Histone demethylase PHF8 promotes prostate cancer metastasis via the E2F1-SNAI1 axis.

Metastasis is the primary culprit behind cancer-related fatalities in multiple cancer types, including prostate cancer. Despite great advances, the precise mechanisms underlying prostate cancer metastasis are far from complete. By using a transgenic mouse prostate cancer model (TRAMP) with and without Phf8 knockout, we have identified a crucial role of PHF8 in prostate cancer metastasis. By complexing with E2F1, PHF8 transcriptionally upregulates SNAI1 in a demethylation-dependent manner. The upregulated SNAI1 subsequently enhances epithelial-to-mesenchymal transition (EMT) and metastasis. Given the role of the abnormally activated PHF8/E2F1-SNAI1 axis in prostate cancer metastasis and poor prognosis, the levels of PHF8 or the activity of this axis could serve as biomarkers for prostate cancer metastasis. Moreover, targeting this axis could become a potential therapeutic strategy for prostate cancer treatment. © 2024 The Pathological Society of Great Britain and Ireland.

Establishment and validation of a gene mutation-based risk model for predicting prognosis and therapy response in acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a malignant clonal proliferative disease of hematopoietic system. Despite tremendous progress in uncovering the AML genome, only a small number of mutations have been incorporated into risk stratification and used as therapeutic targets. In this research, we performed to construct a predictive prognosis risk model for AML patients according to gene mutations. Methods: Next-generation sequencing (NGS) technology was utilized to detect gene mutation from 118 patients. mRNA expression profiles and related clinical information were mined from TCGA and GEO databases. Consensus cluster analysis was applied to obtain molecular subtypes, and differences in clinicopathological features, prognosis, and immune microenvironment of different clusters were systematically compared. According to the differentially expressed genes (DEGs) between clusters, univariate and LASSO regression analysis were applied to identify gene signatures to build a prognostic risk model. Patients were classified into high-risk (HR) and low-risk (LR) groups according to the median risk score (RS). Differences in prognosis, immune profile, and therapeutic sensitivity between two groups were analyzed. The independent predictive value of RS was assessed and a nomogram was developed. Results: NGS detected 24 mutated genes, with higher mutation frequencies in CBL (63 %) and SETBP1 (49 %). Two clusters exhibited different immune microenvironments and survival probability (p = 0.0056) were identified. A total of 444 DEGs were screened in two clusters, and a mutation-associated risk model was constructed, including MPO, HGF, SH2B3, SETBP1, HLA-DRB1, LGALS1, and KDM5B. Patients in LR had a superior survival time compared to HR. Predictive performance of this model was confirmed and the developed nomogram further improved the applicability of the risk model with the AUCs for predicting 1-, 3-, 5-year survival rate were 0.829, 0.81 and 0.811, respectively. HR cases were more sensitive to erlotinib, CI-1040, and AZD6244. Conclusion: These findings supplemented the understanding of gene mutations in AML, and constructed models had good application prospect to provide effective information for predicting prognosis and treatment response of AML.

Prevalence and genotype distribution of HPV infections among women in Chengdu,China.

BACKGROUND: Human papilloma virus (HPV) infection among female is the cause of cervical cancer and genital warts. In China, the HPV vaccination rate and the target population screening rate among females are low, and the aims of this study on the genotype distribution and prevalence of HPV infection were to provide more targeted strategies for the prevention and treatment of cervical cancer and HPV-related diseases. METHODS: Polymerase chain reaction-reverse dot blot (PCR-RDB) was adopted for HPV genotyping test, the prevalence and 23 genotypes distribution of HPV infections among 181,705 women in Chengdu from 2013 to 2020 were analysed. RESULTS: The overall prevalence rate of HPV infection among 181,705 cases was 23.28%, the prevalence of HR-HPV at the age group < 20 years, 60-69 years and ≥ 70 years were higher than the overall prevalence.The prevalence of HPV showed a bimodal U-shaped curve with age; the first and second peak common occurred among females < 20 years old (42.97%) and 60-69 years old (37.56%), respectively.The top five genotypes of HPV infection among females in Chengdu were HPV52/16/58/81/53. Single infection (73.26%) was the main HPV infection pattern, followed by double infection (19.17%) and multiple infection (7.57%), the infection rate of HPV showed a gradual declined as the patterns of HPV coinfections increased, low-risk and high-risk coinfection was higher in low-risk HPV infection (43.68%) and lower in high-risk HPV infection (13.59%). The prevalence of genotypes - 6 and - 81 infection was the second highest at the age group of 20 and 40-59, respectively, while the prevalence of HPV16 was the highest at the age group of ≥ 70 among 23 genotypes among the 181,705 women. CONCLUSIONS: The prevalence of HPV infections among women in Chengdu is higher than domestic certain developed citys, among the five vaccines available, nonavalent vaccine is more suitable for Chengdu females. For young females prioritizing vaccination is essential in the current context.Double screening for HPV DNA is important in middle-aged women (30-49 years), and screening should not be lacking in older women (> 65 years). Additionally,for patients with genital warts, it is necessary to screen for high-risk HPV infection and provide appropriate management and treatment. Given the limitations of this study, future HPV research should aim to achieve full coverage of the target population, and our studies should also include cellular or pathological data of HPV-positive cases, vaccination rates, and various lifestyle details.

Cortical lipid metabolic pathway alteration of early Alzheimer's disease and candidate drugs screen.

BACKGROUND: Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex. METHODS: The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein-protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs. RESULTS: 60 lipid metabolic genes differentially expressed in early AD patients' cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol. CONCLUSIONS: AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.

Effect of oxide interactions on chromium speciation transformation during simulated municipal solid waste incineration.

Chromium released during municipal solid waste incineration (MSWI) is toxic and carcinogenic. The removal of chromium from simulated MSWI flue gas by four sorbents (CaO, bamboo charcoal (BC), powdered activated carbon (PAC), and Al2O3) and the effects of four oxides (SiO2, Al2O3, Fe2O3, and CaO) on chromium speciation transformation were investigated. The results showed that the removal rates of total Cr by the four sorbents were Al2O3 < CaO < PAC < BC, while the removal rates of Cr(VI) by the four sorbents were Al2O3 < PAC < BC < CaO. CaO had a strong oxidizing effect on Cr(III), while BC and PAC had a better-reducing effect on Cr(VI). SiO2 was better for the reduction of Na2CrO4 and K2CrO4 above 1000°C due to its strong acidity, and the addition of CaO significantly inhibited the reduction of Cr(VI). MgCrO4 decomposed above 700°C to form MgCr2O4, and the reaction between MgCrO4 and oxides also existed in the form of a more stable trivalent spinel. Furthermore, when investigating the effect of oxides on the oxidation of Cr(III) in CrCl3, it was discovered that CaO promoted the conversion of Cr(III) to Cr(VI), while the presence of chlorine caused chromium to exist in the form of Cr(V), and increasing the content of CaO and extending the heating time facilitated the oxidation of Cr(III). In addition, silicate, aluminate, and ferrite were generated after the addition of SiO2, Al2O3, and Fe2O3, which reduced the alkalinity of CaO and had an important role in inhibiting the oxidation of Cr(III). The acidic oxides can not only promote the reduction of Cr(VI) but also have an inhibitory effect on the oxidation of Cr(III) ascribed to alkali metals/alkaline earth metals, and the proportion of acidic oxides can be increased moderately to reduce the generation of harmful substances in the hazardous solid waste heat treatment.

H-ferritin-nanocaged gadolinium nanoparticles for ultra-sensitive MR molecular imaging.

Rationale: Magnetic resonance imaging (MRI) is a powerful diagnostic technology by providing high-resolution imaging. Although MRI is sufficiently valued in its resolving morphology, it has poor sensitivity for tracking biomarkers. Therefore, contrast agents are often used to improve MRI diagnostic sensitivity. However, the clinically used Gd chelates are limited in improving MRI sensitivity owing to their low relaxivity. The objective of this study is to develop a novel contrast agent to achieve a highly sensitive tracking of biomarkers in vivo. Methods: A Gd-based nanoprobe composed of a gadolinium nanoparticle encapsulated within a human H-ferritin nanocage (Gd-HFn) has been developed. The specificity and sensitivity of Gd-HFn were evaluated in vivo in tumor-bearing mice and apolipoprotein E-deficient mice (Apoe-/-) by MRI. Results: The Gd-HFn probe shows extremely high relaxivity values (r1 = 549 s-1mM-1, r2 = 1555 s-1mM-1 under a 1.5-T magnetic field; and r1 = 428 s-1mM-1 and r2 = 1286 s-1mM-1 under a 3.0-T magnetic field), which is 175-fold higher than that of the clinically standard Dotarem (Gd-DOTA, r1 =3.13 s-1mM-1) under a 1.5-T magnetic field, and 150-fold higher under a 3.0-T magnetic field. Owing to the substantially enhanced relaxivity values, Gd-HFn achieved a highly sensitive tracking for the tumor targeting receptor of TfR1 and enabled the in vivo MRI visualization of tumors approaching the angiogenic switch. Conclusions: The developed Gd-HFn contrast agent makes MRI a more powerful tool by simultaneously providing functional and morphological imaging information, which paves the way for a new perspective in molecular imaging.

Characterization of T cell receptor repertoire in penile cancer.

Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of complementarity determining region 3 (CDR3) length distribution did not show significant differences between tumor and matched normal tissues. Moreover, analysis of the median Jaccard index indicated a limited overlap of TCR repertoire between these groups. Compared with normal tissues, a significantly lower diversity and higher clonality of TCR repertoire was observed in tumor samples, which was associated with clinical characteristics. Further analysis of transcriptional profiles demonstrated that tumor samples with high clonality showed increased expression of genes associated with CD8 + T cells. In addition, we analyzed the TCR repertoire of CD4 + T cells and CD8 + T cells isolated from tumor tissues. We identified that expanded clonotypes were predominantly in the CD8 + T cell compartment, which presented with an exhausted phenotype. Overall, we comprehensively compared TCR repertoire between penile tumor and normal tissues and demonstrated the presence of distinct T cell immune microenvironments in patients with PSCC.

The diagnostic yield of exome sequencing in liver diseases from a curated gene panel.

Exome sequencing (ES) has been used in a variety of clinical settings but there are limited data on its utility for diagnosis and/or prediction of monogenic liver diseases. We developed a curated list of 502 genes for monogenic disorders associated with liver phenotypes and analyzed ES data for these genes in 758 patients with chronic liver diseases (CLD). For comparison, we examined ES data in 7856 self-declared healthy controls (HC), and 2187 patients with chronic kidney disease (CKD). Candidate pathogenic (P) or likely pathogenic (LP) variants were initially identified in 19.9% of participants, most of which were attributable to previously reported pathogenic variants with implausibly high allele frequencies. After variant annotation and filtering based on population minor allele frequency (MAF ≤ 10-4 for dominant disorders and MAF ≤ 10-3 for recessive disorders), we detected a significant enrichment of P/LP variants in the CLD cohort compared to the HC cohort (X2 test OR 5.00, 95% CI 3.06-8.18, p value = 4.5e-12). A second-level manual annotation was necessary to capture true pathogenic variants that were removed by stringent allele frequency and quality filters. After these sequential steps, the diagnostic rate of monogenic disorders was 5.7% in the CLD cohort, attributable to P/LP variants in 25 genes. We also identified concordant liver disease phenotypes for 15/22 kidney disease patients with P/LP variants in liver genes, mostly associated with cystic liver disease phenotypes. Sequencing results had many implications for clinical management, including familial testing for early diagnosis and management, preventative screening for associated comorbidities, and in some cases for therapy. Exome sequencing provided a 5.7% diagnostic rate in CLD patients and required multiple rounds of review to reduce both false positive and false negative findings. The identification of concordant phenotypes in many patients with P/LP variants and no known liver disease also indicates a potential for predictive testing for selected monogenic liver disorders.

Prevalence and genotype distribution of HPV6/11/16/18 infections among 180,276 outpatient females from a Women's and Children's Central Hospital, 2015-2021, Chengdu, China.

The aims of this study on human papilloma virus (HPV) 6/11/16/18 infection among females in Chengdu were to provide more targeted strategies for the prevention and treatment of cervical cancer and genital warts. In this study, the infection status of 20 genotypes was analysed by gene chip technology. The prevalence rates of HPV-6, -11, -16, and -18 infection among 180,276 cases were 0.94%, 0.57%, 3.22%, and 1.28%, respectively. The prevalence of HPV 6/11/16/18 showed a bimodal U-shaped curve with age; the first and second peak occurred among females < 20 and ≥ 60 years old, respectively. As the multiplicity of infections involving HPV6/11/16/18 increases, the infection rate decreases. The ratios of HPV16 single infection showed a yearly increase. The top five genotypes with HPV-16, -18, -6, and -11 in coinfection were HPV52/58/53/51/33, HPV 52/16/53/58/51, HPV52/16/58/51/53 and HPV16/52/58/59/18, respectively, HPV16/18/6/11 were mainly coinfected with HR-HPV. In sum, among the five vaccines available, nonavalent vaccine is more suitable for Chengdu females. For young females prioritizing vaccination is essential in the current context, while HPV screening remains an effective approach for older females. Additionally, in patients with genital warts, it is necessary to assess the presence of high-risk HPV infection and manage it appropriately in patients with genital warts.

Serum VEGF levels as a predictor of recurrence in patients with advanced­stage esophageal squamous cell carcinoma following curative esophagectomy followed by chemotherapy or concurrent radiotherapy.

The present study evaluated serum levels of vascular endothelial growth factor (VEGF) as a predictor of recurrence in patients with advanced-stage esophageal squamous cell carcinoma (ESCC) following curative esophagectomy followed by chemotherapy or concurrent radiotherapy. Patients with locally advanced resectable ESCC underwent R0 esophagectomy followed by chemotherapy or concurrent radiotherapy as an adjuvant. Serum VEGF levels in 173 patients, including 57 patients with recurrent disease, and 183 healthy controls were determined using a Luminex assay. The results demonstrated that the serum VEGF levels were significantly higher in 57 patients with locally advanced resectable ESCC at recurrence compared with the levels at pre-treatment (P<0.001). The patients with recurrence exhibited significantly higher serum VEGF levels during chemotherapy or concurrent radiotherapy than patients with no recurrence (P<0.05). Patients with low serum VEGF levels had a significantly longer survival time than those with high serum VEGF levels prior to treatment (P<0.01). The median survival times were 70 and 25 months in patients with locally advanced resectable ESCC with serum VEGF levels <161.75 and ≥161.75 pg/ml following treatment, respectively (P<0.01). Compared with patients with VEGF levels <147 pg/ml following treatment, patients with locally advanced resectable ESCC with VEGF levels ≥147 pg/ml had a significantly higher risk of recurrence (P<0.01). Patients with low serum VEGF levels (<147 pg/ml) had significantly higher recurrence-free survival rates than those with high serum VEGF levels (≥147 pg/ml) following treatment (P<0.01). The findings of the present study demonstrate that serum VEGF levels are a potential predictor of recurrence and of the treatment outcomes of chemotherapy or concurrent radiotherapy in patients with locally advanced resectable ESCC.

CLASRP oncogene as a novel target for colorectal cancer.

Clk4-associated serine/arginine-rich protein (CLASRP), an alternative splicing regulator, may be involved in the development and progression of cancer by regulating the activity of the CDC-like kinase (Clk) family. This study explored the biological function of CLASRP in colorectal cancer (CRC). The expression of CLASRP, which is associated with clinicopathological features, was analysed in CRC tissues and paired noncancer tissues by RT-PCR. The roles of CLASRP were investigated in CRC cells transfected with plasmids or shRNA through proliferation, migration and invasion assays in vitro and a xenograft model in vivo. Apoptosis was analysed using CLASRP-overexpressing CRC cells by western blotting. Clk inhibitors were used to perform functional research on CLASRP in CLASRP-overexpressing CRC cells. CLASRP was significantly upregulated in CRC cell lines, while high CLASRP expression was correlated with metastasis in CRC patients. Functionally, overexpression of CLASRP significantly promoted the proliferation, migration and invasion of CRC cells in vitro and tumour growth in vivo. Mechanistically, the proliferation, migration and invasion of CLASRP-overexpressing CRC cells were inhibited by Clk inhibitors, accompanied by low expression of CLASRP at the gene and protein levels. Clk inhibitors induced apoptosis of CLASRP-overexpressing CRC cells, resulting in direct blockade of cell growth. The expression levels of cleaved caspase 3 and cleaved caspase 8 were increased in CLASRP-overexpressing CRC cells treated with Clk inhibitors. CLASRP might serve as a promotional oncogene in CRC cells and be suppressed by Clk inhibitors through activation of caspase pathways.

CRNDE mediated hnRNPA2B1 stability facilitates nuclear export and translation of KRAS in colorectal cancer.

Development of colorectal cancer (CRC) involves activation of Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling. However, the post-transcriptional regulation of KRAS has yet to be fully characterized. Here, we found that the colorectal neoplasia differentially expressed (CRNDE)/heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) axis was notably elevated in CRC and was strongly associated with poor prognosis of patients, while also significantly promoting CRC cell proliferation and metastasis both in vitro and in vivo. Furthermore, CRNDE maintained the stability of hnRNPA2B1 protein by inhibiting E3 ubiquitin ligase TRIM21 mediated K63 ubiquitination-dependent protein degradation. CRNDE/hnRNPA2B1 axis facilitated the nuclear export and translation of KRAS mRNA, which specifically activated the MAPK signaling pathway, eventually accelerating the malignant progression of CRC. Our findings provided insight into the regulatory network for stable hnRNPA2B1 protein expression, and the molecular mechanisms by which the CRNDE/hnRNPA2B1 axis mediated KRAS nucleocytoplasmic transport and translation, deeply underscoring the bright future of hnRNPA2B1 as a promising biomarker and therapeutic target for CRC. By hindering hnRNPA2B1 from binding to the E3 ubiquitin ligase TRIM21, whose mediated ubiquitin-dependent degradation was thereby inhibited, CRNDE protected the stability of hnRNPA2B1's high protein expression in CRC. Supported by the high level of the oncogenic molecule CRNDE, hnRNPA2B1 bound to KRAS mRNA and promoted KRAS mRNA nucleus export to enter the ribosomal translation program, subsequently activating the MAPK signaling pathway and ultimately accelerating the malignant progression of CRC.

Roles of Fascin in Dendritic Cells.

Dendritic cells (DCs) are professional antigen-presenting cells that play a crucial role in activating naive T cells through presenting antigen information, thereby influencing immunity and anti-cancer responses. Fascin, a 55-kDa actin-bundling protein, is highly expressed in mature DCs and serves as a marker protein for their identification. However, the precise role of fascin in intratumoral DCs remains poorly understood. In this review, we aim to summarize the role of fascin in both normal and intratumoral DCs. In normal DCs, fascin promotes immune effects through facilitating DC maturation and migration. Through targeting intratumoral DCs, fascin inhibitors enhance anti-tumor immune activity. These roles of fascin in different DC populations offer valuable insights for future research in immunotherapy and strategies aimed at improving cancer treatments.

The Early Stage of Abnormal Aging: Cognitive Impairment.

Cognitive impairment has become an important aspect affecting the health and quality of life of middle-aged and elderly people, which is defined as the difficulty of thought processing and leads to memory loss, difficulties making decisions, the inability to concentrate, and difficulties learning. The process of cognitive ability decline with age goes through subjective cognitive impairment (SCI) to mild cognitive impairment (MCI). There is abundant evidence supporting the link between cognitive impairment and several modifiable risk factors, such as physical activity, social activity, mental activity, higher education, and management of cardiovascular risk factors (diabetes, obesity, smoking, hypertension, and obesity). Meanwhile, these factors also provide a new perspective for the prevention of cognitive impairment and dementia.

Aldolase A Promotes Colorectal Cancer Progression through Targeting COPS6 and Regulating MAPK Signaling Pathway.

Colorectal cancer (CRC) is a serious threat to human health, and its underlying mechanisms remain to be further explored. Aldolase A (ALDOA) has received increasing attention for its reported association with multiple cancers, but the role and mechanisms of ALDOA in CRC are still unclear. In the current study, high expression levels and enzymatic activity of ALDOA were detected in CRC tissues and cell lines, indicating the clinical significance of ALDOA in human CRC. In addition, silencing ALDOA significantly impaired the proliferation and metastasis of CRC cells in vitro and in vivo. Mechanistically, immunoprecipitation assays and mass spectrometry analysis identified the binding protein COPS6 of ALDOA. Furthermore, the promoting effects of upregulated ALDOA on CRC cell proliferation and metastasis were inhibited by COPS6 depletion, demonstrating COPS6 was required for ALDOA in mediating CRC progress. Moreover, the epithelial-mesenchymal transition (EMT) program and MAPK signaling pathway were found to be activated by ALDOA overexpression as well. In summary, our findings suggested that ALDOA facilitated the proliferation and metastasis of CRC by binding and regulating COPS6, inducing EMT, and activating the mitogen-activated protein kinase (MAPK) signaling pathway. The present study provided evidence for ALDOA as a promising potential biomarker for CRC.

Flower-like Thiourea-Formaldehyde Resin Microspheres for the Adsorption of Silver Ions.

Around a quarter of annual worldwide silver consumption comes from recycling. It remains a primary target for researchers to increase the silver ion adsorption capacity of the chelate resin. Herein, a series of flower-like thiourea-formaldehyde microspheres (FTFM) possessing diameters of 15-20 µm were prepared via a one-step reaction under acidic conditions, and the effects of the monomer molar ratio and reaction time on the micro-flower morphology, specific surface area, and silver ion adsorption performance were explored. The nanoflower-like microstructure showed the maximum specific surface area 18.98 ± 0.949 m2/g, which was 55.8 times higher than that of the solid microsphere control. As a result, the maximum silver ion adsorption capacity was 7.95 ± 0.396 mmol/g, which was 10.9 times higher than that of the control. Kinetic studies showed that the equilibrium adsorption amount of FT1F4M was 12.61 ± 0.016 mmol/g, which was 11.6 times higher than that of the control. Additionally, the isotherm study of the adsorption process was performed, and the maximum adsorption capacity of FT1F4M was 18.17 ± 1.28 mmol/g, which was 13.8 times that of the control according to the Langmuir adsorption model. Its high absorption efficiency, convenient preparation strategy, and low cost recommend FTFM bright for further use in industrial applications.

Expression of TFRC helps to improve the antineoplastic effect of Ara-C on AML cells through a targeted delivery carrier.

BACKGROUND: Currently, high doses of cytarabine arabinoside (Ara-C)-based combined chemotherapy are commonly used in acute myeloid leukemia (AML) therapy, but severe adverse effects and poor suppression effects in leukemia cells limit the clinical therapeutic efficiency of Ara-C-based chemotherapy due to a lack of targeting selectivity. To improve the therapeutic effect of Ara-C in AML, here, since we confirmed that transferrin receptor 1 (TFRC) expression in AML cells was constant, we generated Ara-C@HFn by encapsulating free Ara-C into self-assembled heavy ferritin chain (HFn, the ligand of TFRC) nanocages. RESULTS: The analysis of clinically relevant data suggested that the high expression levels of TFRC from AML cells would not decrease significantly after treatment with Ara-C. Ara-C@HFn can be efficiently internalized by leukemia cells, showing stronger cytotoxic effects in vitro and reducing the burden of leukemia in AML mice more effectively in vivo than free Ara-C. Ara-C@HFn treatment showed no acute toxicity in visceral organs of mice. Moreover, the analysis of clinically relevant data also suggested that there are several drugs (such as tamibarotene and ABT199) that would not cause significant expression down-regulation of TFRC in AML cells (after treatment). CONCLUSION: The above results suggested that TFRC can be used as a constant and effective target for drug targeting delivery of AML cells. Thus Ara-C@HFn treatment can become a safe and efficient strategy for AML therapy by specifically delivering Ara-C to AML cells. Besides, the HFn nanocages are promising for improving antineoplastic effect of other AML-related therapy drugs that do not cause downregulated expression of TFRC in AML cells.

Reduced Graphene Oxide-Doped Porous Thermoplastic Polyurethane Sponges for Highly Efficient Oil/Water Separation.

In this paper, a porous polyurethane sponge with excellent hydrophobicity was prepared through thermal phase separation. Preparation condition modified experiments were systematically carried out, and a sponge with a saturated oil absorption capacity (13.3 g g-1) and a rapid absorption rate (achieving absorption equilibrium within 20 s) was achieved. The thermoplastic polyurethane (TPU) sponge as an oil absorbent is capable of selectively absorbing various oils/organic solvents from oil/water mixtures with a high recovery rate. To further enhance the hydrophobicity and mechanical properties of the porous sponge, 3% reduced graphene oxide was doped to this material. The morphological investigation indicated that the three-dimensional composite sponges have uniformly distributed micropores and nanopores, and the hydrophobicity and mechanical properties were improved. The composite as a whole exhibited remarkable superelasticity, excellent reversible compressibility, and fatigue resistance (strength up to 186 kPa at 80% strain), which allows it to re-absorb oil by simple manual extrusion. The abovementioned properties make this TPU porous material a promising candidate for practical application in water pollution treatment.

Toluene degradation in air/H2O DBD plasma: A reaction mechanism investigation based on detailed kinetic modeling and emission spectrum analysis.

Non-thermal plasma (NTP) is emerging as an attractive method for decomposing volatile organic compounds (VOCs). In this paper, to study toluene degradation mechanism in air/H2O dielectric barrier discharge (DBD) plasma, optical emission spectrometry (OES) was employed to in-situ monitor active species in plasma, with the permanent degradation products being detected by on-line mass spectrometry under various operations. A detailed kinetic model of NTP with incorporation of non-constant electron filed and thermal effects has also been established. A toluene degradation efficiency > 82% could be achieved at P = 115 W, Cin, toluene = 1000 ppm. The relative spectrum intensity of excited OH, O, H and N2 (A3Σ+u) increased with increase of discharge power and was decreased at higher gas flowrates. Toluene degradation was mainly induced by oxidation of OH and O at afterglow stage, while part of toluene was decomposed by attack of electrons and reactive particles N2 (A3Σ+u) in discharge stage. A toluene degradation pathway has been proposed as: toluene→benzyl→benzaldehyde→benzene→phenoxy→cyclopentadiene→polycarbenes/alkynol→CO2/H2O. Benzoquinone, benzaldehyde, cyclopentadiene and cyclopentadienyl are supposed to be important intermediates for the ring-opening of toluene. Clarification of toluene degradation behaviors at discharge and afterglowing stage could provide new insights for plasma-catalytic process in future.

Immunotherapy: Review of the Existing Evidence and Challenges in Breast Cancer.

Breast cancer (BC) is a representative malignant tumor that affects women across the world, and it is the main cause of cancer-related deaths in women. Although a large number of treatment methods have been developed for BC in recent years, the results are sometimes unsatisfying. In recent years, treatments of BC have been expanded with immunotherapy. In our article, we list some tumor markers related to immunotherapy for BC. Moreover, we introduce the existing relatively mature immunotherapy and the markers' pathogenesis are involved. The combination of immunotherapy and other therapies for BC are introduced in detail, including the combination of immunotherapy and chemotherapy, the combined use of immunosuppressants and chemotherapy drugs, immunotherapy and molecular targeted therapy. We summarize the clinical effects of these methods. In addition, this paper also makes a preliminary exploration of the combination of immunotherapy, radiotherapy, and nanotechnology for BC.