We develop an enzyme-triggered permeable DNA hydrogel cover to envelop and release single cells in microwells. The porous structure of the DNA hydrogel allows nutrients and waste to pass through, leading to a cell viability as high as 98%. The design provides a general method to culture, monitor, and manipulate single cells, and has potential applications in cell patterning and studying cell communication.
Currently, most available treatments focus on alleviating the primary motor symptoms including bradykinesia, muscle stiffness, tremors at rest, and other nonmotor disturbances. [3] However, therapeutic effects become limited with disease progression. [4] Thus, the development of novel treatment strategies for the prevention and delay of PD progress is urgently needed. [5] Despite in-depth researches, the detailed etiology of neuronal degeneration in PD is still unclear and controversial. Furthermore, the debate regarding whether apoptosis contributes to neuronal loss in PD is ongoing. [6] Pyroptosis is relevant to PD, as the levels of interleukin (IL)-1β and IL-18 upregulated significantly in the cerebrospinal fluid of PD patients when compared to healthy controls. [7] Emerging evidence from human samples and animal models has demonstrated that neuroinflammatory mechanisms are deleterious factors in neurodegenerative diseases [8] and may be involved in the cascade of events leading to neuronal dopaminergic degeneration. [9] Neuroinflammation occurs in the early stage of PD and leads to dopaminergic neurons damage. [9] Nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3 (NLRP3) inflammasome is a multiprotein complex composed of an NLRP3 sensor, apoptosis-associated speck-like protein (ASC, a signal adaptor), and caspase-1 protease. NLRP3 inflammasome is expressed in microglia, and plays a key role in the progression of PD. [10,11] In response to bacterial toxins, oxidative stress, or oligomeric/fibrillar α-syn aggregation, as well as other pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), the NLRP3 inflammasome assembles rapidly in microglia, resulting in the activation of caspase-1. Activated caspase-1 in turn cleaves the IL-1β precursor into the mature form of IL-1β, [12] thereby mediating proinflammatory responses and pyroptosis. [13] In 2015, the gasdermin protein was identified as a key factor for pyroptosis in inflammatory diseases, autoimmune diseases, and cancer, opening novel therapeutic avenues. [14] The introduction of pyroptosis-related agonists or antagonists is expected to improve the treatment efficacy of inflammatory diseases and may guide the development of better vaccine adjuvants or immunotherapy in the future. [15] However, the identification of Current pharmacological interventions for Parkinson's disease (PD) remain unsatisfactory in clinical settings. Inflammasome-mediated pyroptosis represents a potential therapeutic target for the alleviation of neurodegenerative diseases. The development of inflammasome-mediated pyroptosis agonists or antagonists may transform the treatment of neurodegenerative diseases. However, the identification of specific compounds that inhibit pyroptosis remains challenging. Herein, Prussian blue nanozyme (PBzyme) is revealed as a pyroptosis inhibitor to alleviate the neurodegeneration in mouse and cell models of PD. PBzyme protects the microglia and neurons against 1-methyl-4-phenyl-1...
Nontarget high-resolution mass spectrometry (Nt-HRMS) has been proven useful for the identification of unknown poly- and perfluoroalkyl substances (PFASs) in commercial products and water, but applications to biological samples are limited. China is the major PFAS-manufacturing nation; thus, here, we adapted our Nt-HRMS methods to fish collected from the Yangtze River and Tangxun Lake to discover potentially bioaccumulative PFASs in aquatic organisms destined for human consumption. In addition to traditional PFASs, over 330 other fluorinated analytes belonging to 10 classes of PFASs were detected among the pooled fish livers, including 6 sulfonate classes, 2 amine classes, 1 carboxylate class, and 1 N-heterocycle class. One class was detected in samples from both locations, 8 classes were detected exclusively in Tangxun Lake fish, and 1 class was detected exclusively in Yangtze River fish, 10 km downstream of a fluorochemical manufacturing site where we first reported these substances in wastewater 3 years ago. Overall, 4 of the PFAS classes (>165 analytes) are reported for the first time here. Wider monitoring and toxicological testing should be a priority for understanding the health risks posed to people and wildlife exposed to these substances.
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