Enhanced water stability and catalytic activity of Fe-based metal-organic frameworks with co-ligands for 2,4-dichlorophenol degradation.

Fe-based metal-organic frameworks (MOFs) have good photocatalytic performance, environmental friendliness, low cost, and abundance. However, their applications are limited by low water stability, particularly in the presence of light irradiation and oxidizing agents. In this study, we present a MIL-53(Fe)-based MOF using 1,4-naphthalene dicarboxylic (1,4-NDC) and 1,4-benzenedicarboxylic (H2BDC) acid co-ligands, denoted MIL-53(Fe)-Nx, where Nx represents the ratio of 1,4-NDC. This MOF exhibits high water stability and good photocatalytic activity because of the hydrophobicity of naphthalene. The removal and mineralization rates for 100 mg/L 2,4-dichlorophenol reached 100% and 22%, respectively, within 60 min. After three cycles of use, the Fe leached into the solution from the catalysts was significantly lower than the maximum permissible limit indicated in the European Union standard. Of note, 1,4-NDC can be used to make a rigid MOF, thereby improving the crystallinity, porosity, and hydrophobicity of the resultant materials. It also significantly reduced the bandgap energy and improved the charge separation efficiency of the catalysts. This study provides a route to enhance the water stability of Fe-based MOFs via a mixed-ligand strategy to expand their applications in pollutant control.

Association between GLIM-diagnosed malnutrition and quality of life in older patients with cancer.

BACKGROUND: Older patients with cancer have a higher risk for malnutrition and impaired quality of life (QoL). The present study aimed to investigate the relationship between malnutrition diagnosed according to the Global Leadership Initiative Malnutrition (GLIM) criteria and QoL across various tumor types, and to evaluate the combined prognostic value of malnutrition and QoL in predicting survival among older patients with cancer. METHODS: This multicenter, observational cohort study included 5310 older patients with cancer and 2184 with malnutrition (moderate stage, n = 1023; severe stage, n = 1161). An empirical cumulative distribution curve was performed to illustrate the correlation between malnutrition and QoL. The primary objective was to investigate the association between malnutrition and QoL using logistic regression analysis. Survival analyses were performed to assess the combined prognostic value of malnutrition and QoL. RESULTS: The median age of the patients (66.9% male, 33.1% female) was 70 years (interquartile range [IQR] 67-74 years) years. The median QoL score was highest in patients without malnutrition (91.88 [IQR 84.44-97.44]), followed by those with moderate (86.15 [IQR 76.18-93.85) and severe (82.31 [IQR 69.87-91.11]) malnutrition. Logistics regression revealed that the risk for developing impaired QoL increased 1.98 (95% confidence interval [CI] 1.64-2.38; P < 0.001) and 2.33 (95% CI 1.93-2.81; P < 0.001) times in patients with moderate and severe malnutrition, respectively. Kaplan-Meier curves showed that QoL in combination with GLIM criteria demonstrated a significant discriminative performance for survival and served as an independent prognostic factor among older patients with cancer, especially for lung and gastric cancers. CONCLUSIONS: Malnutrition diagnosed according to the GLIM criteria was a predictor of impaired QoL. Additionally, the combination of QoL and malnutrition demonstrated utility for predicting survival outcomes in older patients with cancer.

[Effects of tetramethylpyrazine on pharmacokinetics in plasma and brain dialysate and neuropathic pain in rat model of spared sciatic nerve injury].

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 µL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 µm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) µg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) µg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.

The multifaceted roles of matrix metalloproteinases in lung cancer.

Background: Though the matrix metalloproteinases (MMPs) are widely investigated in lung cancer (LC), however, almost no review systematically clarify their multi-faced roles in LC. Methods: We investigated the expression of MMPs and their effects on survival of patients with LC, the resistance mechanisms of MMPs in anti-tumor therapy, the regulatory networks of MMPs involved, the function of MMPs inducing CSCLs, MMPs-related tumor immunity, and effects of MMP polymorphisms on risk of LC. Results: High expression of MMPs was mainly related to poor survival, high clinical stages and cancer metastasis. Role of MMPs in LC are multi-faced. MMPs are involved in drug resistance, induced CSCLs, participated in tumor immunity. Besides, MMPs polymorphisms may increase risk of LC. Conclusions: MMPs might be promising targets to restore the anti-tumor immune response and enhance the killing function of nature immune cells in LC.

Case report: Muscle involvement in a Chinese patient with TRNT1-related disorder.

The TRNT1 gene encodes tRNA nucleotidyltransferase 1, which catalyzes the addition of cytosine-cytosine-adenosine (CCA) to the ends of cytoplasmic and mitochondrial tRNAs. The most common clinical phenotype associated with TRNT1 is autosomal recessive sideroblastic anemia with B-cell immunodeficiency, periodic fever, and developmental delay (SIFD). Muscle involvement has rarely been reported in TRNT1-related disorders. Here we report a Chinese patient with incomplete SIFD and hyperCKemia, and explored the skeletal muscle pathological changes. The patient was a 3-year-old boy with sensorineural hearing loss, sideroblastic anemia, and developmental delay since infancy. At the age of 11 months, significantly increased levels of creatine kinase were noted, accompanied by mild muscle weakness. Whole-exome sequencing revealed compound heterozygous variants of the TRNT1 gene, c.443C > T (p.Ala148Val) and c.692C > G (p.Ala231Gly), in the patient. Western blot showed a decreased expression of TRNT1 and cytochrome c oxidase subunit IV (COX IV) in the skeletal muscle of the patient. Electron microscopy observation of skeletal muscle pathology revealed abnormal mitochondria of various sizes and shapes, supporting a diagnosis of mitochondrial myopathy. The present case indicates that in addition to the classic SIFD phenotype, TRNT1 mutations can cause mitochondrial myopathy, a rare clinical phenotype of TRNT1-related disorders.

Quantitative parameters in novel spectral computed tomography: Assessment of Ki-67 expression in patients with gastric adenocarcinoma.

BACKGROUND: The level of Ki-67 expression has served as a prognostic factor in gastric cancer. The quantitative parameters based on the novel dual-layer spectral detector computed tomography (DLSDCT) in discriminating the Ki-67 expression status are unclear. AIM: To investigate the diagnostic ability of DLSDCT-derived parameters for Ki-67 expression status in gastric carcinoma (GC). METHODS: Dual-phase enhanced abdominal DLSDCT was performed preoperatively in 108 patients with gastric adenocarcinoma. Primary tumor monoenergetic CT attenuation value at 40-100 kilo electron volt (kev), the slope of the spectral curve (λHU), iodine concentration (IC), normalized IC (nIC), effective atomic number (Zeff) and normalized Zeff (nZeff) in the arterial phase (AP) and venous phase (VP) were retrospectively compared between patients with low and high Ki-67 expression in gastric adenocarcinoma. Spearman's correlation coefficient was used to analyze the association between the above parameters and Ki-67 expression status. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic efficacy of the statistically significant parameters between two groups. RESULTS: Thirty-seven and 71 patients were classified as having low and high Ki-67 expression, respectively. CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, and Zeff-related parameters were significantly higher, but IC-related parameters were lower in the group with low Ki-67 expression status than the group with high Ki-67 expression status, and other analyzed parameters showed no statistical difference between the two groups. Spearman's correlation analysis showed that CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, Zeff, and nZeff exhibited a negative correlation with Ki-67 status, whereas IC and nIC had positive correlation with Ki-67 status. The ROC analysis demonstrated that the multi-variable model of spectral parameters performed well in identifying the Ki-67 status [area under the curve (AUC) = 0.967; sensitivity 95.77%; specificity 91.89%)]. Nevertheless, the differentiating capabilities of single-variable model were moderate (AUC value 0.630 - 0.835). In addition, the nZeff VP and nICVP (AUC 0.835 and 0.805) showed better performance than CT40 kev-VP, CT70 kev-VP and CT100 kev-VP (AUC 0.630, 0.631 and 0.662) in discriminating the Ki-67 status. CONCLUSION: Quantitative spectral parameters are feasible to distinguish low and high Ki-67 expression in gastric adenocarcinoma. Zeff and IC may be useful parameters for evaluating the Ki-67 expression.

Sustained release silicon from 3D bioprinting scaffold using silk/gelatin inks to promote osteogenesis.

Repairing extensive bone defects that cannot self-heal has been a clinical challenge. The construction of scaffolds with osteogenic activity through tissue engineering can provide an effective strategy for bone regeneration. This study utilized gelatin, silk fibroin, and Si3N4 as scaffold materials to prepare silicon-functionalized biomacromolecules composite scaffolds using three-dimensional printing (3DP) technology. This system delivered positive outcomes when Si3N4 levels were 1 % (1SNS). The results showed that the scaffold had a porous reticular structure with a pore size of 600-700 µm. The Si3N4 nanoparticles were distributed uniformly in the scaffold. The scaffold could release Si ions for up to 28 days. In vitro experiments showed that the scaffold had good cytocompatibility, promoting the osteogenic differentiation of mesenchymal stem cells (MSCs). In vivo experiments on bone defects in rats showed that the 1SNS group facilitated bone regeneration. Therefore, the composite scaffold system showed potential for application in bone tissue engineering.

Characteristics and feasibility of ambulatory respiratory assessment of paediatric neuromuscular disease: an observational retrospective study.

PURPOSE: To investigate the characteristics of respiratory involvement in Chinese paediatric neuromuscular disease (NMD) at early stage and to explore convenient monitoring methods. MATERIALS AND METHODS: Children with NMD (age < 18) diagnosed at a multidisciplinary joint NMD clinic at Peking University First Hospital from January 2016 to April 2021 were included. Overnight polysomnography (PSG) and pulmonary function test (PFT) data were analysed, and the characteristics of four groups: congenital muscular dystrophy (CMD), congenital myopathy, spinal muscular atrophy, and Duchenne muscular dystrophy (DMD) were compared. RESULTS: A total of 83 children with NMD were referred for respiratory assessment, of who 80 children underwent PSG; 41 performed spirometry and 38, both. The duration of pulse oxygen saturation (SpO2) <90% over apnoea and hypopnoea index (AHI) was lowest in DMD and significantly different from CMD (p = 0.033). AHI was positively correlated with the oxygen desaturation index (ODI) (r = 0.929, p = 0.000). The peak expiratory flow (PEF) were positively correlated with forced vital capacity (FVC), both as actual values and percent pred, respectively (r = 0.820, 0.719, p = 0.000). ROC derived sensitivity and specificity of prediction of AHI > 15/h or duration of SpO2<90% ≥ 60 min from FVC <51% pred was 75.8% and 85.7%, respectively. CONCLUSIONS: AHI and hypoxia burden were independent factors in children with NMD in PSG and attention needed to be paid in both. FVC might be a daytime predictor for significant sleep-disordered breathing or hypoxia. Nocturnal consecutive oximetry with diurnal peak flow measurement may be convenient and effective for home monitoring at early stage of respiratory involvement.

Synthesis of N-Vinyl Cinnamaldehyde Nitrones through Atropisomeric Quinoxaline-Derived N,N,O-Ligand-Promoted Chan-Lam Reaction.

A type of quinoxaline-derived tridentate N,N,O-ligand was synthesized in good to excellent yields over three steps through iodination of 2-aryl indoles, sequential Kornblum-type oxidation with DMSO, and capture by 1,2-diaminobenzenes. The prepared atropisomeric N,N,O-ligand was successfully applied in the synthesis of N-vinyl cinnamaldehyde nitrones as only Z-isomers in good yields through the Chan-Lam reaction. The method features an easily accessed tunable tridentate N,N,O-ligand, broad substrate scope, good functional group tolerance, and high Z-isomer for N-vinyl nitrones.

Cinchonidine-Catalyzed Synthesis of Oxazabicyclo[4.2.1]nonanones from N-Aryl-α,ß-unsaturated Nitrones and 1-Ethynylnaphthalen-2-ols.

A variety of oxazabicyclo[4.2.1]nonanone derivatives were prepared in good yields through a cinchonidine-catalyzed cascade reaction of N-aryl-α,ß-unsaturated nitrones and 1-ethynylnaphthalen-2-ols. Mechanistic studies show that the reaction undergoes a [4 + 3] cycloaddition of nitrones to vinylidene o-quinone methide generated in situ from 1-ethynylnaphthalen-2-ols in the presence of cinchonidine, 1,3-rearrangement of N-O vinyl moieties, ring-opening, and finally double intramolecular cyclizations to afford oxazabicyclo[4.2.1]nonanones over five steps in a one-pot reaction.

Standard diffusion-weighted, diffusion kurtosis and intravoxel incoherent motion MR imaging of the whole placenta: a pilot study of volumetric analysis.

Background: Using magnetic resonance imaging (MRI) to explore the changes in microvascular perfusion fraction and the heterogeneity of the placenta during pregnancy. Methods: We retrospectively reviewed 24 patients with normal pregnancies who underwent standard diffusion-weighted, diffusion kurtosis, and intravoxel incoherent motion MRI. The mean, minimum and maximum parameters including the apparent diffusion coefficient (ADC) and exponential ADC (eADC) from standard diffusion-weighted imaging (DWI), the diffusion coefficient (MD) and diffusion kurtosis (MK) from diffusion kurtosis imaging (DKI), and the pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f) from intravoxel incoherent motion MR imaging (IVIM) were calculated from the whole placenta volumetric analysis and correlated with gestational age (GA) and volume of the placenta. Results: A significant positive correlation was found between eADC mean, eADC max, MK mean, MK max, the volume of the whole placenta, and GA, and a negative correlation was found between ADC mean, ADC min, MD min, D mean, D min, D* min and GA. The f mean and MK max values positively correlated with the volume of the whole placenta. Conclusions: eADC mean, eADC max, MK mean, MK max values increased with GA, while ADC mean, ADC min, MD min, D mean, D min, D* min decreased with GA. Secondly, the f mean and MK max also increased with placental volume. These results suggest the potential of diffusion and perfusion parameters to evaluate the placenta during its development using different DWI models.

The Effect of SOCS2 Polymorphisms on Type 2 Diabetes Mellitus Susceptibility and Diabetic Complications in the Chinese Han Population.

BACKGROUND: SOCS2 is downregulated in diabetes, which might be related to diabetes. We explored the effect of SOCS2 polymorphisms on the development of type 2 diabetes mellitus (T2DM) and diabetic complications. METHODS: The subjects consisted of 500 patients with T2DM and 501 healthy controls. Five variants in SOCS2 were genotyped by Agena MassARRAY system. RT-qPCR profiling was performed to detect the expression of SOCS2 mRNA. Logistic regression analysis was utilized to calculate odds ratio (OR) and 95% confidence intervals (95% CIs). RESULTS: Rs3825199 (OR = 1.44, p = 0.007), rs11107116 (OR = 1.39, p = 0.014) and rs10492321 (OR = 1.48, p = 0.004) had an increased T2DM risk of T2DM. Moreover, the contribution of SOCS2 polymorphisms to T2DM risk was associated with age, gender, smoking, drinking, and BMI. SOCS2 variants also had a reduced risk for T2DM patients with diabetic nephropathy, diabetic retinopathy and coronary heart disease. SOCS2 rs10492321 was the best single locus model. SOCS2 mRNA was downregulated in patients with T2DM compared to healthy controls (p = 0.029). CONCLUSION: This study firstly reported that rs3825199, rs11107116 and rs10492321 in SOCS2 conferred to an increased risk for the occurrence of T2DM in the Chinese Han population. Moreover, SOCS2 mRNA was downregulated in patients with T2DM, suggesting that SOCS2 might have an important role in the occurrence of T2DM.

Yeast Selenium Exerts an Antioxidant Effect by Regulating the Level of Selenoprotein to Antagonize Cd-Induced Pyroptosis of Chicken Liver.

Cadmium (Cd) exposure can cause multiple organ damage in humans and animals by causing oxidative stress. Organic selenium can antagonize the toxic damage of heavy metals by exerting antioxidant effects. Oxidative stress can activate NLRP3/Caspase1-dependent pyroptosis, but it is not clear whether yeast selenium (Se Y) can antagonize Cd-induced pyroptosis in the chicken liver. In this experiment, we studied the effects of CdCl2 single, Se Y single, and combined exposure on the pyroptosis of chicken liver. The results showed that Cd exposure induced oxidative stress in the chicken liver, and the expression of Sepx1, SelU, SelT, GPx1, GPx4, Dio1, Dio2, Dio3, TrxR1, TrxR2, TrxR3, SelH, SelI, SelO, SelK, SelPb, Selpp, and Sel15 decreased. In addition, NLRP3 inflammasome complex (NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing (ASC), and pro-Caspase1), Cysteinyl aspartate specific proteinase (Caspase1), Interleukin-ß (IL-1ß), and Interleukin-18 (IL-18) were upregulated. The combined treatment of Se Y and Cd found that the antioxidant level and the expression level of selenoprotein recovered to the Se group, and the liver pyroptosis decreased. Principal component analysis and correlation analysis screened out that selenoprotein O (SelO) is negatively correlated with pyroptosis-related genes. In short, our data shows that Se Y exerts an antioxidant effect by increasing the expression of selenoproteins and antagonizing the pyroptosis of chicken liver induced by Cd. This study provides new ideas for the field of heavy metal toxicology research. And the selected SelO has an important reference significance for follow-up research.

Association between admission hemoglobin level and prognosis in patients with type 2 diabetes mellitus.

BACKGROUND: Anaemia is common in patients with chronic kidney disease (CKD) and is a major risk factor that contributes to mortality in such patients. Type 2 diabetes mellitus (T2DM) is one of the leading causes of CKD. The association between admission hemoglobin levels and renal damage in patients with T2DM remains unclear. AIM: To evaluate the relationship between admission hemoglobin levels and prognosis in patients with T2DM. METHODS: We performed a retrospective analysis of 265 consecutive patients presenting with T2DM between 2011 and 2015. The composite endpoint was end-stage renal disease or a 50% reduction in the estimated glomerular filtration rate. RESULTS: In multivariable-adjusted Cox proportional hazards models (adjusting for demographic factors, traditional risk factors, lipids), the adjusted hazard ratios (HRs) for the highest and middle tertiles compared to the lowest tertile of hemoglobin were 0.82 (95%CI: 0.11-6.26, P = 0.8457) and 0.28 (95%CI: 0.09-0.85, P = 0.0246), respectively. However, after further adjustment for glycaemia control, hemoglobin was positively related to the risk of the composite endpoint (HR: 1.05, 95%CI: 0.14-8.09, P = 0.9602) when the highest tertile was compared to the lowest tertile of hemoglobin. We found a U-shaped relationship between hemoglobin levels and the composite endpoint. The curve tended to reach the lowest level at an optimal hemoglobin level. CONCLUSION: Among patients with T2DM, a U-shaped relationship was observed between hemoglobin levels and renal damage. A lower admission hemoglobin level (hemoglobin < 13.3 g/dL) is an independent predictor of renal damage.

A Study of Piano Timbre Teaching in the Context of Artificial Intelligence Interaction.

This paper provides an in-depth analysis and research on piano timbre teaching in the context of artificial intelligence interaction, a bold vision of piano teaching, proposes a feasible solution in terms of teaching modules in intelligent piano teaching for senior teachers, and proposes an implementation path for the integration of intelligent piano and piano teaching from the four main blocks of piano teaching. Based on the multiplicative harmonic model of monophonic signal, combined with the variability of timbre characteristics, an audio synthesis model with editable timbre is proposed, and the experimental results show that editing the timbre parameters in the model can realize timbre modification, and the synthesized timbre conforms to the piano timbre characteristics. Based on the timbre analysis and the timbre synthesis model, a piano timbre library generation system is designed. The detailed design of the software modules such as audio file reading and writing, audio information analysis, timbre parameter acquisition, timbre synthesis, and simulated performance is given. The system can generate piano timbre libraries of different qualities flexibly and meet the requirements of timbre realism. The teaching experiment designed for teaching practice from solo teaching, and the practice target is first-year undergraduate students in the university, and the practice period is six weeks, and finally, the feasibility of intelligent piano teaching application is analysed by combining the experimental results. Through the teaching objectives, teaching content, and teaching methods, teaching environment reflects intelligent piano teaching to make up for the limitations of traditional piano teaching. Analyse the development trend of intelligent piano teaching in the context of artificial intelligence interaction, and explore the value of intelligent piano teaching.

Pig lung fibrosis is active in the subacute CdCl2 exposure model and exerts cumulative toxicity through the M1/M2 imbalance.

Environmental pollutant cadmium (Cd) can cause macrophage dysfunction, and the imbalance of M1/M2 is involved in the process of tissue fibrosis. In order to explore the effect of subacute CdCl2 exposure on pig lung tissue fibers and its mechanism, based on the establishment of this model, ICP-MS, H&E staining, Masson staining, Immunofluorescence, RT-PCR, and Western Blot methods were used to detect related indicators. The results found that lung tissue fibrosis, Cd content significantly increased, lung tissue ion disturbance, miR-20a-3p down-regulation, M1/M2 imbalance, LXA4/FPR2 content decreased, MDA content increased, NF-κB/NLRP3, TGFß pathway, PPARγ/Wnt pathway activated, and the expression of fibrosis-related factors increased. The above results indicate that subacute CdCl2 exposure increase Cd content in the pig lungs, which leads to M1/M2 imbalance and down-regulates the content of LXA4/FPR2, further activates the oxidative stress/NF-κB/NLRP3 pathway, thereby activating the TGFß and PPARγ/Wnt pathways to induce fibrosis. This study aims to reveal the toxic effects of CdCl2 and will provide new insights into the toxicology of Cd.

Construction of Surface-Modified Polydopamine Nanoparticles for Sequential Drug Release and Combined Chemo-Photothermal Cancer Therapy.

Single chemotherapy often causes severe adverse effects and drug resistance to limit therapeutic efficacy. As a noninvasive approach, photothermal therapy (PTT) represents an attractive option for cancer therapy due to the benefits of remote control and precise treatment methods. Nanomedicines constructed with combined chemo-photothermal properties may exert synergistic effects and improved antitumor efficacy. In this study, we developed polydopamine (PDA)-coated nanoparticles grafted with folic acid (FA) and polyethylene glycol to transport doxorubicin (DOX) for targeted cancer therapy. The results showed that this delivery vehicle has a nanoscale particle size and narrow size distribution. No particle aggregation or significant drug leakage was observed during the stability test. This system presented excellent photothermal conversion capability under near-infrared light (NIR) laser irradiation due to the PDA layer covering. In vitro dissolution profiles demonstrated that sequential and triggered DOX release from nanoparticles was pH-, NIR irradiation-, and redox level-dependent and could be best fitted with the Ritger-Peppas equation. FA modification effectively promoted the intracellular uptake of nanoparticles by HepG2 cells and therefore significantly inhibited cell recovery and induced tumor cell apoptosis. Compared to the free DOX group, nanoparticles reduced the DOX concentration in the heart to avoid drug-related cardiotoxicity. More importantly, the in vivo antitumor efficacy results showed that compared with the single chemotherapy strategy, the nanoparticle group exerted combined and satisfactory tumor growth inhibition effects with good biocompatibility. In summary, this nanocarrier delivery system can organically combine chemotherapy and PTT to achieve effective and precise cancer treatment.

Folic Acid-Modified Erythrocyte Membrane Loading Dual Drug for Targeted and Chemo-Photothermal Synergistic Cancer Therapy.

To overcome the challenges of systemic toxicity and weak tumor selectivity caused by traditional antitumor drugs, numerous nanocarrier systems have been developed in recent decades, and their therapeutic effect has been improved to varying degrees. However, because of the drug resistance effect and metastasis involved in tumor recurrence, a single chemotherapy can no longer satisfy the diversified treatment needs. Recently, the application of chemotherapy in combination with thermotherapy as a synergistic approach has been proven to be more effective, and it provides a new strategy for cancer therapy. In this work, by utilizing the unique properties of erythrocytes, a surface-modified erythrocyte membrane was constructed as a novel nanocarrier system (DOX and ICG-PLGA@RBC nanoparticles, DIRNPs for short) for the simultaneous transportation of chemotherapeutic drugs (doxorubicin, DOX) and photothermal agents (indocyanine green, ICG) to achieve the effects of long-term circulation, active tumor targeting, and triggered drug release. The results indicated that DIRNPs have a nanoscale particle size of 158.4 nm with a narrow size distribution and a negative surface charge of -5.79 mV. No particle aggregation or remarkable drug leakage was observed during the 30 day storage test, and because of the excellent photothermal conversion ability of ICG, the local temperature of DIRNPs could dramatically increase from 33.7 to 49.8 °C in 10 min under near-infrared (NIR) laser irradiation. The in vitro drug dissolution data demonstrated that the DOX release from the DIRNPs was pH-dependent and NIR-triggered. Folic acid modifications of the erythrocyte membrane effectively facilitated the intracellular uptake of DIRNPs by HepG2 cells and, as a result, it significantly inhibited tumor cell growth, promoted reactive oxygen species levels, induced cell apoptosis, and restricted cell recovery and migration. In vivo pharmacokinetics and biodistribution studies indicated that the DIRNPs prolonged the half-life of DOX from 6.03 to 17.6 h and remarkably reduced the DOX level in the heart to avoid drug-related cardiotoxicity. More importantly, the DIRNPs exerted excellent in vivo antitumor efficacy against H22 tumors with superior safety. In conclusion, utilizing the advantageous properties of erythrocytes to construct a tumor-targeted biomimetic nanocarrier for codelivery of chemotherapeutics and photothermal agents to produce synergistic effects is considered an effective method for cancer therapy.

Progress in Pretreatment and Analytical Methods of Coumarins: An Update since 2012 - A Review.

Coumarins are widely used due to their wide range of biological activities, but the long-term or excessive use of coumarin flavors can pose serious health hazards. Therefore, sensitive and specific methods for the quantification of these compounds in different matrices have been developed. In this review, an updated overview of the latest trends in sample preparation techniques and methods used to detect coumarins from March 2012 to April 2019 is provided. This study reviews different analytical methods (such as liquid chromatography coupled with different detectors, electrochemical sensors, capillary electrophoresis, etc.) and different pretreatment methods (such as liquid-liquid extraction, solid-phase extraction, dispersive liquid-liquid microextraction, etc.). Different methods for the pretreatment and determination of coumarins in plant, food, environmental, pharmaceutical and biological samples are summarized, discussed and compared.HighlightsProgress in pretreatment and analytical methods of coumarins are summarized.Fundamentals, instrumentation and applications of purification and quantification are summarized and compared.Optimization of experimental conditions are discussed.Newly emerged eco-friendly methods are introduced.

Impact of and risk factors for pediatric acute kidney injury defined by the pROCK criteria in a Chinese PICU population.

BACKGROUND: The definition of pediatric AKI continues to evolve. We aimed to find a better AKI definition to predict outcomes and identify risk factors for AKI in a Chinese PICU. METHODS: This study consisted of 3338 patients hospitalized in a Chinese PICU between 2016 and 2018. AKI was defined and staged using pROCK criteria, which were compared with KDIGO criteria. AKI outcomes, including mortality, daily cost and length of stay (LOS), were assessed. Risk factors for AKI were also estimated. RESULTS: The incidence of AKI in the PICU was 7.7% according to pROCK criteria. The characteristics of patients with KDIGO-defined AKI who did not meet the pROCK were similar to those without AKI. pROCK outperformed KDIGO in predicting mortality with a higher c index in the Cox models (0.81 versus 0.79, P = 0.013). AKI, as well as AKI stages, were associated with higher mortality (HR: 10.5, 95%CI: 6.66-19.5), daily cost (ß = 2064, P < 0.01) and LOS (ß = 2.30, P < 0.01). Age, comorbidities, mechanical ventilation (MV), pediatric critical illness score (PCIS) and exposure to drugs had significant influence on AKI occurrence. CONCLUSIONS: The mortality predictability of pROCK was slightly greater than that of KDIGO. Older age, underlying comorbidities, MV, decreased PCIS and exposure to drugs were potential risk factors for AKI. IMPACT: Two AKI criteria, pROCK and KDIGO, were significantly associated with an increased risk of mortality and pROCK was slightly greater than that of KDIGO. Older age, comorbidities, mechanical ventilation, decreased PCIS and exposure to drugs were potential risk factors for AKI. This study first used the pROCK criteria to provide an epidemiologic description of pediatric AKI in Chinese PICU. This study compared the AKI outcomes across the pROCK and KDIGO AKI criteria, indicating the prior utility for AKI classification in Chinese children. This study indicated that the potential risk factors for AKI were older age, comorbidities, mechanical ventilation, decreased PCIS and exposure to drugs.