A thiol-functionalized magnetic mesoporous silica material (called SH-mSi@Fe
3O
4), synthesized by a modified Stöber method, has been investigated as a convenient and effective adsorbent for heavy ...metal ions. Structural characterization by powder X-ray diffraction, N
2 adsorption–desorption isotherm, Fourier transform infrared spectroscopy and elemental analyses confirms the mesoporous structure and the organic moiety content of this adsorbent. The high saturation magnetization (38.4
emu/g) make it easier and faster to be separated from water under a moderate magnetic field. Adsorption kinetics was elucidated by pseudo-second-order kinetic equation and exhibited 3-stage intraparticle diffusion mode. Adsorption isotherms of Hg and Pb fitted well with Langmuir model, exhibiting high adsorption capacity of 260 and 91.5
mg of metal/g of adsorbent, respectively. The distribution coefficients of the tested metal ions between SH-mSi@Fe
3O
4 and different natural water sources (groundwater, lake water, tap water and river water) were above the level of 10
5
mL/g. The material was very stable in different water matrices, even in strong acid and alkaline solutions. Metal-loaded SH-mSi@Fe
3O
4 was able to regenerate in acid solution under ultrasonication. This novel SH-mSi@Fe
3O
4 is suitable for repeated use in heavy metal removal from different water matrices.
F-53B, the commercial product of chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs), has been used in Chinese chrome plating industry for 30 years, and was recently identified in the ...environment, which caused great concerns. So far, limited investigations have been performed on their environmental occurrence, fate and impact. In this study, we demonstrated the wide occurrence of Cl-PFESAs and their trophic transfer behavior in marine organisms from Chinese Bohai Sea. 6:2 Cl-PFESA (<0.016–0.575 ng/g wet weight) was the dominant congener, and 8:2 Cl-PFESA (<0.022–0.040 ng/g) was occasionally detected. Compared to other perfluoroalkyl and polyfluoroalkyl substances (PFASs) of concern, the levels of Cl-PFESAs were relatively lower in marine organisms. Based on the comparative analysis of Cl-PFESA contamination in mollusk samples collected in 2010–2014, both the concentrations and detection frequencies of Cl-PFESAs tended to increase in this region. And this kind of chemicals were more vulnerable to be accumulated in marine organisms at relatively higher trophic levels. Similar to perfluorooctanesulfonate (PFOS) and the long chain perfluorinated carboxylates (PFCAs), 6:2 Cl-PFESA could be magnified along the food chain. Accordingly, the potential threat might be posed to the wildlife and human beings due to unintended exposure to Cl-PFESAs.
Quasi‐two‐dimensional (quasi‐2D) perovskites are attracting much attention due to their impressive luminescence properties. However, the introduction of insulating bulky cations reduces the charge ...transport property of mixed‐dimensional perovskites and leads to lowered brightness and increased turn‐on voltage. The trade‐off between high photoluminescence quantum yield (PLQY) and electrical conductivity should be well manipulated to obtain high‐performance perovskite light‐emitting diodes (PeLEDs). Herein, quasi‐2D perovskite BA2(CsPbBr3)n‐1PbBr4‐PEO with high PLQY and excellent carrier injection efficiency is demonstrated by incorporating bulky n‐butylammonium bromide (BABr), CsPbBr3, and polyethylene oxide (PEO). BA can intercalate into the three‐dimensional perovskite framework to form a layered (quasi‐2D) perovskite structure. The ion conductive polymer PEO is used to protect quasi‐2D perovskite crystals. Additional BABr is removed by using anhydrous isopropyl alcohol as a washing agent due to its selective dissolubility. By carefully modulating the optical and electrical properties of quasi‐2D perovskite films, the maximum luminance of PeLEDs is dramatically enhanced from 191 to 33533 cd m−2, which is the brightest green quasi‐2D PeLED reported thus far, leading to an increase in external quantum efficiency from 1.81% to 8.42%. This work provides a promising route to control the optical and electrical properties of quasi‐2D perovskite films for high‐performance optoelectronic devices.
A quasi‐2D perovskite with high photoluminescence quantum yield and excellent carrier injection efficiency is demonstrated by incorporating n‐butylammonium bromide, CsPbBr3 and polyethylene oxide. By modulating the optical and electrical properties of quasi‐2D perovskite films, the maximum luminance of PeLEDs is dramatically enhanced from 191 to 33 533 cd m−2, which is the brightest value yet observed for green quasi‐2D PeLEDs.
Somatic mutation-derived neoantigens, expressed only on tumor cells, may elicit antitumor T-cell responses in cancer immunotherapies with minimal immune tolerance. Neoantigens can be identified by ...multiple bioinformatics technologies, mainly based on whole-exome sequencing. Personalized cancer vaccines and adoptive T cell therapies are two primary treatment modalities targeting neoantigens, and both of them have shown promising therapeutic effects. This review, summarizes the history of neoantigen-related tumor control, introduces recent neoantigen screening and identification methods, and discusses the role of neoantigen in cancer immunotherapies. Moreover, we propose the challenges of targeting neoantigens for cancer treatment.
Abstract
TFE3
-translocation renal cell carcinoma (
TFE3
-tRCC) is a rare and heterogeneous subtype of kidney cancer with no standard treatment for advanced disease. We describe comprehensive ...molecular characteristics of 63 untreated primary
TFE3
-tRCCs based on whole-exome and RNA sequencing.
TFE3
-tRCC is highly heterogeneous, both clinicopathologically and genotypically.
ASPSCR1-TFE3
fusion and several somatic copy number alterations, including the loss of 22q, are associated with aggressive features and poor outcomes. Apart from tumors with
MED15-TFE3
fusion, most
TFE3
-tRCCs exhibit low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis reveals five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which show association with fusion patterns and prognosis. In line with the aggressive nature, the high angiogenesis/stroma/proliferation cluster exclusively consists of tumors with
ASPSCR1-TFE3
fusion. Here, we describe the genomic and transcriptomic features of
TFE3
-tRCC and provide insights into precision medicine for this disease.
Immune checkpoint inhibitors (ICIs), as one of the innovative types of immunotherapies, including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte ...antigen 4 (CTLA-4) inhibitors, have obtained unprecedented benefit in multiple malignancies. However, the immune response activation in the body organs could arise immune-related adverse events (irAEs). Checkpoint inhibitor colitis (CIC) is the most widely reported irAEs. However, some obscure problems, such as the mechanism concerning gut microbiota, the confusing differential diagnosis with inflammatory bowel disease (IBD), the optimal steroid schedule, the reintroduction of ICIs, and the controversial prognosis features, influence the deep understanding and precise diagnosis and management of CIC. Herein, we based on these problems and comprehensively summarized the relevant studies of CIC in patients with NSCLC, further discussing the future research direction of this specific pattern of irAEs.
Scheme for preparation of GSH-Au NCs (a) and application in selective determination of Cr(III) and Cr(VI) (b). Display omitted
► Facile and rapid preparation of fluorescent glutathione-stabilized ...gold nanoclusters. ► New method for selective determination of Cr(III) and Cr(VI) using GSH-Au NCs. ► The detection method possessed simplicity, high throughput, high selectivity and sensitivity.
A novel method for selective determination of Cr(III) and Cr(VI) in environmental water samples was developed based on target-induced fluorescence quenching of glutathione-stabilized gold nanoclusters (GSH-Au NCs). Fluorescent GSH-Au NCs were synthesized by a one-step approach employing GSH as reducing/protecting reagent. It was found that Cr(III) and Cr(VI) showed pH-dependent fluorescence quenching capabilities for GSH-Au NCs, and thus selective determination of Cr(III) and Cr(VI) could be achieved at different pHs. Addition of EDTA was able to effectively eliminate the interferences from other metal ions, leading to a good selectivity for this method. Under optimized conditions, Cr(III) showed a linear range of 25–3800μgL−1 and a limit of detection (LOD) of 2.5μgL−1. The Cr(VI) ion demonstrated a linear range of 5–500μgL−1 and LOD of 0.5μgL−1. The run-to-run relative standard deviations (n=5) for Cr(III) and Cr(VI) were 3.9% and 2.8%, respectively. The recoveries of Cr(III) and Cr(VI) in environmental water samples were also satisfactory (76.3–116%). This method, with its simplicity, low cost, high selectivity and sensitivity, could be used as a promising tool for chromium analysis in environmental water samples.
The flame retardancy of polyurethane (PU) elastomer based on aluminum monomethylphosphinate (MeP-Al) was investigated. Thermal analysis, evolved gas analysis (TG-FTIR), flammability tests (LOI, UL ...94), heat release rate (HRR) (microcombustion calorimeter), and chemical analysis of residues (SEM–EDX and FTIR) were used to investigate the flame-retardant performance and mechanism of the PU/MeP-Al. Results show that adding MeP-Al endows PU desired flame retardancy and anti-dripping property. The sample containing 20 mass% of MeP-Al passes the UL 94 V0 rating with LOI value of 29.6% and no dripping during combustion. Moreover, the heat release during combustion and the amount of organic volatile from PU decomposition are significantly reduced. The good flame retardancy, anti-dripping property, dramatically a reduction in release of heat and organic compounds are attributed to the efficient action of the MeP-Al in both the gas and condensed phase. In the gas phase, the MeP-Al decomposes into monomethylphosphinic acid to inhibit flame and reduces the heat release. In the condensed phase, MeP-Al turns into the tough aluminum pyrophosphonate and promotes PU to form stable carbonaceous char by interacting with PU.
Tislelizumab, an anti‐programmed death protein‐1 (PD‐1) monoclonal antibody, was engineered to minimize binding to the FcγR on macrophages to abrogate antibody‐dependent phagocytosis, a mechanism of ...T‐cell clearance and potential resistance to anti‐PD‐1 therapy. This single‐arm phase 2 trial (NCT04004221/CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab in patients with PD‐L1‐positive urothelial carcinoma who progressed during/following platinum‐containing therapy and had no prior PD‐(L)1 inhibitor treatment. Patients were considered PD‐L1 positive if ≥ 25% of tumor/immune cells expressed PD‐L1 when using the VENTANA™ PD‐L1 (SP263) assay. The primary endpoint was objective response rate by independent review committee. As of September 16, 2019, 113 patients had a median study follow‐up time of 9.4 mo. Most patients (76%) had visceral metastases, including 24% with liver and 23% with bone metastases. Among 104 efficacy‐evaluable patients, confirmed objective response rate was 24% (95% confidence interval, 16, 33), including 10 complete and 15 partial responses. Median duration of response was not reached. Among 25 responders, 17/25 (68%) had ongoing responses. Median progression‐free survival and overall survival times were 2.1 and 9.8 mo, respectively. The most common treatment‐related adverse events were anemia (27%) and pyrexia (19%). Anemia (7%) and hyponatremia (5%) were the only grade 3‐4 treatment‐related adverse events and occurred in ≥ 5% of patients. Three investigator‐assessed deaths were considered to be possibly related to study treatment (hepatic failure, n = 2; respiratory arrest, n = 1). Tislelizumab demonstrated meaningful clinical benefits in patients with previously treated locally advanced or metastatic PD‐L1‐positive urothelial carcinoma and had a manageable safety profile.
Tislelizumab is a unique anti‐PD‐1 antibody that was engineered specifically to minimize FcγR binding in order to limit antibody‐dependent phagocytosis, a potential mechanism of resistance to anti‐PD‐1 therapy. In the current study, tislelizumab demonstrated clinically meaningful antitumor activity in patients with previously treated locally advanced or metastatic PD‐L1‐positive urothelial carcinoma and had a manageable safety profile with no new safety signals compared with other anti‐PD‐L1/PD‐1 therapies. A phase 3 study of tislelizumab as treatment for urothelial carcinoma (NCT03967977) is currently ongoing and is recruiting patients.
Glioblastoma (GBM), a highly aggressive form of brain tumor, responds poorly to current conventional therapies, including surgery, radiation therapy, and systemic chemotherapy. The reason is that the ...delicate location of the primary tumor and the existence of the blood-brain barrier limit the effectiveness of traditional local and systemic therapies. The immunosuppressive status and multiple carcinogenic pathways in the complex GBM microenvironment also pose challenges for immunotherapy and single-targeted therapy. With an improving understanding of the GBM microenvironment, it has become possible to consider the immunosuppressive and highly angiogenic GBM microenvironment as an excellent opportunity to improve the existing therapeutic efficacy. Oncolytic virus therapy can exert antitumor effects on various components of the GBM microenvironment. In this review, we have focused on the current status of oncolytic virus therapy for GBM and the related literature on antitumor mechanisms. Moreover, the limitations of oncolytic virus therapy as a monotherapy and future directions that may enhance the field have also been discussed.