Both Xp11 translocation renal cell carcinomas and the corresponding mesenchymal neoplasms are characterized by a variety of gene fusions involving TFE3. It has been known that tumors with different ...gene fusions may have different clinicopathologic features; however, further in-depth investigations of subtyping Xp11 translocation-associated cancers are needed in order to explore more meaningful clinicopathologic correlations. A total of 22 unusual cases of Xp11 translocation-associated cancers were selected for the current study; 20 cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners. RNA sequencing identified 17 of 20 cases (85%) with TFE3-associated gene fusions, including 4 ASPSCR1/ASPL-TFE3, 3 PRCC-TFE3, 3 SFPQ/PSF-TFE3, 1 NONO-TFE3, 4 MED15-TFE3, 1 MATR3-TFE3, and 1 FUBP1-TFE3. The results have been verified by fusion fluorescence in situ hybridization (FISH) assays or reverse transcriptase polymerase chain reaction (RT-PCR). The remaining 2 cases with specific pathologic features highly suggestive of MED15-TFE3 renal cell carcinoma were identified by fusion FISH assay. We provide the detailed morphologic and immunophenotypic description of the MED15-TFE3 renal cell carcinomas, which frequently demonstrate extensively cystic architecture, similar to multilocular cystic renal neoplasm of low malignant potential, and expressed cathepsin K and melanotic biomarker Melan A. This is the first time to correlate the MED15-TFE3 renal cell carcinoma with specific clinicopathologic features. We also report the first case of the corresponding mesenchymal neoplasm with MED15-TFE3 gene fusion. Additional novel TFE3 gene fusion partners, MATR3 and FUBP1, were identified. Cases with ASPSCR1-TFE3, SFPQ-TFE3, PRCC-TFE3, and NONO-TFE3 gene fusion showed a wide variability in morphologic features, including invasive tubulopapillary pattern simulating collecting duct carcinoma, extensive calcification and ossification, and overlapping and high columnar cells with nuclear grooves mimicking tall cell variant of papillary thyroid carcinoma. Furthermore, we respectively evaluated the ability of TFE3 immunohistochemistry, TFE3 FISH, RT-PCR, and RNA sequencing to subclassify Xp11 translocation-associated cancers. In summary, our study expands the list of TFE3 gene fusion partners and the clinicopathologic features of Xp11 translocation-associated cancers, and highlights the importance of subtyping Xp11 translocation-associated cancers combining morphology, immunohistochemistry, and multiple molecular techniques.
Autophagy is a genetically well-controlled cellular process that is tightly controlled by a set of core genes, including the family of autophagy-related genes (ATG). Autophagy is a "double-edged ...sword" in tumors. It can promote or suppress tumor development, which depends on the cell and tissue types and the stages of tumor. At present, tumor immunotherapy is a promising treatment strategy against tumors. Recent studies have shown that autophagy significantly controls immune responses by modulating the functions of immune cells and the production of cytokines. Conversely, some cytokines and immune cells have a great effect on the function of autophagy. Therapies aiming at autophagy to enhance the immune responses and anti-tumor effects of immunotherapy have become the prospective strategy, with enhanced antigen presentation and higher sensitivity to CTLs. However, the induction of autophagy may also benefit tumor cells escape from immune surveillance and result in intrinsic resistance against anti-tumor immunotherapy. Increasing studies have proven the optimal use of either ATG inducers or inhibitors can restrain tumor growth and progression by enhancing anti-tumor immune responses and overcoming the anti-tumor immune resistance in combination with several immunotherapeutic strategies, indicating that induction or inhibition of autophagy might show us a prospective therapeutic strategy when combined with immunotherapy. In this article, the possible mechanisms of autophagy regulating immune system, and the potential applications of autophagy in tumor immunotherapy will be discussed.
Twelve organophosphorus flame retardants (PFRs) were identified in the sediments and the sediment core collected from the rivers and the estuary in the Pearl River Delta, with the aim of ...investigating their spatial and vertical distributions. The concentrations of PFRs ranged from 8.3 to 470ng/g dry weight with high levels of PFRs in the urban area and the e-waste recycling region. Generally, TPhP, TCPP, TEHP, TCEP, and TBEP were the dominant compounds of the PFRs, the composition of which varied across the different regions, reflecting the different sources of PFRs. In the estuary, the PFRs mainly derived from the Xijiang River and the Shunde sections. Increased concentrations of halogen-containing PFRs have been observed in the upper layers of the sediment core. Conversely, relatively high concentrations of halogen-free PFRs were observed in the lower layers of the sediment core, indicating different usage patterns or environmental behaviors between the halogen and the non-halogen PFRs in the study area.
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•Levels of ∑12PFRs in sediments from the PRD ranged from 8.3–470ng/g dw.•High levels of PFRs were in the urbanized area and e-waste area.•The dominant PFRs were TPhP, TCPP, TEHP, TCEP and TBEP in the PRD.•Composition varied across different regions reflecting various sources of PFRs.•Halogen and non-halogen PFRs exhibited different vertical profile in sediment core.
Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can ...promote or suppress tumor development, so it is a "double-edged sword" in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.
Engineering multifunctional nanocarriers for targeted drug delivery shows promising potentials to revolutionize the cancer chemotherapy. Simple methods to optimize physicochemical characteristics and ...surface composition of the drug nanocarriers need to be developed in order to tackle major challenges for smooth translation of suitable nanocarriers to clinical applications. Here, rational development and utilization of multifunctional mesoporous silica nanoparticles (MSNPs) for targeting MDA‐MB‐231 xenograft model breast cancer in vivo are reported. Uniform and redispersible poly(ethylene glycol)‐incorporated MSNPs with three different sizes (48, 72, 100 nm) are synthesized. They are then functionalized with amino‐β‐cyclodextrin bridged by cleavable disulfide bonds, where amino‐β‐cyclodextrin blocks drugs inside the mesopores. The incorporation of active folate targeting ligand onto 48 nm of multifunctional MSNPs (PEG‐MSNPs48‐CD‐PEG‐FA) leads to improved and selective uptake of the nanoparticles into tumor. Targeted drug delivery capability of PEG‐MSNPs48‐CD‐PEG‐FA is demonstrated by significant inhibition of the tumor growth in mice treated with doxorubicin‐loaded nanoparticles, where doxorubicin is released triggered by intracellular acidic pH and glutathione. Doxorubicin‐loaded PEG‐MSNPs48‐CD‐PEG‐FA exhibits better in vivo therapeutic efficacy as compared with free doxorubicin and non‐targeted nanoparticles. Current study presents successful utilization of multifunctional MSNP‐based drug nanocarriers for targeted cancer therapy in vivo.
Biocompatible, uniform, and redispersible mesoporous silica nanoparticles are developed for cancer‐targeted drug delivery in vivo. The folate‐functionalized mesoporous silica nanoparticles with a core diameter of 48 nm can deliver sufficient amount of doxorubicin into tumor, resulting in a remarkable tumor‐inhibiting effect as compared with those of free doxorubicin and non‐targeted nanoparticles.
Stroke is the most common cerebrovascular disease, the second leading cause of death behind heart disease and is a major cause of long-term disability worldwide. Currently, systemic immunomodulatory ...therapy based on intravenous cells is attracting attention. The immune response to acute stroke is a major factor in cerebral ischaemia (CI) pathobiology and outcomes. Over the past decade, the significant contribution of the spleen to ischaemic stroke has gained considerable attention in stroke research. The changes in the spleen after stroke are mainly reflected in morphology, immune cells and cytokines, and these changes are closely related to the stroke outcomes. Autonomic nervous system (ANS) activation, release of central nervous system (CNS) antigens and chemokine/chemokine receptor interactions have been documented to be essential for efficient brain-spleen cross-talk after stroke. In various experimental models, human umbilical cord blood cells (hUCBs), haematopoietic stem cells (HSCs), bone marrow stem cells (BMSCs), human amnion epithelial cells (hAECs), neural stem cells (NSCs) and multipotent adult progenitor cells (MAPCs) have been shown to reduce the neurological damage caused by stroke. The different effects of these cell types on the interleukin (IL)-10, interferon (IFN), and cholinergic anti-inflammatory pathways in the spleen after stroke may promote the development of new cell therapy targets and strategies. The spleen will become a potential target of various stem cell therapies for stroke represented by MAPC treatment.
Three highly porous metal–organic frameworks (MOFs) with a uniform rht‐type topological network but hierarchical pores were successfully constructed by the assembly of triazole‐containing dendritic ...hexacarboxylate ligands with ZnII ions. These transparent MOF crystals present gradually increasing pore sizes upon extension of the length of the organic backbone, as clearly identified by structural analysis and gas‐adsorption experiments. The inherent accessibility of the pores to large molecules endows these materials with unique properties for the uptake of large guest molecules. The visible selective adsorption of dye molecules makes these MOFs highly promising porous materials for pore‐size‐dependent large‐molecule capture and separation.
Color me pretty: Highly porous metal–organic frameworks with uniform topological networks were constructed by isoreticular extension through click reactions. The accessibility of their pores to large molecules make them highly promising materials for size‐dependent large‐molecule capture and separation, as demonstrated visually by the selective capture of dye molecules (see picture; MeB=methylene blue, R6G=rhodamine 6G, BBR=brilliant blue R).
Near‐infrared phosphor‐converted light‐emitting diodes (NIR pc‐LEDs) have promising applications in food analysis, night vision imaging, and biological probes. Developing NIR phosphors with broadband ...emission and high efficiency has attracted immense interest. Herein, a novel NIR phosphor Ca2LuScAl2Si2O12:Cr3+ (CLSAS:Cr3+) is reported for the first time. Under the excitation of 442 nm light, CLSAS:Cr3+ shows broadband emission from 600 to 900 nm with a full width at half maximum (FWHM) of 142 nm, benefiting from the emissions of two Cr3+ centers in CLSAS, which is proved by the spectra and the decay curves. The internal quantum efficiency (IQE) of 73.7% is achieved and, at 423 K, the emission intensity maintains 76% of the value at room temperature. Combining the CLSAS:Cr3+ phosphor and the 450 nm blue chip, the NIR pc‐LED is fabricated and demonstrated for fast imaging of veins in human palm and fist, as well as night vision for objects.
Ca2LuScAl2Si2O12:Cr3+ shows broad near‐infrared (NIR) emission with a bandwidth of 142 nm. The high internal quantum efficiency of 73.7% and good thermal stability are suitable for fabricating NIR phosphor‐converted light‐emitting diodes, and the fast imaging of veins for human palm and fist and the night vision for objects are obtained.
The photorelease of bioactive molecules has emerged as a valuable tool in biochemistry. Nevertheless, many important bioactive molecules, such as pyridine derivatives, cannot benefit from currently ...available organic photoremovable protecting groups (PPGs). We found that the inefficient photorelease of pyridines is attributed to intramolecular photoinduced electron transfer (PET) from PPGs to pyridinium ions. To alleviate PET, we rationally designed a strategy to drive the excited state of PPG from S1 to T1 with a heavy atom, and synthesized a new PPG by substitution of the H atom at the 3‐position of 7‐dietheylamino‐coumarin‐4‐methyl (DEACM) with Br or I. This resulted in an improved photolytic efficiency of the pyridinium ion by hundreds‐fold in aqueous solution. The PPG can be applied to various pyridine derivatives. The successful photorelease of a microtubule inhibitor, indibulin, in living cells was demonstrated for the potential application of this strategy in biochemical research.
Photorelease of pyridines from their corresponding pyridinium ions in aqueous solution is difficult due to efficient photoinduced electron transfer (PET) from photoremovable protecting groups (PPGs) to the pyridinium. Driving the excited state of coumarin‐based PPG from S1 to T1 by introducing a heavy atom alleviates PET and enhances photolytic efficiency by hundreds‐fold.
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