Efficacy and Safety of Crisaborole Ointment 2% in Chinese Patients Aged ≥ 2 Years with Mild to Moderate Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2 years with mild to moderate AD. METHODS: We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28 days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. RESULTS: Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: -66.34 [95% (confidence interval) CI -71.55 to -61.12] vs. -50.18 [95% CI -58.02 to -42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4-51.1] vs. 33.4% [95% CI 22.5-44.2]) and ISGA success (31.7% [95% CI 24.3-39.0] vs. 21.5% [95% CI 12.1-30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: -1.98 [95% CI -2.34 to -1.62] vs. -1.08 [95% CI -1.63 to -0.53]). No new safety signals were observed. CONCLUSION: Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2 years with mild to moderate AD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04360187.

A 1-year analysis from a natural history study in Chinese individuals with Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a disabling and life-threatening, X-linked recessive disorder caused by mutations in dystrophin. Natural history studies can inform the disease characteristics of DMD, and data from these studies can be used to plan and design clinical trials and as external controls for long-term studies. We report 12-month results from the largest natural history study of individuals with DMD in China receiving standard of care treatment. Methods: This ongoing, multicentre, prospective, single-cohort study (ClinicalTrials.gov: NCT03760029) was conducted in Chinese male participants with DMD (ambulatory aged <6 years [Group 1; n = 99]; ambulatory aged ≥6 years [Group 2; n = 177], and non-ambulatory of any age [Group 3; n = 36]. The follow-up period is ≥24 months, with some participants followed for 30 months. The primary endpoint was time to clinical milestones due to DMD disease progression, and motor, pulmonary, and cardiac function. Secondary endpoints were quality of life (QoL) assessments. Findings: Mean (standard deviation [SD]) age at screening was 3.4 (1.2), 8.6 (2.0), 12.3 (2.7) and 7.4 (3.5) years in Groups 1, 2, 3 and total respectively. Mean (SD) North Star Ambulatory Assessment (NSAA) total score at baseline was 21.2 (5.8) in Group 1, 19.5 (8.3) in Group 2 and 20.0 (7.7) in ambulatory total. Overall, the time to clinical milestones due to DMD disease progression was consistent with previous findings, in which loss of ambulation occurred at 13 years. There was a trend towards a decline over 12 months in NSAA and timed motor function from age 6 years, with the greatest reductions observed thereafter. There were no consistent trends in measures of QoL, although participants of any age generally had poorer outcomes at Month 12 versus their domain scores at baseline. Interpretation: This study improves the understanding of DMD progression according to the current standards of care in the Chinese DMD population and may inform selected endpoints and patient populations in clinical trials. Funding: Pfizer Inc.

Transcriptional regulation of Glis2 in hepatic fibrosis.

The role of Gli-similar 2 (Glis2) in hepatic fibrosis (HF) is controversial. In this study, we focused on the functional and molecular mechanisms involved in the Glis2-mediated activation of hepatic stellate cells (HSCs)-a milestone event leading to HF. The expression levels of Glis2 mRNA and protein were significantly decreased in the liver tissues of patients with severe HF and in mouse fibrotic liver tissues as well as HSCs activated by TGFß1. Functional studies indicated that upregulated Glis2 significantly inhibited HSC activation and alleviated BDL-induced HF in mice. Downregulation of Glis2 was found to correlate significantly with DNA methylation of the Glis2 promoter mediated by methyltransferase 1 (DNMT1), which restricted the binding of hepatic nuclear factor 1-α (HNF1-α), a liver-specific transcription factor, to Glis2 promoters. In addition, the enrichment of DNMT1 in the Glis2 promoter region was mediated by metastasis-associated lung adenocarcinoma transcriptor-1 (MALAT1) lncRNA, leading to transcriptional silencing of Glis2 and activation of HSCs. In conclusion, our findings reveal that the upregulation of Glis2 can maintain the resting state of HSCs. The decreased expression of Glis2 under pathological conditions may lead to the occurrence and development of HF with the expression silencing of DNA methylation mediated by MALAT1 and DNMT1.

Efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥2 years with mild-to-moderate atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease with a significant impact on the overall wellbeing of patients and their families. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis in multiple countries. However, in the key pivotal trials, a low proportion of the overall patient population was Asian, therefore the safety and efficacy of crisaborole in the Asian population with atopic dermatitis remains unclear. CrisADe CLEAR was a multicenter, randomized, double-blind, vehicle-controlled, phase 3 study (NCT04360187) to assess the efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥2 years with mild-to-moderate atopic dermatitis involving ≥5% treatable body surface area. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. The primary endpoint was percentage change from baseline in the Eczema Area and Severity Index total score at day 29. Additional endpoints were improvement and success per Investigator's Static Global Assessment score at day 29 and change from baseline on the Peak Pruritus Numerical Rating Scale at week 4. Safety was assessed using rates of treatment emergent adverse events, serious adverse events, and clinically significant changes in vital signs and clinical laboratory parameters. Crisaborole-treated patients showed a significantly greater reduction versus vehicle in percentage change from baseline in Eczema Area and Severity Index total score at day 29 (P = 0.0002). Response rates for achievement of Investigator's Static Global Assessment improvement and success at day 29 were significantly higher for patients treated with crisaborole versus vehicle (P = 0.0124 and P = 0.0078, respectively). Crisaborole-treated patients showed a significantly greater reduction versus vehicle in change from baseline on the Peak Pruritus Numerical Rating Scale at week 4 (P = 0.0009). No new safety signals were identified. Treatment with crisaborole was effective and well tolerated in Chinese and Japanese patients with mild-to-moderate atopic dermatitis.

A bipolar pyridine-functionalized porphyrin with hybrid charge-storage for dual-ion batteries.

A metal-free porphyrin T4PP with a pyridine group is proposed as a new electrode for lithium/sodium-based dual-ion batteries (LDIBs/SDIBs). The electrochemical performance and reaction mechanism of T4PP are explored thoroughly. The extended porphyrin conjugated structure by the pyridine groups enables an excellent cycle life (5000 cycles) and a high-power density (18.7 kW kg-1). A hybrid charge-storage mechanism with the contribution of both cations and anions benefits fast charge transfer.

GLIS2 Prevents Hepatic Fibrosis by Competitively Binding HDAC3 to Inhibit Hepatic Stellate Cell Activation.

BACKGROUND: The role of GLIS2 in fibrotic diseases is controversial. GLIS2 deficiency has been reported to contribute to renal fibrosis in mice and has also been reported to prevent high lipid-induced mice hepatic fibrosis. METHODS: Hepatic fibrosis in mice was induced by CCl4. Hematoxylin and eosin, Masson, Sirius red, and enzyme-linked immunosorbent assay were used to detect and evaluate the stage of hepatic fibrosis in humans or mice. A study model of tetracycline-responsive GLIS2 knockout hepatic stellate cells (HSCs) was constructed and named GLIS2-SG-Dox. By adding transforming growth factor ß1 to stimulate the transdifferentiation of HSCs, the activation status of HSCs was comprehensively evaluated from the aspects of cell proliferation, migration, and the amount of lipid droplets. In mechanistic studies, dual-luciferase, coimmunoprecipitation, yeast two-hybrid system, chromatin immunoprecipitation, and DNA pulldown were performed to investigate or to prove the molecular mechanism that GLIS2 was involved in regulating liver fibrosis. Throughout the study, real-time fluorescence polymerase chain reaction (quantitative reverse-transcription polymerase chain reaction) was used to detect the relative abundance of messenger RNA expression of each target gene, Western blot was used to detect the relative abundance of protein, and immunohistochemistry or immunofluorescence was used to observe the subcellular localization of the target protein. RESULTS: The expression of GLIS2 was significantly decreased in human liver fibrosis tissues and CCL4-induced mouse liver fibrosis tissues, especially in HSCs. In the GLIS2-SG-Dox cells, the peroxisome proliferator-activated receptor γ (PPAR-γ) pathway was inactive and cells underwent myofibroblastic transdifferentiation transformation. Overexpression of GLIS2 can increase the acetylation level of PPAR-γ and alleviate CCL4-induced liver fibrosis in mice. Mechanically, relatively abundant GLIS2 and histone deacetylase 3 (HDAC3) form chelates to avoid the deacetylation of PPAR-γ, so as to maintain the activation level of PPAR-γ signaling pathway in HSCs cells. In this process, HDAC3 acts as a medium for GLIS2 to influence PPAR-γ signaling. Nonetheless, when GLIS2 is absent, HDAC3 deacetylates PPAR-γ, activates HSCs, and leads to liver fibrosis. CONCLUSIONS: GLIS2 deficiency promotes myofibroblastic transdifferentiation and activation of HSCs. Mechanically, GLIS2 regulates the acetylation of PPAR-γ by competitively binding to HDAC3 in HSCs.

Effects of gross tumor volume and radiation dose on survival and locoregional recurrence in early-stage extranodal NK/T-cell lymphoma treated with intensity-modulated radiation therapy.

PURPOSE: To investigate the prognostic value of gross tumor volume (GTV) in early-stage extranodal NK/T-cell lymphoma (ENKTCL) treated with intensity-modulated radiation therapy (IMRT) and explore the interactive effect of GTV and radiotherapy (RT) dose on locoregional recurrence (LRR). METHODS: The data of 319 early-stage ENKTCL patients who underwent IMRT were reviewed retrospectively. Overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were estimated using Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression was performed to identify independent risk factors for survival outcomes. Penalized spline regression was used to flexibly model the association of continuous predictors (GTV and RT dose) with mortality, progression, and relapse. RESULTS: The 5-year OS, PFS, and LRC for the entire cohort were 72.9, 64.4, and 89.9%, respectively. The risks of disease mortality, progression, and recurrence increased steadily with increasing GTV. Patients with GTV < 35 mL had significantly higher 5-year OS (83.0% vs. 59.4%; P < 0.001), PFS (76.7% vs. 48.4%; P < 0.001), and lower 5-year cumulative LRR rate (4.9% vs. 14.5%; P = 0.004), than patients with GTV ≥ 35 mL. The risk of LRR was low with RT doses of 50-56 Gy, independent of GTV. For patients with GTV ≥ 35 mL, dose ≥ 56 Gy was not associated with decreased LRR. CONCLUSION: Larger GTV is associated with worse survival and higher LRR in early-stage ENKTCL patients treated with IMRT. A dose of 50-56 Gy may be appropriate to achieve lower risk of LRR, regardless of GTV.

Impacts of wet-dry alternations on cadmium and zinc immobilisation in soil remediated with iron oxides.

Chemical immobilisation is extensively used for in-situ remediation of heavy metals contaminated soil. Immobilised heavy metals could be reactivated by multiple factors such as pH, moisture, temperature, rainfall, etc., among which rainfall is very important, especially acid rain in southern China. Wet-dry alternations were used to simulate the leaching of metals by rainwater. The variation of cadmium (Cd) and zinc (Zn) speciation distribution in soil immobilised with iron oxides (goethite (GE) and 2-line ferrihydrite (GLS)) was investigated. The impacts of wet-dry alternations on the properties of the soil and amendments were also assessed. In the soil without amendments (OS) and amended with GE (GS), the stable fractions were reactivated and transformed into labile fractions under wet-dry alternations. In the soil amended with GLS (LS), the exchangeable and carbonate-bound Cd decreased while the soluble, Fe-Mn oxide bound and organic bound Cd increased. The carbonate-bound Zn was transformed into the Fe-Mn oxide-bound Zn. Transformation from the amorphous iron oxide into crystalline iron oxide in GS and LS were 4.9% and 5.3%. The Pearson correlation analysis showed that the soil pH and the iron-oxide speciation were strongly correlated with Cd/Zn fractions in the soil. The specific surface area, pore volume and adsorption capacity of the iron oxides decreased by 9.26%, 38.89% and 62-73% (for GE), 1.88%, 22.22% and 26-55% (for GLS). The altered soil properties and morphological differences between the two iron oxides under wet-dry alternations were important reasons for Cd/Zn reactivation.

Ethynyl and Furyl Functionalized Porphyrin Complexes as New Organic Cathodes Enabling High Power Density and Long-Term Cycling Stability.

Organic cathode materials have recently attracted abundant attention due to their flexible structural tunability and recyclability. However, the low intrinsic electrical conductivity and high solubility in electrolytes of organic electrode materials have significantly limited their practical application. Herein, we present [5,15-bis(ethynyl)-10,20-difurylporphinato] copper(II) (CuDEOP) as a new cathode for rechargeable organic lithium batteries (ROLBs). The combination of both ethynyl and furyl groups of the CuDEOP cathode with a nanorod structure renders it with enhanced structural stability and an extended delocalized π-electron system to deliver excellent cycling stability (capacity retention of 76% after 6000 cycles) and a high power density (16 kW kg-1). The furyl electroactive groups participate in charge storage contribution to achieve a reversible six-electron-transfer redox reaction in a specific voltage range. The mechanism characterizations indicate that the nitrogen atoms on the porphyrin ring act as active sites to alternatively store both PF6- anions and Li+ cations, and the charge storage process is a pseudocapacitive-dominated reaction. This observation will offer a new avenue for designing functionalized molecules for electrochemical energy-storage (EES) systems.

Circular RNA circ_GLIS2 suppresses hepatocellular carcinoma growth and metastasis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of tumour-related death. Here, we investigated the molecular mechanism of HCC by studying the function of circ_GLIS2. METHODS: Human HCC specimens and cell lines were used. Sanger sequencing, actinomycin D and RNase R treatment were performed to validate circular RNA features of circ_GLIS2. qRT-PCR, western blotting, immunostaining, and IHC were employed to examine levels of circ_GLIS2, GLIS2 mRNA, and EMT-related markers. CCK-8, colony formation, flow cytometry, wound healing assay, and transwell assays were performed to evaluate cancer cell proliferation, apoptosis, migration, and invasion. RIP and RNA pull-down assay were used to validate EIF4A3/GLIS2 mRNA interaction. MSP was performed to measure the methylation status of GLIS2 promoter. Nude mouse xenograft model was used to examine tumour growth and metastasis in vivo. RESULTS: Circ_GLIS2 and linear GLIS2 mRNA were reduced in human HCC tissues and cells. Their low levels correlated with a poor survival rate of HCC patients. Overexpression of circ_GLIS2 and GLIS2 suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis. GLIS2 promoter region was hypermethylated in HCC cells. EIF4A3 was directly bound with GLIS2 mRNA and promoted circ_GLIS2/GLIS2 expression. Moreover, overexpression of circ_GLIS2 restrained HCC tumour growth and metastasis in vivo. CONCLUSION: Circ_GLIS2 suppresses HCC growth and metastasis by inhibiting cell proliferation, migration, and invasion, but promoting cell apoptosis. These findings provide molecular insights into the mechanism of HCC and indicate that circ_GLIS2 could serve as a diagnosis marker or therapeutic target for HCC.

Perirenal Fat Thickness Is Significantly Associated With the Risk for Development of Chronic Kidney Disease in Patients With Diabetes.

Perirenal fat is adjacent to kidneys and active in metabolism and adipokine secretion. We aimed to investigate whether perirenal fat is an independent predictor for chronic kidney disease (CKD) and compared it with total, subcutaneous, or visceral fat in patients with diabetes. Perirenal fat thickness (PRFT) was measured by computed tomography, and total body fat (TBF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were assessed by DEXA. In cross-sectional analysis, patients with higher PRFT had a lower estimated glomerular filtration rate (eGFR). Multiple linear regression analysis showed a negative correlation between PRFT and eGFR after confounders adjustment. No association between eGFR and TBF, SAT, or VAT was observed. Longitudinally, 190 patients with type 2 diabetes mellitus (T2DM) without CKD at baseline were followed for 2 years. A total of 29 participants developed CKD. After VAT-based multivariate adjustment, each SD (per-SD) increment in baseline PRFT was associated with a higher incidence of CKD (hazard ratio 1.67, 95% CI 1.04-2.68), while TBF, SAT, and VAT were not. Furthermore, PRFT predicted CKD, with a C-statistic (95% CI) of 0.668 (0.562, 0.774), which was higher than that of TPF [0.535 (0.433, 0.637)], SAT [0.526 (0.434, 0.618)], and VAT [0.602 (0.506, 0.698)]. In conclusion, with perirenal fat there was a higher predictive value for CKD than with total, subcutaneous, or visceral fat in T2DM.

Relationship Between the TyG Index and Diabetic Kidney Disease in Patients with Type-2 Diabetes Mellitus.

BACKGROUND: Diabetic kidney disease (DKD) lacks a simple and relatively accurate predictor. The Triglyceride-Glucose (TyG) Index is a proxy of insulin resistance, but the association between the TyG Index and DKD is less certain. We investigated if the TyG Index can predict DKD onset effectively. MATERIALS AND METHODS: Cross-sectional and longitudinal analyses were undertaken. In total, 1432 type-2 diabetes mellitus (T2DM) patients were included in the cross-sectional analysis. The TyG Index (calculated by ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) was split into three tertiles. Associations of the TyG Index with microalbuminuria and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 were calculated. Longitudinally, 424 patients without DKD at baseline were followed up for 21 (range, 12-24) months. The main outcome was DKD prevalence as defined with eGFR <60 mL/min/1.73 m2 or continuously increased urinary microalbuminuria: creatinine ratio (>30 mg/mL) over 3 months. Cox regression was used to analyze the association between the TyG Index at baseline and DKD. Receiver operating characteristics curve (ROC) analysis was used to assess the sensitivity and specificity of the TyG Index in predicting DKD. RESULTS: In cross-sectional analysis, patients with a higher TyG Index had a higher risk of microalbuminuria (OR = 2.342, 95% CI = 1.744-3.144, p < 0.001), and eGFR <60 mL/min/1.73 m2 (1.696, 95% CI =1.096-2.625, p = 0.018). Longitudinally, 94 of 424 participants developed DKD. After confounder adjustment, patients in the high tertile of the TyG Index at baseline had a greater risk to developing DKD than those in the low tertile (HR = 1.727, 95% CI = 1.042-2.863, p = 0.034). The area under the ROC curve was 0.69 (0.63-0.76). CONCLUSION: The TyG Index is a potential predictor for DKD in T2DM patients. CLINICAL TRIAL: Clinical Trials identification number = NCT03692884.

The application of histone deacetylases inhibitors in glioblastoma.

The epigenetic abnormality is generally accepted as the key to cancer initiation. Epigenetics that ensure the somatic inheritance of differentiated state is defined as a crucial factor influencing malignant phenotype without altering genotype. Histone modification is one such alteration playing an essential role in tumor formation, progression, and resistance to treatment. Notably, changes in histone acetylation have been strongly linked to gene expression, cell cycle, and carcinogenesis. The balance of two types of enzyme, histone acetyltransferases (HATs) and histone deacetylases (HDACs), determines the stage of histone acetylation and then the architecture of chromatin. Changes in chromatin structure result in transcriptional dysregulation of genes that are involved in cell-cycle progression, differentiation, apoptosis, and so on. Recently, HDAC inhibitors (HDACis) are identified as novel agents to keep this balance, leading to numerous researches on it for more effective strategies against cancers, including glioblastoma (GBM). This review elaborated influences on gene expression and tumorigenesis by acetylation and the antitumor mechanism of HDACis. Besdes, we outlined the preclinical and clinical advancement of HDACis in GBM as monotherapies and combination therapies.

Effect of lignosulfonate on the adsorption performance of hematite for Cd(II).

Lignin is a precursor of humus in soil and sediment. Lignin can be separated from vascular plants in the form of lignosulfonate via pulping processes. On the other hand, composites of iron oxide and organic matter can adsorb heavy metals, and thus influence the migration of these heavy metals in the environment. In this paper, a hematite/lignosulfonate composite (HLS) was prepared via coprecipitation to compare the adsorption performance of hematite (α-Fe2O3) toward Cd(II) before and after the incorporation of lignosulfonate (LS). The HLS is found to exhibit a weakly crystalline structure and possess a large number of nanoscale particles. Specific surface area of HLS (291.97 m2/g) is about 11 times that of α-Fe2O3, and the pore volume of HLS (0.22 cm3/g) is twice that of α-Fe2O3. The adsorption of Cd(II) is well illustrated by the pseudo-second-order adsorption kinetics and the initial adsorption rate (h) of HLS is 13.83 times that of α-Fe2O3. The maximum adsorption capacities are significantly improved from 4.89-6.35 mg/g (α-Fe2O3) to 39.03-53.65 mg/g (HLS). A greater affinity and more favorable association between Cd(II) and HLS is observed via fitting models. The incorporation of LS provides HLS with significantly better adsorption properties toward Cd(II) than α-Fe2O3, as is further confirmed by FT-IR and XPS characterization. Fe-O-O-H and Fe-O-H structures as well as more hydroxyl groups are observed, which promote the adsorption performance since the process are mainly influenced by complexation via coordination bonds.

Early-onset type 2 diabetes: A high-risk factor for proliferative diabetic retinopathy (PDR) in patients with microalbuminuria.

We aim to explore the relationship between early-onset diabetes and proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients with microalbuminuria.A total of 461 T2DM patients with microalbuminuria were enrolled. Subjects were defined as early-onset or late-onset based on the age at which they were diagnosed with diabetes (<40 and ≥40 years, respectively). Medical history, anthropometry, and laboratory indicators were documented. PDR was defined as the presence of any of the following changes on fundus photography: neovascularization, vitreous hemorrhage, or preretinal hemorrhage.The prevalence of PDR was 6-fold higher in patients with early-onset than late-onset T2DM [(6.1% vs 1.0%), P = .004]. Univariate correlation analysis showed that early-onset diabetes, use of oral hypoglycemic drugs, and insulin therapy were risk factors for PDR. In multivariate logistic analysis, patients with early-onset diabetes exhibited a 7.00-fold [(95% confidence interval 1.40-38.26), P = .019] higher risk of PDR than subjects with late-onset diabetes after adjusting for sex; T2DM duration; systolic blood pressure; total triglyceride; glycated hemoglobin; insulin therapy; and the use of oral hypoglycemic drugs, antihypertensive drugs, and lipid-lowering drugs.In T2DM patients with microalbuminuria, early-onset diabetes is an independent risk factor for the development of PDR.

ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion.

Glioblastoma (GBM) is the most aggressive primary intracranial tumor in adults. Chemoradiotherapy resistance and recurrence after surgery are the main malignant progression factors, leading to a high mortality rate. Therefore, the exploration of novel biomarkers and molecular mechanisms of GBM is urgent. Differentially expressed genes (DEGs) of GBM were screened in a TCGA dataset. Homo sapiens ZW10 interacting kinetochore protein (ZWINT) was found to be upregulated in GBM, which was confirmed by immunohistochemical staining of a tissue microarray. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. A protein­protein interaction (PPI) network was established by the STRING database, and hub genes were visualized by Cytoscape. The correlation results were verified with the GSE15824 dataset. Bioinformatic analysis confirmed that ZWINT was significantly positively correlated with kinetochore protein NDC80 homolog (NDC80), serine/threonine­protein kinase PLK1 (PLK1) and spindle and kinetochore associated complex subunit 1 (SKA1) and together are involved in regulating mitosis and the cell cycle of GBM. ZWINT expression was knocked down in U251 and U87 MG GBM cells by lentiviral vectors carrying a small hairpin RNA (shRNA) targeting ZWINT. The effect of ZWINT silencing on cell proliferation, invasion and apoptosis was determined by the Celigo assay, MTT assay, Transwell assay, flow cytometry and caspase­3/7 assay in vitro. A subcutaneous xenograft tumor model was established to explore the influence of ZWINT knockdown on GBM growth in vivo. Our preliminary study demonstrated that ZWINT knockdown effectively inhibited proliferation and invasion and induced apoptosis of GBM cells and notably suppressed GBM growth in vivo. Therefore, we speculate that ZWINT may be a potential therapeutic biomarker for GBM, with NDC80 and PLK1 conjointly involved in regulating cell division and the mitotic cell cycle.

[Immobilization Impact of Goethite-Fulvic Acid Composites on Pb-Cd Contaminated Soil].

The Pearl River Delta region is the major economic zone of the Greater Bay Area:it presents a large number of industrial-mining enterprises and is interested by severe heavy metal pollution (mainly caused by Pb and Cd). The research and development of safe and efficient heavy metal remediation materials and technologies is fundamental in order to guarantee regional environmental quality and habitat safety. Goethite-fulvic acid composites were prepared using goethite minerals present in the red soils of the Pearl River Delta region by passivation repair, and were applied to immobilize Pb and Cd in a co-contaminated soil. The results showed that a higher ratio of fulvic acid in the composites enhanced the immobilization effect on Pb and Cd:the immobilization efficiency (IE) of Pb and Cd increased with the passivation time, and then stabilized. Additionally, the exchangeable and carbonate-bound fractions of Pb and Cd in the soil decreased, while the Fe-Mn oxide-bound and residual fractions increased. The cation exchange capacity (CEC), as well as the available K and NH4+-N in the soil increased after the application of the composite materials. We conclude that goethite-fulvic acid composites can be effectively applied to the remediation of Pb-Cd contaminated soil.

NAMPT: A potential prognostic and therapeutic biomarker in patients with glioblastoma.

Glioblastoma (GBM) is the most common primary intracranial malignancy. GBM still exhibits high recurrence and mortality rates even following combined treatment with surgery, radiotherapy and chemotherapy, Therefore, the identification of novel therapeutic targets is urgent. Previous research has shown that nicotinamide phosphoribosyltransferase (NAMPT) plays a key role in cell metabolism and is closely related to the occurrence and development of many tumor types; yet, little is known concerning its relationship with GBM. Oncomine database analysis showed that the expression of NAMPT in GBM was higher than that in normal tissues; this finding was further confirmed by immunohistochemical staining of a tissue microarray. Data analysis with the R2 platform showed that patients with higher expression of NAMPT had worse prognoses than those with lower NAMPT expression. Using the GBM data in TCGA, four pathways enriched in the high NAMPT expression group were identified by gene set enrichment analysis (GSEA). NAMPT expression was knocked down in U87 and U251 GBM cells by lentiviral vectors carrying a small hairpin RNA (shRNA) targeting NAMPT. CCK­8, colony formation, wound healing, Transwell and apoptosis assays were carried out. The results showed that NAMPT knockdown decreased cell proliferation, migration, and invasion and promoted apoptosis. U87 GBM cells were used in a model of subcutaneous tumorigenesis in nude mice. The results showed that NAMPT knockdown slowed the growth of tumors in vivo. Therefore, we speculate that NAMPT may be a potential prognostic and therapeutic biomarker for glioblastoma.