of EGFR and WNT signaling in development and cancer.

Reduction in NGAL at 48 h predicts the progression to CKD in patients with septic associated AKI: a single-center clinical study.

BACKGROUND: In this study, our objective was to investigate the predictive value of serum and urine fluctuations of neutrophil gelatinase-associated lipid transporters (NGAL) in relation to the progression of chronic kidney disease (CKD) among patients with septic associated AKI (SA-AKI). METHODS: A total of 425 SA-AKI patients were enrolled in this study and divided into the recovery group (n = 320) and the AKI-to-CKD group (n = 105) based on 3-month follow-up data. The serum and urine NGAL levels on the day of AKI diagnosis (T0) and 48 h after anti-AKI treatment (T1) were recorded and calculated. RESULTS: The levels of NGAL in serum and urine were found to be higher in the AKI-to-CKD group compared to the recovery group at T1 point (P < 0.05). The reductions of NGAL at 48 h in serum and urine were lower in the AKI-to-CKD group than those observed in the recovery group (P < 0.05). In comparison to T0, a significant decrease was noted for both serum and urine NGAL levels on T1 among patients who recovered from AKI (P < 0.05), whereas no such trend was observed among those with AKI-to-CKD transition (P > 0.05). After adjusting age, sex, and BMI through partial correlation analysis, the reduction of serum NGAL was found to be most strongly associated with the transition from AKI to CKD. ROC analysis showed an AUC of 0.832 for serum NGAL reduction, with a cut-off value of - 111.24 ng/ml and sensitivity and rates of 76.2% and 81.2%, respectively. Logistic regression analysis indicated that a reduction of serum NGAL ≥ - 111.24 ng/ml was the early warning indicator for the progression of CKD in SA-AKI patients. CONCLUSION: The reduction of serum NGAL following 48 h of anti-AKI therapy represents a distinct hazard factor for the advancement of CKD in patients with SA-AKI, independent of other variables.

Efficient treatment of palladium from wastewater by acrolein cross-linked chitosan hydrogels: Adsorption, kinetics, and mechanisms.

Herein we present a study on the preparation and properties of a hydrogel adsorbent for treatment of wasted palladium souring from actial petrochemical industrial wastewater. Chitosan was used as the raw material and acrolein as the cross-linking agent for the hydrogel (A/CS). The adsorption behaviors of the hydrogel for Pd(II) ions were characterized and analyzed. The effect of pH, temperature, adsorption kinetics, and thermodynamics were investigated. Langmuir models were employed to describe the adsorption isotherms, while the pseudo-second-order equation was applied to describe the adsorption kinetics. The experimental results demonstrated that the adsorption was a monolayer chemical adsorption, and the adsorption capacity was found to reach 505.05 mg/g under optimal conditions. In addition, FT-IR and XPS analyses, combined with MS calculations confirmed that chelation and electrostatic attraction were dominated in the adsorption process. Overall, the development of this hydrogel adsorbent will provide a practical approach to the treatment of industrial wastewater containing palladium and have great potential for practical applications.

Konjac glucomannan-based aerogels with excellent thermal stability and flame retardancy for thermal insulation application.

Biomass aerogels are a promising kind of environment-friendly thermal insulation material. However, the flammability, poor water resistance, and thermal instability of biomass aerogels limit their applications. Herein, freeze-drying and thermal imidization were used to create konjac glucomannan (KGM), boron nitride (BN), and polyimide (PI)-based aerogels with a semi-interpenetrating network structure. The introduction of BN was beneficial to improve the mechanical properties and thermal stability of aerogels. The imidization process of PI improved the hydrophobicity, mechanical property, and flame retardancy of the aerogels. The synergistic effect of PI and BN reduced the peak heat release rate and total heat release rate of KGM-based aerogel by 55.8 % and 35 %, respectively, and endowed aerogel with good self-extinguishing performance. Moreover, the results of thermal conductivity and infrared thermal imaging demonstrated that the aerogels had excellent thermal insulation properties, and could effectively manage thermal energy over a wide range of temperatures. This study provides a simple method for the preparation of heat-insulating aerogel with high fire safety, which has broad application prospects in the field of energy saving and emission reduction.

Diazotization-Enabled Deaminative Late-Stage Functionalization of Primary Sulfonamides.

We, for the first time, disclosed a simple and efficient strategy for the late-stage functionalization of primary sulfonamides by diazotization, leading to sulfonyl chlorides, sulfonates, and complex sulfonamides. This protocol obviates the requirement for the prefunctionalization of sulfonamides. Its applicability is exemplified by the late-stage functionalization of sulfonamide-type drugs.

Synthesis and Micellization of Carbosilane Sulfonate Surfactants with Short Alkyl Chains.

Carbosilane surfactants, consisting of carbosilane as a hydrophobic group linked to hydrophilic groups, are one kind of silicone surfactants. In this paper, a series of carbosilane sulfonate surfactants with short alkyl chains (Cn-Si2C-SO3Na (n = 1-6)), Me-Si2C-SO3Na, Et-Si2C-SO3Na, Pr-Si2C-SO3Na, Bu-Si2C-SO3Na, Pen-Si2C-SO3Na, and Hex-Si2C-SO3Na, were prepared and characterized by 29 Si NMR, 1H NMR, and FT-IR spectroscopies. The influence of the alkyl chain length on their micellization was studied using surface tension, dynamic light scattering, conductivity, and transmission electron microscopy. The CMC value decreases with increasing length of the short alkyl group. The γCMC value of Cn-Si2C-SO3Na (n = 1-6) increases as the alkyl chain increases from methyl to propyl, while the γCMC value gradually decreases as the alkyl chain increases from propyl to hexyl. The larger and rigid tetramethyldicarbosilane group functioned synergistically with a short alkyl chain, resulting in carbosilane sulfonate surfactants adsorbing at the air/water interface with a rugby ball shape; accordingly, the Amin values of the investigated carbosilane sulfonate surfactants increase with increasing length of the alkyl chain. The micellization process of carbosilane sulfonate surfactants is enthalpy-driven at lower temperatures and entropy-driven at high temperatures. The ΔHm0 values became more negative and ΔSm0 values more positive as the alkyl chain length increased. Aggregates in the range of 10-800 nm were observed for Cn-Si2C-SO3Na (n = 1-6) in an aqueous solution, and the hydrodynamic diameter (Dh) decreased with increasing length of the short alkyl group.

Laparoscopic Inguinal Hernia Repair for Female Patients: Experience from a High-volume Center in 20 years.

BACKGROUND: Although laparoscopic inguinal hernia repair (LIHR) is widely performed worldwide, few studies have focused on the procedure in female patients. This study investigated the characteristics and outcomes of female patients with inguinal hernias who underwent LIHR. MATERIALS AND METHODS: This study retrospectively analyzed the data of 7380 patients with inguinal hernia admitted to the General Surgery Department of Ruijin Hospital and underwent LIHR from January 2001 to December 2020. The clinical characteristics, surgical outcomes, and complications were assessed. RESULTS: In total, 572 female patients were enrolled in this study. The proportion of femoral hernias in female patients was higher in women than in male patients (17.4% vs. 0.3%, respectively). Mesothelial cysts of the round uterine ligament (MCURL) were noted in 74 patients. The mean age of patients with MCURL was lower than that of patients without MCURL (46.4 vs. 55.6, P =0.018). Seventy cases (93.3%) of MCURL were resected laparoscopically, and 5 cases were resected through an auxiliary small incision. The round ligament was cut off in 335 patients and preserved in 237. No significant differences were observed in the number of hospitalization days, recurrence rates, or complications between the transection and preservation groups. None of the cases were converted to laparotomy, and no recurrence was noted during follow-up. CONCLUSION: LIHR is safe and feasible in female patients. Treatment of femoral hernia, MCURL, and the round ligament of the uterus should be carefully considered during LIHR in female patients.

Effects of nanoscale zinc oxide treatment on growth, rhizosphere microbiota, and metabolism of Aconitum carmichaelii.

Trace elements play a crucial role in the growth and bioactive substance content of medicinal plants, but their utilization efficiency in soil is often low. In this study, soil and Aconitum carmichaelii samples were collected and measured from 22 different locations, followed by an analysis of the relationship between trace elements and the yield and alkaloid content of the plants. The results indicated a significant positive correlation between zinc, trace elements in the soil, and the yield and alkaloid content of A. carmichaelii. Subsequent treatment of A. carmichaelii with both bulk zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO NPs) demonstrated that the use of ZnO NPs significantly enhanced plant growth and monoester-type alkaloid content. To elucidate the underlying mechanisms responsible for these effects, metabolomic analysis was performed, resulting in the identification of 38 differentially expressed metabolites in eight metabolic pathways between the two treatments. Additionally, significant differences were observed in the rhizosphere bacterial communities, with Bacteroidota and Actinobacteriota identified as valuable biomarkers for ZnO NP treatment. Covariation analysis further revealed significant correlations between specific microbial communities and metabolite expression levels. These findings provide compelling evidence that nanoscale zinc exhibits much higher utilization efficiency compared to traditional zinc fertilizer.

Effect of humus on photodegradation of quinclorac under different fertilization modes.

Humus is a specific kind of organic matter widely distributed in soils. The characteristics of humus have significant impacts on the fate of pollutants in the environment. In this study, we examined the effects of fertilization modes from rice rotation systems on the contents, spectral properties, photochemical activity, and photosensitization of quinclorac (QNC) of humic (HA) and fulvic acids (FA). The results showed that under the rice-vegetable rotation system, organic fertilizer treatment decreased the humification degree and molecular weight of HA, but increased the number of oxygen-containing functional groups and the abilities of photoproducing hydroxyl radical (HO·), singlet oxygen (1O2) and photosensitizing QNC, compared with chemical fertilizer treatment. Under organic fertilization mode, the molecular weight of FA was increased, but the number of redox functional groups and the abilities of photoinducing HO· and 1O2 and photosensitizing QNC were decreased. Under rice-shrimp cultivation system, organic-inorganic fertilizer treatment increased the humification degree, molecular weight, number of redox functional groups and oxygen-containing functional groups, and 1O2 photogeneration of HA, but decreased the abilities of photoproducing HO· and photosensitizing QNC, as compared with chemical fertilizer treatment. The humification degree and molecular weight of FA under organic-inorganic fertilization mode were increased, while the abilities of photoproducing HO· and 1O2 and photosensitizing QNC were decreased. In conclusion, organic fertilization could enhance the photochemical activity and photosensitizing efficiency of humus, and further promote the photodegradation of QNC in the environment.

Effects of intravenous sodium thiosulfate on vascular calcification in dialysis patients with end-stage renal disease: a systematic review and meta-analysis.

BACKGROUND: In dialysis patients, vascular calcification is a common complication and is closely related to the morbidity and mortality of cardiovascular disease. We performed a systematic review to determine the efficacy and safety of sodium thiosulfate (STS) in the progression of vascular calcification in dialysis patients with end-stage renal disease. METHODS: The PubMed, Web of Science, Embase, Cochrane Library, Wanfang, CNKI, China Biology Medicine disc and Weipu databases were searched up to 9 March 2022 for clinical trials to synthesise findings on the efficacy and safety of STS in the progression of vascular calcification in dialysis patients. The primary outcome was coronary artery calcification scores (CACS) or abdominal aortic calcification scores (AACS) or Kauppila index. The secondary outcome was pulse-wave velocity (PWV). Laboratory data were shown in safety data. A random-effect model was used to provide the summary measures of effect [standardised mean difference (SMD) and 95% confidence interval (CI)]. RESULTS: Seven randomised, controlled trials and one nonrandomised, controlled trial involving 370 patients were included. Six studies reported that the progression of CACS or AACS was slower in the intravenous STS group compared with the control group (SMD -3.24, 95% CI: -5.29, -1.18, p = 0.002). Two studies showed the increase in PWV was less in the STS group compared with the control group (SMD -0.52, 95% CI: -0.92, -0.13, p = 0.009). During the trial period, a lower high-sensitivity C-reactive protein level (SMD 1.61, 95% CI: 0.19, 3.04, p = 0.03), a decrease in serum bicarbonate level (SMD 0.67, 95% CI: 0.22, 1.11, p = 0.003) and an increase in serum phosphate level (SMD -0.32, 95% CI: -0.62, -0.03, p = 0.03) were noted in the intravenous STS group compared with the control group. However, serum calcium and parathyroid hormone levels showed no difference between the two groups after the trials. The most common adverse events were temporary nausea and vomiting, which occurred in 12.5 to 75% of patients. CONCLUSIONS: Intravenous STS may slow down the progression of vascular calcification and ameliorate arterial stiffness in dialysis patients. Reliably defining the efficacy and safety of intravenous STS in attenuating the progression of vascular calcification requires a high-quality trial with a large sample size.

Qualitative analysis on the transdermal absorption from the dichloromethane extract of the Sambucus adnata wall. based on UPLC-Q-Exactive Orbitrap/MS.

Sambucus adnata Wall.(SAW) has been used to treat osteoarthritis by the Yi nationality in China. The present study established an overall identification strategy based on ultra-high performance liquid chromatography-tandem Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) method to characterize the multiple chemical constituents of SAW before and after percutaneous penetration. Nineteen compounds, including triterpenoids, fatty acids, lignans, flavonoid, and amide, were tentatively identified in the dichloromethane extract of SAW, while fourteen ingredients penetrated the skin. Among them, eleven components were reported for the first time in SAW.

Antibiotic Resistance Patterns and Molecular Characterization of Streptococcus suis Isolates from Swine and Humans in China.

Streptococcus suis is a zoonotic pathogen that causes disease in humans after exposure to infected pigs or pig-derived food products. In this study, we examined the serotype distribution, antimicrobial resistance phenotypes and genotypes, integrative and conjugative elements (ICEs), and associated genomic environments of S. suis isolates from humans and pigs in China from 2008 to 2019. We identified isolates of 13 serotypes, predominated by serotype 2 (40/96; 41.7%), serotype 3 (10/96; 10.4%), and serotype 1 (6/96; 6.3%). Whole-genome sequencing analysis revealed that these isolates possessed 36 different sequence types (STs), and ST242 and ST117 were the most prevalent. Phylogenetic analysis revealed possible animal and human clonal transmission, while antimicrobial susceptibility testing indicated high-level resistance to macrolides, tetracyclines, and aminoglycosides. These isolates carried 24 antibiotic resistance genes (ARGs) that conferred resistance to 7 antibiotic classes. The antibiotic resistance genotypes were directly correlated with the observed phenotypes. We also identified ICEs in 10 isolates, which were present in 4 different genetic environments and possessed differing ARG combinations. We also predicted and confirmed by PCR analysis the existence of a translocatable unit (TU) in which the oxazolidinone resistance gene optrA was flanked by IS1216E elements. One-half (5/10) of the ICE-carrying strains could be mobilized by conjugation. A comparison of the parental recipient with an ICE-carrying transconjugant in a mouse in vivo thigh infection model indicated that the ICE strain could not be eliminated with tetracycline treatment. S. suis therefore poses a significant challenge to global public health and requires continuous monitoring, especially for the presence of ICEs and associated ARGs that can be transferred via conjugation. IMPORTANCE S. suis is a serious zoonotic pathogen. In this study, we investigated the epidemiological and molecular characteristics of 96 S. suis isolates from 10 different provinces of China from 2008 to 2019. A subset of these isolates (10) carried ICEs that were able to be horizontally transferred among isolates of different S. suis serotypes. A mouse thigh infection model revealed that ICE-facilitated ARG transfer promoted resistance development. S. suis requires continuous monitoring, especially for the presence of ICEs and associated ARGs that can be transferred via conjugation.

Efficient cancer modeling through CRISPR-Cas9/HDR-based somatic precision gene editing in mice.

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either Kras or Pik3ca in both normal and hyperplastic mammary glands led to swift tumorigenesis. The resulting tumors shared some histological, transcriptome, and proteome features with tumors induced by lentivirus-mediated expression of the respective oncogenes, but they also exhibited some distinct characteristics, particularly showing less intertumor variation, thus potentially offering more consistent models for cancer studies and therapeutic development. Therefore, this technological advance fills a critical gap between the power of CRISPR technology and high-fidelity mouse models for studying human tumor evolution and preclinical drug testing.

Rigidity-Dependent Emission: Inspired Selection of an ATP-Specific Polyvalent Hydrogen Binding-Lighted Fluorophore for Intracellular Amplified Imaging.

ATP, a small molecule with high intracellular concentration (mM level), provides a fuel to power signal amplification, which is meaningful for biosensing. However, traditional ATP-powered amplification is based on ATP/aptamer recognition, which is susceptible to the complex biological microenvironment (e.g., nuclease). In this work, we communicate a signaling manner termed as ATP-specific polyvalent hydrogen binding (APHB), which is mimetic to ATP/aptamer binding but can avoid interference from biomolecules. The key in APHB is a functional fluorophore that can selectively bind with ATP via polyvalent hydrogen, and the fluorescence was lighted with the changes of the molecular structure from flexibility to rigidity. By designing, synthesizing, and screening a series of compounds, we successfully obtained an ATP-specific binding-lighted fluorophore (ABF). Experimental verification and a complex analogue demonstrated that two melamine brackets in the ABF dominate the polyvalent hydrogen binding between the ABF and ATP. Then, to achieve amplification biosensing, fibroblast activation protein (FAP) in activated hepatic stellate cells was taken as a model target, and a nanobeacon consisting of an ABF, a quencher, and an FAP-activated polymer shell was constructed. Benefiting from the ATP-powered amplification, the FAP was sensitively detected and imaged, and the potential relationship between differentiation of hepatocytes and FAP concentration was first revealed, highlighting the great potential of APHB-mediated signaling for intracellular sensing.

Intensive carbon combustion in sintering packed bed via steam spraying: An experimental study on carbon monoxide emission reduction.

Improving the combustion efficiency of solid fuels is important for reducing carbon monoxide emissions in the iron ore sintering process. In this paper, the surface steam spraying technology is introduced in the sintering process based on the auxiliary combustion effect of steam on coke, and its potential to reduce carbon monoxide emissions is demonstrated. Thermogravimetric analysis experiments of coke breeze in air and air-steam mixed atmosphere are carried out, and the results show that the introduction of steam can reduce the concentration of carbon monoxide in the exhaust gas from 183×10-6 to 78×10-6. At the same time, the mechanisms of carbon monoxide emission reduction by surface steam spraying technology are analyzed from the thermodynamic and kinetic perspectives. Then, a series of laboratory-scale sintering pot tests are carried out under no spraying operation, interval spraying operation, and continuous spraying operation. The results indicate that both interval and continuous spraying operations can reduce carbon monoxide emissions. The optimal mode of steam spraying under the present experimental conditions is continuously spraying for 13 min at a volume rate of 0.053 m3/min. Compared with no spraying, the average carbon monoxide concentration in the exhaust gas is reduced from 7565×10-6 to 6231×10-6, and total carbon monoxide emissions for per ton sinter are reduced from 13.46 m3/t to 9.51 m3/t.

Risk factors for intracerebral hemorrhage in patients undergoing maintenance hemodialysis.

Background: In patients undergoing hemodialysis, intracerebral hemorrhage (ICH) is the main cause of mortality among stroke subtypes. It is unclear whether, along with traditional cardiovascular risk factors, the risk factors unique to the uraemic environment, such as the abnormal metabolism of intact parathyroid hormone (iPTH), can contribute to the risk of ICH in these patients. Methods: This retrospective case-control study included 25 patients undergoing hemodialysis with ICH at a single center between 30 June 2015 and 10 October 2022. The controls were 95 patients undergoing maintenance hemodialysis treated at the same dialysis center in July 2020. We compared the characteristics of patients with ICH with those of the control group to identify factors that contributed to the development of ICH. Results: Intracerebral hemorrhage (ICH) was located in the basal ganglia (14/25), cerebellum (6/25), and brainstem (6/25) in 25 patients. A total of 17 patients died in the first 16 days due to neurological complications. Univariate analysis showed significant differences in systolic BP, diastolic BP, iPTH, and alkaline phosphatase between the two groups (p < 0.05). Multivariate logistic regression analysis showed that higher systolic BP (OR, 1.053; 95% CI, 1.018-1.090; p = 0.003) and higher iPTH (OR, 1.007; 95% CI, 1.003-1.012; p = 0.001) were associated with the onset of ICH. ICH was predicted by systolic BP and iPTH by receiver operating characteristic (ROC) curve analysis, with areas under the curve (AUCs) of 0.732 and 0.624, respectively. The optimal cutoffs for systolic BP and iPTH were 151.9 mmHg and 295.4 pg./ml, respectively. Restricted cubic spline showed that the shape of the association of iPTH with the risk of ICH was approximately J-shaped (P for non-linearity <0.05). Conclusion: Higher systolic BP and abnormal iPTH metabolism might be associated with ICH in patients undergoing hemodialysis. Comprehensive control of hypertension and iPTH may be a fundamental preventive strategy for ICH in these patients.

Neferine ameliorates nonalcoholic steatohepatitis through regulating AMPK pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), peculiarly nonalcoholic steatohepatitis (NASH), has become the main cause of liver transplantation and liver-related death. However, the US Food and Drug Administration has not approved a specific medication for treating NASH. Neferine (NEF), a natural bisbenzylisoquinoline alkaloid separated from the traditional Chinese medicine Nelumbinis plumula, has a variety of pharmacological properties, especially on metabolic diseases. Nevertheless, the anti-NASH effect and mechanisms of NEF remain unclear. PURPOSE: This study aimed to investigate the amelioration of NEF on NASH and the potential mechanisms. STUDY DESIGN: HepG2 cells, hepatic stellate cells (HSCs) and high-fat diet (HFD)+carbon tetrachloride (CCl4) induced C57BL/6 mice were used to observe the effect of NEF against NASH and investigate the engaged mechanism. METHODS: HSCs and HepG2 cells stimulated by oleic acid (OA) were treated with NEF. C57BL/6 mice were fed with HFD+CCl4 to induce NASH mouse model and treated with or without NEF (5 mg/kg or 10 mg/kg, once daily, i.p) for 4 weeks. RESULTS: NEF significantly attenuated the accumulation of lipid droplets, intracellular triglyceride (TG) levels and hepatocytes apoptosis in OA-exposed HepG2 cells. NEF not only enhanced the AMPK and ACC phosphorylation in OA-stimulated HepG2 cells, but also reduced inflammatory response and fibrosis in lipopolysaccharide (LPS)-stimulated HepG2 and in LX-2, respectively. In HFD+CCl4-induced NASH mice, pathological staining confirmed NEF treatment mitigated hepatic lipid deposition, inflammatory cell infiltration as well as hepatic fibrosis. Furthermore, the liver weight, serum and hepatic TG and total cholesterol (TC) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were decreased compared with the model group. HFD+CCl4 also induced the upregulation of specific proteins and genes associated to inflammation (ILs, TNF-α, NLRP3, ASC, CCL2 and CXCL10) and hepatic fibrosis (collagens, α-SMA, TGF-ß and TIPM1), which were also suppressed by NEF treatment. CONCLUSION: Our results demonstrated that NEF played a protective role in hepatic steatosis via the regulation of AMPK pathways, which may serve as an attractive candidate for a potential novel strategy on prevention and treatment of NASH.

Selective adsorption and separation of methylene blue by facily preparable xanthan gum/amantadine composites.

In this work, xanthan gum-based composites were successfully graft-modified by amantadine (XG-Fe3+/AM) with higher adsorption capacity and selectivity on recycling cationic dye (methylene blue, MB) from aqueous solution. The adsorption equilibrium of MB could be achieved approximately within 5 min when the initial concentration was 100 mg/L, and the maximum adsorption capacity was up to 565 mg/g. After 5 desorption-regeneration cycles, the removal rate of XG-Fe3+/AM for MB could still be as high as 95 % with slight decrement. Additionally, the effects of pH, contact time, temperature and initial dye concentration on the adsorption performance of MB were systematically examined. Furthermore, the adsorbent was characterized by FT-IR, BET and XPS analysis. In mixed anionic and cationic dyes, the adsorption selectivity of XG-Fe3+/AM on MB in the mixture of MB and methyl orange (MO) reached up to 99.69 %. Molecular dynamics simulation revealed that the trend of adsorption energy for dyes was in good agreement of the experimental order of adsorption capacities and molecular sizes among seven anionic and cationic dyes based on molecular matching effect and electrostatic interaction. Therefore, XG-Fe3+/AM is an eco-friendly, facile-synthesis and high-selectivity adsorbent, which remove cationic dyes in multi-component systems through electrostatic interaction and molecular matching effect.