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Heterotypic signaling of cancer-associated fibroblasts in shaping the cancer cell drug resistance
No full textThe context-dependent reciprocal interaction between the cancer cells and surrounding fibroblasts is imperative for regulating malignant potential, metabolic reprogramming, immunosuppression, and ECM deposition. However, recent evidence also suggests that cancer-associated fibroblasts induce chemoresistance in cancer cells to various anticancer regimens. Because of the protumorigenic function of cancer-associated fibroblasts, these stromal cell types have emerged as fascinating therapeutic targets for cancer. However, this notion was recently challenged by studies that targeted cancer-associated fibroblasts and highlighted the underlying heterogeneity by identifying a subset of these cells with tumor-restricting functions. Hence, it is imperative to understand the heterogeneity and heterotypic signaling of cancer-associated fibroblasts to target tumor-promoting signaling processes by sparing tumor-restricting ones. In this review, we discuss the heterogeneity and heterotypic signaling of cancer-associated fibroblasts in shaping drug resistance and also list the cancer-associated fibroblast-targeting therapeutics
Newly identified transmembrane protein 106B amyloid fibrils in the human brain: pathogens or by-products?
No full textNeurodegenerative diseases (NDs) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) constitute a spectrum of diseases characterized by the abnormal aggregation of specific amyloid fibrillar proteins; these include β-amyloid (Aβ) and tau in the form of the extracellular Aβ plaques and neuronal neurofibrillary tangles in AD and fibrillar α-synuclein aggregation in the form of Lewy bodies and Lewy neurites in PD. Transmembrane protein 106B (TMEM106B) is a type II transmembrane lysosomal protein that participates in lysosome morphology, localization, acidification, and trafficking; it is involved in the pathogenesis of several NDs, especially frontotemporal lobular degeneration with TAR DNA-binding protein immunoreactive inclusions (FTLD-TDP). Studies from four independent research groups revealed that the luminal domain of TMEM106B (120-254aa) forms amyloid fibrils in several brain regions in patients with a series of NDs and neurologically normal older adults. Given its potentially critical roles in the pathogenesis of NDs and brain aging, this surprising finding has focused attention on TMEM106B and suggested that it is nearly as fundamental as other pathogenic amyloid proteins (e.g., Aβ, tau, α-syn); nevertheless, new questions surrounding TMEM106B must be asked. In this review,we firstly introduce the physiological function of TMEM106B and its involvement in NDs. Then, we elucidate the identification and cryo-electronic microscopic structure of TMEM106B fibrils and analyze the factors that contribute to the polymorphism of TMEM106B fibrils. Finally, the potential pathogenic role of TMEM106B fibrils is discussed, and the future directions for TMEM106 research in NDs are briefly summarized
A new Perspective on Parkinson's disease: exploring the involvement of intestine and vagus lysates in α-synucleinopathy propagation
No full textIn Parkinson's disease (PD), the accumulation of misfolded α-synuclein (α-syn) in the brain is a major characteristic of the pathology. α-Syn formation and aggregation may originate in the enteric nervous system and pathologic α-syn can be transmitted to the central nervous system via the vagus nerve. In this commentary, we summarize the findings of Yang et al.[1] in which they report on the ability of a Parkinson’s disease patient's intestinal and vagus lysates containing pathologic α-syn to template endogenous rat α-syn culminating in the spread of pathologic α-syn, deposition of pathologic α-syn, and neuroinflammation in different brain regions and neurodegeneration of dopamine neurons. These observations are discussed with other studies supporting the significance of the gastrointestinal system in PD pathogenesis and future directions of research are highlighted
Portable green energy out of the blue: hydrogel-based energy conversion devices
No full textTo alleviate the escalating global demands for electricity with a low carbon footprint, we can resort to a green energy source that is conveyed by tiny temperature or moisture gradients. A tremendous source of low-grade energy scatters around us and remains unutilized, which is why thermoelectric and hydrovoltaic devices were invented. Our review focuses on a growing trend of implementing hydrogel-based ionic thermoelectric systems and hydrovoltaic devices as they hold the promise of electric outputs that are several times higher than conventional solid-state inorganic counterparts. This is due to the molecular-level tailorable features of hydrogel polymers and their interactions with water and other functional additives, which provide an ideal platform for low-grade heat and water energy harvesting from fundamental and practical perspectives. This review is divided into three sections. We present working principles, engineering concepts, state-of-art designs, and urgent challenges for hydrogel-based (i) ionic thermoelectric systems; (ii) hydrovoltaic devices; and (iii) their hybrids
Formation of strong and ductile FeNiCoCrB network-structured high-entropy alloys by fluxing
No full textA series of [(FeNiCo)0.85Cr0.15]100-xBx (x = 12, 15, 17) high-entropy alloys with network-like microstructures (N-HEAs) and a wavelength of 3-5 μm was prepared using the fluxing method. The novel N-HEAs exhibited higher strength and ductility compared with samples obtained by suction casting. Neutron diffraction and scanning electron microscopy measurements showed that the network-like structure contained soft face-centered cubic (FCC) and hard tetragonal Cr2B-type sub-networks. The network-like structure was formed during the solidification of the molten alloy from a deeply undercooled state, achieved by removing impurities and most metallic oxides through B2O3 fluxing. The mechanical properties could be tuned by modifying the composition to change the volume fractions of the different sub-networks. When x decreased from 17 to 12, the compressive yield strength decreased from 1.6 to 1.1 GPa, while the compressive strain increased from ~20% to ~70%. The N-HEA samples with x = 12 and 15 also exhibited a good tensile ductility of 19% and 14%, respectively. In situ synchrotron X-ray diffraction results revealed an inhomogeneous deformation behavior, i.e., the soft FCC phase yielded prior to the hard Cr2B-type phase, which bore more stress in the initial stage of the plastic deformation. In the later stage of the plastic deformation, the ductility of the sample was provided by the FCC phase, together with some contributions from the Cr2B-type phase
The human microbiome project at ten years - some critical comments and reflections on “our third genome”, the human virome
No full textThe Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch’s postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease – in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications
Assessment of background plastics contamination from human respiratory tract sample collection vessels
No full textHumans are increasingly exposed to airborne plastic particles due to their widespread contamination of all parts of the environment, yet the extent of inhalation exposure is still widely unknown. Bronchoalveolar lavage (BAL) and Transbronchial needle aspiration (TBNA) are two methodologies that are routinely used to detect micron or sub-micron foreign particles lodged in the human respiratory system. However, disposable plastic sampling and collection equipment is commonly used in these procedures. In this study, the potential of sample contamination due to the migration of particles from a range of containers commonly used in BAL and TBNA sample collection was investigated. PE and PVC were detected at the highest concentrations (1.5-5.6 and 1.2-8.0 g/sample, respectively) and likely originated from the container (PE) or background contamination from the manufacture/shipping process (PVC). The results demonstrated that samples collected with BAL equipment could be confidently used for the quantification of PP, PMMA, PC and PVC. Samples collected with the TBNA equipment could be confidently used for quantification of PMMA and PC, but with further assessment of trace levels from certain pieces of equipment, PP, PET, and PS could also be quantified. The results of this study demonstrate that there is potential to analyze samples collected in plastic hospital collection equipment for certain polymers. As a recommendation, background contamination from materials to be used in sample collection should be assessed before sample collection, and if consistent, then there is the potential for the analysis of a range of target plastics, with the addition of blank subtraction
Extracellular vesicles in phytopathogenic fungi
No full textExtracellular vesicles (EVs) are nano-sized lipid compartments that mediate the intercellular transport of lipids, proteins, nucleic acids and metabolites. During infectious diseases, EVs released by host cells promote immune responses, while those released by pathogens attempt to subvert host immunity. There is a growing body of research investigating the role of fungal EVs in plant pathosystems. It is becoming clear that EVs released by fungal phytopathogens play a role during infection through the transport of protein effectors, toxic metabolites and RNA. Here, we discuss recent findings on EVs in fungal phytopathogens, including the methods employed in their isolation, their characterization, contents and functionality, as well as the key questions remaining to be addressed
Theranostic extracellular vesicles: a concise review of current imaging technologies and labeling strategies
No full textExtracellular vesicles (EVs), or exosomes, are naturally occurring nano- and micro-sized membrane vesicles playing an essential role in cell-to-cell communication. There is a recent increasing interest in harnessing the therapeutic potential of these natural nanoparticles to develop cell-free regenerative medicine and manufacture highly biocompatible and targeted drug and gene delivery vectors, amongst other applications. In the context of developing novel and effective EV-based therapy, imaging tools are of paramount importance as they can be used to not only elucidate the underlying mechanisms but also provide the basis for optimization and clinical translation. In this review, recent efforts and knowledge advances on EV-based therapies have been briefly introduced, followed by an outline of currently available labeling strategies by which EVs can be conjugated with various imaging agents and/or therapeutic drugs and genes. A comprehensive review of prevailing EV imaging technologies is then presented along with examples and applications, with emphasis on imaging probes and agents, corresponding labeling methods, and the pros and cons of each imaging modality. Finally, the potential of theranostic EVs as a powerful new weapon in the arsenal of regenerative medicine and nanomedicine is summarized and envisioned
Acyl transfer-enabled catalytic asymmetric Michael addition of α-hydroxy-1-indanones to nitroolefins
No full textWe report herein an enantioselective acyl transfer protocol via electrophile activation. The reaction cascade sequence encompasses dinuclear zinc-catalyzed asymmetric Michael addition, intramolecular cyclization, and retro-Claisen reaction, which leads to a step- and atom-economic approach to a variety of protected cyclic tertiary α-hydroxyketones in good yields with excellent enantioselectivities (24 examples, 56%-82% yield, 1.5-13 dr and 79%-96% ee). Besides, the large-scale synthesis and further transformation of the products demonstrate the effectiveness of this method for organic synthesis
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